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Background Psoriatic arthritis (PsA) is a chronic, immune-mediated, spondyloarthropathy characterised by musculoskeletal signs and symptoms with associated joint pain and tenderness. The average worldwide PsA prevalence is 133/100,000, while in the Italian population is 90–420/100,000. Traditionally, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs have been used in the treatment of PsA. However, for those patients who are not adequately controlled with conventional therapies, the new biologics compounds represent a valid option. Biologic therapies have been shown to be more effective but also more expensive than conventional systemic treatments. Based on the CHRONOS study, the economic analyses presented in this paper aim to assess the annualised direct costs and the cost-per-responder of biologics in a real-world context assuming the Italian National Health System perspective. Methods The economic assessments were carried out on the overall cohort of patients, and on the tumour necrosis factor alpha inhibitors (TNFi) and the secukinumab subgroup, the most prescribed biologic therapies within the CHRONOS study. Results The annual economic impact of PsA in the overall group was €12,622, €11,725 in the secukinumab subgroup, and €12,791 in the TNFi subgroup. Biologics absorbed the main expenditure costs in the treatment of PsA accounting for about the 93% of total costs. At 6 months, secukinumab performed better in all the considered outcomes: cost-per-responder according to EULAR DAS28 and ACR50 response criteria were €12,661- €28,975, respectively, while they were €13,356 - €33,368 in the overall cohort and €13,138 - €35,166 in the TNFi subgroup. At 12 months secukinumab remained the subgroup with the lowest cost-per-responder ratio in EULAR DAS28 and ACR50 response criteria, while TNFi subgroup was the lowest one considered the ACR20. Conclusion Despite some potential methodological limitations, our cost-per-response analysis provides physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Osteomyelitis represents a challenging condition in the diabetic foot with an associated high risk of major amputation. S53P4 Bioactive Glass (BG) has bacterial inhibiting properties on the market and indicated to be used in osteomyelitis. The objective of the study was to test the efficacy and safety of BG in treating diabetic foot osteomyelitis. This was an observational, retrospective, single-centre study involving subjects with diabetes affected by osteomyelitis of the foot who underwent surgical debridement from 01/2016 to 10/2018. Overall, 44 diabetic patients (14 [31.8%] female, aged 68.0 ± 10.2 years, diabetes duration 26.8 ± 11.9 years) were studied: 22 (50%) treated with surgical debridement and a local application of BG; 22 (50%) treated by means of surgical debridement. The primary outcome was the osteomyelitis resolution. Revascularization was performed before surgical procedure in 31 (70.5%) of patients. Systemic antibiotics were used in both groups. The osteomyelitis resolution rate was significantly higher in subjects treated with BG than in subjects treated with traditional procedure (18 [90%] vs 13 [61.9%], respectively p = .03). The odds of BG to reach osteomyelitis resolution was 5.54 times greater than for traditional treatment (odds ratio 5.54, 95% confidence interval 1.10-30.5). The use of BG was associated with an 81% lower probability to need additional antibiotic therapy compared to subjects treated with traditional procedure (odds ratio 0.19, 95% confidence interval 0.04-0.87). The debridement of osteomyelitis followed by application of BG could be an effective and safe option in the treatment of osteomyelitis of the diabetic foot.

In patients with severe SARS‐CoV‐2 infection the development of cytokine storm induces extensive lung damage, and monocytes play a role in this pathological process. Non‐classical (NC) and intermediate (INT) monocytes are known to be involved during viral and bacterial infections. In this study 30 patients with different manifestations of acute SARS‐CoV‐2 infection were investigated with a flow cytometric study of NC, INT and classical (CL) monocytes. Significantly reduced NC and INT monocytes and a down‐regulated HLA‐DR were found in acute patients with severe SARS‐CoV‐2 symptoms. Conversely in patients with moderate symptoms NC and INT monocytes and CD11b expression were increased. This article is protected by copyright. All rights reserved.

Background Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. Methods We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. Results 257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1–14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33–26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41–9.78). Conclusions UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.

We describe the case of a 79-year-old woman infected by SARS-CoV-2 and purely neurological confusional syndrome without clinically relevant respiratory disease and NMR alterations of the limbic system.

Acting on the cytokine cascade is key to preventing disease progression and death in hospitalised patients with COVID-19. Among anti-cytokine therapies, interleukin (IL)-6 inhibitors have been the most used and studied since the beginning of the pandemic. Going through previous observational studies, subsequent randomised controlled trials, and meta-analyses, we focused on the baseline characteristics of the patients recruited, identifying the most favourable features in the light of positive or negative study outcomes; taking into account the biological significance and predictivity of IL-6 and other biomarkers according to specific thresholds, we ultimately attempted to delineate precise windows for therapeutic intervention. By stimulating scavenger macrophages and T-cell responsivity, IL-6 seems protective against viral replication during asymptomatic infection; still protective on early tissue damage by modulating the release of granzymes and lymphokines in mild-moderate disease; importantly pathogenic in severe disease by inducing the proinflammatory activation of immune and endothelial cells (through trans-signalling and trans-presentation); and again protective in critical disease by exerting homeostatic roles for tissue repair (through cis-signalling), while IL-1 still drives hyperinflammation. IL-6 inhibitors, particularly anti-IL-6R monoclonal antibodies (e.g., tocilizumab, sarilumab), are effective in severe disease, characterised by baseline IL-6 concentrations ranging from 35 to 90 ng/mL (reached in the circulation within 6 days of hospital admission), a ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2) between 100 and 200 mmHg, requirement of high-flow oxygen or non-invasive ventilation, C-reactive protein levels between 120 and 160 mg/L, ferritin levels between 800 and 1600 ng/mL, D-dimer levels between 750 and 3000 ng/mL, and lactate dehydrogenase levels between 350 and 500 U/L. Granulocyte-macrophage colony-stimulating factor inhibitors might have similar windows of opportunity but different age preferences compared to IL-6 inhibitors (over or under 70 years old, respectively). Janus kinase inhibitors (e.g., baricitinib) may also be effective in moderate disease, whereas IL-1 inhibitors (e.g., anakinra) may also be effective in critical disease. Correct use of biologics based on therapeutic windows is essential for successful outcomes and could inform future new trials with more appropriate recruiting criteria.

Some patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience acute hypoxemic respiratory failure progressing toward atypical acute respiratory distress syndrome (ARDS). The aim of the study is to evaluate whether a correlation between ratio of peripheral saturation of oxygen (SpO

Background Differential diagnosis of interstitial lung diseases (ILDs) during the COVID-19 pandemic is difficult, due to similarities in clinical and radiological presentation between COVID-19 and other ILDs on the one hand, and frequent false-negative swab results on the other. We describe a rare form of interstitial and organizing pneumonia resembling COVID-19, emphasizing some key aspects to focus on to get the right diagnosis and treat the patient properly. Case presentation A 76-year-old man presented with short breath and dry cough in the midst of the COVID-19 outbreak. He showed bilateral crackles and interstitial-alveolar opacities on X-ray, corresponding on computed tomography (CT) to extensive consolidations with air bronchograms, surrounded by ground glass opacities (GGO). Although his throat-and-nasopharyngeal swab tested negative, the picture was overall compatible with COVID-19. On the other hand, he showed subacute, rather than hyperacute, clinical onset; few and stable parenchymal consolidations, rather than patchy and rapidly evolving GGO; pleural and pericardial thickening, pleural effusion, and lymph node enlargement, usually absent in COVID-19; and peripheral eosinophilia, rather than lymphopenia, suggestive of hypersensitivity. In the past year, he had been taking amiodarone for a history of ventricular ectopic beats. CT scans, in fact, highlighted hyperattenuation areas suggestive of amiodarone pulmonary accumulation and toxicity. Bronchoalveolar lavage fluid (BALF) investigation confirmed the absence of coronavirus genome in the lower respiratory tract; conversely, high numbers of foamy macrophages, eosinophils, and cytotoxic T lymphocytes with low CD4/CD8 T-cell ratio were detected, confirming the hypothesis of amiodarone-induced cryptogenic organizing pneumonia. Timely discontinuation of amiodarone and initiation of steroid therapy led to resolution of respiratory symptoms, systemic inflammation, and radiographic opacities. Conclusions A comprehensive analysis of medical and pharmacological history, clinical onset, radiologic details, and peripheral and BALF cellularity, is required for a correct differential diagnosis and management of ILDs in the COVID-19 era.

Objectives This study describes the clinical features and outcomes of patients with bloodstream infection (BSI) due to Enterococcus spp. and identified factors predictive of mortality. Methods This analysis is part of a prospective multicentre observational study of consecutive hospitalised patients with BSI conducted from March 2012 to December 2012 in 31 internal medicine wards in Italy. Patients with enterococcal BSI were selected from the entire cohort. Patient characteristics, therapeutic interventions and outcome were reviewed. Cox regression analysis was performed to identify factors associated with in-hospital mortality. Hazard ratios (HRs) and 95% interval confidences (CIs) were calculated. Results Among 533 patients with BSI, 41 (7.7%) had BSI by Enterococcus spp. (28 Enterococcus faecalis, 4 Enterococcus faecium and 3 each of Enterococcus avium, Enterococcus casseliflavus and Enterococcus gallinarum). Six BSIs (14.6%) were polymicrobial. Median (IQR) patient age was 73 (66–85.5) years. In-hospital mortality was 24.4%. Polymicrobial infection (HR = 9.100, 95% CI 1.295–63.949; P = 0.026), age (HR = 1.261, 95% CI 1.029–1.546; P = 0.025) and SOFA score (HR = 1.244, 95% CI 1.051–1.474; P = 0.011) were risk factors for in-hospital mortality. Conversely, receiving an alert from the microbiology laboratory before obtaining final antimicrobial susceptibility results was associated with survival (HR = 0.073, 95% CI 0.007–0.805; P = 0.033). Conclusion BSI due to Enterococcus spp. in elderly patients is associated with high mortality. Polymicrobial infection, age and SOFA score are factors associated with poor outcome. Conversely, early alert from the microbiology laboratory improves patient survival.

Essentials Ultrasound elastography uses tissue deformation to assess the relative quantification of its elasticity. Compression and duplex ultrasonography may be unable to correctly determine the thrombus age. Ultrasound elastography may be useful to distinguish between acute and chronic deep vein thrombosis. The exact determination of the thrombus age could have both therapeutic and prognostic implications. BACKGROUND: Background Ultrasound elastography (UE) imaging is a novel sonographic technique that is commonly employed for relative quantification of tissue elasticity. Its applicability to venous thromboembolic events has not yet been fully established; in particular, it is unclear whether this technique may be useful in determining the age of deep vein thrombosis (DVT). Thus, the aim of this study was to assess the role of UE in distinguishing acute from chronic DVT. Methods Consecutive patients with a first unprovoked acute and chronic (3 months old) DVT of the lower limbs were analyzed. Patients with recurrent DVT or with a suspected recurrence were excluded. The mean elasticity index (EI) values of acute and chronic popliteal and femoral vein thrombosis were compared. The accuracy of the EI in distinguishing acute from chronic DVT was also assessed by measuring the sensitivity, specificity, positive and negative predictive values, and likelihood ratios. Results One-hundred and forty-nine patients (mean age 63.9 years, standard deviation 13.6; 73 males) with acute and chronic DVT were included. The mean EI of acute femoral DVT was higher than that of chronic femoral DVT (5.09 versus 2.46), and the mean EI of acute popliteal DVT was higher than that of chronic popliteal DVT (4.96 versus 2.48). An EI value of > 4 resulted in a sensitivity of 98.9% (95% confidence interval [CI] 93.3-99.9), a specificity of 99.1% (95% CI 94.8-99.9), a positive predictive value of 91.1% (95% CI 77.9-97.1), a negative predictive value of 98.6% (95% CI 91.3-99.9), a positive likelihood ratio of 13.23 (95% CI 93-653) and a negative likelihood ratio of 0.001 (95% CI 0.008-0.05) for acute DVT. Conclusions UE appears to be a promising technique for distinguishing between acute and chronic DVT. Larger prospective studies are warranted to confirm our preliminary findings.

Background in the current pandemic emergency, increased attention has given to treating symptoms that cause suffering in patients with COVID-19. This study aims to describe the role of palliative care in the management of these patients. Methods palliative consultation was requested by the staff as per protocol. In brief, the criteria for referring patients to a palliative care physician or to undergo palliative care were left to the discretion of the physician in charge. We recorded data regarding age, gender, length of stay, type of discharge (dead or alive, and transfer to long-term or hospice facilities). Results Between March 18 to May 8, 2020, 412 patients with COVID-19 were admitted to the Internal Medicine wards of Magenta Hospital, Italy. The palliative care physician was directly involved in 105 cases (25.5%) and performed 236 consultations. Of the 105 patients who received palliative care counselling, 66 (63%) died. The average number of days in care was 2.26 days. The principal reason for counseling was controlling symptoms (54%) and 12% deal with the end of life management. The prevalent symptom, among those which led to the counseling, was restlessness/agitation (41%), followed by emotional issues (26%) such as anxiety, fear, and demoralization. In only 20% of cases, dyspnoea was the reason for symptomatic treatment. Conclusions A large number of hospitalized Covid-19 patients are at high risk of clinical deterioration and death. This leads to the opportunity to integrate a palliative physician into the staff, who treat these patients. There is an urgent need for protocol standardization and formal trials to verify the effectiveness of this approach.

Highlights • There is no evidence that people who have recovered from coronavirus disease 2019 (COVID-19) are protected from a second infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). • People who have recovered from COVID-19 have antibodies to the virus. • No study has evaluated whether the presence of antibodies to SARS-CoV-2 confers immunity to second infection. • Our clinical observation showed that, at least in the short term, reinfection is very unlikely and any antibody immunity protects against recurrence., Background Most studies on SARS-CoV-2 infection show that people who have recovered from COVID-19 have antibodies to the virus. No study has evaluated whether the presence of antibodies to SARS-CoV-2 confers immunity to the infection relapse but however, to date, no human reinfections with SARS-CoV-2 have been confirmed. Material and methods In our prospective, multicenter, cohort study we investigated within three months all patients, with confirmed COVID-19, discharged from two Hospitals (Legnano and Magenta Hospitals), in an area of Italy severely affected by the infection. Telephone follow-up at 1 and 2 months and clinical contact within 3 months was initiated; demographic, clinical, radiologic and laboratory data were recorded in electronic medical records and updated. Results Of 1081 patients involved, 804 (74.3%) were discharged alive. For all these patients we obtained follow-up data. At 1 and 2 months none has died and none has had any signs of recurrence of infectious at both telephone interview and clinical visit. Conclusion Our clinical observation have confirmed two basic points: the reinfection is very unlikely and any antibody immunity protects against recurrence, at least in the short term.

Chest radiography is universally accepted as the method of choice to confirm correct positioning of a nasogastric tube (NGT). Considering also that radiation exposure could increase with multiple insertions in a single patient, bedside abdominal ultrasound (BAU) may be a potentially useful alternative to chest radiography in the management of NGTs.What is the accuracy of BAU in confirming the correct positioning of an NGT?After a specific course consisting of 10 h of training, the authors studied, in a prospective multicenter cohort, the validity of BAU to confirm correct NGT placement. All patients were also evaluated by auscultation (whoosh test) and by chest radiography. Every involved operator was blind to each other. Interobserver agreement and accuracy analyses were calculated.This study evaluated 606 consecutive inpatients with an indication for NGT insertion. Eighty patients were excluded for protocol violation or incomplete examinations and 526 were analyzed. BAU was positive, negative, and inconclusive in 415 (78.9%), 71 (13.5%), and 40 (7.6%), respectively. The agreement between BAU and chest radiography was excellent. Excluding inconclusive results, BAU had a sensitivity of 99.8% (99.3%-100%), a specificity of 91.0% (88.5%-93.6%), a positive predictive value of 98.3% (97.2%-99.5%), and a negative predictive value of 98.6% (97.6%-99.7%). The accuracy of BAU slightly changed according to the different assignments of the uncertain cases and was improved by the exclusion of patients with an altered level of consciousness.These results suggest that BAU has a good positive predictive value and may confirm the correct placement of NGTs when compared with chest radiography. However, considering its suboptimal specificity, caution is necessary before implementing this technique in clinical practice.

For many years, the only pharmacological option for patients with critical limb ischemia (CLI) unsuitable for revascularization has been prostanoids; however, some recent guidelines have become very restrictive regarding their use. We review the available evidence on the use of prostanoids and analyze the guideline positions as well as the possible reasons for changes over time. In most placebo-controlled trials and meta-analyses, prostanoids showed a significant effect in improving rest pain, promoting ulcer healing and reducing major amputations. Results for iloprost were especially consistent. Different prostanoid drugs have different evidence of efficacy, thus using a generic term “prostanoids” is misleading. Unfortunately, the available evidence is often of low quality and probably not sufficient to support an extensive use of prostanoids in all patients, and further high-quality randomized trials are needed. Consequently, some recent guidelines do not recommend treatment with prostanoids in this setting. However, in our opinion, pending definitive evidence, patients with CLI who have a viable limb in whom revascularization is unfeasible or has a poor chance of success, without alternative to amputation, may benefit from treatment with iloprost, balancing harms and benefits in each case.

The growing incidence of diabetes and the need to contain healthcare costs empower the necessity to identify new models of care. Telemedicine offers an acknowledged instrument to provide clinical health care at a distance, increasing patient compliance and the achievement of therapeutical goals. The objective was to test the feasibility and the efficacy in the improvement of the glycemic control of the teleconsultation for patients with type 1 diabetes mellitus. A randomized open-label, parallel arms, controlled trial was conducted in two diabetes centers in Italy. Participants affected by type 1 diabetes mellitus have been randomly (1:1) assigned to receive their visits as standard or a web-based care. Patients in the teleconsultation group can arrange their appointments on a Web site and can also have access to web educational courses or to nutritional and psychological counseling. The primary outcome was the assessment of glycemic control by HbA1c measurement after a 12-month follow-up. Overall 74 participants were followed for 1 year. HbA1c changes were not statistically different within (p = 0.56 for standard care group; p = 0.45 for telemedicine group) and between (p = 0.60) groups when considering differences from baseline to the end of the study. Patients randomized to teleconsultation reported reduced severe hypoglycemic episodes (p = 0.03). In addition, they were largely satisfied with the activities, perceived a good improvement in the self-management of the diabetes, and reported to have a time saving and a cost reduction. In conclusion, TELEDIABE proposes a new system for the management of patients with type 1 diabetes mellitus.

This cross-sectional study explores the frequency of, and rationale for, US Food and Drug Administration approval of high-risk therapeutic medical devices not meeting pivotal study primary end points from 2016 through 2020.

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

The MARI study investigated the prescription patterns of methotrexate (MTX) in patients presenting with rheumatoid arthritis (RA) in Italy. The primary aims of this cross-sectional analysis from the MARI study were to investigate the effect of gender on the prescription patterns and safety of MTX therapy.The study enrolled 1336 patients with RA. Retrospective data included patients' clinical history, previous treatment with MTX and other DMARDs, and MTX modifications in the previous 12-month period. Cross-sectional data included information about current treatment with MTX (dose and route of administration, and adverse events), concomitant medications, disease activity, and modifications of MTX treatment at study entry. The prescription patterns of MTX, rates and causes of MTX modifications were analysed according to gender.There were no significant differences related to gender in the prescription patterns of MTX, either at 6 months after starting MTX or at the time of study entry. In the 12 months prior to study entry, women (4%) were more likely to undergo MTX modifications (dose or route of administration) compared to men (2%, p=0.032), due to subjective intolerance, but this difference was no longer significant after controlling for confounders. At study entry, a higher proportion of women (27%) reported tolerability issues (nausea and weakness) related to MTX compared to men (14%, p=0.001). Although a similar percentage of males and females changed dose or route of administration of MTX at the time of study entry, the reasons for such modifications were dissimilar between genders. Particularly, a higher proportion of women underwent MTX modification due to intolerance (women 6% vs. men 1%, p=0.002).In Italy, prescription patterns of MTX do not differ between genders. However, women seem to be at higher risk of adverse events leading to MTX modifications.

BackgroundRecently we defined a user-friendly tool (FADOI-COMPLIMED scores-FCS) to assess complexity of patients hospitalized in medical wards. FCS-1 is an average between the Barthel Index and the Exton-Smith score, while FCS-2 is obtained by using the Charlson score. The aim of this paper is to assess the ability of the FCS to predict mortality in-hospital and after 1-3-6-12-months. In this perspective, we performed comparisons with the validated Multidimensional Prognostic Index (MPI).MethodsIt is a multicenter, prospective observational study, enrolling patients aged over 40, suffering from at least two chronic diseases and consecutively admitted to Internal Medicine departments. For each patient, data from 13 questionnaires were collected. Survival follow-up was conducted at 1-3-6-12 months after discharge. The relationships between cumulative incidences of death with FCS were investigated with logistic regression analyses. ROC curve analyses were performed in order to compare the predictiveness of the logistic models based on FCS with respect to those with MPI taken as reference.ResultsA cohort of 541 patients was evaluated. A 10-point higher value for FCS-1 and FCS-2 leads to an increased risk of 1-year death equal to 25.0% and 27.1%, respectively. In case of in-hospital mortality, the relevant percentages were 63.1% and 15.3%. The logistic model based on FCS is significantly more predictive than the model based on MPI (which requires an almost doubled number of items) for all the time-points considered.ConclusionsAssessment of prognosis of patients has the potential to guide clinical decision-making and lead to better care. We propose a new, efficient and easy-to-use instrument based on FCS, which demonstrated a good predictive power for mortality in patients hospitalized in medical wards. This tool may be of interest for clinical practice, since it well balances feasibility (requiring the compilation of 34 items, taking around 10 minutes) and performance.

Although myocarditis can be a severe cardiac complication of COVID-19 patients, few data are available in the literature about the incidence and clinical significance in patients affected by SARS-CoV-2. This study aims to describe the prevalence and the clinical features of suspected myocarditis in 3 cohorts of patients hospitalized for COVID-19. We retrospectively evaluated all the consecutive patients admitted for COVID-19 without exclusion criteria. Suspect myocarditis was defined according to current guidelines. Age, sex, in-hospital death, length of stay, comorbidities, serum cardiac markers, interleukin-6, electrocardiogram, echocardiogram, and therapy were recorded. Between March 4 to May 20, 2020, 1169 patients with COVID-19 were admitted in 3 Italian Medicine wards. 12 patients (1%) had suspected acute myocarditis; 5 (41.7%) were men, mean age was 76 (SD 11.34; median 78.5 years); length of stay was 38 days on average (SD 8, median value 37.5); 3 (25%) patients died. 8 (66.7%) had a history of cardiac disease; 7 (58.33%) patients had other comorbidities like diabetes, chronic obstructive pulmonary disease, or renal insufficiency. Myocarditis patients had no difference in sex prevalence, rate of death, comorbidities, elevations in serum cardiac markers as compared with patients without myocardial involvement. Otherwise, there was a significantly higher need for oxygen-support and a higher prevalence of cardiac disease in the myocarditis group. Patients with suspected myocarditis were older, had a higher frequency of previous cardiac disease, and significantly more prolonged hospitalization and a lower value of interleukin-6 than other COVID-19 patients. Further studies, specifically designed on this issue, are warranted.

The chronic course and evolution of chronic obstructive pulmonary disease (COPD) is often characterized by periods of exacerbation of symptoms, which have a negative impact on the quality of life of patients, as well as on the evolution of COPD, and represent a significant cause of medical intervention and hospitalization. Very few data are available on the efficacy of rescue antibiotics in patients with acute exacerbation of COPD (AECOPD) unresponsive to previous treatment. The aim of this study was to evaluate the efficacy of two fluoroquinolones in AECOPD previously treated without success. The FADOI-FLOR study is a randomized, single-blind, non-inferiority comparison between levofloxacin and prulifloxacin. Primary end-point was "therapeutic success" at Day 10 of treatment, defined as disappearance of signs/symptoms or decrease of at least three points of a global score of symptomatology (maximum score = 15). 258 patients were enrolled (128 levofloxacin and 130 prulifloxacin), in 25 centers. A very high proportion of patients in the two groups had therapeutic success at Day-10 (levofloxacin 93.0% vs prulifloxacin 96.7%, population intention-to-treat; 94.6% vs 99.1%, population per-protocol). Earlier therapeutic success (within 7 days) was achieved in 32.0% and 36.2% of patients receiving levofloxacin or prulifloxacin, respectively. At 3-month follow-up, re-exacerbations occurred in 17.8% of patients treated with levofloxacin and 14.2% of those receiving prulifloxacin (p = 0.44). In conclusion, fluoroquinolones are very effective in the treatment of AECOPD resistant to other antibiotics.

BACKGROUND: In countries with public health system, hospital bed reductions and increasing social and medical frailty have led to the phenomenon of “outliers” or “outlying hospital in-patients.” They are often medical patients who, because of unavailability of beds in their clinically appropriate ward, are admitted wherever unoccupied beds are. The present work is aimed to systematically review literature about quality and safety of care for patients admitted to clinically inappropriate wards. METHODS: We performed a systematic review of studies investigating outliers, published in peer-reviewed journals with no time restrictions. Search and screening were conducted by two independent researchers (MLR and ER). Studies were considered potentially eligible for this systematic review if aimed to assess the quality and/or the safety of care for patients admitted to clinically inappropriate units. Our search was supplemented by a hand search of references of included studies. Given the heterogeneity of studies, results were analyzed thematically. We used PRISMA guidelines to report our findings. RESULTS: We collected 17 eligible papers and grouped them into six thematic categories. Despite their methodological limits, the included studies show increased trends in mortality and readmissions among outliers. Quality of care and patient safety are compromised as patients and health professionals declare and risk analysis displays. Reported solutions are often multicomponent, stress early discharge but have not been investigated in the control group. CONCLUSIONS: Published literature cannot definitely conclude on the quality and safety of care for patients admitted to clinically inappropriate wards. As they may represent a serious threat for quality and safety, and moreover often neglected and under valued, well-designed and powered prospective studies are urgently needed.

Objective To develop a risk-scoring tool to predict multidrug-resistant (MDR) etiology in patients with bloodstream infections (BSI) caused by Gram-negative bacilli (GNB). Methods A prospective multicenter study analyzed patients with BSI hospitalized in 31 Internal Medicine wards in Italy from March 2012 to December 2012. Patients with BSI caused by MDR-GNB (non-susceptible to at least one agent in three antimicrobial categories) were compared to those with BSI due to susceptible GNB. A logistic regression to identify predictive factors of MDR-GNB was performed and the odds ratio (OR) were calculated. A score to predict the risk of MDR was developed. Results Of 533 BSI episodes, 253 (47.5%) were caused by GNB. Among GNB-BSI, 122 (48.2%) were caused by MDR-GNB while 131 (51.8%) by non-MDR GNB. At multivariate analysis transfer from long-term care facility (OR 9.013, 95% CI 1.089–74.579, p = 0.041), hospitalization in the last 3 months (OR 2.882, 95% CI 1.580–5.259, p = 0.001), urinary catheter (OR 2.315, 95% CI 1.202–4.459, p = 0.012), antibiotic therapy in the last 3 months (OR 1.882, 95% CI 1.041–3.405, p = 0.036), age ≥ 75 years (OR 1.866, 95% CI 1.076–3.237, p = 0.026) were factors independently associated with MDR etiology. A score ranging from 0 to 10 was useful to recognize patients at lowest risk (0 points: Negative Likelihood Ratio 0.10) and those at highest risk (>6 points, Positive Likelihood Ratio 11.8) of GNB bacteremia due to a MDR strain. Conclusions Specific predictors of MDR etiology are useful to calculate probabilities of MDR etiology among hospitalized patients with blood cultures positive for GNB.

Atrial fibrillation is the most frequent arrhythmia, but few data are available on patients' characteristics and management in the context of Internal Medicine wards.Data were collected at the beginning of 2010 in 18 Internal Medicine units of the regions Liguria and Piemonte (Italy). Each centre reviewed the hospital charts of the last 50 patients discharged during the year 2009 in whom a diagnosis of atrial fibrillation had been made (patient's history or during the hospitalization).A total of 903 atrial fibrillation patients were evaluated. Prevalence of atrial fibrillation among patients hospitalized in Internal Medicine units was 18.2%. More than 85% of patients had at least two diseases other than atrial fibrillation, and 'lone' atrial fibrillation was rare (1.3%). During hospital stay, 80.5% of the patients received at least one treatment for atrial fibrillation: 55.5% received an antithrombotic and 61.8% a drug for arrhythmia, mostly aimed at rate control (47.2%). In-hospital all-cause mortality was 13.4%. At discharge, 70.2 and 68.9% of the patients received prescription of a drug for arrhythmia and for antithrombotic treatment, respectively. Prescription of oral anticoagulants was significantly associated with hypertension, while previous bleeding, age above 75 years, paroxysmal atrial fibrillation, male sex and a number of concomitant drugs of more than four were strong negative predictors.Data from our study confirm that atrial fibrillation is a common finding in patients hospitalized in Internal Medicine units, and this population is characterized by multiple comorbidities and severe prognosis. Discrepancies exist between recommendations by guidelines and real-world management, owing to the complexity of patients and limits of existing treatment strategies.

This letter provides a view on the issue of the organizational model of Primary Care Groups (PCGs), which represent a best practice in continuity and appropriateness of care for chronic patients. Our analysis aimed at estimating the impact of PCGs introduction in terms of efficiency and effectiveness. The results of our study showed a better performance of PCGs compared with the other General Practitioners of Local Health Authority Milano 1, supporting the conclusion that good care cannot be delivered without good organization of care.

Introduction A majority of invasive Candida infections occur in medical wards; however, evidence for management in this setting is scarce and based primarily on the intensive care or surgical setting. On behalf of the Italian Society for Anti-Infective Therapy (SITA) and the Italian Federation of Associations of Hospital Doctors on Internal Medicine (FADOI), the MEDICAL group produced practical management algorithms for patients in internal medicine wards. Methods The MEDICAL group panel, composed of 30 members from internal medicine, infectious disease, clinical pharmacology, clinical microbiology and clinical epidemiology, provided expert opinion through the RAND/UCLA method. Results Seven clinical scenarios were constructed based on clinical severity and probability of invasive candidiasis. For each scenario, the appropriateness of 63 different diagnostic, imaging, management, or therapeutic procedures was determined in two Delphi rounds. The necessity for performing each appropriate procedure, was then determined in a third Delphi round. Results were summarized in algorithms. Discussion The proposed algorithms provide internal medicine physicians and managers with an easy to interpret tool that is exhaustive, clear and suitable for adaption to individual local settings. Attention was paid to individual patient management and resource allocation.

Appropriate management of hyperglycemia is crucial for patients with type 2 diabetes. Aim of the FADOI-DIAMOND study was to evaluate real-world management of type 2 diabetic patients hospitalized in Internal Medicine wards (IMW) and the effects of a standardized educational intervention for IMW staff. DIAMOND has been carried out in 53 Italian IMW, with two cross-sectional surveys interspersed with an educational program (PRE phase and POST phase). In PRE phase, each center reviewed the charts of the last 30 hospitalized patients with known type 2 diabetes. An educational program was conducted in each center by means of the “outreach visit,” a face-to-face meeting between IMW staff and a trained external expert. Six months after, each center repeated the data collection (POST phase), specular to the PRE. A total of 3,167 patients were enrolled (1,588 PRE and 1,579 POST). From PRE phase to POST, patients with registered anthropometric data (54.1 vs. 74.9 %, p < 0.001) and in-hospital/recent measurement of glycated hemoglobin (48.2 vs. 61.4 %, p < 0.005) increased significantly. After educational program, more patients received insulin during hospitalization (68.3 vs. 63.6 %, p = 0.005). A more relevant variation in glycemia during hospitalization was observed in POST phase than PRE (−22.2 vs. −15.5 mg/dL, p < 0.001), without differences as for occurrence of hypoglycemia (12.3 vs. 11.9 %). A one-shot educational intervention led to persistent improvement in the management of hospitalized patients with type 2 diabetes and to significant better glycemic control. Further studies might evaluate the effectiveness of a more aggressive educational program, on both management and outcomes.

Invasive mycoses are a rising problem, not only in traditional categories of patients like hematologic or neutropenic ones, but also in elderly non-neutropenic patients admitted to internal medicine wards. Patients being admitted to medical wards are usually older, have multiple comorbidities, e.g., liver cirrhosis or chronic obstructive respiratory disease, may be malnourished or receive peripheral or total parenteral nutrition, and frequently are undergoing chronic corticosteroid therapy, chemotherapy for cancer or monoclonal antibodies for autoimmune diseases. Such risk factors may be contemporarily present in a single patient increasing the risk for the development of invasive mycoses. Diagnosis of candidemia and invasive aspergillosis is particularly difficult in patients hospitalized on medical wards, since symptoms and signs have low specificity, and most diagnostic tests have been only validated in neutropenic hematologic patients, but not in those without neutropenia. Both candidemia and invasive aspergillosis carry significant morbidity and mortality. The aim of this paper is to provide a simple guide to physicians for a prompt identification and treatment of patients with possible or suspected invasive mycoses. © 2014 SIMI.

OBJECTIVES The purpose of this study was to evaluate benzodiazepine receptor expression on leukocytes from patients with symptomatic or silent myocardial ischemia. BACKGROUND Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Pain can be effectively controlled by various endogenous mechanisms. Benzodiazepines and their receptors play key roles in pain, in interactions with peptide opioids, in inflammation and in the response to stress. METHODS The study group consisted of 57 patients with reproducible exercise-induced myocardial ischemia. The presence of a constant behavior in the anginal pain perception during both exercise-induced ischemia and daily life was the most important inclusion criterion. Venous blood samples were taken from all patients to evaluate the expression of peripheral benzodiazepine receptors by flow cytometry. The study cohort was classified into two groups: 24 patients who had anginal pain both at home and during the exercise stress test and 33 patients who were asymptomatic during both daily life and exercise-induced ischemia. RESULTS Flow cytometry analysis showed increased expression of peripheral benzodiazepine receptors on all types of leukocytes in the asymptomatic patients. The difference was statistically significant for lymphocytes (p < 0.005), monocytes (p < 0.001) and granulocytes (p < 0.001). CONCLUSIONS These data show that expression of peripheral benzodiazepine receptors was higher in patients with silent myocardial ischemia than in symptomatic patients.

Although devoid of proliferative capacity, polymorphonuclear neutrophils (PMN) express receptors for haemopoietic growth factors and need growth factors for survival and functional stimulation. This study showed that in vitro treatment of human PMN with GM-CSF for up to 48 h increases cell surface expression of the β2-integrin molecules CD11b/CD18 and CD11c/CD18 and of the receptor for the chemotactic peptide fMLP. Such modifications are usually expression of PMN activation. PMN treated with GM-CSF also displayed increased phagocytosis of latex particles and enhanced oxidative burst and superoxide anion release. Since integrins mediate PMN adhesion to endothelium, homotypic adhesion, chemotaxis/phagocytosis and the triggering of respiratory burst, our results suggested that functional stimulation of PMN persisted following prolonged exposure of PMN to growth factors and that it was not a temporary phenomenon which lasted only for the first 12-24 h of treatment. We also used oligonucleotides antisense to the Bcr gene mRNA to inhibit expression of the gene and evaluate its function in PMN, following the recent observation that PMN from Bcr-null mutant mice produced increased amounts of reactive oxygen metabolites upon activation. The antisense oligonucleotides had no effect on the parameters investigated. This may indicate that increased production of O 2 - by neutrophils in which the Bcr gene is not expressed requires either that gene expression is absent in the earlier stages of myeloid differentiation/ maturation, so that when inhibition occurs in the terminally differentiated neutrophils their functional status is no longer influenced, or that the residual low-level expression of the gene which may be present in the antisense-treated cells is sufficient to provide a normal response to stimulation.

The aims of this study were to assess the possible role of peripheral benzodiazepine receptors (pBZrs)1 in mediating the in vitro effects of carbamazepine (CBZ) on some neutrophil functions in healthy volunteers and to investigate neutrophil function and pBZr expression in patients with epilepsia on CBZ monotherapy for at least 1 year. In vitro CBZ (42-168 microM) concentration-dependently inhibited chemotaxis induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP) or lipopolysaccharide (LPS)-activated human serum. CBZ did not affect random migration, phagocytosis index, phagocytosis frequency, NBT reduction frequency, C. albicans lethality index and resting superoxide production. The pBZr antagonist PK 11195 (1 microM, per se ineffective) reversed the inhibitory effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP. The pBZr agonist Ro 5-4864 (10-100 microM) mimicked the effect of CBZ on chemotaxis induced by endotoxin-activated serum or FMLP and had no effect on the other parameters. Neutrophils from epileptic patients on chronic CBZ monotherapy had impaired FMLP- and serum-induced chemotaxis and enhanced expression of pBZrs on neutrophils. These data strongly suggest an involvement of pBZrs in mediating the in vitro effects of CBZ on chemotaxis; furthermore, impairment of the same neutrophil function parameters and overexpression of pBZrs in patients are consistent with the hypothesis of an in vivo interaction of CBZ with pBZrs.

Aims acutely ill medical patients are at increased risk of venous thromboembolism (VTE) and often require thromboprophylaxis, but patient selection and adequate therapeutic decisions may be difficult due to the heterogeneity and the complexity of this population. We conducted a survey among a large cohort of Italian physicians to assess their approach to some important “grey” areas of VTE prevention in this setting. Methods a questionnaire was distributed during the meeting of a national society of Internal Medicine (FADOI), held in May 2013. Four clinical scenarios describing areas of clinical uncertainty were administered to participants: the first on a patient with acute ischemic stroke; the second on a patient with severe renal insufficiency; the third on the duration of prophylaxis in the post-acute setting; and the last on a patient at high risk of VTE and at moderate risk of bleeding with preserved mobility. Results 453 questionnaires were returned (participants mean age 48.5 years). About 70% of participants systematically assess VTE and bleeding risk in their clinical practice, but a minority of them use risk assessment models. Prolonged prophylaxis in the post-acute setting was voted by more than eighty percent of participants; replies to the other three clinical scenarios were more heterogeneous with none of the options selected by more than 60% of participant. Conclusion physicians approach to “grey” areas of antithrombotic prophylaxis in the medical setting is quite heterogeneous and sometimes partially in contrast to recent guidelines, reinforcing the need for educational programs and high quality studies in this setting.

Oral anticoagulants offer the best long-term protection against ischemic stroke in patients with atrial fibrillation (AF). However, vitamin K antagonists (VKA) are cumbersome to use and their prescription is far from guidelines recommendations. We report the results of a large survey on the attitudes of prescription of VKA in patients with AF.7148 patients were enrolled by 196 Internal Medicine (MED) and 164 Cardiology (CARD) centers, and VKA specifically analyzed. Thrombotic and hemorrhagic risks were evaluated by means of CHADS2 and CHA2DS2VASc scores, and a study-specific bleeding score (modified HAS-BLED).63.9% of non-valvular patients had a CHADS2 score≥2 (MED: 75.3%-CARD: 53.1%), and 28.4% a bleeding score≥3 (41.9% MED-15.8% CARD). VKA were prescribed in 55.5% of non-valvular patients (46.3% MED and 64.2% CARD), in 81% of high-risk valvular patients and in 58.8% of the overall study population. Among patients at high risk of bleeding (score≥3), VKA were prescribed in 26.9% of subjects, while, in the subgroup at high risk of thrombosis (CHADS2 Score2), these were prescribed in 54.4%. Age≥75, paroxysmal AF, cognitive impairment, need for assistance, CHADS22 and bleeding score≥3 were independent predictors of non-use of VKA.Oral anticoagulants are more frequently used in CARD than in MED, plausibly due to greater complexity of MED patients. Stratification of thrombotic and hemorrhagic risk significantly drives the choice for VKA. However the fraction of patients in whom prescription or non-prescription is based on other individual characteristics is not negligible.

Objectives.This study sought to evaluate the relation, if any, between clinical and angiographic findings in patients with unstable angina and monocyte and neutrophil CD11b/CD18 receptor density. The expression of HLA-DR molecules on T lymphocytes, an index of activation of these cells, was also investigated.Background.Although activation of neutrophils and monocytes has recently been shown in unstable angina, no studies have correlated activation indexes with clinical and angiographic features of patients with this clinical condition.Methods.Sixty patients underwent diagnostic coronary arteriography and simultaneous blood sampling from the aorta and coronary sinus before injection of contrast medium. Cell surface receptors were detected by direct immunofluorescence evaluated by flow cytometry using monoclonal antibodies tagged with fluorescent markers.Results.In 38 patients with unstable angina, neutrophils and monocytes showed a significantly higher expression of CD11b/ CD18 adhesion receptors in coronary sinus than aortic blood (p < 0.0001 and p < 0.001, respectively). When these patients were analyzed according to clinical characteristics or angiographic findings, no difference in CD11b/CD18 receptor expression in coronary sinus blood was found between the various subgroups, except for patients with at least one episode of chest pain at rest within 48 h of coronary arteriography and a higher neutrophil adhesion molecule density than patients who remained asymptomatic (p = 0.04). Lymphocytes in patients with stable and unstable angina showed a similar percent expression of CD2/ CD19 and CD3/HLA-DR antigens, with no difference between aortic and coronary sinus blood.Conclusions.These results in a larger cohort confirm previous data that neutrophil and monocyte CD11b/CD18 adhesion molecules show a higher expression in the coronary sinus blood of patients with unstable angina. Among clinical and angiographic findings in patients with unstable angina, only the occurrence of chest pain within 48 h of coronary angiography was related to significantly higher values of neutrophil fluorescence intensity, suggesting that the degree of neutrophil activation is related to the proximity of rest angina episodes to blood sampling. Finally, our data do not support the concept of systemic or transcardiac lymphocyte activation in unstable angina.

Background Patients with peripheral arterial disease (PAD) at stage IIb, pain-free walking distance (PFWD) less than 100 m and unsuitable for revascularization have both impaired quality of life and severe clinical outcome. Aim of the study was to evaluate the efficacy of the prostacyclin analogue iloprost, added to standard therapy, in these patients. Material and methods Patients were randomized to receive standard medical therapy (Group A) or standard therapy plus iloprost (Group B), for 1 year. Iloprost was administered for 10 days every 3 months. Treadmill test was performed every 3 months, in Group B before starting the 10-day iloprost cycle. Results Fifty patients in Group A and 51 in Group B were enrolled. Mean baseline and 12-month PFWD values were 75·4 ± 21·3 and 128·9 ± 62·9 for iloprost group and 70·3 ± 21·6 and 99·6 ± 62·6 m for controls. Patients treated with iloprost had significantly higher PFWD at 9 and 12 months. This finding was confirmed after carrying forward the last valid observation (124·7 ± 63·4 vs. 88·4 ± 63·1 m, P

Introduction Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in medical patients, and the economic burden of this disease is plausibly relevant as well. However, few data from real-world observations are available on this topic. Aim of our study was to assess the costs of VTE management and antithrombotic prophylaxis in patients hospitalized in Internal Medicine (IM) departments. Materials and methods The in-hospital paths of 160 patients with VTE (VTE group) and 160 patients receiving prophylaxis and without VTE (NO-VTE group) were retrospectively evaluated within 26 IM units in Italy. The economic analysis was undertaken by applying a process analysis, the initial phase of the more comprehensive Activity Based Costing technique. Accordingly to this approach, only information closely linked to VTE or its prevention was registered. Results The total median costs for VTE management were around four-times higher than those for prophylaxis (€ 1,348.68 vs € 373.03). Human resources were the most important cost-driver (55.5% and 65.7% in the VTE and NO-VTE groups), followed by instrumental (24.6% in VTE and 15.5% in NO-VTE) and haematologic tests (12.6% in VTE patients and 13.3% in controls). In the NO-VTE group the direct costs for prophylaxis accounted for 4.5% of total. Conclusions The real-world data of this study confirm the economic burden of in-hospital treatment of VTE, and the relatively low costs of thromboprophylaxis. A greater adherence to evidence-based protocols for VTE prevention could probably reduce the current financial burden of VTE on healthcare systems.

Objective To assess fetal and maternal outcomes in women with systemic sclerosis (SSc). Methods Prospectively collected data on 99 women with SSc from 25 Italian centers were analyzed retrospectively. Women with SSc were observed during 109 pregnancies (from 2000 to 2011), and outcomes were compared to those in the general obstetric population (total of 3,939 deliveries). The maternal age at conception was a mean ± SD 31.8 ± 5.3 years, and the median disease duration at conception was 60 months (range 2–193 months). Results SSc patients, compared to the general obstetric population, had a significantly increased frequency of preterm deliveries (25% versus 12%) and severe preterm deliveries (

In order to elucidate better the immunological effect of opioid abuse in the absence of HIV infection as a confounding factor, granulocyte function was investigated in three groups of HIV-negative subjects, including 20 active parenteral heroin abusers (H), 20 long-term methadone-maintained former opiate abusers (M) and 20 healthy controls (C). Chemotaxis to N-formyl methionyl-leucyl-phenylalanine (fMLP), casein and activated plasma were markedly and similarly reduced (approx. 50%) in both H and M groups, as was true for superoxide production after fMLP and PMA stimulation, 47% decrease of C values. Polymorphonuclear (PMN) of H and M subjects also exhibited a very marked and similar reduction in the expression of CD11b/CD18 integrin receptors after fMLP treatment, with values that were less than 10% of those in controls, as observed by flow cytometry. In parallel, PMN of H and M individuals presented an approximately four-fold increase in opioid receptors numbers compared to controls, a significant inverse correlation existing between the increase in opiate receptors and defective chemotaxis. The possible mechanism underlying the observed changes in PMN of H and M individuals is discussed.

We have evaluated the function of granulocytes in 14 patients suffering from myelodysplastic syndrome (MDS). We also evaluated the functional and immunochemical activities of five monoclonal antibodies (MoAbs) reactive with the CD11/CD18 leucocyte adhesion molecules of granulocytes. Granulocytes showed a decrease in chemotaxis (P < 0.001) and in aggregation (P < 0.01) using various agents as a stimulus. Cytofluorimetric and immunoenzymatic assays with alkaline phosphatase (APAAP) analysis showed decreased expression of the CD11b/CD18 receptor detected by OKM1 (P < 0.001). Despite LFA-1 and-CD11a/CD18 was expressed in normal amounts. The studies of upregulation of granulocytes CD11b/CD18 and image analysis of immunochemical preparation (APAAP) demonstrated decreased expression of CD11b/CD18 in granulocytes from MDS compared to controls (P < 0.001). We conclude that granulocyte dysfunction in MDS may be correlated with decreased expression of surface CD11b/CD18 leucocyte adhesion molecules or their structural modification.

The effect of the opioid agonist morphine and of the (-) and (+) stereoisomers of the antagonist naloxone were studied on superoxide generation from human granulocytes. Morphine or naloxone had no effect on basal or phorbol 12-myristate 13-acetate (PMA)-stimulated superoxide generation. Combined equimolar (-)naloxone and morphine concentrations (0.1 pM - 0.1 μ;M) inhibited PMA-stimulated superoxide generation, while combined (+)naloxone and morphine had no effect. The stereospecific effect of naloxone suggests the involvement of opioid receptors. Thus, inhibition of superoxide generation by combined (-)naloxone and morphine could result from the unmasking of non opioid effects of morphine. It is suggested that the opioid control of oxidative metabolism in human granulocytes could involve multiple receptors mediating opposite effects.

Hospitalised medical patients are at increased risk of venous thromboembolism (VTE), but the incidence of hospitalisation-related VTE in unselected medical inpatients has not been extensively studied, and uncertainties remain about the optimal use of thromboprophylaxis in this setting. Aims of our prospective, observational study were to assess the prevalence of VTE and the incidence of symptomatic, hospitalisation-related events in a cohort of consecutive patients admitted to 27 Internal Medicine Departments, and to evaluate clinical factors associated with the use of thromboprophylaxis. Between March and September 2006, a total of 4,846 patients were included in the study. Symptomatic VTE with onset of symptoms later than 48 hours after admission ("hospital-acquired" events, primary study end-point) occurred in 26 patients (0.55%), while the overall prevalence of VTE (including diagnosis prior to or at admission) was 3.65%. During hospital stay antithrombotic prophylaxis was administered in 41.6% of patients, and in 58.7% of those for whom prophylaxis was recommended according to the 2004 Guidelines of the American College of Chest Physicians. The choice of administering thromboprophylaxis or not appeared qualitatively adherent to indications from randomised clinical trials and international guidelines, and bed rest was the strongest determinant of the use of prophylaxis. Data from our real-world study confirm that VTE is a relevant complication in patients admitted to Internal Medicine Departments, and recommended tromboprophylaxis is still under-used, in particular in some patients groups. Further efforts are needed to better define risk profile and to optimise prophylaxis in the heterogeneous setting of medical inpatients.

Granulocytes defend the body against invading microbes by producing a complex armamentarium of toxic substances, such as proteolytic enzymes, oxygen radicals and arachidonic acid metabolites. Under certain circumstances, however, such compounds may be released in the absence of phagocytosable particles, resulting in injury to normal cell and connective tissue degradation. Recent experimental studies have emphasized the potential role of granulocytes in the pathogenesis of myocardial ischemia. Clinical investigations have also shown alterations in neutrophil function in stable and unstable clinical manifestations of ischemic heart disease. "Priming" of granulocytes in stable forms of coronary disease may predispose to the subsequent development of acute coronary events, whereas activation of neutrophils may lead to alterations in vascular permeability and coronary flow regulation, leading to further myocardial and endothelial injury in acute myocardial infarction, unstable angina and coronary angioplasty.