Micaela La Regina

Familial Mediterranean fever is no longer a rare disease in Italy

Familial Mediterranean fever (FMF) is an autosomal recessive disorder, characterised by short, recurrent attacks of fever with abdominal, chest or joint pain and erysipelas-like erythema. It is an ethnically restricted genetic disease, found commonly among Mediterranean populations, as well as Armenians, Turks, Arabs and Jews. Traditionally, Italians have been considered little affected by FMF, despite the geographical position of Italy (northern Mediterranean basin) and the migratory changes in its population. The objective was to characterise the demographic, clinical and genetic features of FMF in Italy. Patients of Italian origin were recruited from those referred to Italian-French medical centres for FUO (Fever of Unknown Origin) or ‘surgical’ emergencies; clinical history, genealogy and physical examination were recorded; all other possible infectious, neoplastic, auto-immune and metabolic diseases were excluded. Mutational analysis of the gene responsible for FMF (MEFV on 16p13.3) was performed, after which geno-phenotypical correlations were established. Italian FMF patients, 40 women and 31 men, aged from 3 to 75 years, have shown all the clinical manifestations indicative of FMF described in the literature, but with a lower incidence of amyloidosis. The genetic tests have been contributive in 42% of cases. The frequency of each different mutation has been similar to that found in a series of ‘endemic’ countries. The geno-phenotypical correlations have suggested the existence of genetic and/or environmental modifier-factors. Among Italians FMF seems to be more frequent than was believed in the past. The data presented are consistent with their geographical location and their history.

Familial Mediterranean fever: a review for clinical management

Familial Mediterranean Fever (FMF) is a hereditary autosomal recessive, autoinflammatory disorder characterized by recurrent, self-limiting episodes of short duration (mean 24-72 h) of fever and serositis. FMF is the most frequent periodic febrile syndrome among the autoinflammatory syndromes (AS), a heterogeneous group of recently identified diseases clinically characterized by recurrent febrile attacks, in the absence of autoantibodies and antigen-specific T lymphocytes. In FMF, periodic attacks show inter- and intra-individual variability in terms of frequency and severity. Usually, they are triggered by apparently innocuous stimuli and may be preceded by a prodromal period. The Mediterranean FeVer gene (MEFV) responsible gene maps on chromosome 16 (16p13) encoding the pyrin-marenostrin protein. The precise pathologic mechanism is still to be definitively elucidated; however a new macromolecular complex, called inflammasome, seems to play a major role in the control of inflammation and it might be involved in the pathogenesis of FMF. The most severe long-term complication is type AA amyloidosis, principally affecting the kidney and the cause of chronic renal failure. Two types of risk factors, genetic and non-genetic, have been identified for this complication. Currently, the only effective treatment of Familial Mediterranean Fever is the colchicine. New drugs in a few colchicine resistant patients have been tried, but additional studies on larger series are necessary to draw definitive conclusions.

Three-month mortality rate and clinical predictors in patients with venous thromboembolism and cancer. Findings from the RIETE registry

Patients with venous thromboembolism (VTE), and particularly those with cancer, are at increased risk of recurrences, major bleeding, and short- / medium-term mortality. Data from 35,539 patients (6,075 of these with cancer), presenting with symptomatic VTE in the previous three months and enrolled in the worldwide RIETE registry, were evaluated to assess overall and pulmonary embolism (PE)-related mortality, and their potential predictors, with particular focus on patients with cancer. Overall 3-month mortality in the total RIETE population was 7.9%, and death was considered PE-related in 1.4%. Significantly more patients died among those with cancer (26.4%, vs 4.1% in no-cancer group, p<0.001). In 3.0% of cancer patients death was considered PE-related, compared to 1.0% in no-cancer group (p<0.001). Cancer was the strongest independent risk factor for both all-cause and PE-related mortality, and in the subgroup of cancer patients those with advanced disease, reduced mobility, chronic pulmonary disease, and those experiencing PE (vs isolated deep vein thrombosis) were at increased risk of PE-related death. According to the findings of our very large, real-world registry, in the three months following an acute episode VTE remains a substantial cause of mortality. Cancer patients are at particular high risk of VTE-related death. Clinical factors predicting a fatal PE identified in this study (cancer, immobility, comorbidities, increasing age, PE at presentation), could be considered for risk stratification scheme for secondary prophylaxis in daily practice.

Systemic Inflammatory Diseases and Silicone Breast Prostheses: Report of a Case of Adult Still Disease and Review of the Literature

There has been a debate about the possibility of a link between silicone breast implants and the onset of systemic connective tissue diseases (eg, scleroderma, systemic lupus erythematosus, rheumatoid arthritis) and other inflammatory pathologies, such as silicone implant associated syndrome and adult Still disease. We report a case of adult Still disease in a patient with a silicone gel breast implant. The disease regressed with steroidal treatment, and the patient is now no longer steroid-dependent, although the implant is still in place.

Clinical Features, Short-Term Mortality, and Prognostic Risk Factors of Septic Patients Admitted to Internal Medicine Units: Results of an Italian Multicenter Prospective Study.

AbstractOnly a few studies provided data on the clinical history of sepsis within internal Medicine units.The aim of the study was to assess the short-term mortality and to evaluate the prognostic risk factors in a large cohort of septic patients treated in internal medicine units.Thirty-one internal medicine units participated to the study. Within each participating unit, all admitted patients were screened for the presence of sepsis.A total of 533 patients were included; 78 patients (14.6%, 95%CI 11.9, 18.0%) died during hospitalization; mortality rate was 5.5% (95% CI 3.1, 9.6%) in patients with nonsevere sepsis and 20.1% (95%CI 16.2, 28.8%) in patients with severe sepsis or septic shock. Severe sepsis or septic shock (OR 4.41, 95%CI 1.93, 10.05), immune system weakening (OR 2.10, 95%CI 1.12, 3.94), active solid cancer (OR 2.14, 95% CI 1.16, 3.94), and age (OR 1.03 per year, 95% CI 1.01, 1.06) were significantly associated with an increased mortality risk, whereas blood culture positive for Escherichia coli was significantly associated with a reduced mortality risk (OR 0.46, 95%CI 0.24, 0.88).In-hospital mortality of septic patients treated in internal medicine units appeared similar to the mortality rate obtained in recent studies conducted in the ICU setting.

Real-world management of atrial fibrillation in Internal Medicine units: the FADOI 'FALP' observational study.

Background Atrial fibrillation is the most frequent arrhythmia, but few data are available on patients’ characteristics and management in the context of Internal Medicine wards. Methods 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 (patients history or during the hospitalization). Results 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. Conclusion 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.

Pulmonary embolism prognostic factors and length of hospital stay: A cohort study

INTRODUCTION Patients with pulmonary embolism (PE) are commonly admitted to hospital for their initial treatment. We aimed to assess the association of length of hospital stay with commonly available clinical variables and their combinations. METHODS A retrospective multicenter cohort study was conducted on consecutive PE patients admitted to eight Italian centers. Logistic regression analysis was performed to evaluate the association between the length of hospital stay and the Pulmonary Embolism Severity Index (PESI) parameters, National Early Warning Score (NEWS) and other possible determinants. RESULTS We enrolled 391 patients, with a median hospital stay of 10days (IQR 7-14). Among PESI parameters, only oxygen saturation <90% was significantly associated with length of hospital stay at univariable analysis (OR 1.99; 95% CI 1.3-3.2). At multivariable analysis, NEWS ≥5 was associated with prolonged hospitalization (OR 3.14; 95% CI 1.2-8.3). A difference of median hospital stay was found between simplified PESI high and low risk groups (10 and 9days, respectively, p=0.027). DISCUSSION The median duration of hospital stay was generally long and not influenced by single parameters of PESI or common prognostic factors. The difference of one day between the low- and high-risk groups according to simplified PESI was not clinically significant.

Internal medicine wards and the chronic diseases epidemic: it is time to change the standards

Increasing life expectancy, is associated with increasing prevalence of chronic diseases, often variously associated in the same patient leading to complex clinical pictures. The complexity of the management of patients with comorbidities is a real emergency, a kind of epidemic of the third millennium in developed countries. This kind of management is the core competency of Internal Medicine [1]. Nevertheless, the boundaries between inpatient and outpatient medicine are gradually fading away. Internal medicine is the classical ‘‘link discipline’’, providing primary and expert care in the hospital and, in many European countries, also in the outpatient setting [2]. Hospital internal medicine should work with primary physicians warranting a continuum of care for patients who are very weak and who have complex conditions. Unfortunately, in recent years, Italian national health system experienced continuous cuts of hospital beds without parallel development of alternative care pathways outside of the hospital. So, internal medicine wards are always crowded ([80 % of their patients come from the emergency department (ED) and a large number of patients, admitted to internal medicine, in absence of available beds, are temporarily placed in other wards with a subsequent suboptimal care. The current scenario includes long queues in the ED quick, stressful and risky turnover in wards and out of hospital primary care family physicians uncomfortable with the elderly patients affected by multiple pathologies. Too often, unfortunately, the extensive and difficult but hidden work of internists is not adequately recognized by institutions or even within the internists community, which do not know well how they work and what kind of activities they carry out. The Ligurian internal medicine group performed a survey about activities and tasks of hospital internal medicine wards of the region. The Preliminary and partial results are briefly reported. A 28-item questionnaire was sent by email to the heads of 18 Ligurian non-university internal medicine wards at the end of 2012 (collecting data about 2011). Topics were: number of beds and physicians, number of admission per year and mean DRG weight, mean length of stay and bed turnover rate, progressive care organization, number and kind of outpatients activities, clinical competencies, and equipment. The most interesting questions and answers of the survey are listed in Table 1. One of the most impressive results is that, independently of the beds number, in any hospital, internal medicine wards (IMWs) are overcrowded with occupancy rates that are often, 100 % (although the safety treshold is 85 %). The practice of having patients, admitted to IMWs, but placed temporarily in other wards—so called ‘‘outliers’’— is a frequent and recurrent phenomenon even when the mean LOS of the ward is lower than regional average (7 vs 10 days). Physicians are plentiful enough if we refer to the past law about hospital standards; only in 33.3 % of interviewed wards is there a doctor for more than 6.4 patients. This law dates from 1988 (Donat Cattin law) and considers internal medicine and general surgery as general wards providing internal medicine wards with 5 doctors and 17 nurses for every 32 beds and further 3 doctors for every 32 additional beds. Currently, not only in Liguria, Internal medicine, because of the epidemic of acute on chronic diseases, receives unstable patients who need close monitoring and M. La Regina (&) F. Orlandini Department of Internal Medicine, Ligurian East Hospital, La Spezia, Italy e-mail: micaela.laregina@asl5.liguria.it

Non-life-threatening sepsis: report of two cases.

Streptococcus bovis is one of the nonenterococcal species included among the streptococci group D. It is part of the normal bowel flora in humans and animals, but it is also responsible for infectious diseases (10-15% of all cases of bacterial endocarditis). Many cases of bacteremia and metastatic abscesses (spleen, liver, soft tissues, bone, meninges, endocardium) caused by S. bovis were reported as associated with digestive tract diseases, mainly colonic disease, and, in particular colonic neoplasms, or chronic liver diseases. A role in carcinogenesis has been suggested for this microorganism. The authors report two cases of S. bovis sepsis, one associated with colonic neoplasm and the other with liver cirrhosis and gastric carcinoma. Discussion is focused on probable mechanisms that favor gastric colonization and systemic diffusion of S. bovis from the gut in patients with gastrointestinal neoplasms or chronic liver disease and provides clinical recommendations for patients with S. bovis infections.

Predicting resistant etiology in hospitalized patients with blood cultures positive for Gram-negative bacilli

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.