Beatrice Dilaghi

Louse-Borne Relapsing Fever with Meningeal Involvement in an Immigrant from Somalia to Italy, October 2015

INTRODUCTION Borrelia recurrentis, transmitted by Pediculus humanus humanus, is the etiological agent of louse-borne relapsing fever (LBRF). Currently the main focus of endemicity of LBRF is localized in East African countries. From July 2015 to October 2015, 36 cases of LBRF have been diagnosed in Europe in immigrants from the Horn of Africa. Here we report a case of LBRF with meningitis diagnosed in Florence, Italy, in an immigrant arrived from Somalia. CASE STUDY In October 2015, a 19-year-old Somali male presented to the emergency department of the Azienda Ospedaliero Universitaria Careggi, Florence, Italy, with a 3-day history of high fever. The patient had disembarked in Sicily 10 days before admission after a long migration trip from his country of origin. On clinical examination, neck stiffness was found. Main laboratory findings were thrombocytopenia, increased procalcitonin, and increased polymorphonucleates in the cerebrospinal fluid. Suspecting a possible meningitis, the patient was treated with ceftriaxone, pending results of laboratory testing for malaria, and developed severe hypotension that was treated with fluid resuscitation and hydrocortisone. Hemoscopic testing revealed the presence of spirochetes and no malaria parasites. The patient rapidly improved with doxycycline for 7 days and ceftriaxone for 11 days, then was lost to follow-up. Total DNA from blood was extracted, and amplification and sequencing with universal 16S rDNA primers D88 and E94 revealed a 100% identity with B. recurrentis A1. CONCLUSIONS LBRF is a rare but emerging infectious disease among vulnerable displaced immigrants from the Horn of Africa. Since immigrants from endemic areas can carry the vector with them, the infection should be suspected even in subjects with compatible clinical features living in the same place where new arrival immigrants are hosted. Healthcare providers should be aware of this condition to implement adequate diagnostic, therapeutic, and public health measures.

A 64-year-old man admitted to the Emergency Department with an unusual case of intestinal obstruction: decision-making in the Emergency Department

Dr. J. Attene: A 64-year-old man was transported from his home to the Emergency Department (ED) because of a sudden worsening of abdominal pain and vomiting, on 15 February 2007. On admission he denied fever, chest pain, shortness of breath, diarrhea or urinary symptoms. The abdominal pain was localized in the upper abdominal quadrants and did not radiate to the back or arms. There was no history of passing blood per rectally. Passage of flatus and feces was absent in the prior 24 h. The patient had been in good health before admission, did not have a history of previous abdominal pain or exposure to patients with gastroenteritis, and there was no family history of inflammatory bowel disease. He usually smoked cigarettes and drank alcohol (1 L of wine per day), but denied recreational drug use. Is there any question regarding the history?

New evidence in cardiovascular medicine, general practice and public health

Scientific evidence is available with reference to the major role of both blood pressure and low-density lipoprotein cholesterol (LDL-C) in the promotion of coronary artery disease, yet the effect of the concomitant correct control of blood pressure and LDL-C in human beings has not been clarified. A group of US researchers has therefore studied the progression of coronary atheroma in subjects with low LDLC and variable values of systolic blood pressure. The changes in the burden of atheroma were investigated by means of intravascular ultrasound in 3,437 patients affected by coronary artery disease subdivided into four groups: individuals with LDL-C B 70 mg/dl and systolic blood pressure B120 mmHg, individuals with LDL-C B 70 mg/dl and systolic blood pressure[120 mmHg, individuals with LDLC [ 70 mg/dl and systolic blood pressure B120 mmHg, individuals with LDL-C [ 70 mg/dl and systolic blood pressure [120 mmHg. People with very low LDL-C (B70 mg/dl) and normal systolic blood pressure (B120 mmHg) showed a more frequent plaque regression (P = 0.01), less progression in percentage atheroma volume (P \ 0.001) and total atheroma volume (P \ 0.001), and a less frequent plaque progression (P \ 0.001). In subjects with systolic blood pressure[120 mmHg, very low LDL-C was linked to less progression of percentage atheroma volume (?0.30%, 95% confidence interval between -0.17 and 0.77% versus ?0.61%, 95% confidence interval between 0.17 and 1.05%, P = 0.01) and total atheroma volume (-3.9 mm, 95% confidence interval between -7.24 and -0.63 mm versus -1.2 mm, 95% confidence interval between -4.31 and 1.92 mm, P = 0.001). In coronary patients with LDL-C [ 70 mg/dl, normal systolic blood pressure was not associated with less progression of percentage atheroma volume or total atheroma volume. The authors conclude that normal systolic blood pressure and very low low-density lipoprotein cholesterol are linked to the slowest progression of coronary atherosclerosis.

Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia ― The SCELTA Trial ―

BACKGROUND The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes express low levels of CD34 (CD14+CD34lowcells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14+and CD34+cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO2. In ECEPC-treated patients, there was a positive correlation between injected CD14+CD34lowcell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients. CONCLUSIONS This study supports previous trials showing the efficacy of BM-MNC autotransplantation in CLI patients and demonstrates comparable therapeutic efficacy between BM-MNC and EPEPCs.

New evidence in pulmonary and preventive medicine

Chronic obstructive pulmonary disease (COPD) is increasing in prevalence and is usually associated with periodic exacerbations. Roflumilast is an oral anti-inflammatory agent. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of unselected patients with moderate-to-severe COPD. This article was aimed to investigate whether roflumilast reduces the frequency of exacerbations requiring corticosteroids in patients with moderate to severe COPD. Two placebo-controlled, double-blind, multicentre trials (M2-124 and M2-125) with identical design performed in two populations of outpatients with COPD older than 40 years, with severe airflow limitation [postbronchodilator forced expiratory volume in 1 s (FEV1) was 50% or less than the predicted value], bronchitic symptoms (chronic cough and sputum production), and a history of exacerbations (at least one recorded COPD exacerbation requiring systemic glucocorticosteroids or treatment in hospital, or both, in the previous year). Each trial had an initial 4-week run-in period, during which patients took a placebo once a day and recorded their use of shortacting bronchodilator drugs, and production of cough and sputum on their daily diary cards. Patients were then randomly assigned to oral Roflumilast 500 lg once a day or placebo for 52 weeks. Inhaled corticosteroid and longacting anticholinergic inhalators were not allowed. Patient recruitment began in February 2006, and the studies ended in July 2008. 1,523 patients and 1,568 were randomly assigned and treated, respectively, in the M2-124, and in M2-125 study. Change in prebronchodilator (FEV1) during treatment and the rate of COPD moderate or severe exacerbations were the primary endpoints. Analysis was by intention to treat. In the pooled analysis, in this study on patients with moderate to severe COPD prebronchodilator, FEV1 increased by 48 mL with roflumilast compared with placebo (p \ 0.001) and the estimated rate of exacerbations per patient per year was 17% lower in the roflumilast group than in the placebo group (p \ 0.003). Roflumilast improved measures of lung function in prebronchodilator and postbronchodilator period (FEV1, forced vital capacity, and peak expiratory flow) regardless of use of longacting b2 agonists. Patient withdrawal and adherence were similar in all groups. Mortality rate was not different in the different groups. The authors concluded that roflumilast reduced exacerbation rate and significantly improved lung function independently of the smoking status or concomitant medication. The authors outlined that this treatment is not suitable for all COPD patients since gastrointestinal effects or headache are more common in roflumilast group than in placebo group. B. Dilaghi (&) Emergency Department, Azienda Ospedaliera Universitaria Careggi, Viale Morgagni 85, 50134 Florence, Italy e-mail: beatrice.dilaghi@tin.it

New evidence in general practice, internal medicine and cardiovascular medicine

The results of a United Kingdom prospective population based study suggest that the opening hours of general practices influence the behavior of a large number of patients suffering from minor stroke or transient ischemic attack (TIA) occurring out of hours. Transient ischemic attacks are transient short-lasting neurological events. However, even if the majority of the symptoms of TIAs disappear within 60 min, they can go on up to 24 h. Minor strokes and TIAs are emergencies related to a notable risk of recurrence and recent research indicates that diagnosis and management of minor strokes and TIAs within 24 h from their insurgence can significantly lower the risk of recurrent stroke. Nine general practices in the United Kingdom were analysed in the context of a population based prospective study, to evaluate the fall out of general practice opening hours on the behavior in looking for health care on the part of individuals suffering from minor stroke or TIA. The study also assessed the sustainability of clinical evaluation within 24 h from the insurgence of the symptoms. More than 400 (434) subjects with minor stroke and 359 individuals with TIA were considered, and the median time before the call of a general practitioner (GP) in the course of surgery hours was 4 h; approximately two patients out of three (68%) with neurological episodes in the course of surgery hours called doctors within 24 h from the insurgence of symptoms. The median time before the call of the emergency general practitioner service was 1 h, while it was 24.8 h for subjects waiting to call their registered practice (p \ 0.001). In individuals who suffered from neurological episodes out of hours, and waiting to contact their GP, the seeking for medical care was inferior for episodes occurring in weekends than in weekdays (odds ratio 0.10). The majority of patients suffering from minor stroke or transient ischemic attack out of hours, in particular in the course of the night or during the weekends, registered a delay in looking for medical care, waiting for the opening hours of their GP. The results of this prospective population based study therefore suggest that the opening hours of general practices influence the behavior of a large number of patients suffering from minor stroke or transient ischemic attack occurring out of hours.

New evidence in neoplastic and cardiovascular medicine.

The researchers of the European Organization for Research and Treatment of Cancer (EORTC), Radiation Oncology Group and Genito-Urinary Tract Cancer Group conducted a trial to investigate if brief-term androgen suppression (radiotherapy and 6 months of androgen suppression) could maintain quality of life and obtain the general survival rate achieved with long-term androgen suppression (radiotherapy and 3 years of androgen suppression) in individuals with locally advanced prostate cancer. Almost 1,000 subjects (970) who had had external-beam radiotherapy and 6 months of androgen suppression were allocated in a random way to two groups, one receiving no other treatment (brief-term suppression, 483 patients) and the other receiving further treatment with a luteinizing hormone-releasing hormone agonist for 2.5 years (longterm suppression, 487 patients). Ninety-eight patients in the long-term group and 132 patients in the brief-term suppression group were died after a follow-up period of 6.4 years, and 29 were died because of prostate cancer in the long-term suppression group, compared to 47 in the brief-term group. The general mortality at 5 years for the long-term suppression group was 15.2%, compared to an overall mortality of 19% in the brief-term suppression group, with an observed hazard ratio of 1.42. Statistically significant differences were documented between the groups with reference to insomnia (P = 0.006), hot flushes (P \ 0.001) and sexual activity (P \ 0.001). The authors conclude that in patients with locally advanced prostate tumour radiotherapy and 3 years of androgen suppression achieve higher survival if compared with radiotherapy and 6 months of androgen suppression.

New evidence in oncologic and cardiocirculatory medicine

The combined therapy with bortezomib, melphalan and prednisone proved to be more effective than the therapy composed by melphalan and prednisone alone in the treatment of patients affected by recently diagnosed multiple myeloma not candidate to standard therapy at the maximum dosage and to the transplantation of stem cells. A group of international researchers conducted a randomised, phase 3 ‘‘open label’’ study in which 682 symptomatic patients were enrolled with a new diagnosis of multiple myeloma, who could not be treated with maximum therapy and stem cells transplantation because of their age (C65 years) or because of the presence of concomitant diseases. Aim of this study was the comparison of the effectiveness of the treatment with melphalan and prednisone alone with that with the same drugs associated with bortezomib. The enrolled patients were randomised to perform nine cycles of therapy of 6 weeks each during which they assumed melphalan at the dosage of 9 mg/m of body area, and prednisone (60 mg/m) in days from 1 to 4, alone or in combination with bortezomib (1.3 mg/m) in days 1, 4, 8, 11, 22, 25, 29 and 32 during the first 4 cycles and in days 1, 8, 22 and 29 during the other 5 cycles. The major end point was represented by the time to disease progression; secondary end points included the percentage of complete response, the length of the response and total survival. The results of this study show that the time to the progression of the disease in patients receiving bortezomib, melphalan and prednisone (bortezomib group) was 24 months, if compared to 16.6 months of the patients receiving melphalan and prednisone (control group). The risk ratio for the bortezomib group was 0.48 (P \ 0.001). The percentage of patients who had an at least partial response was 71% in the bortezomib group and 35% in the control group; a complete response was recorded in 30 and 4%, respectively (P \ 0.001). The median length of the response was 19.9 months in the first group and 13.1 months in the second one. The risk ratio for total survival was 0.61 for bortezomib group (P = 0.008). The combined therapy with bortezomib, melphalan and prednisone is more effective than the therapy with melphalan and prednisone alone in patients affected by recently diagnosed multiple myeloma who cannot undergo standard therapy at the maximum dosage and stem cells transplantation.

New evidence in infective and cardiovascular medicine

Almost 100,000 cases had been reported worldwide (most deaths in the American continents). The case fatality ratio (around 0.5%, similar to the upper range of that seen for seasonal influenza) vary substantially between countries and deaths have occurred in younger patient than is the case for seasonal flu. A natural definition for the case fatality ratio is the ratio of the total number of deaths from a disease divided by the total number of cases. In a fully ascertained (and complete) epidemic, this simple method works perfectly. However, people who are asymptomatic or have mild infection will be less likely to present to health care, and if they do present they will be less likely to be tested and confirmed. It is therefore likely that there will be a bias towards diagnosis of more severe cases, with the result that the case fatality ratio and other measures of severity are overestimated. A second important source of bias arises from the delay between disease onset and knowledge of the final outcome in severe cases. This effect, known statistically as censoring, means that a case fatality ratio estimated crudely by dividing the cumulative number of reported deaths by the cumulative number of reported cases will be too low and will grow as the epidemic unfolds. This was observed during the severe acute respiratory syndrome (SARS) epidemic, causing concern that the virus was mutating to become more virulent. Strategies to account for these biases based on analysis of the SARS epidemic are presented. Quantitative estimates of the severity of the new influenza A/H1N1 virus are central to healthcare planning over the coming months.