New insights into the treatment of non-healing diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are one of the most serious and devastating complication of diabetes mellitus, affecting about 15% of diabetic patients. This review describes the innovative treatment options currently available in the treatment of non-healing DFUs. The use of Platelet-Rich-Plasma (PRP) is a safe and valid approach in the treatment of DFUs. However, the methods used to obtain and prepare autologous PRP vary between the studies, thus further evidences are eagerly awaited. Adipose tissue-derived mesenchymal stem cells (ADSCs) are a promising tool in the treatment of DFUs, but additional largescale and long-term follow-up clinical trials are needed. Bone marrow mesenchymal stem cells (BM-MSCs) transplantation, on the other hand, revealed effective in reducing incidents and improving the quality of life of patients with amputations. Autologous Peripheral Blood Mononuclear Cells (A-PBMNCs) showed a good efficacy in the treatment of diabetic patients with CLI, but further RCTs are awaited to best investigate this new therapeutic approach. Photobiomodulation (PBM) therapy revealed effective in the treatment of DFUs in two RCTs, but a standardization of therapeutic protocols as well as level-I studies are needed.

[High digoxin serum levels in an elderly patient for the endogenous digoxin-like immunoreactive substances. A case report]. / Elevati livelli di digossinemia in una paziente anziana per ifattori endogeni immunoreattivi digossino-simili. Caso clinico.

UNLABELLED: Digoxin is typically prescribed in the treatment of heart failure. Its limited therapeutic range requires systematic monitoring of plasmatic concentration through immunoreactive tests. Laboratory results, however, can be altered by the presence of digoxin-like immunoreactive factors (DLIF) which are released in all clinical conditions involving volemic expansion. CASE REPORT: An 86-year-old woman arrived in emergency with severe dyspnoea, atrial flutter and a medical history of ischemic cardiopathy. The patient was treated with ACE inhibitor, furosemide, spironolactone and digoxin. The first lab test for digoxin showed levels of digoxin of 7.05 ng/ml. Although the patient did not show any clinical evidence of digital intoxication nor was she treated with drugs which might interfere with digoxin kinetics and even if she had markers of renal function within clinical limits, digoxin was suspended and a treatment was initiated with 0.9% NaCl solution and furosemide. The second lab test showed levels of digoxin of 8.38 ng/ml. A possible interference of DLIF with immunoreactive tests was therefore assumed. MATERIALS AND METHODS: The patient's serum was ultrafiltered and centrifugated to remove possible DLIF; subsequently, the measurement of digoxin levels was repeated. As a result, the digoxin level decreased to 0.25 ng/ml. CONCLUSIONS: DLIF increase in several diseases, including heart failure, end-stage renal disease, pre-eclampsy and acromegaly. High digoxin levels in a patient who does not show any symptoms of digital intoxication should lead to suspect the presence of these factors and to preventively determine DLIF in serum so as not to incur the risk of suspending an important treatment like digoxin in heart failure.

[The use of cardiac markers bed test in acute coronary syndrome in emergency department]. / Utilizzo dei biomarcatori cardiaci bed-test nella sindrome coronarica acuta nel Dipartimento di Emergenza.

AIMS: The evaluation of the patient with chest pain in the emergency department is one of the most common situations that the doctor has to face. The diagnostic procedure supposes an observation period of at least 6-12 hours, a well organized medical facilities and the identification of all SCA cases to reduce inappropriate admission. MATERIALS AND METHODS: In our study we have estimated the utility of the marker assay that is associated to the use of risk scores (TIMI and GRACE risk score) to obtain indication about the most appropriate assistance level. In particular, we used the assay of necrosis markers to highlight the damage along with the assay of natriuretic peptides for their role in the diagnosis and in the monitoring of the patients with cardiac damage. RESULTS: Also PCR has an important role such as marker of plaque stability and of inflammation. These markers associated to the necrosis markers could give important clinical information of independent nature. DISCUSSION: The sensibility of laboratory markers, without important necrosis, is low and it is not possible to exclude in a few time a SCA There is now an alternative strategy: a precocious risk stratification. Using clinical criteria it is possible to do a first evaluation of the probability of SCA and the complications.

[Risk stratification on 206 patients with acute coronary syndrome at Rome Policlinico Umberto I Emergency Department]. / Stratifi cazione del rischio su 206 pazienti con sospetta Sindrome Coronarica Acuta presso il Dipartimento di Emergenza-Urgenza-Accettazione del Policlinico Umberto I di Roma.

OBJECTIVES: The objective of this study on patients with suspected Acute Coronary Disease (ACS) was to verify with the risk stratification any differences between patients in which the AHA/ACC guidelines were not systematically applied and the same patients in which, retrospectively, the AHA/ACC guidelines were adhered to. MATERIALS AND METHODS: Retrospective examination was carried out in our Emergency Department at Rome Policlinico Umberto I on 206 patients (age range 21-88, median age 56.6 +/- 18.9 years) (54.3% males) with symptoms compatible with ACS. All the patients underwent "triage" using code green or code yellow and were sub-divided into 7 subgroups based on degree of risk for death or non-fatal myocardial infarction (MI) at 30 days, (labelled A to G, with A representing highest risk and G the least at-risk) in accordance with the ACC/AHA guidelines. Each patient was then examined for: fi nal outcome, admittance and discharge from hospital, refusal of admittance, death. RESULTS: Of the 206 patients, 48 were judged improperly (23.3%) Of these, 13 were assigned code green rather than code yellow and 11 were assigned code yellow instead of code green. By risk stratification in accordance with the AHA/ACC guidelines, 128 patients (62.1%) belonging to subgroups A,B,C and D should have required hospitalization. Seventy eight patients belonging to subgroups E,F and G should have been sent for observation at the Chest Pain Unit (CPU), 54 from this group would have been potentially discharged after 6-12 hours of negative clinical observation. Actually, hospitalization was requested for 132 patients (64%) of whom 78 accepted, 50 declined and 4 were deceased before admission; 74 patients (35.9%) were discharged after brief observation. Risk stratification for 30 day mortality or non fatal MI emphasizes that 8 of the patients hospitalized should have been treated at the CPU (unwarranted hospitalization). Twenty four of the 50 patients who declined hospitalization should have benefited by brief observation at the Chest pain Unit. Twenty eight of the 78 patients examined in the Emergency Department and later discharged should have been hospitalized (wrong discharge). CONCLUSIONS: This study, even if limited by time restriction, provides enough evidence in support of the effectiveness of the ACC/AHA guidelines to determine subgroups and to correctly determine groups according to level of risk, thus limiting unwarranted hospitalizations and wrong discharges.

[Therapy optimization of heart failure through the evaluation of the plasma concentration variation of B-type natriuretic peptide]. / Ottimizzazione della terapia dello scompenso cardiaco attraverso il monitoraggio delle variazioni delle concentrazioni plasmatiche del peptide natriuretico di tipo B.

AIM: Our research was based over the critical evaluation of the plasmatic concentration variation of B-type Natriuretic Peptide in emergency in patients with heart failure during therapy with diuretics, anti-aldosterone, ACE-inhibitors, beta-blockers and nitroderivates. MATERIALS AND METHOD: We selected 108 patients: 30 control subjects (average 58.40 +/- SD13.32 for 20 M, and 65 +/- SD 14.74 for 10 W), and 78 subjects (average 75.90 +/- SD 9.60 for 41 M, and 77.89 +/- SD 8.62 for 37 W) arrived to the emergency and reception department for dyspnea and/or precordialgia and/or palpitations with heart failure diagnosis according to NYHA Classification. The variation of BNP concentration was evaluated in these subjects at the admission, after 1 week, and 1 month from the beginning of the therapy. RESULTS: Patients with heart failure had a BNP concentration high during all measurements. The values were high during admission, but after 1 week and after 1 month, they reduced reaching the balance. CONCLUSIONS: BNP evaluation is a good indicator for the diagnosis of heart failure and for improving the therapy. The main limit of BNP diagnostic role is the need of knowing in advance the specific values for each patient.

Intermittent left anterior hemiblock. A rare case report.

The Authors report a rare case of intermittent left anterior hemiblock in a 86-year-old man admitted to Department of Emergency Medicine for progressive impoverishment of intellectual functions and episodes of chest pain. They present this rare case of intermittent left anterior hemiblock where the intermittence was not linked to heart rate variations preceding the beginning of the hemiblock being present on the same ECG two different QRS complexes with no modification in frequency or A-V conduction: this finding suggesting a vascular origin of the disturbance. They also stress the importance of a prompt diagnosis in a Department of Emergency Medicine.

[Guidelines for the management of hypertensive crises and simple blood pressure rise. Literature review and clinical experience]. / Linee guida della terapia delle crisi ipertensive e dei rialzi pressori. Rassegna della letteratura ed esperienza personale.

Hypertension is a common clinical problem in the Emergency Department. Beside homologated therapeutical approaches it is necessary in primis to consider the problem in a clinical context and in an appropriate nosographic scheme in order to provide a rational approach to the treatment. In this paper the authors review the nosographic and therapeutical approaches previously reported in literature and then state their proposals derived by their daily experience at the Emergency Department. In authors' opinion it is of primary importance to distinguish between hypertensive crises and simple blood pressure rise. For this end it seems useful to define four syndromic classes: A. Real Hypertensive Crises: 1-Hypertensive Emergencies, 2-Hypertensive Urgencies. B. Simple Blood Pressure Rise: 1-Stable Uncomplicated Hypertension, 2-Transient Hypertension. According to this classification the majority of patients referring to Emergencies Departments for elevated blood pressure can be included in the last two classes. The authors suggest a step-by-step approach to the treatment beginning with benzodiazepines, loop diuretics, beta-blockers or clonidine or ACE inhibitors or calcium channel blockers; In an elevated percentage of cases benzodiazepines alone are effective in appropriately lowering blood pressure.

HIV-associated cardiovascular complications: a new challenge for emergency physicians.

Cardiac complications associated with the AIDS may present to emergency physicians and are often secondary to opportunistic infections or malignancy, but may also be associated with other aspects of the human immunodeficiency virus (HIV) or its treatment. In this review article, we will discuss HIV-associated cardiac disease which may be encountered in the ED, emphasizing the prevalence, pathogenesis, and treatment of related disorders.

ET-1 levels in cardioischemic patients undergoing atrial pacing.

Atrial pacing (AP) procedure was carried out in 11 cardioischemic patients to reproduce tachycardia-induced myocardial ischemia. Six control subjects underwent the same procedure until the maximum pacing rate was reached. During the procedure, endothelin-1 (ET-1) and plasma lactate levels were measured in the coronary sinus and in the aortic root. In all the patients, atrial pacing provoked electrocardiographic signs and metabolic evidence of myocardial ischemia and a significant decrease (p<0.001) in left ventricular ejection fraction. At AP-induced ischemia, coronary sinus (17.31 +/- 4.20 pg/mL) and arterial (9.60 +/- 3.31 pg/mL) ET-1 plasma levels were significantly different (p<0.001) in the patients. On the contrary, at maximum pacing rate, no significant difference (p=0.186) emerged between coronary sinus (9.72 +/- 1.09 pg/mL) and arterial (8.95 +/- 0.75 pg/mL) plasma ET-1 levels in the control group. These results suggest that, in cardioischemic patients, tachycardia can induce the coronary endothelium to release significant amounts of ET-1.

Met-enkephalin levels during PTCA-induced myocardial ischemia.

Met-enkephalin (Met-enk) has been demonstrated to modulate myocardial-ischemia mechanisms via the opioid receptors, but no studies are now available on Met-enk levels in the coronary circulation. In this experience Met-enk levels were evaluated in aortic root and in coronary sinus at baseline (T0), during PTCA induced transient ischemia (T1) and during reperfusion (T2). No significant differences were found at any time. Thus, it appears that there is no Met-enk extraction from the coronary circulation during provoked myocardial ischemia and no Met-enk release from the ischemic heart.

The role of met-enkephalin in silent myocardial ischemia in diabetic patients.

Met-enkephalin plasma levels were evaluated in 20 cardioischemic diabetic patients. All the patients had ECG ischemic signs. Ten patients with diabetic autonomic neuropathy, experienced no pain during myocarial ischemia. Met-enkephalin levels in the diabetic patients with silent myiocardial ischemia were significantly lower compared to those in the symptomatic patients. This demonstrates that the absence of myocardial ischemic pain in neuropathic diabetic patients is not accounted for by met-enkephalin action.

Classification of atrial fibrillation as a model of decisional analysis for the treatment of patients with current atrial fibrillation observed in the emergency department.

Atrial fibrillation (AF) is the most common cardiac arrhythmia observed in the emergency room (ER). We propose a new classification of AF which is useful for the standardization of terms to be used for future clinical trials and for clinical management of this arrhythmia in the ER. We recognized three categories: (1) atrial fibrillation lasting less than 72 hours (AF < 72 h); (2) persistent atrial fibrillation and (3) permanent atrial fibrillation. Atrial fibrillation lasting less than 72 hours can be reconverted to sinus rhythm spontaneously or with pharmacological or electrical cardioversion. If AF < 72 h is not treated and the arrhythmia persists for more than 72 hours we recognize persistent AF. In persistent AF the systemic thrombo-embolism is a significant risk and therapeutic anticoagulation must be associated to pharmacological or electrical cardioversion even though transoesophageal echocardiography does not visualize thrombi or spontaneous echocontrast in the cardiac chambers. These treatments can reconvert the persistent AF to sinus rhythm, but, in the absence of treatment, or if treatment fails, the arrhythmia goes into the permanent category. In permanent AF ventricular rate control and anticoagulation, if suitable, are the first choice for stroke prevention.

Evaluation of long-term efficacy of interferon alpha-2b and ribavirin in combination in naive patients with chronic hepatitis C: an Italian multicenter experience. Ribavirin-Interferon in Chronic Hepatitis Italian Group Investigators.

BACKGROUND/AIMS: A combination of interferon alpha and ribavirin has been suggested to reach a higher rate of sustained virological response in patients with chronic hepatitis C than monotherapy. In this study we assessed the long-term efficacy of this combination therapy in the treatment of selected Italian naive chronic hepatitis C patients compared to interferon alpha monotherapy. METHODS: We enrolled 428 naive patients who were randomly assigned to receive either recombinant interferon alpha-2b and ribavirin for 24 weeks or interferon alpha-2b alone for 48 weeks. The primary end-point of the study was the rate of sustained virological response. Serum HCV RNA levels were determined before treatment; during treatment at weeks 12 and 24 in the patients receiving the combination therapy; at weeks 12, 24, 36 and 48 in the patients receiving monotherapy; and after therapy at weeks 12, 24 and 48 in the patients in both study groups. RESULTS: Sustained virological response was observed in 43% of the patients treated with combination therapy and in 14% of the patients treated with monotherapy. Logistic regression analysis showed that sustained response was associated with the combination therapy, with HCV genotype other than 1b, with an HCV viral load of 3x10(6) copies/ml or less, with an inflammation score of 7 or less, and with an estimated duration of disease of 10 years or less. CONCLUSIONS: A 24-week treatment course with interferon alpha-2b and ribavirin offers a greater chance of sustained virological response compared to treatment with interferon alpha-2b alone for 48 weeks, and may be indicated as initial therapy in such patients.

Clinical course of cardiomyopathy in HIV-infected patients with or without encephalopathy related to the myocardial expression of tumour necrosis factor-alpha and nitric oxide synthase.

OBJECTIVE: To define whether the development of encephalopathy influences the clinical course of HIV-associated cardiomyopathy (HIV-DCM) in relation to the myocardial expression of tumour necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). DESIGN: Prospective study. SETTING: University hospitals and AIDS centres. METHODS: 115 HIV-infected patients with echocardiographic diagnosis of HIV-associated cardiomyopathy (34 with encephalopathy and 81 without encephalopathy) were followed for a mean of 24 +/- 3.2 months. All patients underwent endomyocardial biopsy for determination of myocardial immunostaining intensity of TNF-alpha and iNOS. Cerebrospinal fluid (CSF) from patients with encephalopathy was examined for the presence of viruses. Patients underwent clinical examination every 3 months and echocardiographic examination every 6 months. The intensity of TNF-alpha and iNOS immunostaining was also evaluated on postmortem cerebral tissue of patients who died of congestive heart failure (CHF). RESULTS: A greater impairment of echocardiographic parameters was observed in patients with HIV-associated cardiomyopathy after development of encephalopathy. These parameters tended to worsen progressively during the follow-up period and were inversely correlated with HIV-1 viral load, CD4 cell count, mini mental status score and the intensity of myocardial and cerebral TNF-alpha and iNOS staining. CSF specimens were available in 29 patients with encephalopathy. HIV-1 sequences were detected in CSF of all these patients with cytomegalovirus sequences in two. The mortality rate for CHF was greater among patients with encephalopathy (73% versus 12%). CONCLUSIONS: The development of encephalopathy has an adverse effect on the clinical course of HIV-associated cardiomyopathy. In the relationship between cardiomyopathy and encephalopathy, the activation of iNOS by TNF-alpha may have a significant pathogenetic role in HIV disease.

Intravenous recombinant interferon-beta versus interferon-alpha-2b and ribavirin in combination for short-term treatment of chronic hepatitis C patients not responding to interferon-alpha. Multicenter Interferon Beta Italian Group Investigators.

BACKGROUND: Little is known about the therapeutic role of intravenous interferon-beta in chronic hepatitis C patients unresponsive to a previous treatment with interferon-alpha. METHODS: Two hundred interferon-alpha non-responders were randomized to receive either intravenous recombinant interferon-beta or interferon-alpha-2b and ribavirin for 12 weeks. The responders in both groups were followed up for a further 48 weeks. RESULTS: At week 12 a biochemical and virologic response was documented in 42% of the patients treated with interferon-beta and in 22% of the patients treated with combination therapy. A sustained response was observed in 21% of the patients treated with interferon-beta and in 13% of those treated with combination therapy, with similar differences on intention-to-treat analysis. CONCLUSIONS: Short-term treatment with intravenous interferon-beta seems to offer a chance for sustained response in a subset of interferon-alpha non-responders. The role of long-term therapy in these patients still remains to be explored.

[Iatrogenic sequelae of pulmonary tuberculosis]. / Le sequelae iatrogene della tubercolosi polmonare.

OBJECTIVES: The purpose of this study is to underline how topical is the chapter of the sequelae of pulmonary tuberculosis and to try to make a classification. Pulmonary tuberculosis can be cured definitely or hesitate in disease (BK negative) that is totally independent from tuberculosis about their pathogenesis and clinical features. They are called sequelae. MATERIALS AND METHODS: We made a statistical analysis that investigate a group of 110 patients without active infection (BK negative) admitted in the hospital because of a sequela of pulmonary tuberculosis. Patients were treated in the past by collapse-therapy or by antibiotic-therapy until their spittle became negative for BK. RESULTS: A significant (p < 0.05) relationship between each kind of sequela, among the most important ones (fibrothorax, interstitial fibrosis, bronchiectasis, empyema with or without pleural fistula, parafibrotic emphysema), and type of treatment, results. CONCLUSIONS: The sequelae of tuberculosis of the lung are highly disadvantageous for people who are affected; are observed frequently; are closely dependent on what kind of treatment the patient has received; are classified in iatrogenic, not iatrogenic or mixed.