Rationale and evidence for the adjunctive use of N-acetylcysteine in multidrug-resistant infections.

Bacterial multidrug resistance has been a serious issue for healthcare systems in recent decades, responsible for many infections and deaths. Due to the increasing incidence of antimicrobial resistance and scarce treatment options, research is focused on finding possible therapeutic adjuvants able to increase the efficacy of antibiotics. The aim of this article is a review of available evidence on the use of N-acetylcysteine (NAC). MEDLINE/PubMed was searched for appropriate keywords. In vitro and in vivo preclinical studies, clinical studies, reviews, and meta-analyses were retrieved and selected based on relevance. A narrative review article was written, reporting published evidence and the expert opinion of the authors. Among possible adjunctive treatments, NAC has attracted the interest of researchers as a candidate for re-purposing. It is a widely used drug with a good tolerability profile, mainly used as a mucolytic agent, with antioxidant, anti-inflammatory properties and antibacterial activity. NAC acts on different mechanisms and stages of infections, resulting in inhibition of biofilm formation, disruption of preformed biofilms, and reduction of bacterial viability. NAC may be administered as an aerosol in many types of infections, including cystic fibrosis, bronchiectasis and infective flare of chronic obstructive pulmonary disease (COPD), and by the intravenous route in severe systemic infections (including septic shock) such as those caused by carbapenemase (KPC)-producing Klebsiella pneumoniae (Kp) and Carbapenem-Resistant Acinetobacter baumannii (CR-Ab). A rationale exists for using NAC as an adjunctive treatment in multidrug-resistant (MDR) infections, based on in vitro, in vivo and clinical evidence, and future research is needed to identify candidate patients and optimal schedules for specific clinical conditions.

Procalcitonin variations after Emergency Department admission are highly predictive of hospital mortality in patients with acute infectious diseases.

BACKGROUND AND AIM: To evaluate the diagnostic and prognostic usefulness of procalcitonin (PCT) in patients admitted to the Emergency Department (ED) with signs of infections and to assess the prognostic value of repeated measurements in predicting hospital mortality. MATERIALS AND METHODS: A prospective, observational study was conducted in our 400-bed General Teaching Hospital. 261 patients arriving in ED with signs/symptoms of infection were enrolled. PCT was performed upon arrival in the ED (T0), and 5 days after antibiotic therapy (T5). Blood cultures were performed in all patients upon arrival in the ED. RESULTS: Mean T0 PCT value was 7.1±17.9 ng/ml, and at T5 3±9.1 ng/ml (p < 0.0001). Mean PCT in septic non-survivors was increased at T5 compared to T0 but not significantly. The PCT increase at T5 was an independent factor of mortality (OR = 1.29, p < 0.02) in septic patients. Compared to baseline mean delta % PCT decrease at T5 was 28%. Patients with a decrease delta % PCT > 28% showed a lower number of deaths, with a statistical significant difference if compared to those patients with a < 28% decrease (p < 0.004). ROC curve of delta % PCT for prediction of death has an AUC = 0.82 (p < 0.03). CONCLUSIONS: PCT is a useful marker for diagnosis of systemic and local infections, and for prognostic stratification in patients with acute infectious diseases at their arrival in ED. PCT variations after antibiotic therapy are highly predictive for in-hospital mortality. PCT normalization during antibiotic therapy suggests a good response to infection possibly leading to less infection-related deaths.

Chronic systemic inflammatory syndrome in patients with AECOPD presenting to emergency department.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth cause of dead in the world. Because of high incidence of comorbidities in COPD patients, it has been proposed a new hypothesis that inscribe this disease in a complex contest named chronic systemic inflammatory syndrome (CSIS). Either COPD and the most common comorbidities responsible for its clinical and natural history, like hypertension, diabetes, coronary artery disease, heart failure, recognize a pro-inflammatory state, marked, for example, by elevated C reactive protein (CRP). METHODS: 113 consecutive patients presenting to emergency department (ED) with acute exacerbated COPD were enrolled. They underwent to full medical history and physical examination. CRP was measured at ED arrival, discharge and at 1-6-12 month follow up. CSIS was diagnosed according to specified criteria. RESULTS: CSIS was diagnosed in 84% patients. CRP was maximally increased at admission during the exacerbation, but didn't correlate with the severity of it. At discharge, CRP values were lowest; during follow up, CRP demonstrated a chaotic behavior growing up till 6 month without any correlation with new exacerbation events. At 1 year it decreased, never reaching normal values in the majority of our patients thus confirming the presence of a persistent inflammation in COPD. CONCLUSIONS: CSIS was diagnosed in 84% of our population demonstrating that COPD patients need to be approached in a multidisciplinary way.

Role of biomarkers in patients with dyspnea.

BACKGROUND: The use of biomarkers has been demonstrated useful in many acute diseases both for diagnosis, prognosis and risk stratification. OBJECTIVES: The purpose of this review is to analyze several biomarkers of potential use in patients referring to Emergency Department with acute dyspnea. STATE OF THE ART: The role of natriuretic peptides has a proven utility in the diagnosis, risk stratification, patient management and prediction of outcome in acute and chronic heart failure (HF). New immunoassays are available for the detection of mid-region prohormones in patients with acute dyspnea such as Mid-region pro-adrenomedullin (MR-proADM) and Mid-region pro-atrial natriuretic peptide (MR-proANP). Also procalcitonin, copeptin and D-dimer, which are markers of inflammation, bacterial infections and sepsis, seem to be useful in the differential diagnosis of dyspnea. Conventional and high-sensitivity troponins are fundamental, not only in the diagnosis of acute coronary syndromes, but also as indicators of mortality in patients with acute decompensated heart failure. PERSPECTIVES: Further studies with randomized controlled clinical trials will be needed to prove the theoretical clinical advantages offered by a shortness of breath biomarkers in terms of diagnostic, prognostic, cost effective work-up and management of patients with acute dyspnea. CONCLUSIONS: A multimarker pannel approach performed by rapid and accurate assays could be useful for emergency physicians to promptly identify different causes of dyspnea thus managing to improve diagnosis, treatment and risk stratification.

[Usefulness of magnetic resonance imaging for the diagnosis of acute myocarditis. A case of acute myocarditis as myocardial infarction-like]. / Ruolo della risonanza magnetica nucleare nella diagnosi di miocardite acute. Un caso di miocardite acuta ad esordio simil-infartuale.

According to the Dallas criteria, myocarditis is defined histologically as an inflammatory process involving the myocardium with an inflammatory infiltrate and myocyte necrosis or damage. Clinically, myocarditis is an insidious disease that is usually asymptomatic and commonly underdiagnosed. Infact, the symptoms are often non-specific and the majority of cases recover fully with no sequelae. At present, endomyocardial biopsy remains the gold standard for the diagnosis of myocarditis, despite its limited sensitivity and specificity. However, the lack of an association between biopsy evidence of myocarditis and the presence of autoantibodies in patients with clinical signs of myocarditis, the paucity of the positive biopsy findings in large cohorts of patients with suspected myocarditis, the potential discordance between clinical and histologic features and the inherent limitation of histologic diagnosis, suggest that the diagnosis shouldn't be based on histologic examination alone. The magnetic resonance imaging (MRI) with gadolinium can be useful to visualize the localization, activity and extent of inflammation and may be a powerful noninvasive diagnostic tool in acute myocarditis. Infact, MRI achieves a 100% sensitivity and a 90% specificity. We report the case of a 31-year-old male patient with an acute myocarditis with electrocardiographic manifestations like to acute myocardial infarction, whose diagnosis was based on the clinical signs and on the characteristic pattern of the MRI with paramagnetic contrast. The MRI with gadolinium is suggested as noninvasive study to support the diagnosis of acute myocarditis in the correct clinical setting.

[Humoral and cellular inflammatory mediators in acute lung injury: friends or enemies? ]. / Mediatori infiammatori umorali e cellulari dell'Acute Lung Injury: amici o nemici?

Diffuse lung injury (DLI) is characterised by damage to the alveolar and endothelial epithelium that leads to acute respiratory insufficiency. From the histological point of view, this pathological process proceeds through an initial exudative phase which is followed by the organisation of the inflammatory infiltrate up to the deposit of collagen and fibrin which seriously compromises gaseous exchanges. The clinical expression typical of this pathology consists of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) characterised by hypoxemia resistant to oxygen therapy, tachypnea and the presence of bilateral infiltrates on conventional X-ray of the thorax. Although the etiology is multifactorial, the pathogenesis depends on the uncontrolled activation of the inflammation system in its humoral and cellular components. The present paper examines the principal studies regarding the most important mediators. From an analysis of the literature it emerges that some cytokines (IL-1betha, IL-6, IL-6ra) and cellular mediators (NF-kB, sFasL) are responsible for the epithelial damage by way of complex mechanisms that include apoptosis. Studies carried out up to the present have not however evidenced any independent pathway decisive for pathogenesis. This shows that inflammation is in effect a multiform process that originates precisely as a result of the mutual interaction of the factors implicated in it. The humoral and cell mediators can, however, be used as clinical indicators correlatable with the clinical and physiopathological outcome.

Acute abdominal symptoms in malignant hypertension: clinical presentation in five cases.

Malignant hypertension causes anatomical and functional damage in several target organs, in particular brain, retina, heart and kidneys. Although vascular lesions in the gastroenteric tract are known to occur in several instances, their clinical relevance is unknown. In this study five cases of malignant hypertension, presenting with acute abdominal symptoms, are reported. A history of essential arterial hypertension was present in three patients; while one patient had a previous diagnosis of renovascular hypertension and one patient had renoparenchymal hypertension. However, in all cases the antihypertensive treatment was discontinued and inadequate before the accelerated malignant phase. The acute abdominal symptoms at presentation were due to intestinal infarction in 3 patients and acute pancreatitis in 2 patients. One patient with intestinal infarction died of postoperative cardiogenic shock. Our data are in agreement with previous reports describing the possible intra-abdominal complications of malignant hypertension. The therapeutic approach in such conditions should always consider an effective antihypertensive treatment in conjunction with surgical options.

[Arterial hypertension and macroangiopathic complications in a group of diabetic out-patients]. / Ipertensione arteriosa e complicanze macroangiopatiche in un gruppo di diabetici ambulatoriali.

We have retrospectively studied 814 diabetic outpatients, 407 hypertensives and 407 normotensives. The aim of the study was to investigate on possible associations between macroangiopathic complications (coronary heart disease, peripheral and cerebral arteriopathy) and well recognized risk factors for atherosclerosis. Macroangiopathy was present in 27% of males and 24% of females (p = NS), and in 32% of hypertensives and 18% of normotensives (p < 0.0001). Macroangiopathy associated, in both sexes, with age and duration of diabetes, but did not correlate, instead, with metabolic control, obesity, serum cholesterol and triglycerides. High triglyceride levels were associated strictly with arterial hypertension, in both sexes, but are more elevated in men. Risk factors for atherosclerosis seem not to be simply considered in the same way in diabetic and non diabetic populations.

[The rhabdomyolytic syndrome: a not uncommon occurrence]. / Sindrome rabdomiolitica: una evenienza non infrequente.

The paper examines one aspect of a medical pathology that is rather unusual and often wrongly diagnosed: rhabdomyolysis (RMC). The series examined suggests that the pathology is relatively common and arises in a wide variety of clinical conditions. In view of the fact that the consequences of rhabdomyolysis may be serious, emphasis is placed on the fact that correct diagnosis may be obtained by the careful consideration of simple clinical parameters such as subjective symptoms, urine colour, urine strip test and serum CPK assays.

[Prolonged treatment of hypertension in diabetic patients with enalapril. 1-year follow-up]. / Trattamento prolungato dell'ipertensione nel diabetico con Enalapril. Follow-up a 1 anno.

In view of the pharmacological and chemical reasons for using ACE-inhibitors to treat diabetic hypertension, a group of 40 outpatients were treated with Enalapril. The sample consisted of 20 outpatients, 6 males, 14 females aged 48-76 (mean age 63.75), 18 of whom had type II and 2 type I diabetes and 11 under treatment by diet and hypoglycaemic drugs or insulin. All these patients presented slight or moderate essential arterial hypertension (diastolic pressure less than 115 mmHg). For about one year 17 of the patients were given 20 mg/die Enalapril and the remaining three 10 mg/die in a single morning dose. In 16 cases no other treatment was given. In 4 a non-potassium conserving diuretic was also given. Check-ups before six months into and at the end of treatment showed: a statistically significant reduction in systolic (p less than 0.05) and diastolic (p less than 0.01) pressure. In contrast no significant change was noted in heart beat, glycaemia before or after meals, body weight, glycosylated haemoglobin or any other blood chemical parameter considered. In one case only there was a slight increase in proteinuria that was however present at the start of treatment. As far as side effects are concerned there was one case of cardiac palmus during treatment and one case of coughing that regressed totally when treatment was suspended but nothing else of significance. It should be noted that the antidiabetic treatment remained unchanged throughout the period considered in most cases and at most was subjected to minimal qualitative and quantitative adjustments.

Insulin degradation in human erythrocyte: effects of cations.

Insulin degradation by human erythrocyte fractions was studied using the TCA-precipitation method. Hemolysate exhibited an insulin degrading activity higher than membranes. Triton X-100 treatment of membranes led to the appraisal of Triton-soluble degrading activity and of a more efficient Triton-not-soluble degrading activity. Monovalent cations (Na+, K+, Li+) did not modify the insulin degradation by any of the erythrocyte fractions. Divalent cations, Ca++ and Zn++ selectively enhanced insulin degradation by the membranous fractions, and Cu++ and Zn++ strongly inhibited insulin degradation by all the erythrocyte fractions. The results supported the hypothesis of the existence of at least two different degrading systems in human erythrocytes: soluble (cytosolic) Ca++ and Mg++ insensitive system(s) and membrane associated Ca++ and Mg++ sensitive system(s).