Immune reconstitution inflammatory syndrome in tuberculous pleurisy and ulcerative colitis: a case report.

We present the case of a 46-year-old Caucasian male, affected by ulcerative colitis, who developed tuberculous pleurisy during immunosuppressive therapy; despite proper therapy, worsening of the radiological findings was observed. The case was discussed among an online group of Italian physicians and diagnosis of immune reconstitution inflammatory syndrome (IRIS) tuberculosis was established. Therapy was continued and full recovery was obtained. IRIS is a syndrome initially described during opportunistic infections in HIV infected after being placed in anti-retroviral therapy. It reveals itself through a wide variety of manifestations, including fever, lymphadenopathies, worsening of lung infiltrates, pleural or pericardial effusion, central nervous system involvement. Few data are available regarding the best therapeutic options. IRIS is an insidious and potentially serious complication of opportunistic infections in immunocompromised patients. The always wider diffusion of immunosuppressive therapies increases the number of patients at risk, therefore physicians need to be aware of the issue.

A real life evaluation of non invasive ventilation in acute cardiogenic pulmonary edema: a multicenter, perspective, observational study for the ACPE SIMEU study group.

BACKGROUND: During the past three decades conflicting evidences have been published on the use of non-invasive ventilation (NIV) in patients with acute cardiogenic pulmonary edema (ACPE). The aim of this study is to describe the management of acute respiratory failure (ARF) due to ACPE in twelve Italian emergency departments (EDs). We evaluated prevalence, characteristics and outcomes of ACPE patients treated with oxygen therapy, continuous positive airway pressure (CPAP) or Bi-level positive airway pressure (BiPAP) on admission to the EDs. METHODS: In this multicenter, prospective, observational study, consecutive adult patients with ACPE were enrolled in 12 EDs in Italy from May 2009 to December 2013. Three study groups were identified according to the initial respiratory treatment: patients receiving oxygen therapy, those treated with CPAP and those treated with BiPAP. Treatment failure was evaluated as study outcome. RESULTS: We enrolled 1293 patients with acute cardiogenic pulmonary edema. 273 (21%) began with oxygen, 788 (61%) with CPAP and 232 (18%) with BiPAP. One out of four patient who began with oxygen was subsequently switched to NIV and initial treatment with oxygen therapy had an odds ratio for treatment failure of 3.65 (95% CI: 2.55-5.23, p < 0.001). CONCLUSIONS: NIV seems to be the first choice for treatment of ARF due to ACPE, showing high clinical effectiveness and representing a rescue option for patients not improving with conventional oxygen therapy.

Salmeterol improves fluid clearance from alveolar-capillary membrane in COPD patients: a pilot study.

UNLABELLED: The cardiovascular component associated with chronic obstructive pulmonary disease (COPD) plays a major role in disease prognosis, accounting for 25% of the deaths. Experimental and initial clinical data suggest that beta-adrenergic agonists accelerate fluid clearance from the alveolar airspace, with potentially positive effects on cardiogenic and noncardiogenic pulmonary oedema. This pilot study investigated the acute effects of the long-acting beta-2 agonist, salmeterol, on alveolar fluid clearance after rapid saline intravenous infusion by evaluating diffusive and mechanical lung properties. Ten COPD and 10 healthy subjects were treated with salmeterol or placebo 4 h before the patient's mechanical and diffusive lung properties were measured during four non consecutive days, just before and after a rapid saline infusion, or during a similar period without an infusion. RESULTS: In both COPD and healthy subjects, rapid saline infusion with placebo or salmeterol premedication lead to a significant decrease in diffusion capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1). Nonetheless, salmeterol pretreatment lead to a significantly reduced gas exchange impairment caused by saline infusion (-64% of DLCO reduction compared with placebo), whereas it did not affect changes in FEV1. In the control setting with no infusion, we found no significant change in either DLCO or mechanical properties of the lung. CONCLUSIONS: Salmeterol appears to provide a protective effect, not related to bronchodilation, against an acute alveolar fluid clearance challenge secondary to lung fluid overload in COPD patients.

Biomarkers in lower respiratory tract infections.

This review aims to provide physicians with an overview of the potential of biomarkers to complement existing clinical severity scores and in conjunction with clinical parameters to improve the diagnosis, risk-stratification and management of lower respiratory tract infections (LRTIs). The usefulness of biomarkers for diagnosing LRTIs is still unclear. However, the specificity of pneumonia diagnosis is high when high sensitivity C-reactive protein (CRP) and procalcitonin (PCT) are used. PCT, CRP and particularly pro-atrial natriuretic peptide (MR-proANP), pro-vasopressin (CT-proAVP) and proadrenomedullin (proADM) levels can reliably predict LRTIs mortality. These markers do not significantly improve the severity scores predictive values, confirming that biomarkers are meant to complement, rather than supersede, clinician's judgment and validated severity scores. Biomarkers, and particularly PCT, are useful tools as antibiotic treatment duration indicators both in pneumonia and exacerbations of chronic obstructive pulmonary disease (COPD). Even if more data are required to fully appreciate the role of biomarkers in LRTIs management, there is emerging evidence that biomarkers have the potential to improve the daily clinical management of LRTIs.

Acidemia does not affect outcomes of patients with acute cardiogenic pulmonary edema treated with continuous positive airway pressure.

INTRODUCTION: A lack of data exists in the literature evaluating acidemia on admission as a favorable or negative prognostic factor in patients with acute cardiogenic pulmonary edema (ACPE) treated with non-invasive continuous positive airway pressure (CPAP). The objective of the present study was to investigate the impact of acidemia on admission on outcomes of ACPE patients treated with CPAP. METHODS: This was a retrospective, observational study of consecutive patients admitted with a diagnosis of ACPE to the Emergency Department of IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy, between January 2003 and December 2006, treated with CPAP on admission. Two groups of patients were identified: subjects with acidemia (acidotic group), and those with a normal pH on admission (controls). The primary endpoint was clinical failure, defined as switch to bi-level ventilation, switch to endotracheal intubation or inhospital mortality. RESULTS: Among the 378 patients enrolled, 290 (77%) were acidotic on admission. A total of 28 patients (9.7%) in the acidotic group and eight patients (9.1%) among controls experienced a clinical failure (odds ratio = 1.069, 95% confidence interval = 0.469 to 2.438, P = 0.875). Survival analysis indicates that, among acidotic patients, the time at which 50% of patients reached the 7.35 threshold was 173 minutes (95% confidence interval = 153 to 193). Neither acidemia (P = 0.205) nor the type of acidosis on admission (respiratory acidosis, P = 0.126; metabolic acidosis, P = 0.292; mixed acidosis, P = 0.397) affected clinical failure after adjustment for clinical and laboratory factors in a multivariable logistic regression model. CONCLUSIONS: Neither acidemia nor the type of acidosis on admission should be considered risk factors for adverse outcomes in ACPE patients treated with CPAP.

Cefditoren versus levofloxacin in patients with exacerbations of chronic bronchitis: serum inflammatory biomarkers, clinical efficacy, and microbiological eradication.

BACKGROUND: The aim of this open-label, randomized, parallel-group pilot study was to evaluate the efficacy of cefditoren pivoxil and levofloxacin in terms of speed of reduction in inflammatory parameters, clinical recovery, and microbiological eradication. METHODS: Forty eligible patients with acute exacerbation of chronic bronchitis (AECB) were randomized to receive cefditoren 200 mg twice a day for 5 days (n = 20) or levofloxacin 500 mg once daily for 7 days (n = 20). RESULTS: The inflammatory parameters which were significantly reduced at test-of-cure with respect to visit 1 were Krebs von den Lundgen-6 (KL-6) and interleukin-6. KL-6 decreased both in the overall study population (from 19 ± 11 UI/mL to 6 ± 8 UI/mL, P = 0.000) and in the cefditoren (from 19 ± 13 UI/mL to 8 ± 10 UI/mL, P = 0.006) and levofloxacin (from 19 ± 10 UI/mL to 5 ± 5 UI/mL, P = 0.000) arms. Similarly, interleukin-6 decreased both in the overall study population (from 13.35 ± 16.41 pg/mL to 3 ± 4.7 pg/mL, P = 0.000) and in the cefditoren (from 15.90 ± 19.54 pg/mL to 4.13 ± 6.42 pg/mL, P = 0.015) and levofloxacin (from 10.80 ± 12.55 pg/mL to 1.87 ± 1.16 pg/mL, P = 0.003) arms. At the end of treatment (test-of-cure, 6-9 days after drug initiation), the clinical success rate in the overall study population was 78%; the clinical cure rate was 80% in the cefditoren arm and 75% in the levofloxacin arm. Globally, bacteriological eradication at test-of-cure was obtained in 85% of the overall study population. Both treatments were well tolerated. CONCLUSION: Cefditoren represents a valid option in the treatment of mild to moderately severe cases of AECB in the outpatient care setting. Moreover, the use of this cephalosporin is associated with a significant reduction of interleukin-6 and KL-6, two key mediators of lung inflammation and epithelial damage.

Low CURB-65 is of limited value in deciding discharge of patients with community-acquired pneumonia.

BACKGROUND: The relationship between clinical judgment and indications of the CURB-65 score in deciding the site-of-care for patients with community-acquired pneumonia (CAP) has not been fully investigated. The aim of this study was to evaluate reasons for hospitalization of CAP patients with CURB-65 score of 0 and 1. METHODS: An observational, retrospective study of consecutive CAP patients was performed at the Fondazione Cà Granda, Milan, Italy, between January 2005 and December 2006. The medical records of hospitalized patients with CAP having a CURB-65 score of 0 and 1 were identified and reviewed to determine whether there existed a clinical basis to justify hospitalization. RESULTS: Among the 580 patients included in the study, 218 were classified with a CURB-65 score of 0 or 1. Among those, 127 were hospitalized, and reasons that justified hospitalization were found in 104 (83%) patients. Main reasons for hospitalization included the presence of hypoxemia on admission (35%), failure of outpatient therapy (14%) and the presence of cardiovascular events on admission (9.7%). Used as the sole indicator for inappropriate hospitalization, the CURB-65 score had a poor positive predictive value of 52%. CONCLUSIONS: Although the CURB-65 has been proposed as a tool to guide the site of care decision by international guidelines, this score is not ideal by itself, and should not be regarded as providing decision support information if a score of 0 and 1 is present. In CAP patients with CURB-65 scores of 0 or 1, further evaluations should be performed and completed by clinical judgment.

Prophylactic antibiotic therapy in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) represents a huge epidemiological burden and is associated with a high incidence of morbidity and mortality. The disease is characterized by chronic inflammation and bacterial colonization. Chronic bacterial colonization leads to chronic inflammation and epithelial damage that in turn may increase bacterial colonization and predispose to acute bacterial infection. Acute exacerbations are a major cause of hospitalization and lead to a deterioration in pulmonary function. Antibiotic treatment of acute bacterial exacerbations is a cornerstone of medical treatment. Conversely, the role of antibiotic prophylaxis in COPD in the stable state is controversial. From a theoretical point of view, antibiotic prophylaxis is intriguing as it could break the vicious circle between chronic bacterial colonization, inflammation and epithelial damage; however, evidence is scarce. This paper reviews the literature and focuses on the most recent data shedding light on this fascinating dilemma.

Mortality in acute cardiogenic pulmonary edema treated with continuous positive airway pressure.

OBJECTIVE: To investigate mortality in acute cardiogenic pulmonary edema (ACPE) patients treated with continuous positive airway pressure (CPAP) and to identify clinical and laboratory characteristics associated with mortality. DESIGN: Observational, retrospective study. SETTING: Emergency Medicine Department. PATIENTS AND PARTICIPANTS: A total of 454 consecutive ACPE patients treated with CPAP. MEASUREMENTS AND RESULTS: Demographics, past medical history, clinical characteristics, laboratory evaluation, in-hospital mortality data were collected. Potential predictors of in-hospital mortality that were considered of clinical relevance and immediately accessible on admission were investigated by multivariable logistic regression. ACPE-related mortality rate was 3.8% (17/452 patients) and the in-hospital mortality rate was 11.4% (50/440 patients). Significant independent predictors of increased risk of in-hospital mortality were: advanced age (P = 0.012), normal-to-low blood pressure (P < 0.001), low PaO(2)/FiO(2) ratio (P = 0.020), hypocapnia (P = 0.009) and anemia (P = 0.05). CONCLUSIONS: Values recorded within few minutes from arrival to the hospital can predict mortality in ACPE patients treated with CPAP who has been tested, for the first time, in a real life study. This can allow physicians to quickly recognize more severe ACPE patients treated with CPAP and plan for aggressive monitoring and treatment and for deciding the better site of care.

Acute effects of positive end-expiratory pressure on left ventricle diastolic function in healthy subjects.

We evaluated the acute effect of the application of positive end-expiratory pressure (PEEP) on LV diastolic function in 10 healthy subjects. We assessed load dependent diastolic function by Doppler examination of transmitral flow and load independent diastolic function by color M-mode propagation velocity of early flow into the LV cavity (Vp). During the application of PEEP in comparison to the baseline, we found a significant reduction of the E wave peak velocity [79 (64-83) vs. 65 (57-72) cm/s; p = 0.028] and a significant reduction in Vp [84 (73-97) vs. 53 (48-66); p = 0.012]. Moreover, we found a significant reduction in left atrial area [15 (13-18) vs. 12 (10-14) cm(2); p = 0.018] and right atrial area [12 (11-15) vs. 11 (9-12) cm(2); p = 0.015]. No difference was found in global LV systolic function. The application of PEEP acutely modifies the diastolic flow pattern across the mitral valve, and reduces atrial dimensions.

Usefulness of simplified acute physiology score II in predicting mortality in patients admitted to an emergency medicine ward.

The Objective of this prospective observational study was to evaluate the applicability of the simplified acute physiology score (SAPS II) in patients admitted to an Emergency Medicine Ward in the Emergency Medicine Ward of a tertiary university hospital. We studied consecutive patients admitted to an Emergency Medicine Ward from the emergency department. The SAPS II was assessed in predicting overall in-hospital mortality in terms of sensitivity, specificity and receiver operating characteristic (ROC) curve. A total of 211 consecutive patients were admitted over a period of 2 months. Median SAPS II score was 28 (range 6-93), with a mean risk of in-hospital mortality of 0.17 (range 0.01-0.97) for the whole population, and an observed mortality of 15%. The area under the receiver operator curve (ROC) was 0.84 (0.77-0.91). Considering a cut-off value of SAPS II of 49, the sensitivity was 0.50 (95% CI 0.42-0.56), the specificity was 0.95 (0.92-0.98), the positive predictive value (PPV) was 0.64 (0.58-0.71), and the negative predictive value (NPV) was 0.91 (0.87-0.95), the positive likelihood ratio (pLH) was 9.9, and the negative likelihood ratio (nLH) was 0.5. If contrarily a cut-off value of SAPS II of 22 were used, the sensitivity would be 1.0, the specificity would be 0.21 (0.16-0.26), the PPV would be 0.18 (0.13-0.23), the NPV would be 1.0, the pLH would be 1.3, and the nLH would be 0.0. In this preliminary study, SAPS II predicted in-hospital mortality in patients admitted to an Emergency Ward.