Publications by authors named "Christian Folli"

11 Publications

  • Page 1 of 1

Henoch-Schönlein purpura with renal and gastrointestinal involvement in course of COVID-19: a case report.

Clin Exp Rheumatol 2021 Mar-Apr;39 Suppl 129(2):191-192. Epub 2021 Mar 24.

High-Intensity Care Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

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May 2021

Increasing dosages of low-molecular-weight heparin in hospitalized patients with Covid-19.

Intern Emerg Med 2021 08 3;16(5):1223-1229. Epub 2021 Jan 3.

A. Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Via Pace 9, 20122, Milan, Italy.

We conducted an observational cohort study in adult patients consecutively admitted for the respiratory illness Covid-19 to our hub hospital from March 9 to April 7, 2020. The high observed rate of venous thromboembolism prompted us to increase the prophylactic doses of enoxaparin from 40 mg daily up to 1 mg/kg twice daily in patients admitted to intensive care units (ICU), 0.7 mg/kg twice daily in high-intensity of care wards and 1 mg/kg daily in low-intensity of care wards. Patients on high enoxaparin doses were compared to those who received prophylaxis with the standard dosage. Efficacy endpoints were mortality, clinical deterioration, and the occurrence of venous thromboembolism, safety endpoint was the occurrence of major bleeding. Of 278 patients with Covid-19, 127 received prophylaxis with high enoxaparin doses and 151 with standard dosage. At 21 days, the incidence rate of death and clinical deterioration were lower in patients on higher doses than in those on the standard dosage (hazard ratio 0.39, 95% confidence interval 0.23-0.62), and the incidence of venous thromboembolism was also lower (hazard ratio 0.52, 95% confidence interval 0.26-1.05). Major bleeding occurred in four of 127 patients (3.1%) on the high enoxaparin dosage. In conclusion, in the cohort of patients with Covid-19 treated with high enoxaparin dosages we observed a 60% reduction of mortality and clinical deterioration and a 50% reduction of venous thromboembolism compared to standard dosage prophylaxis. However, 3% of patients on high enoxaparin dosages had non-fatal major bleeding.
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August 2021

Major hemorrhages in patients treated with oral anticoagulants: choice of management in the emergency room.

Eur J Intern Med 2018 09 18;55:e25-e26. Epub 2018 Jul 18.

High-Intensity Care Internal Medicine, IRCCS Ca' Granda Maggiore Hospital Foundation, Milan, Italy. Electronic address:

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September 2018

Diagnostic accuracy of combined cardiac troponin and copeptin assessment for early rule-out of myocardial infarction: a systematic review and meta-analysis.

Eur Heart J Acute Cardiovasc Care 2014 Mar 20;3(1):18-27. Epub 2013 Nov 20.

University Hospital, Clermont-Ferrand, France.

Aims: This systematic review aimed to investigate the diagnostic accuracy of combined cardiac troponin (cTn) and copeptin assessment in comparison to cTn alone for early rule-out of acute myocardial infarction (AMI).

Methods: Primary studies were eligible if they evaluated diagnostic accuracy for cTn with and without copeptin in patients with symptoms suggestive of AMI. AMI was defined according to the universal definition, using detection of cTn as a marker for myocardial necrosis. Eligible studies were identified by searching electronic databases (Medline, EMBASE, Science Citation Index Expanded, CINAHL, Pascal, and Cochrane) from inception to March 2013, reviewing conference proceedings and contacting field experts and the copeptin manufacturer.

Results: In 15 studies totalling 8740 patients (prevalence of AMI 16%), adding copeptin improved the sensitivity of cTn assays (from 0.87 to 0.96, p=0.003) at the expense of lower specificity (from 0.84 to 0.56, p<0.001). In 12 studies providing data for 6988 patients without ST-segment elevation, the summary sensitivity and specificity estimates were 0.95 (95% CI 0.89 to 0.98) and 0.57 (95% CI 0.49 to 0.65) for the combined assessment of cTn and copeptin. When a high-sensitivity cTnT assay was used in combination with copeptin, the summary sensitivity and specificity estimates were 0.98 (95% CI 0.96 to 1.00) and 0.50 (95% CI 0.42 to 0.58).

Conclusion: Despite substantial between-study heterogeneity, this meta-analysis demonstrates that copeptin significantly improves baseline cTn sensitivity. Management studies are needed to establish the effectiveness and safety of measuring copeptin in combination with high-sensitivity cTnT for early rule-out of AMI without serial testing.
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March 2014

Thirty and ninety days mortality predictive value of admission and in-hospital procalcitonin and mid-regional pro-adrenomedullin testing in patients with dyspnea. Results from the VERyfing DYspnea trial.

Am J Emerg Med 2014 Apr 3;32(4):334-41. Epub 2014 Jan 3.

Emergency Department, Sant'Andrea Hospital, School of Medicine and Psychology "Sapienza" Univesity, Rome, Italy. Electronic address:

Introduction: Mid-regional pro-atrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) demonstrated usefulness for management of emergency department patients with dyspnea.

Methods: To evaluate in patients with dyspnea, the prognostic value for 30 and 90 days mortality and readmission of PCT, MR-proADM, and MR-proANP, a multicenter prospective study was performed evaluating biomarkers at admission, 24 and 72 hours after admission. Based on final diagnosis, patients were divided into acute heart failure (AHF), primary lung diseases, or both (AHF + NO AHF).

Results: Five hundred one patients were enrolled. Procalcitonin and MR-proADM values at admission and at 72 hours were significantly (P < .001) predictive for 30-day mortality: baseline PCT with an area under the curve (AUC) of 0.70 and PCT at 72 hours with an AUC of 0.61; baseline MR-proADM with an AUC of 0.62 and MR-proADM at 72 hours with an AUC of 0.68. As for 90-day mortality, both PCT and MR-proADM baseline and 72 hours values showed a significant (P < .0001) predictive ability: baseline PCT with an AUC of 0.73 and 72 hours PCT with an AUC of 0.64; baseline MR-proADM with an AUC of 0.66 and 72 hours MR-proADM with an AUC of 0.71. In AHF, group biomarkers predicted rehospitalization and mortality at 90 days, whereas in AHF + NO AHF group, they predict mortality at 30 and 90 days.

Conclusions: In patients admitted for dyspnea, assessment of PCT plus MR-proADM improves risk stratification and management. Combined use of biomarkers is able to predict in the total cohort both rehospitalization and death at 30 and 90 days.
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April 2014

Diagnostic role of copeptin in patients presenting with chest pain in the emergency room.

Eur J Intern Med 2013 Mar 9;24(2):189-93. Epub 2012 Oct 9.

UO Medicina d'Urgenza e Pronto Soccorso IRCCS Fondazione Policlinico Milano, Italy.

Background: Chest pain is a frequent symptom leading patients to the Emergency Room. Copeptin, the C-terminal fragment of arginin-vasopressin, is a marker of stressful situations. Recent studies showed that normal levels of copeptin combined with normal troponin accurately rule out the diagnosis of acute coronary syndrome (ACS). In this observational, prospective, multicenter study we evaluated if negative levels of copeptin combined with negative troponin (Tn-T) can correctly rule out the diagnosis of ACS and also of other life-threatening causes of chest pain.

Results: Of 472 enrolled patients (64.6% males, mean age 60.1yrs), 28 (5.9%) were diagnosed with ST-elevation myocardial infarction (STEMI), 28 (5.9%) with non ST-elevation myocardial infarction (NSTEMI), 43 (9.1%) with unstable angina (UA), 13 (2.8%) with potentially life-threatening non-ACS pathologies (aortic dissection, pulmonary embolism, pulmonary edema, sepsis), 360 (76.2%) with benign causes of chest pain. Copeptin levels were significantly higher in ACS patients with STEMI and NSTEMI than in those with other diagnoses, but not in those with UA. The combination of copeptin and troponin-T attained a negative predictive value of 86.6% for ACS, of 97.9% for other potentially life-threatening non-ACS diseases and of 85% for all potentially lethal diseases (ACS plus others).

Conclusions: The combined use of troponin and copeptin significantly improved the diagnostic accuracy of troponin alone both in ACS (STEMI and NSTEMI) and in other life-threatening diseases. Measurement of this marker might be therefore considered not only for a rule-out strategy but also as a warning sign of a life-threatening disease.
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March 2013

Causes and correlates of anemia in 200 patients with acute cardiogenic pulmonary edema.

Eur J Intern Med 2012 Dec 18;23(8):733-7. Epub 2012 Jul 18.

Emergency Medicine Unit, Department of Medicine and Medical Specialties, IRCCS Ca' Granda Maggiore Policlinico Hospital Foundation, Milan, Italy.

Background: Acute heart failure has a poor prognosis and the presence of anemia may increase the risk of adverse outcomes. However, the clinical and laboratory characteristics of anemia in acute heart failure are poorly known. We aimed to assess the causes and the clinical and laboratory correlates of anemia in patients with acute cardiogenic pulmonary edema (ACPE).

Methods: This observational study, performed in an Emergency Unit, enrolled 200 patients treated with medical therapy and continuous positive airway pressure.

Results: Anemia was found in 36% of patients (38.5% of females and 32.5% of males) and was severe (hemoglobin <9 g/dL) in 6.9% of cases. The most frequent causes of anemia were chronic renal failure (27.8%), chronic inflammatory states (27.8%) and the clustering of multiple factors (18.1%). A wider spectrum of etiological factors was found in females than in males. Microcytic anemia was observed only in females (20% of those anemic), mainly due to iron deficiency/chronic blood loss. Glomerular filtration rate, serum iron, serum albumin, total cholesterol and diastolic blood pressure were independently associated with hemoglobin levels.

Conclusions: The etiology of anemia in ACPE is heterogeneous, with several causal factors besides impaired renal function. The pattern of anemia is different between genders, suggesting that sex-specific diagnostic and therapeutic targets should be implemented.
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December 2012

Thromboembolic and haemorrhagic events in permanent atrial fibrillation: observational study in an emergency department.

Eur J Intern Med 2009 Dec 24;20(8):756-9. Epub 2009 Sep 24.

Emergency Division, IRCCS Fondazione Policlinico, Mangiagalli e Regina Elena, Milano, Italy.

Background: Atrial fibrillation (AF) is the most common arrhythmia in patients admitted to Emergency Departments. However, the management of permanent AF in order to prevent thromboembolism in clinical practice is still widely discussed. We aimed to evaluate this management and the occurrence of clinical events in a cohort of patients with permanent AF admitted to our Emergency Department.

Methods: We enrolled in this observational study 582 patients with permanent AF consecutively seen in our Emergency Room.

Results: Mean age was 80.1 +/- 9.6 years. Two or more comorbidities were present in 67% of patients. 28% of patients were treated with oral anticoagulant therapy (OT) at the time of admission to the Emergency Department, 34.2% with anti-platelet therapy (APT), while 37.8% were taking no anti-thrombotic therapy. There was no correspondence between three observed groups of treatment and the risk stratification according to CHADS2. In the groups of patients at high or intermediate risk a higher number of ischemic stroke was observed in patients taking APT than in OT patients (16.1% vs 31.5%, p=0.001). A low frequency of total and cerebral haemorrhagic events was observed in all groups. Only the non severe bleeds were significantly more frequent in patients on OT.

Conclusions: OT is well-tolerated even in elderly patients, with a low rate of haemorrhagic events. In clinical practice OT is underused, in particular in older patients, in spite of a high number of thrombotic events.
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December 2009

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

Intern Emerg Med 2009 Jun 23;4(3):241-7. Epub 2009 Apr 23.

Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, U.O. Medicina d'Urgenza, Gruppo NIV Policlinico, Via F. Sforza, 35, 20122 Milan, Italy.

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.
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June 2009

Natural history and clinical impact of cryoglobulins in chronic hepatitis C: 10-year prospective study of 343 patients.

Gastroenterology 2007 Sep 3;133(3):835-42. Epub 2007 Jul 3.

Division of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico Maggiore Hospital Fondazione Policlinico, Mangiagalli e Regina Elena, Centro A. M. & A. Migliavacca, University of Milan, Milan, Italy.

Background & Aims: Serum cryoglobulins (CGs) are present in patients with chronic hepatitis C virus (HCV) infection, but their long-term clinical importance has not been established. We assessed the development rates, morbidity, and influence on the evolutionary course of hepatitis C of CG.

Methods: A cohort of 343 HCV-RNA seropositive outpatients (173 men; age, 58 y; 82 with cirrhosis; 61 treated with interferon) with persistently increased aminotransferase levels and histologically defined liver disease was investigated. Patients initially were investigated for the presence, amount, and type of CG and prospectively followed up with clinical and laboratory examinations every 6 months.

Results: At enrollment, CGs were found in 163 (47%) patients at a mean level of 173 +/- 142 mg/L; 80% were type III, and associated to female sex (61% vs 40%, P = .0002) and cirrhosis (29% vs 19%, P = .04). Over the course of 17-130 months (median, 116 mo), de novo CG developed in 25 patients (2.3% per year), including 5 with cryoglobulinemic syndrome (.3% per year). The 10-year rates of progression to cirrhosis and of liver and extrahepatic complications were similar in CG (+) and CG (-) patients (32% vs 34%; 23% vs 16%; 5% vs 3%). The 10-year survival rates were lower for cirrhotic than for noncirrhotic patients (57% vs 91%, P < .00001), independently of CGs.

Conclusions: CGs are common in patients with chronic HCV infection, mainly are type III, and do not influence the clinical course of hepatitis C during the first decades, except for the few rare cases of cryoglobulinemic syndrome.
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September 2007