Publications by authors named "Antonio Mirijello"

82 Publications

Transthoracic ultrasound shear wave elastography for the study of subpleural lung lesions.

Ultrasonography 2021 Apr 15. Epub 2021 Apr 15.

Unit of Interventional and Diagnostic Ultrasound, Department of Internal Medicine, IRCCS Fondazione Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.

Purpose: The aim of this study was to assess whether new-generation shear wave elastography (SWE) is suitable for the characterization of lung subpleural lesions.

Methods: In total, 190 consecutive patients with subpleural lung lesions received ultrasonography and SWE. Patients with suspected malignancy underwent ultrasound-guided transthoracic needle biopsy. Final diagnoses were made on the basis of patients' clinical course, microbiological studies, and histological results. SWE was also performed in 25 healthy volunteers.

Results: We found no statistically significant differences in stiffness between lung carcinomas, lung metastases, and pneumonia (P=0.296) or between different histological types of lung cancer (P=0.393). Necrosis was associated with reduced stiffness in pneumonia. Excluding necrotic lesions, pneumonia showed higher stiffness than lung carcinomas (2.95±0.68 m/s vs. 2.60±0.54 m/s, P=0.006). Chronic pneumonia showed increased stiffness (3.03±0.63 m/s), probably due to the presence of fibrotic tissue on histology. Pleural effusion was associated with a statistically significant reduction in stiffness, both in lung carcinomas (P=0.004) and lung metastases (P=0.002). The presence of air in healthy lung tissue may lead to incorrect speed estimates due to shear wave reflection (very high values, 14.64±2.19 m/s).

Conclusion: Transthoracic SWE could not distinguish lung malignancy from pneumonia, or between different histological types of lung carcinomas. In particular, SWE seems unable to resolve the clinical dilemma of chronic subpleural consolidations.
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http://dx.doi.org/10.14366/usg.21021DOI Listing
April 2021

Neutropenic Enterocolitis and Sepsis: Towards the Definition of a Pathologic Profile.

Medicina (Kaunas) 2021 Jun 20;57(6). Epub 2021 Jun 20.

Section of Legal Medicine, Department of Clinical and Experimental Medicine, University of Foggia, Ospedale Colonnello D'Avanzo, Viale Europa 12, 71100 Foggia, Italy.

Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. : A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. : To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. : Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic "neutropenic enterocolitis and sepsis" appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile.
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http://dx.doi.org/10.3390/medicina57060638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234962PMC
June 2021

A "Galactic" Chest X-ray.

Diagnostics (Basel) 2021 May 18;11(5). Epub 2021 May 18.

Unit of Pathology, Department of Services, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

Clinical manifestations accompanying respiratory failure with insidious and rapidly progressive onset are often non-specific. Symptoms such as a cough, dyspnea, and fever are common to a large number of inflammatory, infectious, or neoplastic diseases. During the COVID-19 pandemic it is essential to limit the use of hospital services and inappropriate diagnostic techniques. A particular radiological pattern can orient the clinical and laboratory scenario and guide the diagnostic workup. A 58-year-old woman was admitted to our COVID-19 unit for suspected coronavirus infection. She was complaining of worsening dyspnea, tachycardia, and low grade fever. A chest X-ray showed diffuse, alveolar, and interstitial lung involvement with micronodules tending to coalescence. This radiographic pattern known as "galaxy sign", consistent with diffuse, coalescing nodular miliary pulmonary involvement, simulating a non-specific alveolar opacification of the lungs is typical of a few pneumological differential diagnoses, represented by sarcoidosis, tuberculosis, pneumoconiosis, and metastatic lesions, and virtually excludes an interstitial viral pneumonitis. The use of endoscopic techniques can, in such cases, confirm the clinical suspicion for initiating appropriate targeted therapies.
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http://dx.doi.org/10.3390/diagnostics11050899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158502PMC
May 2021

More on SARS-CoV-2 Infection after Vaccination in Health Care Workers.

N Engl J Med 2021 07 12;385(2):e8. Epub 2021 May 12.

Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy.

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http://dx.doi.org/10.1056/NEJMc2106004DOI Listing
July 2021

Delta-Procalcitonin and Vitamin D Can Predict Mortality of Internal Medicine Patients with Microbiological Identified Sepsis.

Medicina (Kaunas) 2021 Apr 1;57(4). Epub 2021 Apr 1.

Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

: The management of septic patients hospitalized in Internal Medicine wards represents a challenge due to their complexity and heterogeneity, and a high mortality rate. Among the available prognostic tools, procalcitonin (PCT) is considered a marker of bacterial infection. Furthermore, an association between vitamin D deficiency and poor sepsis-related outcomes has been described. To evaluate the prognostic accuracy of two consecutive PCT determinations (Delta-PCT) and of vitamin D levels in predicting mortality in a population of patients with microbiological identified sepsis admitted to Internal Medicine wards. : This is a sub-analysis of a previous prospective study. A total of 80 patients had at least two available consecutive PCT determinations, while 63 had also vitamin D. Delta-PCT was defined as a reduction of PCT > 50% after 48 h, >75% after 72 h, and >85% after 96 h. Mortality rate at 28- and 90-days were considered as main outcome. Mortality rate was 18.7% at 28-days and 30.0% at 90-days. Baseline PCT levels did not differ between survived and deceased patients (28-days: 0.525; 90-days: 0.088). A significantly higher proportion of survived patients showed Delta-PCT (28-days: 0.002; 90-days: < 0.001). Delta-PCT was associated with a lower 28-days ( 0.007; OR = 0.12, 95%CI 0.02-0.46) and 90-days mortality ( 0.001; OR = 0.17, 95%CI 0.06-0.48). A significantly higher proportion of deceased patients showed severe vitamin D deficiency (28-days: 0.047; 90-days: 0.049). Severe vitamin D deficiency was associated with a higher 28-days ( 0.058; OR = 3.95, 95%CI 1.04-19.43) and 90-days mortality ( 0.054; OR = 2.94, 95%CI 1.00-9.23). : Delta-PCT and vitamin D represent two useful tests for predicting prognosis of septic patients admitted to Internal Medicine wards.
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http://dx.doi.org/10.3390/medicina57040331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066199PMC
April 2021

Low Sensitivity of Admission Lung US Compared to Chest CT for Diagnosis of Lung Involvement in a Cohort of 82 Patients with COVID-19 Pneumonia.

Medicina (Kaunas) 2021 Mar 4;57(3). Epub 2021 Mar 4.

Unit of Interventional and Diagnostic Ultrasound of Internal Medicine, Department of Medical Sciences, IRCCS Fondazione Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

: The potential role of lung ultrasound (LUS) in characterizing lung involvement in Coronavirus disease 2019 (COVID-19) is still debated. The aim of the study was to estimate sensitivity of admission LUS for the detection of SARS-CoV-2 lung involvement using Chest-CT (Computed Tomography) as reference standard in order to assess LUS usefulness in ruling out COVID-19 pneumonia in the Emergency Department (ED). : Eighty-two patients with confirmed COVID-19 and signs of lung involvement on Chest-CT were consecutively admitted to our hospital and recruited in the study. Chest-CT and LUS examination were concurrently performed within the first 6-12h from admission. Sensitivity of LUS was calculated using CT findings as a reference standard. : Global LUS sensitivity in detecting COVID-19 pulmonary lesions was 52%. LUS sensitivity ranged from 8% in case of focal and sporadic ground-glass opacities (mild disease), to 52% for a crazy-paving pattern (moderate disease) and up to 100% in case of extensive subpleural consolidations (severe disease), although LUS was not always able to detect all the consolidations assessed at Chest-CT. LUS sensitivity was higher in detecting a typical Chest-CT pattern (60%) and abnormalities showing a middle-lower zone predominance (79%). : As admission LUS may result falsely negative in most cases, it should not be considered as a reliable imaging tool in ruling out COVID-19 pneumonia in patients presenting in ED. It may at least represent an expanded clinical evaluation that needs integration with other diagnostic tests (e.g., nasopharyngeal swab, Chest-CT).
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http://dx.doi.org/10.3390/medicina57030236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001137PMC
March 2021

Diagnosis of COVID-19 in Patients with Negative Nasopharyngeal Swabs: Reliability of Radiological and Clinical Diagnosis and Accuracy Versus Serology.

Diagnostics (Basel) 2021 Feb 25;11(3). Epub 2021 Feb 25.

Unit of Internal Medicine, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

Background: The diagnosis of Coronavirus disease 2019 (COVID-19) relies on the positivity of nasopharyngeal swab. However, a significant percentage of symptomatic patients may test negative. We evaluated the reliability of COVID-19 diagnosis made by radiologists and clinicians and its accuracy versus serology in a sample of patients hospitalized for suspected COVID-19 with multiple negative swabs.

Methods: Admission chest CT-scans and clinical records of swab-negative patients, treated according to the COVID-19 protocol or deceased during hospitalization, were retrospectively evaluated by two radiologists and two clinicians, respectively.

Results: Of 254 patients, 169 swab-confirmed cases and one patient without chest CT-scan were excluded. A total of 84 patients were eligible for the reliability study. Of these, 21 patients died during hospitalization; the remaining 63 underwent serological testing and were eligible for the accuracy evaluation. Of the 63, 26 patients showed anti-Sars-Cov-2 antibodies, while 37 did not. The inter-rater agreement was "substantial" (kappa 0.683) between radiologists, "moderate" (kappa 0.454) between clinicians, and only "fair" (kappa 0.341) between radiologists and clinicians. Both radiologic and clinical evaluations showed good accuracy compared to serology.

Conclusions: The radiologic and clinical diagnosis of COVID-19 for swab-negative patients proved to be sufficiently reliable and accurate to allow a diagnosis of COVID-19, which needs to be confirmed by serology and follow-up.
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http://dx.doi.org/10.3390/diagnostics11030386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996330PMC
February 2021

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study.

J Am Coll Cardiol 2020 12;76(25):2982-3021

University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, USA.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.
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http://dx.doi.org/10.1016/j.jacc.2020.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755038PMC
December 2020

Wernicke's Encephalopathy in Alcohol Use Disorder Patients after Liver Transplantation: A Case Series and Review of Literature.

J Clin Med 2020 Nov 25;9(12). Epub 2020 Nov 25.

Alcohol Use Disorder and Alcohol Related Disease Unit, Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Wernicke's encephalopathy (WE) is an acute neurological disorder resulting from thiamine deficiency, commonly found in alcohol use disorder (AUD) patients. Liver transplantation (LT) could represent a risk factor for the onset of WE in AUD patients, due to the onset of chronic depletion of thiamine in this population and the high metabolic demand of surgery and the postoperative period. However, few data are available about the risk of the onset of WE in AUD patients after LT. Here we report three cases of AUD patients who developed WE with confusion and delirium after LT. Prompt parenteral administration of thiamine led to a rapid improvement of the clinical condition and a complete remission of neurological symptoms after 3-4 days. In addition, a search of the available English literature was conducted in order to perform a review of the possible association between the onset of WE and LT in AUD patients. A prophylactic treatment regimen based on the administration of thiamine could be suggested in AUD patients before and after LT. Further studies are needed to determine the optimal regimen of thiamine in the prevention of WE in this setting.
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http://dx.doi.org/10.3390/jcm9123809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761291PMC
November 2020

New Strategies for Treatment of Sepsis.

Medicina (Kaunas) 2020 Oct 10;56(10). Epub 2020 Oct 10.

Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, 00168 Rome, Italy.

Sepsis represents a major global health concern and is one of the most feared complications for hospitalized patients, being the cause, directly or indirectly, of about half of all hospital deaths. According to the last definition, sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and defined septic shock as a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to significantly increase mortality. Sepsis is a time-dependent disease and requires a prompt recognition and a standardized treatment. The Special Issue "New Strategies for Treatment of Sepsis" has been thought to connect the experience of physicians involved in the diagnosis, management, and treatment of sepsis at every stage of disease, from emergency departments to general and intensive wards. The focus will be pointed on new approaches to this syndrome, such as early recognition based on clinical features and biomarkers, management in non-ICUs, non-invasive treatment strategies, including non-antimicrobial agents, and, of course, invasive approaches. This Special Issue will highlight the many different facets of sepsis, seen through the eyes of different specialists. We hope to spread the knowledge of a new blueprint for treatment.
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http://dx.doi.org/10.3390/medicina56100527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599752PMC
October 2020

Reduction of ADAMTS13 Levels Predicts Mortality in SARS-CoV-2 Patients.

TH Open 2020 Jul 30;4(3):e203-e206. Epub 2020 Aug 30.

Research Unit of Thrombosis and Hemostasis, Fondazione IRCCS "Casa Sollievo della Sofferenza," San Giovanni Rotondo, Italy.

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http://dx.doi.org/10.1055/s-0040-1716379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456602PMC
July 2020

Long-term blood pressure variability, incidence of hypertension and changes in renal function in type 2 diabetes.

J Hypertens 2020 11;38(11):2279-2286

University of Genoa and IRCCS Ospedale Policlinico San Martino, Genova.

Objectives: Long-term visit-to-visit SBP variability (VVV) predicts cerebro-cardiovascular and renal events in patients with hypertension. Whether VVV predicts hypertension and/or chronic kidney disease is currently unknown. We assessed the role of VVV on the development of hypertension and changes in renal function in patients with type 2 diabetes and normal blood pressure (NBP) in a real-life clinical setting.

Methods: Clinical records from 8998 patients with type 2 diabetes, NBP, and normal estimated glomerular filtration rate (eGFR) were analyzed. VVV was measured by SD of the mean SBP recorded in at least four visits during 2 consecutive years before follow-up. Hypertension was defined as SBP at least 140 mmHg and DBP at least 90 mmHg or the presence of antihypertensive treatment. Renal function was defined as worsening of albuminuria status and/or a reduction in eGFR at least 30% from baseline.

Results: After a mean follow-up time of 3.5 ± 2.8 years, 3795 patients developed hypertension (12.1 per 100 person-years). An increase of 5 mmHg VVV was associated with a 19% (P < 0.0001) and a 5% (P = 0.008) independent increased risk of developing hypertension and worsening of albuminuria, respectively. We found no association between VVV and eGFR decrease from baseline. Patients with VVV in the upper quartile (>12.8 mmHg) showed a 50% increased risk of developing hypertension (P < 0.0001) and an almost 20% increased risk of worsening albuminuria (P = 0.004) as compared with those in the lower one (<6.9 mmHg).

Conclusion: Increased VVV independently predicts incident hypertension and albuminuria worsening in type 2 diabetes and NBP.
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http://dx.doi.org/10.1097/HJH.0000000000002543DOI Listing
November 2020

Make Mission Impossible Feasible: The Experience of a Multidisciplinary Team Providing Treatment for Alcohol Use Disorder to Homeless Individuals.

Alcohol Alcohol 2020 Aug;55(5):547-553

Internal Medicine and Alcohol Related Disease Unit, Department of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Aim: People experiencing homelessness are often excluded from treatment programs for alcohol use disorder (AUD). The goal of this study was to describe the impact of a multidisciplinary treatment program on alcohol consumption and social reintegration in individuals with AUD experiencing homelessness.

Methods: Thirty-one individuals with AUD experiencing homelessness were admitted to an inpatient unit for 5-6 days for clinical evaluation and to treat potential alcohol withdrawal syndrome. A group of volunteers, in collaboration with the Community of Sant'Egidio, provided social support aimed to reintegrate patients. After inpatient discharge, all patients were followed as outpatients. Alcohol intake (number drinks/day), craving and clinical evaluation were assessed at each outpatient visit. Biological markers of alcohol use were evaluated at enrollment (T0), at 6 months (T1) and 12 months (T2).

Results: Compared with T0, patients at T1 showed a significant reduction in alcohol consumption [10 (3-24) vs 2 (0-10); P = 0.015] and in γ-glutamyl-transpeptidase [187 (78-365) vs 98 (74-254); P = 0.0021]. The reduction in alcohol intake was more pronounced in patients with any housing condition [10 (3-20) vs 1 (0-8); P = 0.008]. Similarly, compared with T0, patients at T2 showed significant reduction in alcohol consumption [10 (3-24) vs 0 (0-15); P = 0.001], more pronounced in patients with any housing condition [10 (3-20) vs 0 (0-2); P = 0.006]. Moreover, at T2 patients showed a significant reduction in γ-glutamyl-transpeptidase [187 (78-365) vs 97 (74-189); P = 0.002] and in mean cell volume [100.2 (95-103.6) vs 98.3 (95-102); P = 0.042].

Conclusion: Patients experiencing homelessness may benefit from a multidisciplinary treatment program for AUD. Strategies able to facilitate and support their social reintegration and housing can improve treatment outcomes.
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http://dx.doi.org/10.1093/alcalc/agaa052DOI Listing
August 2020

Comment on Matricardi PM et al.

Pediatr Allergy Immunol 2020 11 12;31(8):997. Epub 2020 Jun 12.

Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.

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http://dx.doi.org/10.1111/pai.13277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276801PMC
November 2020

Electrocardiographic alterations and raised procalcitonin levels during anaphylactic shock.

BMJ Case Rep 2020 Jan 21;13(1). Epub 2020 Jan 21.

Department of Medical Sciences, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Anaphylaxis represents a systemic disease occurring after the exposure to an allergen. Drugs for the treatment of anaphylactic reactions (ie, corticosteroids and adrenalin) could induce autonomic alterations, such as tachycardia, hyperthermia, tachypnoea and leucocytosis. We describe the case of a 52-year-old woman presenting with a severe allergic reaction after the ingestion of amoxicillin-clavulanate. The occurrence of ECG alterations, laboratory abnormalities and procalcitonin (PCT) elevation will be discussed with particular emphasis on the possible misleading role of PCT during anaphylactic shock.
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http://dx.doi.org/10.1136/bcr-2019-233521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035842PMC
January 2020

Gut microbiota compositional and functional fingerprint in patients with alcohol use disorder and alcohol-associated liver disease.

Liver Int 2020 04 3;40(4):878-888. Epub 2020 Feb 3.

Institute of Internal Medicine and Gastroenterology, Catholic University of Rome, Rome, Italy.

Background & Aims: Alcohol use disorder (AUD) represents the most common cause of liver disease. The gut microbiota plays a critical role in the progression of alcohol-related liver damage. Aim of this study was to characterize the gut microbial composition and function in AUD patients with alcohol-associated liver disease (AALD).

Methods: This study included 36 AUD patients (14 with cirrhosis) who were active drinkers and an equal number of matched controls. Stool microbial composition, serum levels of lipopolysaccharide, cytokines/chemokines and gut microbiota functional profile were assessed.

Results: AUD patients had a decreased microbial alpha diversity as compared to controls (0.092 vs 0.130, P = .047) and a specific gut microbial signature. The reduction of Akkermansia and the increase in Bacteroides were able to identify AUD patients with an accuracy of 93.4%. Serum levels of lipopolysaccharide (4.91 vs 2.43, P = .009) and pro-inflammatory mediators (tumour necrosis factor alpha 60.85 vs 15.08, P = .001; interleukin [IL] 1beta 4.43 vs 1.72, P = .0001; monocyte chemoattractant protein 1 225.22 vs 16.43, P = .006; IL6 1.87 vs 1.23, P = .008) were significantly increased in AUD patients compared to controls and in cirrhotic patients compared to non-cirrhotic ones (IL6 3.74 vs 1.39, P = .019; IL8 57.60 vs 6.53, P = .004). The AUD-associated gut microbiota showed an increased expression of gamma-aminobutyric acid (GABA) metabolic pathways and energy metabolism.

Conclusions: AUD patients present a specific gut microbial fingerprint, associated with increased endotoxaemia, systemic inflammatory status and functional alterations that may be involved in the progression of the AALD and in the pathogenesis of AUD.
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http://dx.doi.org/10.1111/liv.14383DOI Listing
April 2020

The use of procalcitonin for the management of sepsis in Internal Medicine wards: current evidence.

Panminerva Med 2020 Mar 11;62(1):54-62. Epub 2019 Nov 11.

Internal Medicine Unit, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy -

Procalcitonin (PCT) is a circulating polypeptide produced in response to bacterial infections. Studies conducted in the Intensive Care Unit (ICU) setting have demonstrated its utility as a biomarker of bacterial infection and sepsis. Thus, PCT is widely used to distinguish between sepsis and SIRS, and to guide antibiotic therapy. At present sepsis represents a frequent diagnosis among patients admitted to internal medicine (IM) departments. Basing on the knowledge derived from ICU studies, the use of PCT has become routine in non-intensive wards, contributing to improve the management of sepsis. However, some differences between the two populations of patients - the IM being older, affected by multiple chronic comorbidities and lacking of invasive monitoring - could limit the generalizability of ICU results. Most of the studies on PCT conducted in the IM setting have focused on chronic obstructive pulmonary disease, pneumonia and sepsis. Although PCT represents one of the best biomarker available in routine clinical practice, there are uncertainties on the optimal cut-offs to be used for starting or discontinuing antibiotic treatment in patients with suspected bacterial infection or sepsis, for predicting outcome and on the role of PCT variations during antibiotic treatment. Moreover, several diseases can produce an elevation of PCT levels, thus producing false positive results. This represents a narrative review summarizing current evidences on PCT for the management of sepsis in an Internal Medicine wards, highlighting differences with ICU, with a special focus on the role of PCT variations as predictor of outcomes in non-ICU wards.
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http://dx.doi.org/10.23736/S0031-0808.19.03809-6DOI Listing
March 2020

Diagnosis and Management of Alcohol Use Disorder in Patients with Liver Disease: Lights and Shadows.

Neurotherapeutics 2020 01;17(1):127-141

Fondazione Policlinico Universitario A Gemelli IRCCS Research Hospital, Rome, Italy.

Alcohol use disorder is the most common cause of advanced liver disease in the Western world. Diagnosis of alcohol use disorder can be difficult because patients with liver disease tend to deny alcohol intake for the fear of being excluded from treatment and because available biomarkers of alcohol intake have poor specificity in these patients. Alcohol abstinence is the cornerstone of the therapy in these patients. However, pharmacological treatments for alcohol use disorders have not been formally tested in patients with advanced liver disease, except for baclofen. Psychosocial intervention became crucial in these patients considering the limited pharmacological choice. However, psychosocial approach and an appropriate team to manage these patients are not still well defined. In this review, we critically discuss the diagnosis and the management of alcohol use disorder in patients with liver disease.
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http://dx.doi.org/10.1007/s13311-019-00802-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007485PMC
January 2020

Lung Ultrasonography in Pediatric Cardiac Surgery: A Complementary Diagnostic Tool.

Ann Thorac Surg 2020 06 6;109(6):1946. Epub 2019 Nov 6.

Unit of Internal Medicine, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.

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http://dx.doi.org/10.1016/j.athoracsur.2019.09.046DOI Listing
June 2020

Impact of CVOTs in primary and secondary prevention of kidney disease.

Diabetes Res Clin Pract 2019 Nov 30;157:107907. Epub 2019 Oct 30.

Università degli Studi and IRCCS Ospedale Policlinico San Martino, Genoa, Italy. Electronic address:

Type 2 diabetes mellitus is the leading cause of end stage renal disease worldwide. Diabetic kidney disease, whose main clinical manifestations are albuminuria and decline of glomerular filtration rate, affects up to 40% of patients. Sodium Glucose cotransporter-2 inhibitors (SGLT2-is) and Glucagon-like peptide-1 receptor agonists (GLP-1ras) are new classes of anti-hyperglycemic drugs which have demonstrated to improve renal outcome. Renal benefits of both SGLT2-is and GLP-1ras are acknowledged from data of large randomized phase III clinical trials conducted to assess their cardiovascular safety. In this review, we will focus on renal results of major cardiovascular outcome trials, and we will describe direct and indirect mechanisms through which they confer renal protection.
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http://dx.doi.org/10.1016/j.diabres.2019.107907DOI Listing
November 2019

'Bony' heart.

BMJ Case Rep 2019 Aug 30;12(8). Epub 2019 Aug 30.

Department of Medical Sciences, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

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http://dx.doi.org/10.1136/bcr-2019-231793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721137PMC
August 2019

Takotsubo Syndrome and Inflammatory Bowel Diseases: Does a Link Exist?

Dig Dis 2020 13;38(3):204-210. Epub 2019 Aug 13.

Internal Medicine Unit, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Background: Takotsubo syndrome (TTS) is an acute cardiac dysfunction in the absence of viral causes or obstructive coronary disease completely reversible within 4-8 weeks. Inflammatory bowel diseases (IBD) are a group of diseases caused by the interaction between immune system, genetic, and environmental factors against intestinal mucosa. Both these syndromes are characterized by complex mechanisms involving endothelial dysfunction and affective disorders.

Aim: To assess the possibility of an association between IBD and TTS.

Methods: First, we present a case of TTS in a patient affected by active stenosing Crohn's disease. Articles in English language were collected from PubMed and Google Scholar databases with the search terms "takotsubo," "IBD," "crohn disease," "ulcerative colitis".

Results: Both TTS and IBD show multiple common features: preference for female patients, recurrent course of disease, association with endothelial dysfunction, and affective disorders. Patients affected by IBD could show specific triggers for TTS, such as malabsorption, electrolytes disturbances, and affective disorders.

Conclusions: Despite pathophysiological similarities between TTS and IBD in active phase, future studies are needed to confirm this apparently possible association and to assess the presence of a pathophysiological link between these diseases.
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http://dx.doi.org/10.1159/000502088DOI Listing
July 2020

Lung ultrasonography in pulmonary tuberculosis: Integrating chest radiology?

Eur J Intern Med 2019 11 30;69:e17-e18. Epub 2019 Jul 30.

Unit of Internal Medicine, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Unit of Interventional and Diagnostic Ultrasound in Internal Medicine, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

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http://dx.doi.org/10.1016/j.ejim.2019.07.023DOI Listing
November 2019

Predictors of mortality of bloodstream infections among internal medicine patients: Mind the complexity of the septic population!

Eur J Intern Med 2019 10 17;68:e22-e23. Epub 2019 Jul 17.

Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.ejim.2019.07.008DOI Listing
October 2019

The role of medical history in the diagnostic process of unexplainable weight loss.

BMJ Case Rep 2019 Jul 10;12(7). Epub 2019 Jul 10.

Department of Medical Sciences, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.

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http://dx.doi.org/10.1136/bcr-2019-231182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626464PMC
July 2019

Zolpidem high-dose abuse: what about the liver? Results from a series of 107 patients.

Expert Opin Drug Saf 2019 Aug 14;18(8):753-758. Epub 2019 Jun 14.

c Department of Internal Medicine and Gastroenterology, Catholic University of Rome , Rome , Italy.

: Z-Drugs (ZDs) have been developed to limit benzodiazepines (BZDs) abuse for sleep disorders. Data on the liver toxicity of zolpidem (ZLM) are lacking or anecdotal. The authors evaluated the presence of drug-induced liver injury (DILI) among a cohort of high-dose ZLM abusers. : Retrospective study analyzing clinical records of 1112 consecutive patients admitted for BZDs detoxification from 2003 to 2018. Inclusion criteria: age >18 y.o.; ZLM abuse/dependence; high-dose ZDs abuse. Exclusion criteria: missing lab data; lack of informed consent. Main outcome was the presence of DILI measured as elevation of ALT/AST levels >250 U/l. : A total of 107 patients met the eligibility criteria. Liver enzymes alterations were present in 9.3% (95% CI 4.6-16.5%); one patient (0.9%, 95% CI 0.0-2.8%) showed DILI criteria. BMI significantly influenced transaminases levels. No correlations between duration nor doses of ZLM abuse and transaminases levels were found. : The present study shows a very low prevalence of DILI among high-dose ZLM abusers. The prevalence of hypertransaminasemia was in line with general population. On one hand ZLM has a substantially safe liver profile but on the other hand ZLM abuse and dependence, especially at very high doses, represents an emerging problem.
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http://dx.doi.org/10.1080/14740338.2019.1628216DOI Listing
August 2019

Long-term blood pressure variability and development of chronic kidney disease in type 2 diabetes.

J Hypertens 2019 04;37(4):805-813

Università degli Studi and Policlinico San Martino-IST, Genova.

Objective: Long-term visit-to-visit SBP variability (VVV) has been shown to predict cerebro-cardiovascular events and end-stage renal disease in chronic kidney disease (CKD) patients. Whether SBP VVV is also a predictor of CKD development in diabetes is currently uncertain. We assessed the role of SBP VVV on the development of CKD in patients with type 2 diabetes (T2D) and hypertension in real life.

Methods: Clinical records from 30 851 patients with T2D and hypertension, with normal estimated glomerular filtration rate (eGFR) and regular visits during a 4-year follow-up were analyzed. SBP variability was measured by three metrics: coefficient of variation; SD of the mean SBP and average absolute difference of successive values in each individual. CKD was defined as eGFR less than 60 and/or a reduction in eGFR at least 30% from baseline.

Results: Over the 4-year follow-up, 9.7% developed eGFR less than 60 and 4.5% an eGFR reduction at least 30% from baseline. Several clinical characteristics (older age, male sex, SBP, DBP, albuminuria, glycated hemoglobin, insulin treatment) were related to intraindividual SBP variability. Patients with VVV in the upper quintile showed an increased risk of developing both components of CKD [adjusted odds ratio (OR) 1.21, P < 0.001 and 1.32, P < 0.001, respectively]. The multivariable adjusted ORs of SBP coefficient of variation quintiles 2-5 for the incidence of CKD were incrementally higher (OR 1.04, P = 0.601, OR 1.05, P = 0.520, OR 1.21, P < 0.017 and OR 1.42, P < 0.001 as compared with the first quintile).

Conclusion: Increased long-term BP variability predicts CKD in patients with T2D and hypertension.
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http://dx.doi.org/10.1097/HJH.0000000000001950DOI Listing
April 2019

Management of celiac disease in daily clinical practice: do not forget depression!

Eur J Intern Med 2019 04 28;62:e17. Epub 2018 Dec 28.

Department of Internal Medicine, Gastroenterology and Hepatology, Alcohol Use Disorder Unit, Catholic University of Rome, Rome, Italy.

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http://dx.doi.org/10.1016/j.ejim.2018.12.011DOI Listing
April 2019

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes.

BMC Nephrol 2018 12 4;19(1):347. Epub 2018 Dec 4.

Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza", IRCCS Casa Sollievo della Sofferenza, v.le Cappuccini, 71013, San Giovanni Rotondo, FG, Italy.

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage ≥3 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage ≥3 CKD in a large cohort of patients affected by T1DM.

Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage ≥3 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated.

Results: The mean estimated GFR was 98 ± 17 mL/min/1.73m and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m were independent risk factors for stage ≥3 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline.

Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage ≥3 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening.
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http://dx.doi.org/10.1186/s12882-018-1136-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280443PMC
December 2018

Baclofen for the Treatment of Alcohol Use Disorder in Patients With Liver Cirrhosis: 10 Years After the First Evidence.

Front Psychiatry 2018 1;9:474. Epub 2018 Oct 1.

"Alcohol Use Disorder and Related Disease" Unit, Department of Internal Medicine and Gastroenterology, Catholic University of Rome, Rome, Italy.

Alcohol Use Disorder (AUD) is a chronic and relapsing condition characterized by harmful alcohol intake and behavioral-cognitive changes. AUD is the most common cause of liver disease in the Western world. Alcohol abstinence is the cornerstone of therapy in alcoholic patients affected with liver disease. Medical recommendations, brief motivational interventions and psychosocial approach are essential pieces of the treatment for these patients; however, their efficacy alone may not be enough to achieve total alcohol abstinence. The addition of pharmacological treatment could improve clinical outcomes in AUD patients. Moreover, pharmacological treatments for AUD are limited in patients with advanced liver disease, since impaired liver function affects drugs metabolism and could increase the risk of drugs-related hepatotoxicity. At present, only baclofen has been tested in RCTs in patients with advanced liver disease. This medication was effective to reduce alcohol intake, to promote alcohol abstinence and to prevent relapse in AUD patients affected by liver cirrhosis. In addition, the drug showed a safe profile in these patients. In this review, clinical studies about efficacy and safety of baclofen administration in patients with AUD and advanced liver disease will be reviewed. Open question about the most appropriate dose of the drug, duration of the treatment and need of additional studies will also be discussed.
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http://dx.doi.org/10.3389/fpsyt.2018.00474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174362PMC
October 2018