Publications by authors named "Giulia Marchetti"

124 Publications

Impact of HCV Eradication on Lipid Metabolism in HIV/HCV Coinfected Patients: Data from ICONA and HepaICONA Foundation Cohort Study.

Viruses 2021 07 19;13(7). Epub 2021 Jul 19.

Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London WC1N 1EH, UK.

Objectives: HCV shows complex interactions with lipid metabolism. Our aim was to examine total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) changes in HIV/HCV coinfected patients, after achieving sustained virological response (SVR), according to different HCV genotypes and specific antiretroviral use.

Methods: HIV/HCV coinfected patients, enrolled in the ICONA and HepaICONA cohorts, who achieved DAA-driven SVR were included. Paired t-tests were used to examine whether the pre- and post-SVR laboratory value variations were significantly different from zero. ANCOVA regression models were employed to estimate the causal effect of SVR and of PI/r use on lipid changes. The interaction between the effect of eradication and HCV genotype was formally tested.

Results: six hundred and ninety-nine HIV/HCV coinfected patients were enrolled. After HCV eradication, a significant improvement in liver function occurred, with a significant decrease in AST, ALT, GGT, and total plasmatic bilirubin. TC and LDL-C significantly increased by 21.4 mg/dL and 22.4 mg/dL, respectively ( < 0.001), after SVR, whereas there was no evidence for a change in HDL-C ( = 0.45) and triglycerides ( = 0.49). Notably, the TC and LDL-C increase was higher for participants who were receiving darunavir/ritonavir, and the TC showed a more pronounced increase among HCV genotype 3 patients (interaction- value = 0.002).

Conclusions: complex and rapid changes in TC and LDL-C levels, modulated by HCV genotype and PI/r-based ART combinations, occurred in HIV/HCV coinfected patients after SVR. Further studies are needed to evaluate the clinical impact of these changes on the long-term risk of cardiovascular disease.
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http://dx.doi.org/10.3390/v13071402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310285PMC
July 2021

Clinical Determinants of Disease Progression in Patients With Beta-Sarcoglycan Gene Mutations.

Front Neurol 2021 1;12:657949. Epub 2021 Jul 1.

Unit of Neurology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico Cà Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Milan, Italy.

Limb-girdle muscular dystrophy 2E (LGMD 2E), recently renamed as autosomal recessive limb-girdle muscular dystrophy-4 (LGMDR4), is characterized by the lack of beta-sarcoglycan, normally expressed in skeletal muscles and cardiomyocytes. We hypothesized that progressive respiratory and left ventricular (LV) failure in LGMDR4 could be associated with the age and interrelated phenomena of the disease's natural history. We conducted a retrospective review of the records of 26 patients with LGMDR4. Our primary objective was to compare the rates of decline among creatine phosphokinase (CPK) values, pulmonary function test (PFT) measures, and echocardiographic estimates and to relate them to patients' age. The rates of decline/year of CPK, PFTs, and LV function estimates are significatively bound to age, with the LV ejection fraction (EF) being the strongest independent variable describing disease progression. Moreover, the rate of decline of CPK, PFTs, and LV differed in patients grouped according to their genetic mutations, demonstrating a possible genotype-phenotype correlation. The parallel trend of decline in CPK, PFT, and EF values demonstrates the presence in LGMDR4 of a simultaneous and progressive deterioration in muscular, respiratory, and cardiac function. This study expands the current knowledge regarding the trend of CPK values and cardiac and respiratory impairment in patients with LGMDR4, to optimize the monitoring of these patients, to improve their quality of life, and to provide clinical indices capable of quantifying the effects of any new gene or drug therapy.
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http://dx.doi.org/10.3389/fneur.2021.657949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280524PMC
July 2021

Women are from venus: implications for diversified sex-based preexposure prophylaxis approaches.

AIDS 2021 08;35(10):1691-1693

Division of Infectious Diseases, University of California Davis Medical Center, Sacramento, CA, USA.

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http://dx.doi.org/10.1097/QAD.0000000000002995DOI Listing
August 2021

A Quantitative Estimate of the Expected Shortening of the Median Isolation Period of Patients With COVID-19 After the Adoption of a Symptom-Based Strategy.

Front Public Health 2021;9:639347. Epub 2021 Jun 10.

Department of Health Sciences, Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.

A long period of isolation was observed in patients hospitalized for COVID-19 in Milan over March-September 2020 (45; IQR: 37-54 days). A significantly shorter period would have been observed by the application of May-WHO (22, IQR: 17-30 days, < 0.001) and October-Italian (26, IQR: 21-34 days, < 0.001) Guidelines. The adoption of the new symptom-based criteria is likely to lead to a significant reduction in the length of the isolation period with potential social, economic and psychological benefits, particularly in the younger population with mild/moderate disease and no comorbidities. In our opinion, the release from isolation after 21 days from symptoms onset, even without a PCR diagnostic test, in most cases seems the most adequate strategy that could balance precautions to prevent SARS CoV-2 transmission and unnecessary prolonged isolation or overuse of diagnostic testing.
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http://dx.doi.org/10.3389/fpubh.2021.639347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222664PMC
June 2021

Case Report: The Association Between Chromosomal Anomalies and Cluster A Personality Disorders: The Case of Two Siblings With 16p11.2 Deletion and a Review of the Literature.

Front Psychiatry 2021 8;12:689359. Epub 2021 Jun 8.

Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Although several studies have shown the correlation between chromosomal rearrangements and the risk of developing psychotic disorders, such as schizophrenia, little attention has been given to identifying the genetic basis of pre-disposing personality so far. In this regard, a limited but significant number of studies seem to indicate an association between chromosomal anomalies and cluster A personality disorders (CAPD). Starting from the clinical description of two brothers affected by familial 16p11 deletion syndrome (OMIM #611913), both sharing cluster A and C personality traits, the aim of the present study is to critically review the literature regarding the correlation between chromosomal rearrangements and CAPD. A bibliographic search on PubMed has been conducted, and eight studies were finally included in our review. Most of the studies highlight the presence of schizotypal personality disorder in the 22q11.2 deletion syndrome, whose evolutionary course toward psychotic pictures is well-known. One study also identified a paranoid personality disorder in a patient with a deletion on chromosome 7q21.3. No studies have so far identified the presence of paranoid personality disorder in 16p11 deletion, as in the case of the two siblings we report, while its association with psychosis and autism is already known. Although further epidemiologic studies on broader populations are indicated, our observations might pave the way for the definition of new diagnostic subgroups of CAPD and psychotic disorders, in order to implement the clinical management of such complex conditions.
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http://dx.doi.org/10.3389/fpsyt.2021.689359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217436PMC
June 2021

Renal microsporidiosis due to Encephalitozoon cuniculi in an HIV/AIDS patient with persistent fever and kidney injury.

Clin Microbiol Infect 2021 Jun 15. Epub 2021 Jun 15.

Clinic of Infectious Diseases and Tropical Medicine, San Paolo Hospital, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy.

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http://dx.doi.org/10.1016/j.cmi.2021.06.011DOI Listing
June 2021

Inflammation and microbial translocation measured prior to combination antiretroviral therapy (cART) and long-term probability of clinical progression in people living with HIV.

BMC Infect Dis 2021 Jun 12;21(1):557. Epub 2021 Jun 12.

Clinic of Infectious Diseases, Department of Health Sciences, University of Milan, "ASST Santi Paolo e Carlo, Milan, Italy.

Background: Despite the effectiveness of cART, people living with HIV still experience an increased risk of serious non-AIDS events, as compared to the HIV negative population. Whether pre-cART microbial translocation (MT) and systemic inflammation might predict morbidity/mortality during suppressive cART, independently of other known risk factors, is still unclear. Thus, we aimed to investigate the role of pre-cART inflammation and MT as predictors of clinical progression in HIV+ patients enrolled in the Icona Foundation Study Cohort.

Methods: We included Icona patients with ≥2 vials of plasma stored within 6 months before cART initiation and at least one CD4 count after therapy available. Circulating biomarker: LPS, sCD14, EndoCab, hs-CRP. Kaplan-Meier curves and Cox regression models were used. We defined the endpoint of clinical progression as the occurrence of a new AIDS-defining condition, severe non-AIDS condition (SNAEs) or death whichever occurred first. Follow-up accrued from the data of starting cART and was censored at the time of last available clinical visit. Biomarkers were evaluated as both binary (above/below median) and continuous variables (logescale).

Results: We studied 486 patients with 125 clinical events: 39 (31%) AIDS, 66 (53%) SNAEs and 20 (16%) deaths. Among the analyzed MT and pro-inflammatory markers, hs-CRP seemed to be the only biomarker retaining some association with the endpoint of clinical progression (i.e. AIDS/SNAEs/death) after adjustment for confounders, both when the study population was stratified according to the median of the distribution (1.51 mg/L) and when the study population was stratified according to the 33% percentiles of the distribution (low 0.0-1.1 mg/L; intermediate 1.2-5.3 mg/L; high > 5.3 mg/L). In particular, the higher the hs-CRP values, the higher the risk of clinical progression (p = 0.056 for median-based model; p = 0.002 for 33% percentile-based model).

Conclusions: Our data carries evidence for an association between the risk of disease progression after cART initiation and circulating pre-cART hs-CRP levels but not with levels of MT. These results suggest that pre-therapy HIV-driven pro-inflammatory milieu might overweight MT and its downstream immune-activation.
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http://dx.doi.org/10.1186/s12879-021-06260-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196504PMC
June 2021

Association between previous infection with SARS CoV-2 and the risk of self-reported symptoms after mRNA BNT162b2 vaccination: Data from 3,078 health care workers.

EClinicalMedicine 2021 Jun 31;36:100914. Epub 2021 May 31.

Occupational Health Unit, International Centre for Rural Health, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.

Background: Health care workers (HCWs) are at high risk of contracting an infection by SARS CoV-2 and thus they are a priority for vaccination. We hereby aim to investigate whether the risk of severe and moderate systemic symptoms (MSS) after vaccination is higher in HCWs with a history of previous COVID-19.

Methods: An online questionnaire was offered to the cohort all HCWs undergoing anti-SARS CoV-2 mRNA BNT162b2 vaccination between January 4th and February 9th 2021 in two large tertiary hospitals (ASST Santi Paolo and Carlo) in Milan, Italy. Previous SARS-CoV-2 infection/COVID-19 was recorded. Local and systemic symptoms after each of the two doses were reported. MSS were those either interfering with daily activities or resulting in time off-work. Factors associated to MSS were identified by logistic regression.

Findings: 3,078 HCW were included. Previous SARS-CoV-2 infection/COVID-19 occurred in 396 subjects (12·9%). 59·6% suffered from 1 local or systemic symptom after the first and 73·4% after the second dose. MSS occurred in 6·3% of cases (14·4% with previous vs 5·1% with no COVID-19 <0·001) and in 28·3% (24·5% in COVID-19 vs 28·3% no COVID,  = 0·074) after the first and second dose, respectively. Subjects already experiencing COVID-19 had an independent 3-fold higher risk of MSS after the first and a 30% lower risk after the second dose. No severe adverse events were reported.

Interpretation: Our data confirm in a real-world setting, the lack of severe adverse events and the short duration of reactogenicity in already infected HCWs. Possible differences in immune reactivity are drivers of MSS among this group of HCWs, as well as among females and younger individuals.

Funding: None.
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http://dx.doi.org/10.1016/j.eclinm.2021.100914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165130PMC
June 2021

Determinants of loss to care and risk of clinical progression in PLWH who are re-engaged in care after a temporary loss.

Sci Rep 2021 05 5;11(1):9632. Epub 2021 May 5.

National Institute for Infectious Diseases 'L. Spallanzani', Via Portuense 292, 00149, Rome, Italy.

The risk of developing AIDS is elevated not only among those with a late HIV diagnosis but also among those lost to care (LTC). The aims were to address the risk of becoming LTC and of clinical progression in LTC patients who re-enter care. Patients were defined as LTC if they had no visit for ≥ 18 months. Of these, persons with subsequent visits were defined as re-engaged in care (RIC). Factors associated with becoming LTC and RIC were investigated. The risk of disease progression was estimated by comparing RIC with patients continuously followed. Over 11,285 individuals included, 3962 became LTC, and of these, 1062 were RIC. Older age, presentation with AIDS and with higher HIV-RNA were associated with a reduced risk of LTC. In contrast, lower education level, irregular job, being an immigrant and injecting-drug user were associated with an increased LTC probability. Moreover, RIC with HIV-RNA > 200 copies/mL at the re-entry had a higher risk of clinical progression, while those with HIV-RNA ≤ 200 copies/mL had a higher risk of only non-AIDS progression. Patients re-entering care after being LTC appeared to be at higher risk of clinical progression than those continuously in care. Active strategies for re-engagement in care should be promoted.
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http://dx.doi.org/10.1038/s41598-021-88367-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099893PMC
May 2021

Plasmacytoid Dendritic Cells Depletion and Elevation of IFN-γ Dependent Chemokines CXCL9 and CXCL10 in Children With Multisystem Inflammatory Syndrome.

Front Immunol 2021 26;12:654587. Epub 2021 Mar 26.

Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

Background: SARS-CoV-2 occurs in the majority of children as COVID-19, without symptoms or with a paucisymptomatic respiratory syndrome, but a small proportion of children develop the systemic Multi Inflammatory Syndrome (MIS-C), characterized by persistent fever and systemic hyperinflammation, with some clinical features resembling Kawasaki Disease (KD).

Objective: With this study we aimed to shed new light on the pathogenesis of these two SARS-CoV-2-related clinical manifestations.

Methods: We investigated lymphocyte and dendritic cells subsets, chemokine/cytokine profiles and evaluated the neutrophil activity mediators, myeloperoxidase (MPO), and reactive oxygen species (ROS), in 10 children with COVID-19 and 9 with MIS-C at the time of hospital admission.

Results: Patients with MIS-C showed higher plasma levels of C reactive protein (CRP), MPO, IL-6, and of the pro-inflammatory chemokines CXCL8 and CCL2 than COVID-19 children. In addition, they displayed higher levels of the chemokines CXCL9 and CXCL10, mainly induced by IFN-γ. By contrast, we detected IFN-α in plasma of children with COVID-19, but not in patients with MIS-C. This observation was consistent with the increase of ISG15 and IFIT1 mRNAs in cells of COVID-19 patients, while ISG15 and IFIT1 mRNA were detected in MIS-C at levels comparable to healthy controls. Moreover, quantification of the number of plasmacytoid dendritic cells (pDCs), which constitute the main source of IFN-α, showed profound depletion of this subset in MIS-C, but not in COVID-19.

Conclusions: Our results show a pattern of immune response which is suggestive of type I interferon activation in COVID-19 children, probably related to a recent interaction with the virus, while in MIS-C the immune response is characterized by elevation of the inflammatory cytokines/chemokines IL-6, CCL2, and CXCL8 and of the chemokines CXCL9 and CXL10, which are markers of an active Th1 type immune response. We believe that these immunological events, together with neutrophil activation, might be crucial in inducing the multisystem and cardiovascular damage observed in MIS-C.
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http://dx.doi.org/10.3389/fimmu.2021.654587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033149PMC
April 2021

Long-Term Suppressive cART Is Not Sufficient to Restore Intestinal Permeability and Gut Microbiota Compositional Changes.

Front Immunol 2021 26;12:639291. Epub 2021 Feb 26.

Clinic of Infectious Diseases, Department of Health Sciences, University of Milan, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, Milan, Italy.

We explored the long-term effects of cART on markers of gut damage, microbial translocation, and paired gut/blood microbiota composition, with a focus on the role exerted by different drug classes. We enrolled 41 cART naïve HIV-infected subjects, undergoing blood and fecal sampling prior to cART (T0) and after 12 (T12) and 24 (T24) months of therapy. Fifteen HIV-uninfected individuals were enrolled as controls. We analyzed: (i) T-cell homeostasis (flow cytometry); (ii) microbial translocation (sCD14, EndoCab, 16S rDNA); (iii) intestinal permeability and damage markers (LAC/MAN, I-FABP, fecal calprotectin); (iv) plasma and fecal microbiota composition (alpha- and beta-diversity, relative abundance); (v) functional metagenome predictions (PICRUSt). Twelve and twenty four-month successful cART resulted in a rise in EndoCAb ( = 0.0001) and I-FABP ( = 0.039) vis-à-vis stable 16S rDNA, sCD14, calprotectin and LAC/MAN, along with reduced immune activation in the periphery. Furthermore, cART did not lead to substantial modifications of microbial composition in both plasma and feces and metabolic metagenome predictions. The stratification according to cART regimens revealed a feeble effect on microbiota composition in patients on NNRTI-based or INSTI-based regimens, but not PI-based regimens. We hereby show that 24 months of viro-immunological effective cART, while containing peripheral hyperactivation, exerts only minor effects on the gastrointestinal tract. Persistent alteration of plasma markers indicative of gut structural and functional impairment seemingly parallels enduring fecal dysbiosis, irrespective of drug classes, with no effect on metabolic metagenome predictions.
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http://dx.doi.org/10.3389/fimmu.2021.639291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952451PMC
September 2021

Sensitivity of SARS-CoV-2 Detection With Nasopharyngeal Swabs.

Front Public Health 2020 26;8:593491. Epub 2021 Jan 26.

Divisione di Medicina Generale II, ASST Santi Paolo e Carlo, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy.

SARS-CoV-2-infected subjects have been proven contagious in the symptomatic, pre-symptomatic and asymptomatic phase. The identification of these patients is crucial in order to prevent virus circulation. No reliable data on the sensitivity of nasopharyngeal swabs (NPS) are available because of the lack of a shared reference standard to identify SARS-CoV-2 infected patients. The aim of our study was to collect data on patients with a known diagnosis of COVID-19 who underwent serial testing to assess NPS sensitivity. The study was a multi-center, observational, retrospective clinical study with consecutive enrollment. We enrolled patients who met all of the following inclusion criteria: clinical recovery, documented SARS-CoV-2 infection (≥1 positive rRT-PCR result) and ≥1 positive NPS among the first two follow-up swabs. A positive NPS not preceded by a negative nasopharyngeal swab collected 24-48 h earlier was considered a true positive. A negative NPS followed by a positive NPS collected 24-48 h later was regarded as a false negative. The primary outcome was to define sensitivity of SARS-CoV-2 detection with NPS. Three hundred and ninety three NPS were evaluated in 233 patients; the sensitivity was 77% (95% CI, 73 to 81%). Sensitivity of the first follow-up NPS ( = 233) was 79% (95% CI, 73 to 84%) with no significant variations over time. We found no statistically significant differences in the sensitivity of the first follow-up NPS according to time since symptom onset, age, sex, number of comorbidities, and onset symptoms. NPS utility in the diagnostic algorithm of COVID-19 should be reconsidered.
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http://dx.doi.org/10.3389/fpubh.2020.593491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870983PMC
February 2021

Time spent with HIV-RNA ≤ 200 copies/ml in a cohort of people with HIV during the U=U era.

AIDS 2021 06;35(7):1103-1112

Clinical Epidemiology Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.

Objective: Zero risk of linked HIV transmission in serodiscordant couples when the HIV-infected partner had viral load less than 200 copies/ml ('U status') was found in observational studies. We aimed at estimating the proportion of time in which 'U status' was maintained and identifying factors associated with the risk of losing it.

Design: Observational cohort study.

Methods: We included participants in the ICONA cohort who had reached an established 'U status' (viral load ≤200 copies/ml for >6 months) as of December 2010. The outcome was the number of person-days of follow-up (PDFU) above a viral load greater than 200 copies/ml, relative to the total number of PDFU observed. A logistic regression model was used to identify factors independently associated with the risk of losing 'U status'.

Results: Eight thousand, two hundred and forty-one persons living with HIV were included in the analysis who contributed 2 670 888 PDFU. Of these, 1648 (20%) were women, 768 (9%) were people who inject drugs (PWID), and 2066 (25%) were foreign-born. The median of viral load measurements was 9 (IQR: 4-15). Overall, only 3.1% of PDFU were observed when viral load was above 200 copies/ml. The proportion of PDFU with viral load more than 200 copies/ml was higher than average in women (5.3%), unemployed (5.4%), PWID (4.7%), and in people with more than three previous virologic failures (6.3%). These variables were significant predictors of losing 'U status' in the multivariable logistic regression.

Conclusion: Our results reinforce the validity of the U=U message in real-world setting. However, we identified subsets of our study population at higher risk of losing the 'U status' for whom additional efforts are needed.
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http://dx.doi.org/10.1097/QAD.0000000000002825DOI Listing
June 2021

A 20-year-old girl with an unusual febrile illness.

Intern Emerg Med 2021 Jan 5. Epub 2021 Jan 5.

Department of Health Sciences, Clinic of Infectious Diseases, ASST Santi Paolo E Carlo, University of Milan, via A Di Rudinì, 8 20142, Milan, Italy.

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http://dx.doi.org/10.1007/s11739-020-02605-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782573PMC
January 2021

Long-term positive effect of an educational antimicrobial stewardship program implemented in an Internal Medicine Department: a prospective analysis and a point prevalence survey on long-term effect.

J Chemother 2021 Jul 29;33(4):238-244. Epub 2020 Dec 29.

Clinic of Infectious and Tropical Diseases, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.

The study aims to evaluate antimicrobial consumption and appropriateness one year after the implementation of an antimicrobial stewardship (AMS) program in an Internal Medicine Department in Milan. AMS program structured in two phases: "AMS phase", 5 months AMS-program based on an "audit-and-feedback model"; the "follow-up phase", 5 months long point prevalence survey conducted one year later. Outcomes of the study: antimicrobial consumption and appropriateness of antimicrobial therapy. Secondary outcomes: in-hospital mortality and length of stay (LOS). During the "AMS phase", we obtained a mean decrease of -11.4% of total antibiotic consumption as compared to the previous year (67.9 defined daily dose (DDD)/100 bed-days (bd) vs. 79.4 DDD/100bd,  = 0.07). Antibiotic consumption remained stable during "follow-up phase" (66.3 DDD/100bd,  = 0.9). Rate of appropriateness during the project increased from 48% to 85% ( < 0.01). No difference in in-hospital mortality and in LOS were observed. The study documents a positive long-term effect of AMS program on consumption and appropriate use of antibiotics.
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http://dx.doi.org/10.1080/1120009X.2020.1861515DOI Listing
July 2021

The effect of Roux-en-Y gastric bypass in the treatment of hypertension and diabetes.

Rev Col Bras Cir 2020 23;47:e20202655. Epub 2020 Nov 23.

- Irmandade de Misericórdia da Santa Casa de São Paulo, Cirurgia Geral - São Paulo - SP - Brasil.

Introduction: obesity has become a public health problem in Brazil and worldwide, due to its high prevalence. It is considered a risk factor for systemic arterial hypertension (SAH) and type 2 diabetes mellitus T2DM. Although lifestyle changes can control and even achieve complete T2DM remission, most patients have difficulty controlling blood glucose. Recent studies show that the Roux-en-Y gastric bypass (RYGB) is efficient for weight loss and control of T2DM and SAH in obese individuals.

Objective: to analyze the effect of the RYGB technique on the control and treatment of comorbidities related to obesity.

Method: this is a retrospective cohort study, with information obtained from the review of medical records, with data collection in the pre and postoperative period of patients undergoing bariatric surgery. We selected those with T2DM and SAH for the study.

Results: 252 patients underwent RYGB in the service. Seventy-nine (31.3%) had T2DM and 64 had SAH associated with T2DM. Regarding T2DM and SAH, 37.9% and 43,7%, respectively, showed total remission of the disease after surgery. There was a reduction in the postoperative use of Metformin, insulin / Gliclazide, Propranolol, Losartan and Hydrochlorothiazide in 62%, 10.1%, 100%, 26.5% and 22.8% of patients, respectively.

Conclusion: the RYGB technique is effective in the remission of T2DM and SAH. Even in cases where there was no total remission of the diseases, there was a significant drop in the use of medicines used for their treatment.
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http://dx.doi.org/10.1590/0100-6991e-20202655DOI Listing
January 2021

Heightened Circulating Interferon-Inducible Chemokines, and Activated Pro-Cytolytic Th1-Cell Phenotype Features Covid-19 Aggravation in the Second Week of Illness.

Front Immunol 2020 20;11:580987. Epub 2020 Oct 20.

Department of Health Sciences, Clinic of Infectious Diseases, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.

Covid-19 features a delayed onset of critical illness occurring approximately one week from the beginning of symptoms, which corresponds to the bridging of innate and adaptive immunity. We reasoned that the immune events occurring at the turning point of disease might mark the direction toward pathogenic protective inflammatory responses. Subjects with either severe (s; PaO2/FiO2 ratio <200) or mild (m; PaO2/FiO2 ratio>300) Covid-19 were enrolled. A range of chemokines and cytokines as well as reactive oxygen species (ROS) were measured in plasma. Dendritic and NK cell frequency, monocyte and B-/T-cell phenotype and SARS-CoV-2-specific T-cell responses were assessed in PBMC. Twenty mCovid-19 and 20 sCovid-19 individuals were studied. sCovid-19 patients displayed higher non-classical monocytes, plasma chemokines (CXCL8, CXCL9, CXCL10), cytokines (IL-6, IL-10), and ROS mCovid-19. sCovid-19 also showed significantly increased activated CD38+HLA-DR+ T-lymphocyte, and granzyme-B+/perforin+ pro-cytolytic T-cells. All Covid-19 patients showed SARS-CoV-2 specific-T-cell response with a predominance of Th1 bi- or trifunctional IFN-/IL-2/TNF--expressing CD4+, while no difference according to disease severity was observed. Severe Covid-19 features heightened circulating IFN-inducible chemokines and activated pro-cytolytic Th1 cell phenotype in the second week of illness, yet SARS-CoV-2-specific responses are similar to that of mild illness. Altogether, our observations suggest Th1 polarization coupled to higher cytolytic profile in sCovid-19 as correlate of disease pathogenesis and as potential targets to be investigated in the roadmap to therapy and vaccine development.
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http://dx.doi.org/10.3389/fimmu.2020.580987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606391PMC
December 2020

Preliminary observations on IGRA testing for TB infection in patients with severe COVID-19 eligible for immunosuppressive therapy.

Respir Med 2020 12 6;175:106204. Epub 2020 Nov 6.

Regional TB Reference Centre and Laboratory, Villa Marelli Institute/ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Stop TB Italia ONLUS, Milan, Italy.

COVID-19, the novel coronavirus pandemic, has already spread around the globe affecting more than 18 million people. As previously observed with other coronaviruses, SARS-CoV-2 deeply dysregulate the immune system eliciting respiratory failure and a state of systemic hyperinflammation in severely ill individuals. Immunotherapy is often used to downgrade the detrimental effects of the disease sustained by high-level of cytokines. Those treatments, however, are known to undermine patients' ability to contain tuberculosis (TB) infection. This study aims to describe interferon-γ release assay (IGRA) results in severe COVID-19 patients eligible for immunosuppressive treatment. Aggregate data were gathered from five hospitals in Milan, Italy, from March 1 to May 15, 2020 and retrospectively analyses. Results were summarized using absolute frequencies and percentages and compared using a two-sided Chi-squared test. Overall, 462 COVID-19 patients were eligible for immunosuppressive therapy, among which 335 were tested using IGRA testing. More than one-third of them (122/335; 36.4%) had an indeterminate IGRA result because of insufficient immune response to mitogen control, 19 (5.7%) tested positive and 194 (57.9) negative. The majority of patients with lymphocytopenia (i.e., total lymphocyte count [TLC] below 1000 cells/mm) had indeterminate IGRAs (81/155; 52.3%). The proportion becomes even higher in patients with severe lymphocytopenia (i.e., TLC<500 cells/mm) (36/57; 63%). Our results suggest a possible negative impact of COVID-19 related immune dysregulation on TB infection assessment and management. Close monitoring of individuals with or without retesting of individuals with indeterminate IGRAs and further basic science investigations should to be sought to better comprehend their implication on TB epidemiology.
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http://dx.doi.org/10.1016/j.rmed.2020.106204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645275PMC
December 2020

Impact of daily versus weekly service of infectious diseases consultation on hospital antimicrobial consumption: a retrospective study.

BMC Infect Dis 2020 Nov 7;20(1):812. Epub 2020 Nov 7.

Clinic of Infectious and Tropical Diseases, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, Via A. di Rudinì 8, 20142, Milan, Italy.

Background: To verify whether a daily service of Infectious Diseases consultation (ID-cons) is more effective than a weekly service in reducing antibiotic (ATB) consumption without worsening of clinical outcomes.

Methods: Two-year observational analysis of the ID-cons provided in a hospital setting in Milan, Italy. ID-cons resulted in: start-of-ATB; no-ATB; confirmation; modification-of-ATB. The impact of a weekly (September 1, 2016 - August 31, 2017 versus a daily (September 1, 2017 - September 30, 2018) service of ID-cons was evaluated in terms of: time-from-admission-to-first-ID-cons, type of ATB-intervention and number-of-ID-cons per 100 bed-days (bd). Primary outcomes: reduction of hospital ATB consumption overall and by department and classes expressed as Defined Daily Dose (DDD)/100bd (by Wilcoxon test for paired data).

Secondary Outcomes: overall and sepsis-related in-hospital annual mortality rates (as death/patient's admissions).

Results: Overall 2552 ID-cons in 1111 patients (mean, 2.3 ID-cons per patient) were performed (18.6% weekly vs 81.4% daily). No differences in patient characteristics were observed. In the daily-service, compared to the weekly-service, patients were seen by the ID-consultant earlier (time-from-admission-to-ID-cons: 6 days (IQR 2-13) vs 10 days (IQR 6-19), p < 0.001) and ATB was more often started by the ID-consultant (Start-of-ATB: 11.6% vs 8%, p = 0.02), rather than treating physicians. After switching to daily-service, the number-of-ID-cons increased from 0.4/100bd to 1.5/100bd (p = 0.01), with the greatest increase in the emergency department (1.5/100bd vs 6.7/100bd, p < 0.001). Total ATB consumption decreased from 64 to 60 DDD/100bd. As for the number-of-cons, the consumption of ATB decreased mainly in the emergency area. According to ATB classes, glycopeptides consumption was reduced from 3.1 to 2.1 DDD/100bd (p = 0.02) while carbapenem use decreased from 3.7 to 3.1 DDD/100bd (p = 0.07). No changes in overall mortality (5.2% vs 5.2%) and sepsis-related mortality (19.3% vs 20.9%; p = 0.7) were observed among the two time-period.

Conclusions: Daily-ID-cons resulted in a more comprehensive management of the infected patient by the ID-consultant, especially in the emergency area where we also observed the highest rate of reduction of ATB-usage. No change in mortality was observed.
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http://dx.doi.org/10.1186/s12879-020-05550-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648268PMC
November 2020

Enhancing care for people living with HIV: current and future monitoring approaches.

Expert Rev Anti Infect Ther 2021 04 15;19(4):443-456. Epub 2020 Oct 15.

Infectious Diseases Clinic, San Martino Hospital - IRCCS, Genoa, Italy - Department of Health Sciences, University of Genoa, Genova, Italy.

Introduction: Antiretroviral therapy (ART) is the most significant advance in the medical management of HIV-1 infection. Given the fact that HIV cannot be eradicated from the body, ART has to be indefinitely maintained. New approaches need to be defined for monitoring HIV-infected individuals (PLWHIV), including clinical, virologic, immunological parameters and also ways to collect individual points of view and quality of life.

Areas Covered: We discuss which tests may be used to improve the management of PLWHIV and respond to a comprehensive health demand.

Expert Opinion: Viral load and CD4 counts are well-validated outcome measures and we still need them, but they do not completely depict the health status of PLWHIV. We need to better understand and to apply to clinical practice what happens in sanctuaries, what is the role of HIV DNA, what is the meaning of low-level viremia. Most of these questions do not yet have a definitive response. Further, we need to understand how to modify these variables in order to improve outcomes.Similar points may be raised for immunological measures and for tests exploring the tolerability of drugs. The goal must be the evolution from a viro/immunologic-based to a comprehensive quality-of-health-based evaluation of PLWHIV.
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http://dx.doi.org/10.1080/14787210.2021.1823217DOI Listing
April 2021

Do Combination Antiretroviral Therapy Regimens for HIV Infection Feature Diverse T-Cell Phenotypes and Inflammatory Profiles?

Open Forum Infect Dis 2020 Sep 13;7(9):ofaa340. Epub 2020 Aug 13.

Department of Health Sciences, Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.

Immune abnormalities featuring HIV infection persist despite the use of effective combination antiretroviral therapy (cART) and may be linked to the development of noninfectious comorbidities. The aim of the present narrative, nonsystematic literature review is to understand whether cART regimens account for qualitative differences in immune reconstitution. Many studies have reported differences in T-cell homeostasis, inflammation, coagulation, and microbial translocation parameters across cART classes and in the course of triple vs dual regimens, yet such evidence is conflicting and not consistent. Possible reasons for discrepant results in the literature are the paucity of randomized controlled clinical trials, the relatively short follow-up of observational studies, the lack of clinical validation of the numerous inflammatory biomarkers utilized, and the absence of research on the effects of cART in tissues. We are currently thus unable to establish if cART classes and regimens are truly accountable for the differences observed in immune/inflammation parameters in different clinical settings. Questions still remain as to whether an early introduction of cART, specifically in the acute stage of disease, or newer drugs and novel dual drug regimens are able to significantly impact the quality of immune reconstitution and the risk of disease progression in HIV-infected subjects.
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http://dx.doi.org/10.1093/ofid/ofaa340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513927PMC
September 2020

The importance of patients' case-mix for the correct interpretation of the hospital fatality rate in COVID-19 disease.

Int J Infect Dis 2020 Nov 17;100:67-74. Epub 2020 Sep 17.

Clinic of Infectious Diseases, Department of Health Science, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.

Objective: We aimed to document data on the epidemiology and factors associated with clinical course leading to death of patients hospitalised with COVID-19.

Methods: Prospective observational cohort study on patients hospitalised with COVID-19 disease in February-24th/May-17th 2020 in Milan, Italy. Uni-multivariable Cox regression analyses were performed. Death's percentage by two-weeks' intervals according to age and disease severity was analysed.

Results: A total of 174/539 (32.3%) patients died in hospital over 8228 person-day follow-up; the 14-day Kaplan-Meier probability of death was 29.5% (95%CI: 25.5-34.0). Older age, burden of comorbidities, COVID-19 disease severity, inflammatory markers at admission were independent predictors of increased risk, while several drug-combinations were predictors of reduced risk of in-hospital death. The highest fatality rate, 36.5%, occurred during the 2nd-3rd week of March, when 55.4% of patients presented with severe disease, while a second peak, by the end of April, was related to the admission of older patients (55% ≥80 years) with less severe disease, 30% coming from long-term care facilities.

Conclusions: The unusual fatality rate in our setting is likely to be related to age and the clinical conditions of our patients. These findings may be useful to better allocate resources of the national healthcare system, in case of re-intensification of COVID-19 epidemics.
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http://dx.doi.org/10.1016/j.ijid.2020.09.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497732PMC
November 2020

Anxiety and depression symptoms after virological clearance of COVID-19: A cross-sectional study in Milan, Italy.

J Med Virol 2021 02 30;93(2):1175-1179. Epub 2020 Sep 30.

Department of Health Sciences, ASST Santi Paolo e Carlo, Clinic of Infectious Diseases, San Paolo Hospital, University of Milan, Milan, Italy.

Prevalence of anxiety or depression was investigated in 105 coronavirus disease 2019 (COVID-19) patients at 1 to 3 months from virological clearance by hospital anxiety and depression scale (HADS-A/D). 30% of patients displayed pathological HADS-A/D, 52.4% showed persistent symptoms. Pathological patients with HADS-A/D more commonly reported symptom persistence, even after adjustment for age, gender, and disease severity. Psychological assessments should be encouraged in COVID-19 patients' follow-up.
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http://dx.doi.org/10.1002/jmv.26459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461061PMC
February 2021

Efficacy and safety of dalbavancin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and other infections in a real-life setting: data from an Italian observational multicentric study (DALBITA study).

Expert Rev Anti Infect Ther 2020 12 14;18(12):1271-1279. Epub 2020 Aug 14.

Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo E Carlo, University of Milan , Milan, Italy.

Objectives: We evaluated the efficacy and safety of dalbavancin in ABSSSI and 'other sites' infections' (OTA).

Methods: Observational study involving 11 Italian hospitals including patients that received ≥1 dose of dalbavancin in 2016-2019. The outcome was end-of-treatment efficacy and safety in ABSSSI and OTA in a real-life setting.

Results: 206 patients enrolled (males 50%, median age 62 [IQR 50-76] years), 60.2% ABSSSI, 39.8% OTA. 69.7% ABSSSI 90.7% OTA (p = 0.003) and 46.3% ABSSSI 37.2% OTA (p = 0.786) received previous and concomitant antibiotics, respectively. 82.5% reached clinical cure . Eleven (5.4%) patients had non-serious adverse events (AE). OTA patients showed longer hospitalization (13.5 days, 5.5-22 3, 0-11.7; p<0.0001) and received longer previous (18 days, 9-30 11, 7-19; p = 0.007)/concomitant antibiotic treatments (21 days, 14-52 11, 8-14; p < 0.0001), compared to ABSSSI. ABSSSI and OTA showed similar efficacy (85.5% 75%, p = 0.459) and safety (no AE: 81.5% 64.3%, p = 0.258); efficacy was independent of previous/concomitant therapies.

Conclusions: Dalbavancin demonstrated a success rate of >80%, with similar efficacy/safety in ABSSSI and off-label indications. The preferential use of dalbavancin as second-line or combination therapy would seem to suggest the need for in-depth studies focused on its off-label use.
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http://dx.doi.org/10.1080/14787210.2020.1798227DOI Listing
December 2020

Effectiveness of hydroxychloroquine in COVID-19 disease: A done and dusted deal?

Int J Infect Dis 2020 10 29;99:75-76. Epub 2020 Jul 29.

Centre for Clinical Research, Epidemiology, Modelling and Evaluation, Institute for Global Health, University College London, London, UK.

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http://dx.doi.org/10.1016/j.ijid.2020.07.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388856PMC
October 2020

Adverse events and mortality: comparative analysis between diagnostic and interventional endoscopic ultrasound.

Scand J Gastroenterol 2020 Aug 14;55(8):995-1001. Epub 2020 Jul 14.

Endoscopy Department, Hospital 9 de Julho, São Paulo, Brazil.

Background And Aims: Escalating an indication of EUS for diagnosis and treatment justifies the evaluation of the conditions associated with the adverse events (AE) and related deaths. The aim is to evaluate and compare the incidence of AE and deaths after diagnostic-EUS (D-EUS) and interventional-EUS (I-EUS).

Methods: This retrospective study included patients undergoing D-EUS and I-EUS, in two centers for 28 years (03/1992 to 12/2019). Were noted parameters such as: age, gender, indication of EUS, modality, time of occurrence and severity of AE, type of treatment imposed and whether there was death. Descriptive analysis was performed using means, standard deviation and frequencies of the variables of interest.

Results: 13,196 procedures performed, 9843 D-EUS and 3353 I-EUS. Thirty-seven (0.3%) had AE with six deaths (0.04%). The overall rate of AE for D-EUS and I-EUS was 0.08% and 0.86%, respectively ( > .05). Three deaths (0.03%) occurred after D-EUS and three (0.09%) after I-EUS. AE were immediate and early in 70% and 30%, respectively, with no late complications. Perforation was detected immediately in 80% and early in 20%, being more frequent after D-EUS than I-EUS. Acute pancreatitis occurred immediately in 70% and early in 30%. The AE were mild, moderate, and severe in 35.1%, 27%, and 37.8%, respectively. Overall, D-EUS presented the majority of AE as severe (87.5%), while I-EUS presented mild AE in most cases (41.4%), followed by severe complications (24.1%).

Conclusions: Despite the low incidence of AE and mortality after EUS, the occurrence of severe complications, especially perforation in D-EUS, may support the review of therapeutic protocols, aiming to ensure that a quality and safety process is implemented in the practice of EUS.
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http://dx.doi.org/10.1080/00365521.2020.1792975DOI Listing
August 2020

Long-term outcome of prosthesis-patient mismatch after transcatheter aortic valve replacement.

Int J Cardiol 2020 Nov 5;318:27-31. Epub 2020 Jul 5.

Interventional Cardiology Unit, Cardio-Thoracic-Vascular Department, University Hospital of Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy. Electronic address:

Background: Incidence and long-term clinical consequences of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) are still unclear.

Methods: We enrolled 710 consecutive patients who underwent TAVR. PPM was defined as absent if the index orifice area (iEOA) was >0.85 cm2/m2, moderate if the iEOA was between 0.65 and 0.85 cm2/m2 or severe if the iEOA was <0.65 cm2/m2.

Results: Among the 566 patients fulfilling the study criteria, the distribution of PPM was as follows: 50.5% none (n = 286), 43% moderate PPM (n = 243) and 6.5% severe PPM (n = 37). At 5-year follow-up, patients with severe PPM had a significantly higher incidence of the combined endpoint of cardiovascular death, acute myocardial infarction and stroke (p = .025) compared with the other patients. After adjusting the results for possible confounders, severe PPM remained an independent predictor of long-term adverse outcome (HR: 2.46; 95% Confidence Interval: 1.10-5.53). The independent predictors of severe PPM were valve-in-valve procedure and body mass index. Balloon-expandable valves were not associated with higher rates of severe PPM in comparison with self-expandable valves (8% vs. 5%, respectively, p = .245).

Conclusions: In our study severe PPM emerged as a risk factor for long-term major adverse cardiac and cerebrovascular events.
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http://dx.doi.org/10.1016/j.ijcard.2020.06.033DOI Listing
November 2020

Immune response in children with COVID-19 is characterized by lower levels of T-cell activation than infected adults.

Eur J Immunol 2020 09 29;50(9):1412-1414. Epub 2020 Jul 29.

Department of Clinical and Experimental Sciences, University of Brescia and A. Nocivelli Institute of Molecular Medicine, Brescia, Italy.

Study of immunological features of immune response in 14 children (aged from 12 days up to 15 years) and of 10 adults who developed COVID-19 show increased number of activated CD4 and CD8 cells expressing DR and higher plasmatic levels of IL-12 and IL-1β in adults with COVID-19, but not in children. In addition, plasmatic levels of CCL5/RANTES are higher in children and adults with COVID-19, while CXCL9/MIG was only increased in adults. Higher number of activated T cells and expression of IL-12 and CXCL9 suggest prominent Th1 polarization of immune response against SARS-CoV2 in infected adults as compared with children.
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http://dx.doi.org/10.1002/eji.202048724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361574PMC
September 2020
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