Is a radiological score needed to define the severity of Nontuberculous mycobacteria lung disease?

High-resolution CT-scan (HRCT) plays a major role in the diagnosis of Nontuberculous mycobacteria lung disease (NTM-LD), but its role in follow-up is controversial. Our aim was first to conceive a radiological score able to quantify the severity of pulmonary involvement by NTM infection and, second, to check its association with the NTM-LD clinical burden. We also intended, if possible, to verify the potential influence of NTM specific treatment on the radiological score. We retrospectively collected the clinical, microbiological and radiological data of all patients who were admitted to our hospital from 1 January 2012 to 1 January 2020 with a confirmed diagnosis of NTM-LD. A radiological score was applied to evaluate lung involvement on HRCT at diagnosis and at 6-18 months follow-up. Twenty-eight patients with NTM-LD performed follow-up HRCT. No association was found between radiological and clinical score (Spearman R -0.05, 95%CI -0.41 to 0.33). Repeated measures analysis showed a significant increase in radiological score over time (change 1.11, 95%CI 0.10 to 2.11; p-value 0.032), while Mann-Whitney test did not show any difference between treated and untreated patients (p value 0.922). Further studies are needed to assess the usefulness of routine radiological follow-up in patients with NTM-LD.

Running out of bullets: The challenging management of acute hepatitis and SARS-COV-2 from the SMatteo COvid19 Registry (SMACORE).

Liver impairment is frequent in patients with novel coronavirus disease (COVID-19) and direct viral tropism for the liver has been proven. Since several of the currently administered drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are possibly hepatotoxic, the management of patients with COVID-19 and liver failure is still an almost unexplored field. Taking this challenging case of acute HBV with persistent hyperbilirubinemia and SARS-COV-2 infection with respiratory distress as a starting point, we here loop through this condition. Where the available therapeutic options are scarce, we here propose hemoperfusion (HP) as an attractive alternative to both delay any late-stage progression of hyper inflammation process in COVID-19 and remove the toxins involved in acute liver failure.

The obesity paradox: Analysis from the SMAtteo COvid-19 REgistry (SMACORE) cohort.

BACKGROUND AND AIMS: Obesity has been suggested as a possible risk factor for a more severe course of COVID-19; however, conclusive evidence is lacking and few studies have investigated the role of BMI as a risk factor for admission to intensive care unit (ICU) and mortality. We retrospectively analyzed a COVID-19 cohort recruited during the first 40 days of the epidemic in Italy. We examined the association between obesity and 30-day mortality, admission to ICU, mortality and length of hospital stay in patients with COVID-19. METHODS AND RESULTS: Demographic, clinical and outcome data were retrospectively analyzed in 331 patients with COVID-19 admitted to hospital between 21 February and 31 March 2020. The predictive effect of obesity on mortality was assessed using a Cox proportional-hazard regression model, its effect on ICU admission and mortality in the ICU using logistic regressions, and its effect on length of hospital stay using a linear regression. Seventy-four of 331 patients had a BMI ≥30 kg/m2. Among obese patients, 21 (28.4%) required admission in ICU and 25 died (33.8%). After controlling for sex, age, comorbidities and clinical data, obesity was not significantly associated with mortality, mortality in ICU and length of hospital stay. The effect of obesity on ICU admission remained significant after controlling for sex, age, interstitial lung disease, heart disease and serum C-reactive protein. CONCLUSIONS: Obese patients with COVID-19 were more likely to be admitted to ICU than non-obese patients. However, there were no significant differences in mortality between the two groups.

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020.

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21-28 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age > 65 years, antiviral treatment and for severe disease, lactate dehydrogenase > 300 mg/dL.

The impact of HIV infection and men who have sex with men status on hepatitis A infection: The experience of two tertiary centres in Northern Italy during the 2017 outbreak and in the 2009-2016 period.

Hepatitis A is a self-limiting infection representing the most common cause of viral hepatitis worldwide. Despite being a low incidence region, in the European Union, an increasing number of cases have been reported since summer 2016, resulting in a large outbreak in 2017, involving mainly men who have sex with men (MSM). Some reports described a different clinical course of hepatitis A virus in patients infected by human immunodeficiency virus (HIV) or MSM. We consecutively collected all the hospitalized cases of hepatitis A referred to two tertiary centres in Northern Italy in 2017 and retrospectively analysed the electronic records of the 2009-2016 period (pre-2017). We evaluated demographics data, risk factors, comorbidities and laboratory results to see whether MSM status or HIV infection influenced the disease. Overall, 117 cases were identified in 2017:107 (91%) were male, 78 reported themselves as MSM (66%) and 17 (14.5%) were infected by HIV. For the pre-2017 period, 48 cases were reported: 29 (60%) were male and 3 (6.2%) were infected by HIV. After stratification for HIV infection, MSM status and occurrence period, no differences were found in aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase; bilirubin, alkaline phosphatase and bilirubin values, hospitalization length, HIV viral load and CD4 + cells count. HIV-positive patients presented a higher number of patients with INR > 1.5 at admission. MSM status and HIV infection did not affect neither the clinical course nor the severity of hepatitis A.

Optimizing Antibiotic Therapy for Intravenous Drug Users: A Narrative Review Unraveling Pharmacokinetics/Pharmacodynamics Challenges.

Intravenous drug users (IVDUs) face heightened susceptibility to life-threatening gram-positive bacterial infections, particularly methicillin-resistant Staphylococcus aureus (MRSA). While the standard antibiotic dosing strategies for special patients, such as obese or critically ill individuals, are known to be inadequate, raising concerns about treatment efficacy, a similar sort of understanding has not been assessed for IVDUs yet. With this in mind, this review examines the pharmacokinetic/pharmacodynamic characteristics of antibiotics commonly used against gram-positive bacteria in IVDUs. Focusing on daptomycin, vancomycin, teicoplanin, aminoglycosides, and the novel lipoglycopeptide dalbavancin, the study reveals significant pharmacokinetic variations in IVDUs, suggesting the need for personalized dosing. Concomitant opioid substitution therapy and other factors, such as malnutrition, contribute to altered pharmacokinetics/pharmacodynamics, emphasizing the importance of targeted therapeutic drug monitoring. Overall, our study calls for increased awareness among clinicians regarding the unique pharmacokinetic/pharmacodynamic challenges in IVDUs and advocates for tailored antibiotic dosing strategies to enhance treatment outcomes in this marginalized population.

The possible role of serum bactericidal titres in long-term suppressive antibiotic treatment for infective endocarditis: report of three cases.

INTRODUCTION: long term suppressive antibiotic treatment may be the only feasible option for patients with infective endocarditis (IE) not suitable for surgery. CASE REPORTS: we present three cases of prosthetic valve endocarditis (PVE) caused by Enterococcus faecalis and Streptococcus gallolyticus which could not undergo surgical intervention due to high risk. Despite this, patients were successfully managed only by medical approach. Following intravenous targeted antimicrobial therapy, patients received chronic suppressive antimicrobial therapy (SAT) for at least twelve months with oral amoxicillin. In all cases, no further febrile episodes nor bacteraemia were observed and in two cases a complete positron emission tomography (PET) response was achieved. Due to a priori uncertainty about antimicrobial exposure during oral SAT, serum bactericidal titres (SBTs) were obtained and compared to those obtained during parenteral therapy. CONCLUSIONS: long term oral amoxicillin was effective and well-tolerated. SBTs after switch to oral therapy were quite heterogeneous, in some cases not reaching the conventionally established titre to assess bactericidal effect (1:8).Key pointsendovascular infection in non-suitable-for-surgery patients can be managed with long-term oral suppressive therapy.serum bactericidal assay confirmed high effectiveness of parenteral antibiotic therapy.serum bactericidal assay showed highly variable titres during oral therapy.

Mortality due to COVID-19 during the pandemic: A comparison of first, secondo and third SMAtteo COvid19 REgistry (SMACORE).

COVID-19 tide had shattered on European countries with three distinct and tough waves, from March and April, 2020; October and November, 2020 and March and April, 2021 respectively. We observed a 50% reduction in the hazard of death during both wave II and III compared with wave I (HR 0.54, 95%CI 0.39-0.74 and HR 0.57, 95%CI 0.41-0.80, respectively). Sex and age were independent predictors of death. We compare in-hospital mortality of COVID-19 patients admitted at our Referral Hospital of Northern Italy during the different waves, discuss the reasons of the observed differences and suggest approaches to the challenges ahead.

Impact of Pneumococcal Urinary Antigen Testing in COVID-19 Patients: Outcomes from the San Matteo COVID-19 Registry (SMACORE).

Despite low rates of bacterial co-infections, most COVID-19 patients receive antibiotic therapy. We hypothesized that patients with positive pneumococcal urinary antigens (PUAs) would benefit from antibiotic therapy in terms of clinical outcomes (death, ICU admission, and length of stay). The San Matteo COVID-19 Registry (SMACORE) prospectively enrolls patients admitted for COVID-19 pneumonia at IRCCS Policlinico San Matteo, Pavia. We retrospectively extracted the data of patients tested for PUA from October to December 2020. Demographic, clinical, and laboratory data were recorded. Of 469 patients, 42 tested positive for PUA (8.95%), while 427 (91.05%) tested negative. A positive PUA result had no significant impact on death (HR 0.53 CI [0.22-1.28] p-value 0.16) or ICU admission (HR 0.8; CI [0.25-2.54] p-value 0.70) in the Cox regression model, nor on length of stay in linear regression (estimate 1.71; SE 2.37; p-value 0.47). After adjusting for age, we found no significant correlation between urinary antigen positivity and variations in the WHO ordinal scale and laboratory markers at admission and after 14 days. We found that a positive PUA result was not frequent and had no impact on clinical outcomes or clinical improvement. Our results did not support the routine use of PUA tests to select COVID-19 patients who will benefit from antibiotic therapy.

Discordant Liver Fibrosis Predictors in Virologically Suppressed People Living with HIV without Hepatitis Virus Infection.

Severe liver fibrosis (LF) is associated with poor long-term liver-related outcomes in people living with HIV (PLWH). The study aimed to explore the prevalence and predictors of LF and the concordance between different non-invasive methods for the estimation of LF in HIV-infected individuals without hepatitis virus infection. We enrolled PLWH with HIV-1-RNA <50 copies/mL for >12 months, excluding individuals with viral hepatitis. LF was assessed by transient elastography (TE) (significant >6.65 kPa), fibrosis-4 (FIB-4) (significant >2.67), and AST-to-platelet ratio index (APRI) (significant >1.5). We included 234 individuals (67% males, median age 49 years, median time from HIV diagnosis 11 years, 38% treated with integrase strand transfer inhibitors). In terms of the TE, 13% had ≥F2 stage; FIB-4 score was >1.5 in 7%; and APRI > 0.5 in 4%. Higher body mass index, diabetes mellitus, detectable baseline HIV-1 RNA and longer atazanavir exposure were associated with higher liver stiffness as per TE. Predictors of higher APRI score were CDC C stage and longer exposure to tenofovir alafenamide, while HBcAb positivity and longer exposure to tenofovir alafenamide were associated to higher FIB-4 scores. Qualitative agreement was poor between FIB-4/TE and between APRI/TE by non-parametric Spearman correlation and kappa statistic. In our study, in the group of PLWH without viral hepatitis, different non-invasive methods were discordant in predicting liver fibrosis.

Competing-risk analysis of coronavirus disease 2019 in-hospital mortality in a Northern Italian centre from SMAtteo COvid19 REgistry (SMACORE).

An accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. All consecutive hospitalised patients from February 21st to March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality and discharge. 426 adult patients [median age 68 (IQR 56 to 77 years)] were admitted with confirmed COVID-19 over a 5-week period; 292 (69%) were male. By 21 April 2020, 141 (33%) of these patients had died, 239 (56%) patients had been discharged and 46 (11%) were still hospitalised. Among these 46 patients, updated as of 30 May, 2020, 5 (10.9%) had died, 8 (17.4%) were still in ICU, 12 (26.1%) were transferred to lower intensity care units and 21 (45.7%) were discharged. Regression on the CIFs for in-hospital mortality showed that older age, male sex, number of comorbidities and hospital admission after March 4th were independent risk factors associated with in-hospital mortality. Older age, male sex and number of comorbidities definitively predicted in-hospital mortality in hospitalised patients with COVID-19.

Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE).

Objective: This study aimed to assess the role of Tocilizumab therapy (TCZ) in terms of ICU admission and mortality rate of critically ill patients with severe COVID-19 pneumonia. Design: Patients with COVID-19 pneumonia were prospectively enrolled in SMAtteo COvid19 REgistry (SMACORE). A retrospective analysis of patients treated with TCZ matched using propensity score to patients treated with Standard Of Care (SOC) was conducted. Setting: The study was conducted at IRCCS Policlinico San Matteo Hospital, Pavia, Italy, from March 14, 2020 to March 27, 2020. Participants: Patients with a confirmed diagnosis of COVID-19 hospitalized in our institution at the time of TCZ availability. Interventions: TCZ was administered to 21 patients. The first administration was 8 mg/kg (up to a maximum 800 mg per dose) of Tocilizumab intravenously, repeated after 12 h if no side effects were reported after the first dose. Main Outcomes and Measures: ICU admission and 7-day mortality rate. Secondary outcomes included clinical and laboratory data. Results: There were 112 patients evaluated (82 were male and 30 were female, with a median age of 63.55 years). Using propensity scores, the 21 patients who received TCZ were matched to 21 patients who received SOC (a combination of hydroxychloroquine, azithromycin and prophylactic dose of low weight heparin). No adverse event was detected following TCZ administration. This study found that treatment with TCZ did not significantly affect ICU admission (OR 0.11; 95% CI between 0.00 and 3.38; p = 0.22) or 7-day mortality rate (OR 0.78; 95% CI between 0.06 and 9.34; p = 0.84) when compared with SOC. Analysis of laboratory measures showed significant interactions between time and treatment regarding C-Reactive Protein (CRP), alanine aminotransferase (ALT), platelets and international normalized ratio (INR) levels. Variation in lymphocytes count was observed over time, irrespective of treatment. Conclusions: TCZ administration did not reduce ICU admission or mortality rate in a cohort of 21 patients. Additional data are needed to understand the effect(s) of TCZ in treating patients diagnosed with COVID-19.