Acyclovir eco-geno-toxicity in freshwater organisms.

This study explores the eco-geno-toxic impact of Acyclovir (ACV), a widely used antiviral drug, on various freshwater organisms, given its increasing detection in surface waters. The research focused on non-target organisms, including the green alga Raphidocelis subcapitata, the rotifer Brachionus calyciflorus, the cladoceran crustacean Ceriodaphnia dubia, and the benthic ostracod Heterocypris incongruens, exposed to ACV to assess both acute and chronic toxicity. The results indicate that while acute toxicity occurs at environmentally not-relevant concentrations, a significant chronic toxicity for C. dubia (EC50 = 0.03 µg/L, NOEC = 0.02·10-2 µg/L), highlighted substantial environmental concern. Furthermore, DNA strand breaks and reactive oxygen species detected in C. dubia indicate significant increase at concentrations exceeding 200 µg/L. Regarding environmental risk, the authors identified chronic exposures to acyclovir causing inhibitory effects on reproduction in B. calyciflorus at hundreds of µg/L and hundredths of µg/L for C. dubia as environmentally relevant environmental concentrations. The study concludes by quantifying the toxic and genotoxic risks of ACV showing a chronic risk quotient higher than the critical value of 1and a genotoxic risk quotient reaching this threshold, highlighting the urgent need for a broader risk assessment of ACV for its significant implications for aquatic ecosystems.

Concomitant Resistance to Cefiderocol and Ceftazidime/Avibactam in Two Carbapenemase-Producing Klebsiella pneumoniae Isolates from Two Lung Transplant Patients.

In this study, we present two cases of Klebsiella pneumoniae, one KPC-33- and one NDM-1-producing, showing resistance to cefiderocol and ceftazidime/avibactam, collected in the intensive care unit of a hospital in Northern Italy from two patients who had recently undergone lung transplantation. Whole-genome sequencing was performed to investigate the molecular features of these strains.

Diclofenac eco-geno-toxicity in freshwater algae, rotifers and crustaceans.

This study assessed the eco-genotoxic impact of diclofenac (DCF) in sentinel species of the freshwater ecosystem. DCF residues are found in freshwater from few ng/L to tens of µg/L due to the inability of conventional wastewater treatment plants to ensure removal efficiency of the drug. An ample body of literature reports on the acute toxicity of DCF in non-target organisms without addressing potential chronic long-term effects on organisms at actual, environmental concentrations. Herein, assessment for acute and chronic toxicity was performed on organisms in vivo exposed to DCF, specifically on the green alga Raphidocelis subcapitata, the rotifer Brachionus calyciflorus and the crustacean Ceriodaphnia dubia. Furthermore, potential DNA damage and expression of antioxidant genes (MnSOD, Cu/ZnSOD and CAT) were evaluated in crustacean neonates. The toxicological risk of DCF was assessed as well as its. GENOTOXIC RISK: The acute toxicity was observed at concentrations far from those of environmental concern. Rotifers and crustaceans were much more chronically sensitive than the algae to DCF, observing besides, the median effect concentrations at tens of µg/L. In crustaceans, DNA damage was noted at units of µg/L, revealing concentrations of environmental concern. The dysregulated activity of SOD and CAT also showed the ability of DCF to provoke oxidative stress. On assessment of environmental risk, the chronic Risk Quotient (RQ) was above the threshold value of 1. Nevertheless, the genotoxic RQ was significantly greater than the chronic RQ, thus, the need of regulatory bodies to acknowledge the genotoxic impact as an environmental risk factor. To our knowledge, this study is the first investigation to perform environmental genotoxic risk assessment of DCF.

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.

Ventilator-Associated Pneumonia Due to MRSA vs. MSSA: What Should Guide Empiric Therapy?

The guidelines on ventilator-associated pneumonia (VAP) recommend an empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) according to its prevalence rate. Considering the MRSA and MSSA VAP prevalence over the last 9 years in our tertiary care hospital, we assessed the clinical value of the MRSA nasal-swab screening in either predicting or ruling out MRSA VAP. We extracted the data of 1461 patients with positive bronchoalveolar lavage (BAL). Regarding the MRSA nasal-swab screening, 170 patients were positive for MRSA or MSSA. Overall, MRSA had a high prevalence in our ICU. Despite the COVID-19 pandemic, there was a significant downward trend in MRSA prevalence, while MSSA remained steady over time. Having VAP due to MRSA did not have any impact on LOS and mortality. Finally, the MRSA nasal-swab testing demonstrated a very high negative predictive value for MRSA VAP. Our results suggested the potential value of a patient-centered approach to improve antibiotic stewardship.

Post-acute coronavirus disease 2019 (COVID 19) syndrome: HLH and cholangiopathy in a lung transplant recipient.

Background: Sars-CoV2 can cause severe pneumonia and acute respiratory distress syndrome (ARDS). In COVID-19-associated respiratory failure, lung transplantation might be an option (Bharat A). Case report: A previously healthy 63-year-old man with a nasopharyngeal swab positive for SarsCoV2 and radiological evidence of interstitial lung consolidations developed acute respiratory distress that required intubation and veno-venous extracorporeal membrane oxygenation support (VV ECMO). Because of no recovery of his lung function, he underwent a bilateral lung transplant. ICU stay was complicated by several episodes of bacterial superinfections and an increase of liver function tests (LFTs). Afterward, he faced a progressive clinical worsening associated to severe anemia, further rise of indices of cholestasis, hypertriglyceridemia and hyperferritinemia. Bone marrow smear showed a picture compatible with haemophagocytic lymphohistocytosis (HLH) and first and second line therapy were started. In addition, a transjugular hepatic biopsy was performed with histopathological evidence of portal and periportal fibrosis, compatible with Covid 19-related cholangiopathy. During the hospital stay, he developed several MDR opportunistic infections. The patient died few months later from multiorgan failure secondary to septic shock. A post-mortem confirmed a diagnosis of cholangiopathy, and medullary erythro-haemophagocytosis. Conclusion: Post Covid19 syndrome is a clinical entity that includes novel and old sequelae following recovery from Sars-CoV2 infections. Early identification of these diseases is crucial for adequate management and might influence the long term prognosis of these patients.

Sars-Cov 2 versus Flu: ECMO-associated bloodstream infections.

SARS-CoV-2 and flu may lead to severe acute respiratory distress syndrome (ARDS) requiring extracorporeal membrane oxygenation (ECMO). The aim of the present study is to compare the incidence of bloodstream infections (BSIs) and outcome in patients with flu and SARS-CoV-2 infection hospitalized in ICU and undergoing ECMO. This study is a retrospective analysis of the San Matteo COVID-19 Registry (SMACORE) cohort. The study was conducted from January 2018 to April 2020. Demographic data and microbiological data were recorded during hospitalization. BSIs occurring during ECMO were analyzed. Eighteen patients treated with ECMO, 22 subjects with SARS-CoV-2 infection and 7 with flu, median age 61years for SARS-CoV-2 and 50 for flu (p=NS). Median ECMO duration was similar in the two pathologies. Median time to bloodstream infection from ECMO initiation was similar. Bloodstream infection incidence rate was 2.65 per 100 patients/days for flu and 2.2 per 100 patients/days for SARS-CoV-2. Global infection rate was 5 per 100 patients/days for SARS-CoV-2 patients and 5.3 per 100 patients/days for flu. Mortality during ECMO was 40.9% (5 out of 22 patients) for SARS-CoV-2 infection while none died among flu patients. ECMO-associated mortality was higher in SARS-CoV-2 infection compared with flu infection.

Robust and Persistent B- and T-Cell Responses after COVID-19 in Immunocompetent and Solid Organ Transplant Recipient Patients.

The development and persistence of SARS-CoV-2-specific immune response in immunocompetent (IC) and immunocompromised patients is crucial for long-term protection. Immune response to SARS-CoV-2 infection was analysed in 57 IC and 15 solid organ transplanted (TX) patients. Antibody responses were determined by ELISA and neutralization assay. T-cell response was determined by stimulation with peptide pools of the Spike, Envelope, Membrane, and Nucleocapsid proteins with a 20-h Activation Induced Marker (AIM) and 7-day lymphoproliferative assays. Antibody response was detected at similar levels in IC and TX patients. Anti-Spike IgG, IgA and neutralizing antibodies persisted for at least one year, while anti-Nucleocapsid IgG declined earlier. Patients with pneumonia developed higher antibody levels than patients with mild symptoms. Similarly, both rapid and proliferative T-cell responses were detected within the first two months after infection at comparable levels in IC and TX patients, and were higher in patients with pneumonia. T-cell response persisted for at least one year in both IC and TX patients. Spike, Membrane, and Nucleocapsid proteins elicited the major CD4+ and CD8+ T-cell responses, whereas the T-cell response to Envelope protein was negligible. After SARS-CoV-2 infection, antibody and T-cell responses develop rapidly and persist over time in both immunocompetent and transplanted patients.

A challenging case of SARS-CoV-2- AIDS and Nocardiosis coinfection from the SMatteo COvid19 REgistry (SMACORE).

The COVID-19 pandemic is posing an unprecedented threat worldwide. One issue that has faltered, though, concerns the underestimated risk to trade all for COVID-19, misdiagnosing other potentially life-threatening diseases. Further still, the presence of respiratory symptoms in AIDS patients should stimulate more vigilant efforts to uncover other or additional infections. This case report highlights the pitfalls of diagnosing a rare pulmonary infection during the COVID-19 pandemic.

Predictors of starting antimicrobial treatment in patients with nontuberculous mycobacterial lung disease in the Italian scenario: A SITA GIOVANI-IRENE promoted web-survey.

The disease burden due to nontuberculous mycobacteria is growing worldwide, consequently to improved diagnostic abilities and an increase in the individuals at risk. Uncertainties exist about the right moment on which start treatment. We investigated the clinical features associated with starting an antimicrobial treatment in patients with nontuberculous mycobacterial lung disease among Italian physicians involved in the field. We found that in real life predictors of starting antimicrobial treatment are quite adherent to international guidelines, with some uncertainties regarding the implication of immunosuppressive drugs.

Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts.

OBJECTIVE: The aim of this study was to analyze the clinical, radiologic, and biological features associated with human herpesvirus 6 (HHV-6) encephalitis in immunocompetent and immunocompromised hosts to establish which clinical settings should prompt HHV-6 testing. METHODS: We performed a retrospective research in the virology database of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) for all patients who tested positive for HHV-6 DNA in the CSF and/or in blood from January 2008 to September 2018 and separately assessed the number of patients meeting the criteria for HHV-6 encephalitis in the group of immunocompetent and immunocompromised hosts. RESULTS: Of the 926 patients tested for HHV-6 during the period of interest, 45 met the study criteria. Among immunocompetent hosts (n = 17), HHV-6 encephalitis was diagnosed to 4 infants or children presenting with seizures or mild encephalopathy during primary HHV-6 infection (CSF/blood replication ratio <<1 in all cases). Among immunocompromised hosts (n = 28), HHV-6 encephalitis was diagnosed to 7 adolescents/adults with hematologic conditions presenting with altered mental status (7/7), seizures (3/7), vigilance impairment (3/7), behavioral changes (2/7), hyponatremia (2/7), and anterograde amnesia (1/7). Initial brain MRI was altered only in 2 patients, but 6 of the 7 had a CSF/blood replication ratio >1. CONCLUSIONS: The detection of a CSF/blood replication ratio >1 represented a specific feature of immunocompromised patients with HHV-6 encephalitis and could be of special help to establish a diagnosis of HHV-6 encephalitis in hematopoietic stem cell transplant recipients lacking radiologic evidence of limbic involvement.

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.

Minimally invasive procedure for removal of infected ventriculoatrial shunts.

BACKGROUND: Ventriculoatrial shunts were one of the most common treatments of hydrocephalus in pediatric and adult patients up to about 40 years ago. Thereafter, due to the widespread recognition of the severe cardiac and renal complications associated with ventriculoatrial shunts, they are almost exclusively implanted when other techniques fail. However, late infection or atrial thrombi of previously implanted shunts require removal of the atrial catheter several decades after implantation. Techniques derived from management of central venous access catheters can avoid cardiothoracic surgery in such instances. METHODS: We retrospectively investigated all the patients requiring removal of a VA shunt for complications treated in the last 5 years in our institution. RESULTS: We identified two patients that were implanted 28 and 40 years earlier. Both developed endocarditis with a large atrial thrombus and were successfully treated endovascularly. The successful percutaneous removal was achieved by applying, for the first time in this setting, the endoluminal dilation technique as proposed by Hong. After ventriculoatrial shunt removal and its substitution with an external drainage, both patients where successfully weaned from the need for a shunt and their infection resolved. CONCLUSION: Patients carrying a ventriculoatrial shunt are now rarely seen and awareness of long-term ventriculoatrial shunt complications is decreasing. However, these complications must be recognized and treated by shunt removal. Endovascular techniques are appropriate even in the presence of overt endocarditis, atrial thrombi, and tight adherence to the endocardial wall. Moreover, weaning from shunt dependence is possible even decades after shunting.

Cardiac involvement at presentation in patients hospitalized with COVID-19 and their outcome in a tertiary referral hospital in Northern Italy.

The correlation between myocardial injury and clinical outcome in COVID-19 patients is gaining attention in the literature. The aim of the present study was to evaluate the role of cardiac involvement and of respiratory failure in a cohort of COVID-19 patients hospitalized in an academic hospital in Lombardy, one of the most affected Italian (and worldwide) regions by the epidemic. The study included 405 consecutive patients with confirmed COVID-19 admitted to a medical ward from February 25th to March 31st, 2020. Follow-up of surviving patients ended either at hospital discharge or by July 30th, 2020. Myocardial injury was defined on the basis of the presence of blood levels of hs-TnI above the 99th percentile upper reference limit. Respiratory function was assessed as PaO2/FiO2 (P/F) ratio. The primary end-point was death for any cause. During hospitalization, 124 patients died. Death rate increased from 7.9% in patients with normal hs-TnI plasma levels and no cardiac comorbidity to 61.5% in patients with elevated hs-TnI and cardiac involvement (p < 0.001). At multivariable analysis, older age, P/F ratio < 200 (both p < 0.001) and hs-TnI plasma levels were independent predictors of death. However, it must be emphasized that the median values of hs-TnI were within normal range in non-survivors. Cardiac involvement at presentation was associated with poor prognosis in COVID-19 patients, but, even in a population of COVID-19 patients who did not require invasive ventilation at hospital admission, mortality was mainly driven by older age and respiratory failure.

Calcineurin Inhibitor-Based Immunosuppression and COVID-19: Results from a Multidisciplinary Cohort of Patients in Northern Italy.

The role of immunosuppression in SARS-CoV-2-related disease (COVID-19) is a matter of debate. We here describe the course and the outcome of COVID-19 in a cohort of patients undergoing treatment with calcineurin inhibitors. In this monocentric cohort study, data were collected from the COVID-19 outbreak in Italy up to April 28th 2020. Patients were followed at our hospital for solid organ transplantation or systemic rheumatic disorders (RMDs) and were on calcineurin inhibitor (CNI)-based therapy. Selected patients were referred from the North of Italy. The aim of our study was to evaluate the clinical course of COVID-19 in this setting. We evaluated 385 consecutive patients (220 males, 57%; median age 61 years, IQR 48-69); 331 (86%) received solid organ transplantation and 54 (14%) had a RMD. CNIs were the only immunosuppressant administered in 47 patients (12%). We identified 14 (4%) COVID-19 patients, all transplanted, mainly presenting with fever (86%) and diarrhea (71%). Twelve patients were hospitalized and two of them died, both with severe comorbidities. No patients developed acute respiratory distress syndrome or infectious complications. The surviving 10 patients are now fully recovered. The clinical course of COVID-19 patients on CNIs is generally mild, and the risk of superinfection seems low.

Cryptococcosis in an HIV-negative, HCV positive, immunosenescent patient: a case report.

Cryptococcus species is still a very common opportunistic infection in AIDS patients. However, it is increasingly responsible for disease in otherwise immunocompromised individuals, such as transplant recipients and the heterogeneous group of patients with underlying immunologic diseases, hematologic disorders and organ failure syndromes. Clinical presentation, prognosis, and outcomes are difficult to define given these varied host groups, and tailoring treatments to fit the necessities of each patient is likewise challenging. Our patient was on treatment with steroids and direct-acting antiviral agents (DAAs) for a chronic HCV-related hepatitis, worsened by cryoglobulinemia, membranoproliferative glomerulonephritis and a lowgrade B cells lymphoma. We report a case of systemic cryptococcal infection in an immunosenescent, HIV-negative patient.

Primary Spinal Epidural Abscesses Not Associated With Pyogenic Infectious Spondylodiscitis: A New Pathogenetic Hypothesis.

Introduction: Spinal epidural abscess (SEA) incidence is rising. However, most series do not differentiate between SEAs associated with pyogenic infectious spondylodiscitis (PS) and SEAs limited to the epidural space. Methods: We retrospectively reviewed the records and radiological images of all patients admitted to our institutions with a diagnosis of SEA not associated with PS between January 2013 and December 2018. Results: We found three males and four females; five of the seven were intravenous drug users. All patients presented with pain: in six, it was associated with acute motor and sensory deficits, while one had only pain and paresthesias. Staphylococcus aureus was cultured from abscesses and/or from multiple blood cultures in four patients. Abscesses were localized to the cervical spine in one patient, thoracic in three, lumbar in one, and in two, the SEAs involved multiple segments. All patients but one underwent urgent open surgery. This patient had a multisegmental abscess and was successfully treated by percutaneous aspiration when pain became intractable. After abscess evacuation, the neurological deficits improved in all patients except one. The patients that were treated without spine instrumentation did not develop delayed kyphosis or instability at follow-up. Conclusion: Patients with SEAs not associated with PS are likely to present with pain and motor deficits, appear to benefit from urgent abscess evacuation, and seem to be less dependent on spine instrumentation to avoid delayed spinal deformities compared to SEA associated with PS. Finally, the lack of initial involvement of bone and intervertebral disks may suggest that at least some of the SEAs without PS originate from infection of epidural lymphatic vessels that are not present inside those structures.

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.