Swab test in biological fluids as predictor of COVID-19 transmission risk during surgery: a prospective cross-sectional study from an Italian COVID center.

BACKGROUND: The contamination of body fluids by Severe Acute Respiratory Syndrome Coronavirus 2 during surgery is current matter of debate in the scientific literature concerning CoronaVIrus Disease 2019. Surgical guidelines were published during the first wave of the COVID-19 pandemic and recommended to avoid laparoscopic surgery as much as possible, in fear that the chimney effect of high flow intraperitoneal gas escape during, and after, the procedure would increase the risk of viral transmission. AIM: The aim of this study was to evaluate the possibility of SARS-CoV-2 transmission during surgery by searching for viral RNA in serial samplings of biological liquids. METHODS: This is a single center prospective cross-sectional study. We used a real-time reverse transcriptase (RT) polymerase chain reaction (PCR) test to perform swab tests for the qualitative detection of nucleic acid from SARS-CoV-2 in abdominal fluids, during emergency surgery and on the first post-operative day. In the case of thoracic surgery, we performed a swab test of pleural fluids during chest drainage placement as well as on the first post-operative day. RESULTS: A total of 20 samples were obtained: 5 from pleural fluids, 13 from peritoneal fluids and two from biliary fluid. All 20 swabs performed from biological fluids resulted negative for SARS-CoV-2 RNA detection. CONCLUSION: To date, there is no scientific evidence of possible contagion by laparoscopic aerosolization of SARS-CoV-2, neither is certain whether the virus is effectively present in biological fluids.

COVID-19: identifying the main outcome predictors. A retrospective cohort study in Northern Italy.

OBJECTIVE: The need for efficient drugs and early treatment of patients with SARS-CoV-2 infection developing COVID-19 symptoms is of primary importance in daily clinical practice and it is certainly among the most difficult medical challenges in the current century. Recognizing those patients who will need stronger clinical efforts could effectively help doctors anticipate the eventual need for intensification of care (IoC) and choose the best treatment in order to avoid worse outcomes. PATIENTS AND METHODS: We enrolled 501 patients, consecutively admitted to our two COVID hospitals, and collected their clinical, anamnestic and laboratory data on admission. The aim of this retrospective study was to identify those data that are strictly associated with COVID-19 outcomes (IoC and in-hospital death) and that could somehow be intended as predictors of these outcomes. This allowed us to provide a "sketch" of the patient who undergoes, more often than others, an intensification of care and/or in-hospital death. RESULTS: Males were found to have a double risk of needing an IoC (OR=2.11) and a significant role was played by both the PaO2/FiO2 ratio on admission (OR=0.99) and serum LDH (OR=1.01). The main predictors of in-hospital death were age (OR=1.08) and the PaO2/FiO2 ratio on admission (OR=0.99). CONCLUSIONS: Male patients with high serum LDH on admission are those who undergo more often an intensification of care among COVID-19 inpatients. Both age and respiratory performances on admission modify the prognosis within the hospitalization period.

SARS-CoV-2 infection and H1N1 vaccination: does a relationship between the two factors really exist? A retrospective analysis of a territorial cohort in Ferrara, Italy.

OBJECTIVE: SARS-CoV-2 has been compared with other strains of coronaviruses, SARS-CoV and MERS-CoV, and with the flu viruses: all of them manifest themselves with respiratory symptoms and, although their genetic patterns are similar, the spread of SARS-CoV-2 infection has quickly reached global dimensions, demonstrating that SARS-CoV-2 is a virus with greater spreading capacity, albeit less lethal. Compared with influenza viruses, coronaviruses have a longer incubation period and the patients with coronaviruses' syndromes develop more severe diseases requiring frequent hospitalizations and intensive care admissions. The aim was to explore the relationships between seasonal influenza vaccination and coronavirus infection and to understand whether this hypothetic role by the flu vaccines modifies SARS-CoV-2 infection's outcomes. PATIENTS AND METHODS: In this retrospective, multicenter study, we enrolled 952 patients diagnosed with SARS-CoV-2 infection; 448 were admitted to our two main hospitals in Ferrara territory, while the remaining 504 were isolated at home. We compared the group of patients who had been vaccinated for influenza in the previous 12 months to that of unvaccinated patients. RESULTS: Significant differences were found for both the need for hospitalization and 30-day mortality between vaccinated and unvaccinated patients. We found age to be the only independent risk factor for a worse 30-day prognosis, while gender, influenza vaccinations and age itself were independent risk factors for undergoing hospitalization. CONCLUSIONS: In our groups of patients, we found a relationship between seasonal influenza vaccinations and SARS-CoV-2 infection. Age seems to be the main risk factor for short-term mortality in COVID-19 inpatients, while the influenza vaccination is, together with gender and age itself, a determining factor in predicting the need for hospitalization.

SARS-CoV-2 and finding of vein thrombosis: can IMPROVE and IMPROVEDD scores predict COVID-19 outcomes?

OBJECTIVE: Diffuse thrombosis represents one of the most predominant causes of death by COVID-19 and SARS-CoV-2 infection seems to increase the risk of developing venous thromboembolic diseases (VTE). Aim of this study is to analyze the relationship between validated predictive scores for VTE such as IMPROVE and IMPROVEDD and: (1) Intensification of Care (IoC, admission to Pulmonology Department or Intensive Care Unit) (2) in-hospital mortality rate 3) 30-days mortality rate. PATIENTS AND METHODS: We retrospectively evaluated 51 adult patients with laboratory diagnosis of SARS-CoV-2 infection and calculated IMPROVE and IMPROVEDD scores. All patients underwent venous color-Doppler ultrasound of the lower limbs to assess the presence of superficial vein thrombosis (SVT) and/or deep vein thrombosis (DVT). Patients with normal values of D-dimer did not receive heparin therapy (LMWH); patients with ≥ 4 ULN values of D-dimer or with a diagnosis of DVT were treated with therapeutic LMWH dosage, while the remaining patients were treated with prophylactic LMWH dosages. RESULTS: We found strong relations between IMPROVE score and the need for IoC and with the in-hospital mortality rate and between the IMPROVEDD score and the need for IoC. We defined that an IMPROVE score greater than 4 points was significantly associated to in-hospital mortality rate (p = 0.05), while an IMPROVEDD score greater than 3 points was associated with the need for IoC (p = 0.04). Multivariate logistic analysis showed how IMPROVE score was significantly associated to in-hospital and 30-days mortality rates. CONCLUSIONS: IMPROVE score can be considered an independent predictor of in-hospital and 30-days mortality.

First case of acute cholestatic hepatitis attributed to oseltamivir in a young girl with ah1n1 influenza.

Abstract: Oseltamivir caryboxylase is a potent inhibitor of the enzyme neuramidase of the influenza virus particle and it is active against both influenza A and B viruses. Oseltamivir is indicated for therapy or post-exposure prevention of influenza A and B. Side effects are uncommon and include mild nausea, gastrointestinal upset, dizziness and headache. Despite its widespread use, oseltamivir has not been associated with clinically apparent liver injury. To the best of our knowledge, this is the first case report in the literature linking the development of acute hepatitis to the consumption of oseltamivir in a patient suffering from influenza H1N1 infection.

Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era.

COronaVIrus Disease 19 (COVID-19) is caused by the infection of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are respiratory, many patients also display acute myocardial injury and chronic damage to the cardiovascular system. Understanding both direct and indirect damage caused to the heart and the vascular system by SARS-CoV-2 infection is necessary to identify optimal clinical care strategies. The homeostasis of the cardiovascular system requires a tight regulation of the gene expression, which is controlled by multiple types of RNA molecules, including RNA encoding proteins (messenger RNAs) (mRNAs) and those lacking protein-coding potential, the noncoding-RNAs. In the last few years, dysregulation of noncoding-RNAs has emerged as a crucial component in the pathophysiology of virtually all cardiovascular diseases. Here we will discuss the potential role of noncoding RNAs in COVID-19 disease mechanisms and their possible use as biomarkers of clinical use.

Prediction of in-hospital mortality of patients with SARS-CoV-2 infection by comorbidity indexes: an Italian internal medicine single center study.

OBJECTIVE: Clinical outcomes in patients hospitalized for severe acute respiratory syndrome due to coronavirus (SARS-CoV-2) infection seems to be closely related with burden of comorbidities. A comorbidity score could help in clinical stratification of patients admitted to internal medicine units. Our aim was to assess a novel modified Elixhauser index (mEi) and the Charlson Comorbidity Index (CCI) for predicting in-hospital mortality (IHM) in internal medicine patients with SARS-CoV-2 infection. PATIENTS AND METHODS: This single-center retrospective study enrolled all consecutive patients discharged from internal medicine unit with confirmed SARS-CoV-2 infection. Both the mEi and CCI were easily calculated from administrative data. Comorbidity scores were tested using receiver operating characteristic (ROC) analysis, and the respective area under the curve (AUC). RESULTS: The total sample consisted of 151 individuals, and 30 (19.9%) died during their hospital stay. Deceased subjects were older (82.8±10.8 vs. 63.3±18.1 years; p<0.001) and had a higher burden of comorbidities: the mEi and CCI were 29.9±11 vs. 8.8±9.2 and 4.6±2.6 vs. 1.2±2 (p<0.001), respectively. Only the mEi was independently associated with IHM (OR 1.173), and ROC curves analysis showed that the AUCs were 0.863 and 0.918 for the CCI and for mEi, respectively. CONCLUSIONS: In patients admitted to internal medicine wards with SARS-CoV-2 infection, the mEi showed a better performance in predicting IHM than CCI.

Assessing the efficiency and eco-sustainability of bioremediation strategies for the reclamation of highly contaminated marine sediments.

Coastal sediments subjected to high anthropogenic impacts can accumulate large amounts of polycyclic aromatic hydrocarbons (PAHs) and metals, demanding effective and eco-sustainable remediation solutions. In this study, we carried out bioremediation experiments on marine sediments highly contaminated with PAHs and metals. In particular, we investigated the effects of biostimulation (by the addition of inorganic nutrients), bioaugmentation (by the addition of fungi belonging to Aspergillus sp.) and microbial fuel cell-based strategies on PAH degradation and on changes in metal partitioning. Results reported here indicate that all biotreatments determined a significant decrease of PAH concentrations (at least 60%) in a relatively short time interval (few weeks) and that biostimulation was the most effective approach (>90%). Biostimulation determined a faster degradation rate of high than low molecular weight PAHs, indicating a preferential biodegradation of specific PAH congeners. At the same time, the biotreatments changed the partitioning of metals, including their solubilization, suggesting the need of parallel environmental risk assessment. Our findings also suggest that ex situ biotreatments can have a lower carbon footprint than current management options of contaminated sediments (i.e., landfill disposal and/or disposal in confined aquatic facilities), but integration with other strategies for metal removal (e.g. through bioleaching) from sediments is needed for their safe re-use. Overall, results presented here provide new insights into the development of effective and eco-sustainable bioremediation strategies for the reclamation of highly contaminated marine sediments.

Morning vs. evening administration of antiviral therapy in COVID-19 patients. A preliminary retrospective study in Ferrara, Italy.

OBJECTIVE: At the end of 2019, the Novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), spread rapidly from China to the whole world. Circadian rhythms can play crucial role in the complex interplay between viruses and organisms, and temporized schedules (chronotherapy) have been positively tested in several medical diseases. We aimed to compare the possible effects of a morning vs. evening antiviral administration in COVID patients. PATIENTS AND METHODS: We retrospectively evaluated all patients admitted to COVID internal medicine units with confirmed SARS-CoV-2 infection, and treated with darunavir-ritonavir (single daily dose, for seven days). Age, sex, length of stay (LOS), pharmacological treatment, and timing of antiviral administration (morning or evening), were recorded. Outcome indicators were death or LOS, and laboratory parameters, e.g., variations in C-reactive protein (CRP) levels, ratio of arterial oxygen partial pressure (PaO2, mmHg) to fractional inspired oxygen (FiO2) (PaO2/FiO2), and leucocyte count. RESULTS: The total sample consisted of 151 patients, 33 (21.8%) of whom were selected for antiviral treatment. The mean age was 61.8±18.3 years, 17 (51.5%) were male, and the mean LOS was 13.4±8.6 days. Nine patients (27.3%) had their antiviral administration in the morning, and 24 (72.7%) had antiviral administration in the evening. No fatalities occurred. Despite the extremely limited sample size, morning group subjects showed a significant difference in CRP variation, compared to that in evening group subjects (-65.82±33.26 vs. 83.32±304.89, respectively, p<0.032). No significant differences were found for other parameters. CONCLUSIONS: This report is the first study evaluating temporized morning vs. evening antiviral administration in SARS-CoV-2 patients. The morning regimen was associated with a significant reduction in CRP values. Further confirmations with larger and multicenter samples of patients could reveal novel potentially useful insights.

ß-Diversity partitioning of moth communities within and between different forest types.

The partitioning of ß-diversity is a recurrent practice in biogeographic and ecological studies that can provide key insights for land management, such as identification of biodiversity hot-spots. In this study, we used Baselga's metrics to measure the contribution of spatial turnover (ßsim) and nestedness-resultant dissimilarity (ßnes) to overall ß-diversity (ßsor) within- and between-forest types. We analyzed a presence/absence dataset concerning 593 species of nocturnal Lepidoptera sampled within chestnut, silver fir, beech, and black pine forests of southern Italy. Ordination methods and analysis of similarities were used to assess the relative contribution of ßsim and ßnes to ßsor, and to assess their relationships with variables linked to the experimental design and known to be determinant for insect diversity and abundance. We found that ßsor was mostly due to turnover, around 98.5% in ß-diversity assessment of the whole sample, and around 91% in ß-diversity assessment of individual forests. Using ordination analyses based on ßsim, stands were grouped according to forest type, while ßnes alone was used to ordinate stands coherently with their species richness. Nevertheless, the addition of ßnes to ßsim produced a more ecologically coherent grouping of stands within individual forest types, and ßnes alone was able to recognize patterns determined by human disturbance. In conclusion, we demonstrate that ß-diversity partitioning can help to detect differences in magnitude and role of processes determining the composition of forest moth communities as in different forests the same pattern can be due to opposite processes, providing strong ecological insights into managing forest biodiversity.

Percutaneous Spinal Ablation in a Sheep Model: Protective Capacity of an Intact Cortex, Correlation of Ablation Parameters with Ablation Zone Size, and Correlation of Postablation MRI and Pathologic Findings.

BACKGROUND AND PURPOSE: Despite the growing use of percutaneous ablation therapy for the treatment of metastatic spine disease, several issues have yet to be fully addressed. Our aims were to determine whether the vertebral body cortex protects against ablation-induced spinal cord injury; correlate radiofrequency, cryo-, and microwave ablation parameters with resulting spinal ablation zone dimensions and describe normal spinal marrow postablation changes on MR imaging. MATERIALS AND METHODS: Ten thoracolumbar vertebrae in 3 sheep were treated with radiofrequency ablation, cryoablation, or microwave ablation under fluoroscopic guidance. Technique parameters were chosen to produce ablation zones that exceeded the volume of the vertebral bodies in sheep 1 and were confined to the vertebrae in sheep 2 and 3. Expected ablation zone dimensions were based on data provided by the device manufacturers. Postablation MR imaging was performed at 48 hours (sheep 1) or 7 days (sheep 2 and 3). RESULTS: In sheep 1, cryoablation and microwave ablations extended into the spinal canal and caused histologically confirmed neurologic injury, but radiofrequency ablation did not. The mean difference between the lengths of the radiofrequency ablation zone dimensions measured on gross pathology compared with those expected was 9.6 ± 4.1 mm. The gross pathologic cryo- and microwave ablation zone dimensions were within 1 mm of those expected. All modalities produced a nonenhancing ablation zone with a rim of enhancement, corresponding histologically to marrow necrosis and hemorrhagic congestion. CONCLUSIONS: An intact cortex appears to protect against radiofrequency ablation-induced spinal cord injury, but not against non-impedance-based modalities. Ablation dimensions produced by microwave and cryoablation are similar to those expected, while radiofrequency ablation dimensions are smaller. Ablation of normal marrow produces a rim of enhancement at the margin of the ablation zone on MR imaging.

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

BACKGROUND: In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. METHODS: Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml-1) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. RESULTS: At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, P<0.001), 10-year MFS (84.8% versus 92.0%, P=0.003), 10-year PCSS (94.3% versus 98.2%, P=0.007) and 10-year OS (75.8% versus 82.5%, P=0.01), as compared to men with an undetectable EOR PSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, P<0.001; NCCN risk level: HR 2.01, 95% CI 0.74-5.42, P=0.168). Main study limitations are retrospective study design and associated biases. CONCLUSIONS: EOR PSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

Validation of plasma microRNAs as biomarkers for myotonic dystrophy type 1.

Non-invasive and simple to measure biomarkers are still an unmet need for myotonic dystrophy type 1 (DM1). Indeed, muscle biopsies can be extremely informative, but their invasive nature limits their application. Extracellular microRNAs are emerging humoral biomarkers and preliminary studies identified a group of miRNAs that are deregulated in the plasma or serum of small groups of DM1 patients. Here we adopted very stringent selection and normalization criteria to validate or disprove these miRNAs in 103 DM1 patients and 111 matched controls. We confirmed that 8 miRNAs out of 12 were significantly deregulated in DM1 patients: miR-1, miR-27b, miR-133a, miR-133b, miR-206, miR-140-3p, miR-454 and miR-574. The levels of these miRNAs, alone or in combination, discriminated DM1 from controls significantly, and correlated with both skeletal muscle strength and creatine kinase values. Interestingly, miR-133b levels were significantly higher in DM1 female patients. Finally, the identified miRNAs were also deregulated in the plasma of a small group (n = 30) of DM2 patients. In conclusion, this study proposes that miRNAs might be useful as DM1 humoral biomarkers.

Comparison of pollutant concentrations from weekly discrete versus composite samples for residential dry-weather runoff.

As urbanization has increased, so has degradation of urban streams. Urban water quality monitoring has focused on storm runoff sampling, but in arid climates, dry-weather runoff is a significant contributor of pollutants to aquatic systems. The majority of dry-weather runoff studies sample a small window of the entire dry-season. For this study constituent concentrations were compared using two sampling protocols. The first protocol repeatedly collected samples on the same day of the week at the same time of day. The second protocol collected samples during two week-long intensive sampling events consisting of sample collection every hour for 24 h for seven consecutive days. The two protocols were compared to determine if sampling at the same time of the week was representative of the entire week. For nitrate, total phosphorous, fipronil, permethrin, total organic carbon, and total suspended solids, sampling at the same time was not representative of the weekly mean; however, variability was observed between sites and constituents. For those constituent concentrations with significant differences seen between the two protocols, load adjustment factors (LAF) were determined, using a ratio of treatment means, and employed to adjust dry-season load estimates. Future work should include determining if LAF values can be used at similar sites excluded from the study or for similar constituents from the current sampling sites.

Implication of Long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing.

Long noncoding RNAs (lncRNAs) are non-protein coding RNAs regulating gene expression. Although for some lncRNAs a relevant role in hypoxic endothelium has been shown, the regulation and function of lncRNAs is still largely unknown in the vascular physio-pathology. Taking advantage of next-generation sequencing techniques, transcriptomic changes induced by endothelial cell exposure to hypoxia were investigated. Paired-end sequencing of polyadenylated RNA derived from human umbilical vein endothelial cells (HUVECs) exposed to 1% O2 or normoxia was performed. Bioinformatics analysis identified ≈2000 differentially expressed genes, including 122 lncRNAs. Extensive validation was performed by both microarray and qPCR. Among the validated lncRNAs, H19, MIR210HG, MEG9, MALAT1 and MIR22HG were also induced in a mouse model of hindlimb ischemia. To test the functional relevance of lncRNAs in endothelial cells, knockdown of H19 expression was performed. H19 inhibition decreased HUVEC growth, inducing their accumulation in G1 phase of the cell cycle; accordingly, p21 (CDKN1A) expression was increased. Additionally, H19 knockdown also diminished HUVEC ability to form capillary like structures when plated on matrigel. In conclusion, a high-confidence signature of lncRNAs modulated by hypoxia in HUVEC was identified and a significant impact of H19 lncRNA was shown.

Divergent effects of RIP1 or RIP3 blockade in murine models of acute liver injury.

Necroptosis is a recently described Caspase 8-independent method of cell death that denotes organized cellular necrosis. The roles of RIP1 and RIP3 in mediating hepatocyte death from acute liver injury are incompletely defined. Effects of necroptosis blockade were studied by separately targeting RIP1 and RIP3 in diverse murine models of acute liver injury. Blockade of necroptosis had disparate effects on disease outcome depending on the precise etiology of liver injury and component of the necrosome targeted. In ConA-induced autoimmune hepatitis, RIP3 deletion was protective, whereas RIP1 inhibition exacerbated disease, accelerated animal death, and was associated with increased hepatocyte apoptosis. Conversely, in acetaminophen-mediated liver injury, blockade of either RIP1 or RIP3 was protective and was associated with lower NLRP3 inflammasome activation. Our work highlights the fact that diverse modes of acute liver injury have differing requirements for RIP1 and RIP3; moreover, within a single injury model, RIP1 and RIP3 blockade can have diametrically opposite effects on tissue damage, suggesting that interference with distinct components of the necrosome must be considered separately.

A method to Quantify the Affinity of Cabazitaxel for PLA-PEG Nanoparticles and Investigate the Influence of the Nano-Assembly Structure on the Drug/Particle Association.

PURPOSE: To study the impact of the size and the structure of the nano-assembly on the drug/particle association, determining the intrinsic partition coefficient, in order to better master the encapsulation and release properties of the carrier. METHODS: An experimental methodology is proposed to characterize the drug/nanoparticle association by mean of a partition coefficient between the PLA-PEG nanoparticles and the suspending aqueous medium, referred to as Kp. The determination was made from apparent values (referred to as Kp (ap)) measured in the presence of solubilizing agents (albumin and hydroxypropyl-ßcyclodextrin) and extrapolation to zero concentration. The structure of nanoparticles was investigated by Transmission Electron Microscopy and static light scattering. RESULTS: Depending on the manufacturing process and the PEG length of the copolymer, the nanoparticles structured either as aggregates of copolymer chains or micelles exhibiting significantly different Kp values. CONCLUSION: The methodological tool described here showed that the difference in cabazitaxel/nanoparticle association between aggregates and micelles could be attributed to the difference in PLA-PEG chains packing.