Early Light Chains Removal and Albumin Levels with a Double Filter-Based Extracorporeal Treatment for Acute Myeloma Kidney

Renal impairment in Multiple Myeloma (MM) represents one of the most important factors that influences patient survival. In fact, before the introduction of modern chemotherapy, less than 25% of patients with acute kidney injury (AKI) and MM who required dialysis recovered sufficient renal function to become independent from dialysis, with a median overall survival of less than 1 year. There are many other factors involved in determining patient survival. In this study we aimed to investigate the role of double filter-based extracorporeal treatment for removal of serum free light chains (sFLC) in acute myeloma kidney (AKI for MM) and to evaluate patient overall survival. All patients received Bortezomib-based chemotherapy and extracorporeal treatment for sFLC removal. For each session 2 dialyzers of the same kind were used. The dialytic dose was not related to the degree of renal function but to the removal of sFLC. The factors that have been found to be significantly associated with lower mortality were reduction of sFLC at day 12 and day 30, >50% reduction of sFLC at day 30, number of sessions and independence from dialysis. Among baseline characteristics, albumin level was statistically associated with the patients’ outcome. Our analysis highlights the importance of the early treatment for removal of sFLC in AKI for MM. These results indicate that the early removal of sFLC can improve patient’s outcome

Serum KL-6 could represent a reliable indicator of unfavourable outcome in patients with COVID-19 pneumonia

KL-6 is a sialoglycoprotein antigen which proved elevated in the serum of patients with different interstitial lung diseases, especially in those with a poorer outcome. Given that interstitial pneumonia is the most common presentation of SARS-CoV2 infection, we evaluated the prognostic role of KL-6 in patients with COVID-19 pneumonia. Patients with COVID-19 pneumonia were prospectively enrolled. Blood samples were collected at the time of enrolment (TOE) and on day 7 (T1). Serum KL-6 concentrations were measured by chemiluminescence enzyme immunoassay using a KL-6 antibody kit (LUMIPULSE G1200, Fujirebio) and the cut-off value was set at > 1000 U/mL. Fifteen out of 34 enrolled patients (44.1%) died. Patients with unfavourable outcome showed significantly lower P/F ratio and higher IL-6 values and plasmatic concentrations of KL-6 at TOE compared with those who survived (median KL-6: 1188 U/mL vs. 260 U/mL, p 1000 U/mL resulted independently associated with death (aOR: 11.29, p 1000 U/mL resulted independently associated with death and showed good accuracy in predicting a poorer outcome. KL-6 may thus represent a quick, inexpensive, and sensitive parameter to stratify the risk of severe respiratory failure and death

COVID-19 prevention and multiple sclerosis management: The SAFE pathway for the post-peak

Background We hereby report on our experience from Naples (South Italy), where the peak of coronavirus disease 2019 (COVID-19) has already passed. Methods Assuming that COVID-19 will be circulating until vaccination and/or herd immunity is achieved (possibly not earlier than 2021), we have developed a protocol for the long-term management of multiple sclerosis (MS). Results We have defined a pathway for the access to the MS Centre with logistic, preventative and clinical recommendations, and have also included 14-day self-isolation and COVID-19 testing before some disease modifying treatments. Discussion Overall, we believe our experience could be helpful for MS management in the upcoming months

RNA localization is a key determinant of neurite-enriched proteome

Protein subcellular localization is fundamental to the establishment of the body axis, cell migration, synaptic plasticity, and a vast range of other biological processes. Protein localization occurs through three mechanisms: protein transport, mRNA localization, and local translation. However, the relative contribution of each process to neuronal polarity remains unknown. Using neurons differentiated from mouse embryonic stem cells, we analyze protein and RNA expression and translation rates in isolated cell bodies and neurites genome-wide. We quantify 7323 proteins and the entire transcriptome, and identify hundreds of neurite-localized proteins and locally translated mRNAs. Our results demonstrate that mRNA localization is the primary mechanism for protein localization in neurites that may account for half of the neurite-localized proteome. Moreover, we identify multiple neurite-targeted non-coding RNAs and RNA-binding proteins with potential regulatory roles. These results provide further insight into the mechanisms underlying the establishment of neuronal polarity. Subcellular localization of RNAs and proteins is important for polarized cells such as neurons. Here the authors differentiate mouse embryonic stem cells into neurons, and analyze the local transcriptome, proteome, and translated transcriptome in their cell bodies and neurites, providing a unique resource for future studies on neuronal polarity

Prevalence of HSV1/2 Congenital Infection Assessed Through Genome Detection on Dried Blood Spot in Individuals with Autism Spectrum Disorders

Background/Aim: Etiopathogenesis of autism spectrum disorders (ASD) remains to be elucidated. Congenital infections, particularly viral infections, have repeatedly been associated with the onset of such disorders. Our study aimed at assessing the prevalence of herpes simplex type 1 and 2 (HSV1/2) congenital infections in patients with ASD. Materials and Methods: In our case-control study, a total of 38 children with ASD were compared to 44 age- and sex-matched controls regarding the presence of HSV1/2 infection though viral DNA polymerase chain reaction performed on dried blood spots collected at birth. Results: No HSV congenital infection was detected in either group. Conclusion: Our negative finding is in agreement with other studies that failed to demonstrate a definitive role of HSV on the onset of ASD. Further investigation of congenital HSV prevalence in larger and more powerful studies is needed to undeniably discard a role of such virus in the etiopathogenesis of ASD

Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted

L'Italia come modello per l'Europa e per il mondo nelle politiche sanitarie per il trattamento dell'epatite cronica da HCV

The World Health Organization foresees the elimination of HCV infection by 2030. In light of this and the curre nt, nearly worldwide, restriction in direct-acting agents (DAA) accessibility due to their high price, we aimed to evaluate the cost-effectiveness of two alternative DAA treatment policies: Policy 1 (universal): treat all patients, regardless of the fibrosis stage; Policy 2 (prioritized): treat only priori tized patients and delay treatment of the remaining patients until reaching stage F3. T he model was based on patient’s data from the PITER cohort. We demonstrated that extending HC V treatment of patients in any fibrosis stage improves health outcomes and is cost-effective

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV

Prevention of mother-to-child transmission of hepatitis B virus and hepatitis C virus.

About 240 million people worldwide are chronically infected with hepatitis B virus (HBV). Vertical transmission is the most important mechanism of infection persistence in endemic areas. About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). Mother-to-child transmission of HCV, which occurs in 3-10\% of cases, is the leading route of infection in childhood. This review focuses on strategies to reduce the vertical transmission of HBV and HCV. The at-birth prophylaxis of newborns of HBV-infected mothers with specific immunoglobulin and vaccine plus administration of antivirals (tenofovir or telbivudine) in the third trimester of pregnancy (in case of high maternal viral load) greatly reduces the risk of transmission. In contrast, currently there is no drug able to reduce the vertical transmission of HCV infection. We discuss the possibility of reducing mother-to-child HCV transmission using newly available antivirals or antivirals in the pipeline for the treatment of hepatitis C

Is it possible to predict HCV-related liver cirrhosis non-invasively through routine laboratory parameters?

It is estimated that hepatitis C virus (HCV) infects chronically about 160 million people worldwide. Between 15 and 56\% of these chronic carriers will evolve towards liver cirrhosis during their lifetimes. In managing subjects with HCV chronic infection, it is crucial to perform accurate staging of the disease and specifically to ascertain whether or not they have liver cirrhosis for at least three reasons: 1) the presence of cirrhosis has prognostic relevance as it entails a relatively high risk of developing decompensation (e.g., ascites, encephalopathy, jaundice, oesophageal variceal bleeding) or evolution toward hepatocellular carcinoma (HCC); 2) the presence of liver cirrhosis is the main indication for urgent treatment and paradoxically a factor predicting a poor response to currently available therapies. The timing of therapy is particular important considering that the new era of interferon-free antivirals will be a reality in a few years; 3) finally, in the presence of liver cirrhosis current guidelines recommend periodical screening for the presence of oesophageal varices and HCC. With the exception of the most advanced stages, the diagnosis of liver cirrhosis is obtained by performing a percutaneous liver biopsy, which is an invasive technique and therefore is associated with a low but non-negligible rate of complications and even death. Finally, it has a non-null rate of false negative for the diagnosis of liver cirrhosis when compared with surgical biopsy. For these reasons several authors have devised non-invasive scores to predict cirrhosis using different means. The most useful are based on liver stiffness (fibroscan), on a panel of blood tests and a proprietary algorithm (fibrotest) or on routinely available parameters. This review focuses on the different scores based on routine parameters that differ in their ease of calculation, in their diagnostic power and in the information provided. Further studies are required to compare the diagnostic performance of different non-invasive scores with the histologic evaluation and other non-invasive methods (fibroscan or fibrotest) on independent cohorts of patients