Retreatment with Immune Checkpoint Inhibitors in the New Scenario of Immunotherapy in Non-Small Cell Lung Cancer.

The advent of immunotherapy has transformed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC). In the past few years, several studies have investigated the potential role of immune checkpoint inhibitors (ICIs) in resectable and unresectable locally advanced disease, achieving remarkable results that led to their approval in clinical practice. However, there is limited evidence on immunotherapy rechallenge after recurrence, with the majority of available knowledge coming from retrospective studies which involve heavily pretreated patients with advanced NSCLC.

A synthetic thiol molecule releasing N-acetyl-l-cysteine and cysteamine drives early up-regulation of immunoproteasome subunits in the lymph nodes of mice infected with LP-BM5 leukemia retrovirus.

Thiol molecules have been recently re-considered as drug candidates in viral infections because of their ability to induce redox changes which interfere with virus life cycle and modulate the host immune response. Little is known about the molecular mechanisms of their immunomodulatory properties. Here we show that I-152, a thiol molecule metabolized to release N-acetyl-l-cysteine and cysteamine and acting as a pro-glutathione agent, causes early up-regulation of immunoproteasome subunits in the lymph nodes of murine leukemia virus infected mice.

Rituximab in steroid-refractory immune-related pancreatitis: a case report.

The use of immune checkpoint inhibitors (ICIs) for treating several types of cancer is increasing, but they may be associated with immune-related adverse events (irAEs). Pancreatitis is a rare irAE, mostly responsive to steroid treatment. There are no published data on the management of steroid-refractory ICI-induced pancreatitis.

The influence of redox modulation on hypoxic endothelial cell metabolic and proteomic profiles through a small thiol-based compound tuning glutathione and thioredoxin systems.

Reduction in oxygen levels is a key feature in the physiology of the bone marrow (BM) niche where hematopoiesis occurs. The BM niche is a highly vascularized tissue and endothelial cells (ECs) support and regulate blood cell formation from hematopoietic stem cells (HSCs). While in vivo studies are limited, ECs when cultured in vitro at low O (<5%), fail to support functional HSC maintenance due to oxidative environment.

Targeting SARS-CoV-2 by synthetic dual-acting thiol compounds that inhibit Spike/ACE2 interaction and viral protein production.

The SARS-CoV-2 life cycle is strictly dependent on the environmental redox state that influences both virus entry and replication. A reducing environment impairs the binding of the spike protein (S) to the angiotensin-converting enzyme 2 receptor (ACE2), while a highly oxidizing environment is thought to favor S interaction with ACE2. Moreover, SARS-CoV-2 interferes with redox homeostasis in infected cells to promote the oxidative folding of its own proteins.

The (AAT)n repeat of the cannabinoid CB1 receptor gene influences disease progression in relapsing multiple sclerosis.

Background: Genetic and pharmacological inactivation of cannabinoid CB(1) receptors (CB(1)Rs) exacerbates disease course in experimental autoimmune encephalomyelitis, suggesting that CB(1)Rs might play a role in the neurodegenerative damage associated with multiple sclerosis (MS).

Objectives: To see whether CNR1 gene polymorphism could influence disease progression in relapsing-remitting MS.

Methods: The genotype of 350 patients for the number of AAT repeats was characterized and correlation studies were performed with measures of disease severity and progression.

Genetic polymorphisms of glutathione S-transferases GSTM1, GSTT1, GSTP1 and GSTA1 as risk factors for schizophrenia.

Oxidative damage is thought to play a role in the predisposition to schizophrenia. We determined if the polymorphisms of the GSTP1, GSTM1, GSTT1 and GSTA1 genes, which affect the activity of these enzymes against oxidative stress, have a role as susceptibility genes for schizophrenia, analyzing 138 schizophrenic patients and 133 healthy controls. We found that the combination of the absence of GSTM1 gene with the of the GSTM1 gene with the polymorphism GSTA1*B/*B, and the presence of the GSTT1 gene, represents a risk factor for schizophrenia, indicating that the combination of different GST polymorphisms has a role in the predisposition to schizophrenia, probably affecting the capacity of the cell to detoxify the oxidized metabolites of catecholamines.

Thrombin-activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss.

Objective: To investigate the possible association between selected thrombin-activatable fibrinolysis inhibitor (TAFI) single nucleotide polymorphisms (SNPs) and recurrent pregnancy loss (RPL).

Design: Case-control study.

Setting: University hospital.

Impact of storage conditions on genetic analysis or viral load determination in clinical specimens.

Background: Storage and shipment conditions of clinical specimens affect the quality of nucleic acids and may interfere with molecular analysis. The aim of our study was to verify whether blood storage at room temperature affects single nucleotide polymorphisms analysis; moreover, we analysed the consequences of serum storage at 4°C on viral load determination of hepatitis B and C viruses.

Methods: For single nucleotide polymorphism screening, genomic DNA was extracted from EDTA whole blood samples stored at room temperature for different times, quantified photometrically, and Factor V Leiden point mutation analysis was performed.

Comparison between 24-h proteinuria, urinary protein/creatinine ratio and dipstick test in patients with nephropathy: patterns of proteinuria in dipstick-negative patients.

Objective: Three main tests are commonly employed for the measurement of proteinuria: the dipstick test, the urinary protein/creatinine ratio (P/C) and the 24-h urine collection. The aim of this study was to evaluate the correlation between these methods, comparing linear regression and ROC curve data.

Material And Methods: A total of 297 consecutive outpatients with different renal diseases were included in the study.

Cardiac natriuretic hormones, neuro-hormones, thyroid hormones and cytokines in normal subjects and patients with heart failure.

The derangement of neuro-endocrine control of circulation influences both disease evolution and response to treatment in patients with heart failure, but little data are available about the complex relationships between the degree of neuro-hormonal activation and clinical severity. We studied the relationships between cardiac natriuretic hormones (CNHs) and several neuro-hormones and immunological markers in a prospective cohort of 105 consecutive patients with cardiomyopathy (77 men and 28 women, mean age 66.7+/-12.

In vivo total antioxidant capacity: comparison of two different analytical methods.

Several methods to assess the total antioxidant capacity (TAC) are available. However, the final value of measured TAC in the sample depends on the procedure used in every specific assay. This makes crucial the comparison of different analytical methods.

Thyroid hormones homeostasis in pediatric patients during and after cardiopulmonary bypass.

The concentrations of thyroid hormones were measured in 14 pediatric patients before, during, and after cardiopulmonary bypass. The ages of the patients ranged between 18 months and 14 years. Patients were kept normothermic, or moderate or deep hypothermia was induced depending on the specific pathologic condition involved.

Systematic differences between commercial immunoassays for free thyroxine and free triiodothyronine in an external quality assessment program.

Data collected in a national external quality assessment program for free thyroxine (fT4) and free triiodothyronine (fT3) were analyzed to evaluate the performance of 10 method/kits with 26 control samples distributed to approximately 170 laboratories. The control materials were normal serum pools, pooled sera supplemented with thyroid hormones, a pregnancy serum pool, serum pooled from patients with familial dysalbuminemic hyperthyroxinemia (FDH), and a normal serum pool progressively diluted. The between-laboratory variability (CV) was approximately constant in normal and supplemented pools for fT4 (15.

Analytical performance of CA 19.9, CA 125 and CA 15.3 assays as observed through an external quality assessment program.

Immunoassays of the tumor markers CA 19.9, CA125 and CA 15.3 are generally acknowledged to be a useful tool in the management of cancer patients.

Immunoassay of CEA, CA 19-9, CA 125, and CA 15-3 on the automated systems ES 300 and ES 600: methodological evaluation from a multicentre collaborative study.

The analytical performance of the automated Enzymun Test System ES 300 and ES 600 (developed by Boehringer Mannheim) for the assay of the tumour markers CEA, CA 19-9, CA 125, and CA 15-3, was assessed from data collected in a multicentre collaborative study in which eleven laboratories were involved. Results of the 1990 cycle of the external quality assessment (EQA) scheme for tumour markers, supported by the Italian National Research Council (CNR), were also used in this evaluation. The within-assay and between-assay precision was found to be 2.

External quality assurance of the carcinoembryonic antigen (CEA) assay: main findings in six years' experience.

In 1984 we initiated a national external quality assessment (EQA) program (supported by the Italian National Research Council, CNR) for the CEA assay; at present, about 200 Italian laboratories are participating in the program. The laboratories assayed the quality control (QC) samples according to their routine procedures and returned the results together with the name of the method/kit they used. The collected results were computer-processed and reports were sent back to the participants.

The CNR external quality assessment program for immunoassays: statistical analysis and reports for participants.

The results collected in the CNR/Tecno-standard external quality assessment (EQA) program for immunoassays of hormones and tumor markers are computer-processed to prepare a "periodic" report and an "end-of-period" report to be sent back to the participants in the survey. The aim of the periodic report is to allow comparison between the result obtained by a laboratory on a single EQA sample with those of all the other laboratories and with the users of the same method/kit; the report contains a histogram of all results and the mean, SD, CV, median and range (computed after trimming of outliers). The same statistics are also reported for data grouped according to the method/kit used.

Increased circulating concentrations of interleukin 2 receptor during rejection episodes in heart- or kidney-transplant recipients.

Concentrations of interleukin 2 receptor (sIL-2R) have been suggested as a marker of rejection episodes after organ transplantation. To evaluate the analytical performance of a "sandwich-type" enzyme immunoassay method for sIL-2R and to verify whether increased concentrations of sIL-2R might be a useful marker of allograft rejection, we quantified sIL-2R in serum samples from heart- or kidney-transplant patients. The mean (+/- SD) pre-transplant value of sIL-2R (592 +/- 209 kilo-units/L) in heart-transplant patients was significantly higher (P less than 0.

A new chemiluminescence immunoassay for triiodothyronine and thyroxine: evaluation using quality control sera assayed in an interlaboratory survey.

A recently developed chemiluminescence immunoassay system (LIA-mat) for triiodothyronine and thyroxine, set up by Byk-Sangtec Diagnostica (Dietzenbach, Germany), has been evaluated and compared with radioimmunoassays and with a chemiluminescence enhanced enzyme immunoassay (Amerlite), using control materials circulated in a national interlaboratory quality control, as well as patient sera. The LIA-mat assays are competitive methods which use coated monoclonal antibodies and triiodothyronine- or thyroxine-ABEI (aminobutylethylisoluminol) conjugate as tracers. The working range of LIA-mat T3 (computed from the within-assay precision profile) extended from 1.

Methodological evaluation of a new chemiluminescence immunoassay for thyrotropin using acridinium ester-labelled antibody.

A recently available immunochemiluminometric assay (ICMA) for TSH developed by Ciba Corning Corp. has been evaluated. This system (Magic Lite) uses an acridinium-ester-labelled antibody and magnetizable particle for bound-free separation.