Disease Recurrence during Adjuvant Immune Checkpoint Inhibitor Treatment in Metastatic Melanoma: Clinical, Laboratory, and Radiological Characteristics in Patients from a Single Tertiary Referral Center.

Despite the dramatic improvements in recurrence-free survival in patients with metastatic melanoma treated with immune checkpoint inhibitors (ICI), a number of patients develop metastases during adjuvant therapy. It is not currently possible to predict which patients are most likely to develop disease recurrence due to a lack of reliable biomarkers. Thus, we retrospectively analyzed the case records of all patients who commenced adjuvant ICI therapy between January 2018 and December 2021 in a single university skin cancer center (n = 46) (i) to determine the rates of disease recurrence, (ii) to examine the utility of established markers, and (iii) to examine whether re-challenge with immunotherapy resulted in clinical response.

Dacarbazine in the management of metastatic melanoma in the era of immune checkpoint therapy: a valid option or obsolete?

Despite the dramatic improvement in both overall survival (OS) and progression-free survival (PFS) in patients with metastatic melanoma treated with immune checkpoint inhibitors, up to 60% will develop treatment resistance and 50% will die from their disease. Therefore, although dacarbazine is no longer a mainstay of modern melanoma management, we examined the extent to, and in which context, it may still play a role. A retrospective analysis of electronic medical records of patients who had received dacarbazine treatment between October 2014 and October 2021, following innate or acquired resistance to immune checkpoint inhibitors, was performed to determine PFS and OS and examine tolerability.

The treatment of Merkel cell carcinoma with immune checkpoint inhibitors: implications for patients with rheumatoid arthritis.

Objectives: Merkel cell carcinoma (MCC) is a rare, highly aggressive neuroendocrine skin cancer, which typically affects elderly and immunocompromised and/or immunosuppressed patients. The checkpoint inhibitor avelumab, a mAb targeting the anti-programmed cell death ligand 1 (anti-PD-L1), has revolutionized the treatment of metastatic MCC, achieving dramatic improvements in disease control and overall survival. However, checkpoint inhibitors are associated with the development of immune-related adverse events, such as exacerbation of pre-existing RA.

The impact of the Covid-19 pandemic on quality of life in skin cancer patients.

With more than 82 million cases worldwide and almost two million deaths, the Covid-19 global pandemic shows little sign of abating. However, its effect on quality of life (QoL) in skin cancer patients has not been systematically evaluated to date. Given that QoL impairments may be associated with increased psychological morbidity, and may interfere with engagement with cancer therapy and follow-up, we prospectively evaluated quality of life in skin cancer patients using the Covid-19 Emotional Impact Survey (C-19EIS) and the EORTC QLQ-C30 questionnaires.

Low-dose ipilimumab combined with anti-PD-1 immunotherapy in patients with metastatic melanoma following anti-PD-1 treatment failure.

Combined immunotherapy is associated with a significant risk of severe and potentially fatal immune-related adverse events (irAEs). Therefore, we retrospectively analyzed the side profile and efficacy of low-dose ipilimumab (1 mg/kg, IPI1) combined with anti-PD-1 immunotherapy in patients who progressed after anti-PD-1 monotherapy. Nine patients with unresectable stage III or IV melanoma treated with combined low-dose ipilimumab (1 mg/kg, IPI1) and anti-PD-1 immunotherapy, following progression after anti-PD-1 treatment, were identified.

Prospective validation of microseminoprotein-β added to the 4Kscore in predicting high-grade prostate cancer in an international multicentre cohort.

Objectives: To prospectively evaluate the performance of a pre-specified statistical model based on four kallikrein markers in blood (total prostate-specific antigen [PSA], free PSA, intact PSA, and human kallikrein-related peptidase 2), commercially available as the 4Kscore, in predicting Gleason Grade Group (GG) ≥2 prostate cancer at biopsy in an international multicentre study at three academic medical centres, and whether microseminoprotein-β (MSP) adds predictive value.

Patients And Methods: A total of 984 men were prospectively enrolled at three academic centres. The primary outcome was GG ≥2 on prostate biopsy.

Urinary CD80 Discriminates Among Glomerular Disease Types and Reflects Disease Activity.

Introduction: Heterogeneity of nephrotic diseases and a lack of validated biomarkers limits interventions and reduces the ability to examine outcomes. Urinary CD80 is a potential biomarker for minimal change disease (MCD) steroid-sensitive nephrotic syndrome (NS). We investigated and validated a CD80 enzyme-linked immunosorbent assay (ELISA) in urine in a large cohort with a variety of nephrotic diseases.

Hydrogen sulfide reduces the activity of human endothelial cells.

Introduction: The volatile endogenous mediator hydrogen sulfide (H2S) is known to impair thrombus formation by affecting the activity of human platelets. Beside platelets and coagulation factors the endothelium is crucial during thrombogenesis.

Objective: This study evaluates the effect of the H2S donor GYY4137 (GYY) on human umbilical vein endothelial cells (HUVECs) in vitro.

The slow releasing hydrogen sulfide donor GYY4137 reduces neointima formation upon FeCl3 injury of the carotid artery in mice.

Introduction: Neointima formation is closely linked to vascular stenosis and occurs after endothelial damage. Hydrogen sulfide is an endogenous pleiotropic mediator with numerous positive effects on the cardio vascular system.

Objective: This study evaluates the effect of the slow releasing hydrogen sulfide donor GYY4137 (GYY) on neointimal formation in vivo.

Kallikrein markers performance in pretreatment blood to predict early prostate cancer recurrence and metastasis after radical prostatectomy among very high-risk men.

Background: To assess whether a prespecified statistical model based on the four kallikrein markers measured in blood-total, free, and intact prostate-specific antigen (PSA), together with human kallikrein-related peptidase 2 (hK2)-or any individual marker measured in pretreatment serum were associated with biochemical recurrence-free (BCR) or metastasis-free survival after radical prostatectomy (RP) in a subgroup of men with very high-risk disease.

Methods: We identified 106 men treated at Mayo Clinic from 2004 to 2008 with pathological Gleason grade group 4 to 5 or seminal vesicle invasion at RP. Univariable and multivariable Cox models were used to test the association between standard predictors (Kattan nomogram and GPSM [Gleason, PSA, seminal vesicle and margin status] score), kallikrein panel, and individual kallikrein markers with the outcomes.

Reference Intervals: Comparison of Calculation Methods and Evaluation of Procedures for Merging Reference Measurements From Two US Medical Centers.

Objectives: To analyze consistency of reference limits and widths of reference intervals (RIs) calculated by six procedures and evaluate a protocol for merging intrainstitutional reference data.

Methods: The differences between reference limits were compared with "optimal" bias goals. Also, widths of the RIs were compared.

Roles of kallikrein-2 biomarkers (free-hK2 and pro-hK2) for predicting prostate cancer progression-free survival.

Free human kallikrein 2 (free-hK2) and hK2 pro-form (pro-hK2) have been found to be increased in tumor tissues and serum from patients with prostate cancer. We established semiautomatic assays for free-hK2 and pro-hK2 using a research version of the Beckman Coulter ACCESS2 system. Serum samples from a cohort of 189 men undergoing radical prostatectomy for known high-risk disease were assayed for Prostate-Specific Antigen (PSA), free-PSA, free-hK2, and pro-hK2.

Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer.

Objective: To examine the use of the Prostate Health Index (PHI) as a continuous variable in multivariable risk assessment for aggressive prostate cancer in a large multicentre US study.

Materials And Methods: The study population included 728 men, with prostate-specific antigen (PSA) levels of 2-10 ng/mL and a negative digital rectal examination, enrolled in a prospective, multi-site early detection trial. The primary endpoint was aggressive prostate cancer, defined as biopsy Gleason score ≥7.

A global multicenter study on reference values: 2. Exploration of sources of variation across the countries.

Objectives: The intent of this study, based on a global multicenter study of reference values (RVs) for serum analytes was to explore biological sources of variation (SVs) of the RVs among 12 countries around the world.

Methods: As described in the first part of this paper, RVs of 50 major serum analytes from 13,396 healthy individuals living in 12 countries were obtained. Analyzed in this study were 23 clinical chemistry analytes and 8 analytes measured by immunoturbidimetry.

Criteria for assigning laboratory measurands to models for analytical performance specifications defined in the 1st EFLM Strategic Conference.

This paper, prepared by the EFLM Task and Finish Group on Allocation of laboratory tests to different models for performance specifications (TFG-DM), is dealing with criteria for allocating measurands to the different models for analytical performance specifications (APS) recognized in the 1st EFLM Strategic Conference Consensus Statement. Model 1, based on the effect of APS on clinical outcome, is the model of choice for measurands that have a central role in the decision-making of a specific disease or clinical situation and where cut-off/decision limits are established for either diagnosing, screening or monitoring. Total cholesterol, glucose, HbA1c, serum albumin and cardiac troponins represent practical examples.

Interleukins 6 and 8 and abdominal fat depots are distinct correlates of lipid moieties in healthy pre- and postmenopausal women.

Unlabelled: Available data associate lipids concentrations in men with body mass index, anabolic steroids, age, and certain cytokines. Data were less clear in women, especially across the full adult lifespan, and when segmented by premenopausal and postmenopausal status.

Subjects: 120 healthy women (60 premenopausal and 60 postmenopausal) in Olmsted County, MN, USA, a stable well studied clinical population.

Multiple calibrator measurements improve accuracy and stability estimates of automated assays.

Objectives: The effects of combining multiple calibrations on assay accuracy (bias) and measurement of calibration stability were investigated for total triiodothyronine (TT3), vitamin B12 and luteinizing hormone (LH) using Beckman Coulter's Access 2 analyzer.

Methods: Three calibration procedures (CC1, CC2 and CC3) combined 12, 34 and 56 calibrator measurements over 1, 2, and 3 days. Bias was calculated between target values and average measured value over 3 consecutive days after calibration.

Androgen Receptor Upregulation Mediates Radioresistance after Ionizing Radiation.

Clinical trials have established the benefit of androgen deprivation therapy (ADT) combined with radiotherapy in prostate cancer. ADT sensitizes prostate cancer to radiotherapy-induced death at least in part through inhibition of DNA repair machinery, but for unknown reasons, adjuvant ADT provides further survival benefits. Here, we show that androgen receptor (AR) expression and activity are durably upregulated following radiotherapy in multiple human prostate cancer models in vitro and in vivo.

The prostate health index selectively identifies clinically significant prostate cancer.

Purpose: The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S.

Serum concentrations of prostate-specific antigen measured using immune extraction, trypsin digestion, and tandem mass spectrometry quantification of LSEPAELTDAVK peptide.

Context: Prostate-specific antigen (PSA) is a 34-kDa glycoprotein with chymotrypsin-like enzyme activity that circulates both in free forms and complexed to various enzyme inhibitors including antichymotrypsin and α2-macroglobulin. Prostate-specific antigen bound to α2-macroglobulin is not detected by commercial PSA immunoassays.

Objective: To develop a mass spectrometry assay that detects the same forms of PSA as the immunoassays, which could serve as a reference for harmonizing PSA immunoassays.