Feasibility and Impact of Embedding an Extended DNA and RNA Tissue-Based Sequencing Panel for the Routine Care of Patients with Advanced Melanoma in Spain.

Targeted NGS allows a fast and efficient multi-gene analysis and the detection of key gene aberrations in melanoma. In this study, we aim to describe the genetic alterations in a series of 87 melanoma cases using the oncomine focus assay (OFA), relate these results with the clinicopathological features of the patients, and compare them with our previous study results in which we used a smaller panel, the oncomine solid tumor (OST) DNA kit. Patients diagnosed with advanced melanoma at our center from 2020 to 2022 were included and DNA and RNA were extracted for sequencing.

Flanagan's condensed protocol for neurodegenerative diseases. Implementation in a clinical autopsy setting with partial supervision of a neuropathologist.

The Condensed Protocol (CP) was originally developed for the evaluation of Alzheimer's Disease (AD) and other neurodegenerative diseases as a workable alternative to the complex and costly established autopsy guidelines. The study objective is to examine the degree of implementation of the CP in the pathology department of a third level university hospital in a period of 5 years. Clinical autopsies performed between 2016 and 2021 on patients aged 65 years or over and did not require a specific neuropathological examination were reviewed.

Human papillomavirus and p53 status define three types of vulvar squamous cell carcinomas with distinct clinical, pathological, and prognostic features.

Introduction: Based on their etiological relationship with human papillomavirus (HPV), the 2020 WHO classification has divided vulvar squamous cell carcinomas (VSCC) into two distinct types, HPV-associated and HPV-independent, and HPV-independent tumours have recently been divided according to p53 status. Nevertheless, the clinical and prognostic significance of this classification has not been clearly established. We analysed the differential clinical, pathological, and behavioural characteristics of these three types of VSCC in a large series of patients.

Vulvar squamous cell carcinoma arising on human papillomavirus-independent precursors mimicking high-grade squamous intra-epithelial lesion: a distinct and highly recurrent subtype of vulvar cancer.

Aims: Each category of vulvar squamous cell carcinoma (VSCC), human papillomavirus (HPV)-associated and HPV-independent, arises on a specific intra-epithelial precursor: high-grade squamous intra-epithelial lesions (HSIL) and differentiated vulvar intra-epithelial neoplasia (dVIN), respectively. However, a subset of HPV-independent VSCC arises on an intra-epithelial precursor closely mimicking HSIL. We aimed to explore the clinicopathological features of the HPV-independent tumours with HSIL-like lesions and compare them with HPV-independent VSCC with dVIN and HPV-associated tumours with HSIL.

Dermoscopy and Reflectance Confocal Microscopy to Estimate Breslow Index and Mitotic Rate in Primary Melanoma.

Introduction: Non-invasive imaging techniques offer the possibility to optimize the first approach to melanoma. Reflectance Confocal Microscopy (RCM) has a promising role in predicting the main prognostic events in the dermo-epidermal and papillary dermis.

Objectives: To identify pre-surgical criteria that can predict the main prognostic features of melanoma.

Prognostic role of microsatellites in melanoma and implications in the American Joint Committee on Cancer classification system: A cohort study.

Background: There is limited information on microsatellite survival outcomes in patients with melanoma.

Objective: To evaluate survival outcomes in patients with microsatellites, assess their role within stage III stratification of the American Joint Committee on Cancer classification, and assess the results of sentinel lymph node biopsies in patients with microsatellites.

Methods: A retrospective bicenter cohort study from 1998 to 2019 included patients with a diagnosis of invasive cutaneous melanoma.

Morphological evaluation of melanocytic lesions with three-dimensional line-field confocal optical coherence tomography: correlation with histopathology and reflectance confocal microscopy. A pilot study.

Background: Line-field confocal optical coherence tomography (LC-OCT) is a new in vivo emerging technique that provides cellular resolution, allows deep imaging (400 μm) and produces real-time images in both the horizontal and vertical plane and in three dimensions. No previous description of different subtypes of melanocytic lesions and their correlation with histopathology and reflectance confocal microscopy has been reported.

Aim: To describe the features of melanocytic lesions by LC-OCT and their correlation with histopathology and reflectance confocal microscopy (RCM) findings.

COVID-19, rejection, and cutaneous mucormycosis in a long-term liver transplant recipient - the vicious cycle of immunosuppression and opportunistic infections.

Opportunistic infections, including fungal infections, are dreaded complications of liver transplantation, particularly early after transplant. We describe the case of a patient that presented 6 years after liver transplant with a -infected leg ulcer, following previous COVID-19 infection and moderate rejection requiring steroid pulses. The patient required long-term antifungal therapy, repeated surgical debridement and eventually wound coverage with meshed split-thickness skin graft.

Reflectance Confocal Microscopy and Electrical Impedance Spectroscopy in the Early Detection of Melanoma in Changing Lesions during Long-term Follow-up of Very High-risk Patients.

Electrical impedance spectroscopy has clinical relevance in diagnosing malignancy in melanocytic lesions. Sixty-eight lesions with changes during digital follow-up of patients at very high risk of developing melanoma were prospectively included in this study from February to December 2016. Electrical impedance spectroscopy and reflectance confocal microscopy were performed to evaluate their performance in this subset of difficult lesions.

Boosting the Discovery of Small Molecule Inhibitors of Glucose-6-Phosphate Dehydrogenase for the Treatment of Cancer, Infectious Diseases, and Inflammation.

We present an overview of small molecule glucose-6-phosphate dehydrogenase (G6PD) inhibitors that have potential for use in the treatment of cancer, infectious diseases, and inflammation. Both steroidal and nonsteroidal inhibitors have been identified with steroidal inhibitors lacking target selectivity. The main scaffolds encountered in nonsteroidal inhibitors are quinazolinones and benzothiazinones/benzothiazepinones.

Stabilization of glucose-6-phosphate dehydrogenase oligomers enhances catalytic activity and stability of clinical variants.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic trait that can cause hemolytic anemia. To date, over 150 nonsynonymous mutations have been identified in G6PD, with pathogenic mutations clustering near the dimer and/or tetramer interface and the allosteric NADP-binding site. Recently, our lab identified a small molecule that activates G6PD variants by stabilizing the allosteric NADP and dimer complex, suggesting therapeutics that target these regions may improve structural defects.

Mitochondrial Fusion, Fission, and Mitophagy in Cardiac Diseases: Challenges and Therapeutic Opportunities.

Mitochondria play a critical role in the physiology of the heart by controlling cardiac metabolism, function, and remodeling. Accumulation of fragmented and damaged mitochondria is a hallmark of cardiac diseases. Disruption of quality control systems that maintain mitochondrial number, size, and shape through fission/fusion balance and mitophagy results in dysfunctional mitochondria, defective mitochondrial segregation, impaired cardiac bioenergetics, and excessive oxidative stress.

Accurate Quantification of T Cells in Copy Number Stable and Unstable DNA Samples Using Multiplex Digital PCR.

An accurate T-cell quantification is prognostically and therapeutically relevant in various malignancies. We previously developed a digital PCR-based approach offering a precise T-cell enumeration in small amounts of DNA. However, it may be challenging to apply this method in malignant specimens, as genetic instability can disturb the underlying mathematical model.

Treatment strategies for glucose-6-phosphate dehydrogenase deficiency: past and future perspectives.

Glucose-6-phosphate dehydrogenase (G6PD) maintains redox balance in a variety of cell types and is essential for erythrocyte resistance to oxidative stress. G6PD deficiency, caused by mutations in the G6PD gene, is present in ~400 million people worldwide, and can cause acute hemolytic anemia. Currently, there are no therapeutics for G6PD deficiency.