Evaluation of Heterogeneity in the Coding Region of BRAF, MAP2K1, and MAP2K2 Genes in Primary and Metastatic Melanomas.

Introduction: The incidence of melanoma has been increasing in recent decades. BRAF mutations appear in 50%-70% of melanomas. The BRAF-targeted therapy increased the disease-free survival of patients with metastatic melanoma, but this response may be short, due to several resistance mechanisms, such as the presence of other subclones with mutations.

Mutational profile of the KIT gene and its heterogeneity in primary and metastatic melanomas.

Background: This study investigates the mutational profile of the KIT gene in primary and metastatic melanomas, highlighting the significance of genetic heterogeneity.

Methods: This research is a retrospective cohort that includes formalin-fixed and paraffin-embedded melanoma samples obtained from Hospital São Paulo, Brazil, between the years of 1996 and 2010. The research encompasses primary melanomas of the superficial spreading (SSM) and acral lentiginous (AL) subtypes and their metastases, using next-generation sequencing to explore genetic heterogeneity.

The Impact of Next-generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Desmoplastic Melanocytic Neoplasms.

Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs).

Transient anti-cytokine autoantibodies superimpose the hyperinflammatory response in Kawasaki disease and multisystem inflammatory syndrome in children: a comparative cohort study on correlates of disease.

Background: Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C.

Role of Serum Lipids, Blood Glucose and Blood Pressure in Breast Cancer Risk for Women with Type 2 Diabetes Mellitus.

Purpose: Women with type 2 diabetes mellitus (T2DM) have an increased risk of breast cancer. We aimed to determine the contribution of lipids, glucose and blood pressure to this risk based on the multifactorial nature of T2DM.

Patients And Methods: This population-based cohort study used data from a Dutch database (the Groningen Initiative to Analyse Type 2 Diabetes Treatment) for the period 2004-2013.

Revision of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis Classification Schema for Melanocytic Lesions: A Consensus Statement.

Importance: A standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.

Objective: To revise the MPATH-Dx version 1.

Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020.

The Value of Glycemic Control Prior to Cancer Diagnosis on All-Cause Mortality among Patients with Type 2 Diabetes in Dutch Primary Care.

Background: Poor glycemic control prior to cancer diagnosis for patients with preexisting type 2 diabetes (T2DM) may predict a worse cancer diagnosis. We investigated the association between pre-diagnosis glycemic control and all-cause mortality in patients with T2DM who develop cancer.

Methods: This prospective cohort study linked data from three sources covering 1989 to 2019: a T2DM benchmarking database, the Netherlands Cancer Registry, and the Personal Records Database.

Including measures of chronic kidney disease to improve cardiovascular risk prediction by SCORE2 and SCORE2-OP.

Aims: The 2021 European Society of Cardiology (ESC) guideline on cardiovascular disease (CVD) prevention categorizes moderate and severe chronic kidney disease (CKD) as high and very-high CVD risk status regardless of other factors like age and does not include estimated glomerular filtration rate (eGFR) and albuminuria in its algorithms, systemic coronary risk estimation 2 (SCORE2) and systemic coronary risk estimation 2 in older persons (SCORE2-OP), to predict CVD risk. We developed and validated an 'Add-on' to incorporate CKD measures into these algorithms, using a validated approach.

Methods: In 3,054 840 participants from 34 datasets, we developed three Add-ons [eGFR only, eGFR + urinary albumin-to-creatinine ratio (ACR) (the primary Add-on), and eGFR + dipstick proteinuria] for SCORE2 and SCORE2-OP.

Impact of Next-generation Sequencing on Interobserver Agreement and Diagnosis of Spitzoid Neoplasms.

Atypical Spitzoid melanocytic tumors are diagnostically challenging. Many studies have suggested various genomic markers to improve classification and prognostication. We aimed to assess whether next-generation sequencing studies using the Tempus xO assay assessing mutations in 1711 cancer-related genes and performing whole transcriptome mRNA sequencing for structural alterations could improve diagnostic agreement and accuracy in assessing neoplasms with Spitzoid histologic features.

Type 2 Diabetes Mellitus and Clinicopathological Tumor Characteristics in Women Diagnosed with Breast Cancer: A Systematic Review and Meta-Analysis.

Poor prognosis caused by type 2 diabetes mellitus (T2DM) in women with breast cancer is conferred, while the association between T2DM and breast tumor aggressiveness is still a matter of debate. This study aimed to clarify the differences in breast cancer characteristics, including stage, size, lymph node status, grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (Her2), between patients with and without pre-existing T2DM. PubMed, Embase, and Web of Science were searched for studies from 1 January 2010 to 2 July 2021.

The Risk of Cutaneous Squamous Cell Carcinoma Among Patients with Type 2 Diabetes Receiving Hydrochlorothiazide: A Cohort Study.

Background: Because of continuous hyperglycemia and hyperinsulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2 diabetes, and to determine whether thiazide-like diuretics, another drug in the same class with HCTZ, would be safer.

Methods: We linked the benchmarking database in Dutch primary care, the Netherlands Cancer Registry, and the Dutch Personal Records Database (1998-2019).

Glycemic Control for Colorectal Cancer Survivors Compared to Those without Cancer in the Dutch Primary Care for Type 2 Diabetes: A Prospective Cohort Study.

Cancer survivors with diabetes tend to have worse glycemic control after their cancer diagnosis, which may increase the risk of cardiovascular diseases. We aimed to investigate whether glycemic control differs between colorectal cancer (CRC) survivors and those without cancer, among patients with type 2 diabetes being treated in the Dutch primary care. The Zwolle Outpatient Diabetes project Integrating Available Care database was linked with the Dutch Cancer Registry ( = 71,648, 1998-2014).

Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families.

Background: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited.

Methods: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime.

Improving Isotonic Maintenance Intravenous Fluid Use at a Tertiary Children's Hospital.

Objectives: Maintenance intravenous fluids (IVFs) are routinely used in the care of hospitalized children. The American Academy of Pediatrics (AAP) published clinical practice guidelines in November 2018 that recommended the use of isotonic maintenance IVF. Our primary aim was to increase the proportion of hospital days pediatric inpatients were exclusively administered isotonic maintenance IVF to ≥80% by May 2020 at our institution.

Incorporating kidney disease measures into cardiovascular risk prediction: Development and validation in 9 million adults from 72 datasets.

Background: Chronic kidney disease (CKD) measures (estimated glomerular filtration rate [eGFR] and albuminuria) are frequently assessed in clinical practice and improve the prediction of incident cardiovascular disease (CVD), yet most major clinical guidelines do not have a standardized approach for incorporating these measures into CVD risk prediction. "CKD Patch" is a validated method to calibrate and improve the predicted risk from established equations according to CKD measures.

Methods: Utilizing data from 4,143,535 adults from 35 datasets, we developed several "CKD Patches" incorporating eGFR and albuminuria, to enhance prediction of risk of atherosclerotic CVD (ASCVD) by the Pooled Cohort Equation (PCE) and CVD mortality by Systematic COronary Risk Evaluation (SCORE).

Is Gliclazide Associated with a Lower Obesity-Related Cancer Risk Compared to Other Sulfonylureas? A Long-term Prospective Cohort Study.

Background: Gliclazide has been suspected to be associated with a lower obesity-related cancer risk; however, current evidence is limited by important methodologic shortcomings. This study aimed to evaluate whether gliclazide is preferred over other sulfonylureas regarding obesity-related cancer risk.

Methods: In this prospective cohort study, an annual benchmarking database in Dutch primary care (Zwolle Outpatient Diabetes project Integrating Available CareZODIAC, 1998-2014) was linked to the Netherlands Cancer Registry and the Dutch Personal Record Database.

Nonspecific Symptoms in Children Referred to a Lyme Borreliosis Center.

Background: Nonspecific symptoms in children suspected of Lyme borreliosis (LB) are challenging for clinicians. We assessed whether nonspecific symptoms are more prevalent among children with positive immunoglobulin G (IgG) serology or a history of clinical LB.

Methods: We included children (<18 years) suspected of LB who visited the Lyme Center Apeldoorn of Gelre Hospital between 2008 and 2017.

Demographic, Clinical, and Pathologic Features of Patients With Cutaneous Melanoma: Final Analysis of the Brazilian Melanoma Group Database.

Purpose: National epidemiologic data on melanoma are scarce in Brazil. The current work presents final demographic, clinical, and pathologic results from the Brazilian Melanoma Group database to detail how patients with melanoma present at diagnosis.

Methods: The online database includes patients diagnosed between 1982 and 2015 and evaluated at their centers of origin between 2001 and 2016.