Evolution of Rapid Clonal Dynamics and Non-Cross-Resistance in Response to Alternating Targeted Therapy and Chemotherapy in BRAF-V600E-Mutant Colon Cancer.

Purpose: Combined BRAF, MEK, and EGFR inhibition can induce clinical responses in BRAF-V600E-mutant colon cancer, but rapid resistance often occurs.

Methods: We use serial monitoring of circulating tumor DNA cell-free plasma DNA (cfDNA) in a patient case study in addition to organoids derived from mouse models of BRAF-V600E-mutant intestinal cancer, which emulated the patient's mutational profile to assess drug treatment efficacy.

Results: We demonstrate dynamic evolution of resistance to combined EGFR/BRAF/MEK inhibition in a pediatric patient with metastatic BRAF-V600E-mutant, mismatch repair-stable colon cancer.

Late-stage borreliosis and substance abuse.

Background: Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick bites and increasing multisystem symptoms, yet diagnosis and treatment were delayed.

Iatrogenic Vertebral Artery Dissection with Posterior Fossa and Lateral Medullary Stroke After Uncomplicated Cervical Nerve Ablation.

Background: A cervical radiofrequency ablation is a procedure that can be performed to treat arthritis-related pain in the neck and upper back. There have been no large studies reporting complications after this procedure. We report a case of a 55-year-old woman with iatrogenic vertebral artery dissection of C3-C4 with segmental occlusion leading to a posterior fossa stroke and lateral medullary stroke after a high-grade cervical nerve ablation.

In Vitro Organoid-Based Assays Reveal SMAD4 Tumor-Suppressive Mechanisms for Serrated Colorectal Cancer Invasion.

Colon cancer is the third most prominent cancer and second leading cause of cancer-related deaths in the United States. Up to 20% of colon cancers follow the serrated tumor pathway driven by mutations in the MAPK pathway. Loss of SMAD4 function occurs in the majority of late-stage colon cancers and is associated with aggressive cancer progression.

Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1-2 study.

Background: Patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma for whom treatment has failed with both Bruton tyrosine kinase (BTK) inhibitor and venetoclax have few treatment options and poor outcomes. We aimed to evaluate the efficacy and safety of lisocabtagene maraleucel (liso-cel) at the recommended phase 2 dose in patients with relapsed or refractory chronic lymphocytic leukaemia or small lymphocytic lymphoma.

Methods: We report the primary analysis of TRANSCEND CLL 004, an open-label, single-arm, phase 1-2 study conducted in the USA.

Adolescents with chronic conditions: Engagement with children's mental health systems during the Covid-19 pandemic.

Purpose: The Covid-19 pandemic contributed to adverse adolescent mental health outcomes globally. Adolescents with chronic conditions have four times the odds of self-harm than peers. Little evidence exists to guide pediatric nurses on how to engage this vulnerable population with mental health support as the pandemic continues.

Object Shape and Depth of Word Representations in Preschoolers.

This study examined the effect of a shape cue (i.e., co-speech gesture) on word depth.

Quality measures in endoscopy: A systematic analysis of the overall scientific level of evidence and conflicts of interest.

Quality measures were established to develop standards to help assess quality of care, yet variation in endoscopy exists. We performed a systematic review to assess the overall quality of evidence cited in formulating quality measures in endoscopy. A systematic search was performed on multiple databases from inception until November 15, 2020, to examine the quality measures proposed by all major societies.

The Relationship Between Neighborhood Disadvantage and Kidney Disease Progression in the Chronic Kidney Disease in Children (CKiD) Cohort.

Rationale & Objective: To examine the relationship between neighborhood poverty and deprivation, chronic kidney disease (CKD) comorbidities, and disease progression in children with CKD.

Study Design: Observational cohort study.

Setting & Participants: Children with mild to moderate CKD enrolled in the CKiD (Chronic Kidney Disease in Children) study with available US Census data.

The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma.

Background: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL.

Patients And Methods: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study.

Comparative genomic analysis of clinical isolates identifies multiple polymorphic loci that can improve existing multilocus sequence typing strategy.

is the second leading cause of candidemia in many countries and is one of the most concerning yeast species of nosocomial importance due to its increasing rate of antifungal drug resistance and emerging multidrug-resistant isolates. Application of multilocus sequence typing (MLST) to clinical isolates revealed an association of certain sequence types (STs) with drug resistance and mortality. The current MLST scheme is based on single nucleotide polymorphisms (SNPs) at six loci and is therefore relatively laborious and costly.

Esophageal cancer: the rise of adenocarcinoma over squamous cell carcinoma in the Asian belt.

Esophageal cancer is a common cancer worldwide with a high associated mortality rate. Amongst the two most frequent subsets of disease, squamous cell carcinoma (SCC) and adenocarcinoma (AC), there has been an epidemiologic shift towards adenocarcinoma over the last few decades. However, squamous cell carcinoma still predominates worldwide.

Value-based chronic care model approach for vulnerable older patients with multiple chronic conditions.

"" (Suborne 2007). The rising rate of the global aging population is predicted to create a health care crisis within the next three decades. Vulnerable older adults suffer from multiple chronic conditions (MCCs) in addition to cognitive and physical decline during the process of aging resulting in an inability to optimally achieve self-management.

State of the art vaccination strategies as primary prevention to reduce incidence of gastrointestinal cancers.

Immunizations have influenced the epidemiology of numerous gastrointestinal cancers. Human papillomavirus (HPV) is a common sexually transmitted infection (STI). Although most infections are transient and asymptomatic, persistent infections with oncogenic strains of HPV can progress to cervical, anal, penile, vaginal, vulvar, and oropharyngeal cancers.

A discussion of the gut microbiome's development, determinants, and dysbiosis in cancers of the esophagus and stomach.

The microbiome refers to a population of microbes that colonize the skin, nasopharynx, oral cavity, gastrointestinal tract, and urogenital tract. The human microbiome consists of bacteria, archaea, fungi, viruses, and phages. Recent advances in genomic sequencing have catalyzed a deeper understanding of complex microbe-microbe and host-microbe interactions.