Clinicomolecular Profile and Efficacy of Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Therapy for -Amplified Advanced Biliary Tract Cancer.

Purpose: This study aimed to investigate the clinicomolecular profiles and the efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy in -amplified biliary tract cancer (BTC).

Methods: This study was an international collaboration that used combined data from the prospective SCRUM-Japan GOZILA and MONSTAR-SCREEN in Japan and retrospective reviews in the United States; patients with advanced BTC who had received systemic therapy were included. The clinicomolecular profiles were evaluated in an exploratory cohort, whereas the efficacy of HER2-targeted therapy was assessed in a biomarker-selected cohort.

Systemic therapy for pretreated advanced biliary tract cancer: past developments and recent advances.

Biliary tract cancer (BTC) remains among the most challenging malignancies with a poor prognosis and limited treatment options, particularly in pretreated patients. As most patients experience disease progression after first-line treatment, effective second-line and subsequent treatments are required. Although the addition of modified FOLFOX (fluorouracil, leucovorin, and oxaliplatin) to active symptom control improved the overall survival of patients with progressing advanced BTC despite gemcitabine plus cisplatin treatment, its efficacy was modest.

Overcoming Financial and Access Barriers in Global Cancer Care With Low-Dose Immunotherapy: A Systematic Review.

Purpose: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various malignancies. However, the high cost of these therapies limits access for much of the global population. This systematic review aims to evaluate the efficacy of low-dose ICIs compared with standard doses in different malignancies, addressing financial and access barriers in global cancer care.

Tucatinib in the treatment of HER2-overexpressing gastrointestinal cancers: current insights and future prospects.

Introduction: Over the past 20 years, the treatment landscape of HER2-amplified tumors has considerably evolved. Until now, no approved targeted therapies were available for patients with HER2-amplified metastatic colorectal cancer (mCRC). Tucatinib, a highly selective tyrosine kinase inhibitor, demonstrated significant efficacy in combination with trastuzumab in patients with refractory mCRC, leading to its approval by the Food and Drug Administration (FDA).

Treatment options for HER2-expressing colorectal cancer: updates and recent approvals.

Colorectal cancer is a leading cause of cancer-related mortality worldwide. Approximately 3-5% of colorectal tumors harbor human epidermal growth factor receptor () amplification which is associated with a higher incidence of intracranial metastasis and overall worse outcomes. In the setting of refractory metastatic wild-type tumors, evidence supports the use of various HER2-blocking agents, including monoclonal antibodies, tyrosine kinase inhibitors, and novel antibody-drug conjugates.

Targeting ERBB2/HER2 genetic alterations: an expanding therapeutic opportunity in gastrointestinal cancers.

HER2 amplification and/or activating variations of its protein, human epidermal growth factor receptor 2 (HER2), are associated with distinct clinical and pathological features in gastrointestinal tumors, including a worse overall prognosis and a higher incidence of metastastic lesions in the central nervous system. Notably, the role of HER2 as a therapeutic target continues to expand beyond the scope of breast and gastroesophageal tumors, now encompassing colorectal and biliary tract cancers (BTCs), among others. In parallel, there is a burgeoning array of therapeutic agents designed to inhibit the activity of the HER2 pathway, including monoclonal antibodies, orally available tyrosine kinase inhibitors, bispecific antibodies, and antibody-drug conjugate compounds.

Methylation Analyses Reveal Promoter Hypermethylation as a Rare Cause of "Second Hit" in Germline BRCA1-Associated Pancreatic Ductal Adenocarcinoma.

Background And Objective: Pancreatic ductal adenocarcinoma (PDAC) is characterized by the occurrence of pathogenic variants in BRCA1/2 in 5-6% of patients. Biallelic loss of BRCA1/2 enriches for response to platinum agents and poly (ADP-ribose) polymerase 1 inhibitors. There is a dearth of evidence on the mechanism of inactivation of the wild-type BRCA1 allele in PDAC tumors with a germline BRCA1 (gBRCA1) pathogenic or likely pathogenic variant (P/LPV).

Medical marijuana knowledge and attitudes amongst internal medicine residents.

Background: Mounting evidence suggests the safety and efficacy of medical marijuana (MM) in treating chronic ailments, including chronic pain, epilepsy, and anorexia. Despite incremental use of medical and recreational cannabinoids, current limited evidence shows generalized unpreparedness of medical providers to discuss or recommend these substances to their patients. Herein, the present study aims to examine internal medicine residents' knowledge of marijuana and their attitude towards its medical use.

Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma.

Chromothripsis is detectable in 20-30% of newly diagnosed multiple myeloma (NDMM) patients and is emerging as a new independent adverse prognostic factor. In this study we interrogate 752 NDMM patients using whole genome sequencing (WGS) to investigate the relationship of copy number (CN) signatures to chromothripsis and show they are highly associated. CN signatures are highly predictive of the presence of chromothripsis (AUC = 0.

Whole-genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities.

Multiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n = 15) are characterized by later initiation in the patient's life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity.

Routine Evaluation of Minimal Residual Disease in Myeloma Using Next-Generation Sequencing Clonality Testing: Feasibility, Challenges, and Direct Comparison with High-Sensitivity Flow Cytometry.

The 2016 International Myeloma Working Group consensus recommendations emphasize high-sensitivity methods for minimal residual disease (MRD) detection, treatment response assessment, and prognostication. Next-generation sequencing (NGS) of IGH gene rearrangements is highly specific and sensitive, but its description in routine clinical practice and performance comparison with high-sensitivity flow cytometry (hsFC) remain limited. In this large, single-institution study including 438 samples from 251 patients, the use of NGS targeting the IGH and IGK genes for clonal characterization and monitoring, with comparison to hsFC, is described.

Advances in Acute Myeloid Leukemia: Recently Approved Therapies and Drugs in Development.

Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy comprised of various cytogenetic and molecular abnormalities that has notoriously been difficult to treat with an overall poor prognosis. For decades, treatment options were limited to either intensive chemotherapy with anthracycline and cytarabine-based regimens (7 + 3) or lower intensity regimens including hypomethylating agents or low dose cytarabine, followed by either allogeneic stem cell transplant or consolidation chemotherapy. Fortunately, with the influx of rapidly evolving molecular technologies and new genetic understanding, the treatment landscape for AML has dramatically changed.

Cardiovascular mortality among chronic myeloid leukemia patients in the pre-tyrosine kinase inhibitor (TKI) and TKI eras: a surveillance, epidemiology and end results (SEER) analysis.

Despite remarkable efficacy, there is an emerging concern regarding TKI-associated cardiovascular toxicity in CML. Long term follow-up studies on association between TKI therapy and cardiovascular outcome have been limited. CML patients were accessed from the SEER 18 database from 1992 to 2011.

Association of admission clinical predictors and functional outcome in patients with Cerebral Venous and Dural Sinus Thrombosis.

Objectives: Cerebral venous sinus thrombosis (CVST) is a rare subtype of stroke that most commonly affects younger women. While most patients treated with anticoagulation therapy have good outcomes, a significant number go on to experience disability. The primary aim of this study was to identify objective, easily reproducible, clinical admission predictors of poor outcome at discharge in patients with CVST.

Decreases in Blood Pressure During Thrombectomy Are Associated With Larger Infarct Volumes and Worse Functional Outcome.

Background and Purpose- After large-vessel intracranial occlusion, the fate of the ischemic penumbra, and ultimately final infarct volume, largely depends on tissue perfusion. In this study, we evaluated whether blood pressure reduction and sustained relative hypotension during endovascular thrombectomy are associated with infarct progression and functional outcome. Methods- We identified consecutive patients with large-vessel intracranial occlusion ischemic stroke who underwent mechanical thrombectomy at 2 comprehensive stroke centers.

Effect of Intracranial Stenosis Revascularization on Dynamic and Static Cerebral Autoregulation.

Introduction: Severe intracranial stenosis might lead to acute cerebral ischemia. It is imperative to better assess patients who may benefit from immediate reperfusion and blood pressure management to prevent injury to peri-infarct tissue.

Methods: We assessed cerebral autoregulation using static and dynamic methods in an 81-year-old woman suffering acute cerebral ischemia from severe intracranial stenosis in the petrous segment of the left internal carotid artery (LICA).

Lipid Management in Chronic Kidney Disease: Systematic Review of PCSK9 Targeting.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and CKD is considered a coronary artery disease risk equivalent. So far, statins have been the mainstay of primary and secondary prevention of cardiovascular disease in the general population. However, their benefit on outcomes is limited and controversial in CKD patients and new therapeutic approaches to reduce cardiovascular risk are needed.

Lesinurad: what the nephrologist should know.

Lesinurad is an oral inhibitor of the monocarboxylic/urate transporter URAT1 encoded by the gene. Market authorization was granted in February 2016 in Europe and December 2015 in the USA. As a potentially nephrotoxic uricosuric drug acting on the kidney, nephrologists should become familiar with its indications and safety profile.