Assessment of real-world, prospective outcomes in patients treated with cervical radiofrequency ablation for chronic pain (RAPID).

Introduction: Cervical facet joint syndrome (CFJS) is a common cause of chronic neck pain. While numerous studies have demonstrated the effectiveness of radiofrequency ablation (RFA) for facetogenic pain, its use in treating CFJS remains a subject of ongoing debate.

Objective: Here, we sought to evaluate real-world clinical outcomes in cervical RFA-treated patients with chronic cervical facetogenic pain.

Cancer Testis Antigen Expression Correlates With Immune Activation and Survival in Small Bowel Neuroendocrine Tumors.

Purpose: Small bowel neuroendocrine tumors (SBNET) frequently present with metastatic disease, and the efficacy of available systemic therapies, especially immune checkpoint blockade, is limited. Toward developing novel immunomodulatory strategies, we interrogated the tumor immune microenvironment of SBNETs using bulk transcriptional and digital spatial profiling (DSP).

Methods: Patients with SBNET who underwent resection from 2003 to 2016 were retrospectively evaluated.

Epidemiology of Neuroendocrine Neoplasms in the US.

Importance: Neuroendocrine neoplasms (NENs) are increasing in incidence; prevalence and at the same time, practice patterns have also evolved, impacting classification and survival of these malignant neoplasms. However, updated epidemiological data are lacking.

Objective: To define the epidemiological and survival trends of patients with NENs in the US.

Assessment of real-world, prospective outcomes in patients treated with lumbar radiofrequency ablation for chronic pain (RAPID).

Background: Lumbar facet joint syndrome (LFJS) is one of most common forms of chronic low back pain. Despite several decades of real-world use and a plethora of published studies, debate still exists regarding the effectiveness of Radiofrequency Ablation (RFA) as a therapy in LFJS-diagnosed patients.

Objective: Here, we sought to evaluate real-world clinical outcomes in RFA-treated patients with chronic lumbar facetogenic pain participating in one of the largest studies of its kind published to date.

Alpha radioligand therapy in neuroendocrine neoplasms: current landscape and spotlight on RYZ101.

The therapeutic landscape for neuroendocrine tumors (NETs) has rapidly evolved over the last three decades with the influx of a myriad of treatment options, such as somatostatin analogs (SSAs), targeted therapies, alkylating chemotherapies, and radioligand therapy (RLT). While the advent and regulatory approval of beta emitting RLT such as 177Lu-DOTATATE has offered a valuable therapeutic option for patients with NETs, there is still very significant room to tap the maximal therapeutic potential of RLT. Alpha RLT agents such as RYZ101 (225Ac-DOTATATE) offer a potential advantage over beta RLT due to more complex double-stranded DNA breaks and targeted cytotoxicity, as well as potential for minimizing off-target side-effects.

Phase II Trial of Atezolizumab and Bevacizumab for Treatment of HPV-Positive Unresectable or Metastatic Squamous Cell Carcinoma of the Anal Canal.

Purpose: Anti-PD-L1 antibodies are associated with responses in <25% of patients with metastatic human papillomavirus-associated malignancies. VEGF signaling causes immune evasion and immune suppression within the tumor. We evaluated the anti-PD-L1 antibody atezolizumab and anti-VEGF antibody bevacizumab for patients with unresectable, advanced anal cancer.

Phase Ib/II study of Pembrolizumab with Lanreotide depot for advanced, progressive Gastroenteropancreatic neuroendocrine tumors (PLANET).

While performing a study of immune checkpoint blockade with the anti-PD-1 antibody pembrolizumab combined with the somatostatin analogue (SSA) lanreotide in patients with low- and intermediate-grade gastroenteropancreatic neuroendocrine tumors (GEP-NETs), we studied whether there were any immune correlates of response to the anti-PD-1 therapy that could guide future attempts to integrate immunotherapy into the treatment of NETs. Patients with grade 1 and 2 GEP-NETs who had progressed on a prior SSA received lanreotide 90 mg subcutaneously and pembrolizumab 200 mg intravenously every 3 weeks until progression or intolerable toxicity. Objective response rate (ORR) at any time in the study, clinical benefit rate (CBR, defined as stable disease or better), progression-free survival (PFS), and overall survival (OS) were measured.

The Clinical Utility of a Next-Generation Sequencing-Based Approach to Detecting Circulating HPV DNA in Patients with Advanced Anal Cancer.

Background: To extend the practicality of liquid biopsy beyond the historical HPV circulating tumor DNA (ctDNA) assays, we evaluated the clinical relevance of a novel next-generation sequencing HPV ctDNA assay in patients with locally advanced and metastatic squamous cell cancer of the anal canal (mSCCA).

Methods: ctDNA isolated from the plasma of patients with mSCCA was sequenced using a 1.4 Mb hybrid-capture target-enrichment panel covering the whole genome sequences of all 193 HPV types.

Delta-like ligand 3 (DLL3) landscape in pulmonary and extra-pulmonary neuroendocrine neoplasms.

Delta-like Ligand 3 (DLL3) targeting therapies are promising in small cell lung cancer (SCLC) treatment. However, DLL3 expression in SCLC and other neuroendocrine neoplasms (NEN) is heterogeneous and not well characterized. We describe the landscape of DLL3 at the mRNA and protein levels across SCLC, large cell neuroendocrine carcinoma (LCNEC), and non-small cell lung cancer.

Molecular, Socioeconomic, and Clinical Factors Affecting Racial and Ethnic Disparities in Colorectal Cancer Survival.

Importance: Disparity in overall survival (OS) and differences in the frequency of driver gene variants by race and ethnicity have been separately observed in patients with colorectal cancer; however, how these differences contribute to survival disparity is unknown.

Objective: To quantify the association of molecular, socioeconomic, and clinical covariates with racial and ethnic disparities in overall survival among patients with colorectal cancer.

Design, Setting, And Participants: This single-center cohort study was conducted at a tertiary-level cancer center using relevant data on all patients diagnosed with colorectal cancer from January 1, 1973, to March 1, 2023.

Masking for COVID-19 and other respiratory viral infections: implications of the available evidence.

The use of face masks has been widely promoted and at times mandated to prevent coronavirus disease 2019 (COVID-19). The 2023 publication of an updated Cochrane review on mask effectiveness for respiratory viruses as well as the unfolding epidemiology of COVID-19 underscore the need for an unbiased assessment of the current scientific evidence. It appears that the widespread promotion, adoption, and mandating of masking for COVID-19 were based not primarily on the strength of evidence for effectiveness but more on the imperative of decision-makers to act in the face of a novel public health emergency, with seemingly few good alternatives.

VARista: a free web platform for streamlined whole-genome variant analysis across T2T, hg38, and hg19.

With the increasing importance of genomic data in understanding genetic diseases, there is an essential need for efficient and user-friendly tools that simplify variant analysis. Although multiple tools exist, many present barriers such as steep learning curves, limited reference genome compatibility, or costs. We developed VARista, a free web-based tool, to address these challenges and provide a streamlined solution for researchers, particularly those focusing on rare monogenic diseases.

International Prognostic Score for Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

Purpose: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL.

Methods: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate.

A role of BPTF in viral oncogenicity delineated through studies of heritable Kaposi sarcoma.

Kaposi sarcoma (KS), caused by Herpesvirus-8 (HHV-8; KSHV), shows sporadic, endemic, and epidemic forms. While familial clustering of KS was previously recorded, the molecular basis of hereditary predilection to KS remains largely unknown. We demonstrate through genetic studies that a dominantly inherited missense mutation in BPTF segregates with a phenotype of classical KS in multiple immunocompetent individuals in two families.

Somatostatin Receptor Subtype-2 Targeting System for Specific Delivery of Temozolomide.

Temozolomide (TMZ) is a DNA alkylating agent that produces objective responses in patients with neuroendocrine tumors (NETs) when the DNA repair enzyme O-methylguanine-DNA methyltransferase (MGMT) is inactivated. At high doses, TMZ therapy exhausts MGMT activity but also produces dose-limiting toxicities. To reduce off-target effects, we converted the clinically approved radiotracer Ga-DOTA-TOC into a peptide-drug conjugate (PDC) for targeted delivery of TMZ to somatostatin receptor subtype-2 (SSTR2)-positive tumor cells.

Transformation of G1-G2 neuroendocrine tumors to neuroendocrine carcinomas following peptide receptor radionuclide therapy.

We observed that some patients with well-differentiated neuroendocrine tumors (NET) who received peptide receptor radionuclide therapy (PRRT) with Lutetium-177 (177Lu) DOTATATE developed rapid disease progression with biopsy-proven histologic transformation to neuroendocrine carcinoma (NEC), an outcome that has not been previously described. Therefore, we conducted a retrospective review of all patients with well-differentiated G1-G2 NET who received at least one cycle of PRRT with (177Lu) DOTATATE at our center from January 2019 to December 2020. Among 152 patients, we identified 7 patients whose NET transformed to NEC.

mutation causes sex-dependent neurologic disorder.

Background: Sex-specific predilection in neurological diseases caused by mutations in autosomal genes is a phenomenon whose molecular basis is poorly understood. We studied females of consanguineous Bedouin kindred presenting with severe global developmental delay and epilepsy.

Methods: Linkage analysis, whole exome sequencing, generation of CRISPR/cas9 knock-in mice, mouse behaviour and molecular studies RESULTS: Linkage analysis and whole exome sequencing studies of the affected kindred delineated a ~5 Mbp disease-associated chromosome 2q35 locus, containing a novel homozygous frameshift truncating mutation in , in line with recent studies depicting similar putative loss-of-function human phenotypes with female preponderance.

Methodology of the SORENTO clinical trial: a prospective, randomised, active-controlled phase 3 trial assessing the efficacy and safety of high exposure octreotide subcutaneous depot (CAM2029) in patients with GEP-NET.

Background: The current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET) requires initiation of first-generation somatostatin receptor ligand (SRL) therapy, octreotide and lanreotide, which provide safe and efficacious tumour/symptom control in most patients. However, disease progression can occur with SoC SRL treatment and the optimal dose response of SRL remains unknown. Octreotide subcutaneous depot (CAM2029) is a novel, long-acting, high-exposure formulation that has shown greater bioavailability and improved administration than octreotide long-acting release (LAR) with a well-tolerated safety profile.

Aryl hydrocarbon receptor restricts axon regeneration of DRG neurons in response to injury.

Injured neurons sense environmental cues to balance neural protection and axon regeneration, but the mechanisms are unclear. Here, we unveil aryl hydrocarbon receptor (AhR), a ligand-activated bHLH-PAS transcription factor, as a molecular sensor and key regulator of acute stress response at the expense of axon regeneration. We demonstrate responsiveness of DRG sensory neurons to AhR signaling, which functions to inhibit axon regeneration.