The impact of mutations on the clinical outcome and immune response following immunotherapy for pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second leading cause of cancer-related death by 2030. This is driven by a high case-fatality rate with most patients even with radiologically localized PDAC at diagnosis ultimately relapsing with metastatic disease. mutations present in 90% to 95% of PDAC drive these poor statistics through its role in driving cellular growth, inhibition of apoptosis, and immunosuppression.

CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.

Out of Bounds: Physician Licensing Board Disciplinary Cases related to Opioid Prescribing.

Physician prescribing practices contributed to the US opioid epidemic, leading to increased regulation of opioid prescribing. In some instances, prescribers are unscrupulous or corrupt. They are criminally investigated and subject to prosecution.

Guidance Directed Care of Spontaneous Coronary Artery Dissection: A Healthcare System-Based Experience.

Introduction: Data on treatment of spontaneous coronary artery dissection (SCAD) has evolved with guidance from national societies beginning around 2018. Given emerging guidance and relatively uncommon presentation of SCAD, we hypothesized that a specialized SCAD clinic would improve guidance-based care.

Methods: We utilized a system-wide electronic medical record search to identify individuals with SCAD diagnosis from 2018 to 2023.

Implementation of social needs screening for minoritized patients newly diagnosed with breast cancer: a mixed methods evaluation in a pragmatic patient navigation trial.

Background: Social needs inhibit receipt of timely medical care. Social needs screening is a vital part of comprehensive cancer care, and patient navigators are well-positioned to screen for and address social needs. This mixed methods project describes social needs screening implementation in a prospective pragmatic patient navigation intervention trial for minoritized women newly diagnosed with breast cancer.

Neutrophils in pancreatic ductal adenocarcinoma: bridging preclinical insights to clinical prospects for improved therapeutic strategies.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a dismal five-year survival rate of less than 10%. Neutrophils are key components of the innate immune system, playing a pivotal role in the PDAC immune microenvironment.

Areas Covered: This review provides a comprehensive survey of the pivotal involvement of neutrophils in the tumorigenesis and progression of PDAC.

Surgical and local control outcomes after sequential short-course radiation therapy and chemotherapy for rectal cancer.

Background: Total neoadjuvant therapy (TNT) is an accepted approach for the management of locally advanced rectal cancer (LARC) and is associated with a decreased risk of development of metastatic disease compared to standard neoadjuvant therapy. However, questions remain regarding surgical outcomes and local control in patients who proceed to surgery, particularly when radiation is given first in the neoadjuvant sequence. We report on our institution's experience with patients who underwent short-course radiation therapy, consolidation chemotherapy, and surgery.

Circulating Tumor DNA to Predict Radiographic and Pathologic Response to Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

Despite advances in treatment and response assessment in locally advanced rectal cancer (LARC), it is unclear which patients should undergo nonoperative management (NOM). We performed a single-center, retrospective study to evaluate post-total neoadjuvant therapy (TNT) circulating tumor DNA (ctDNA) in predicting treatment response. We found that post-TNT ctDNA had a sensitivity of 23% and specificity of 100% for predicting residual disease upon resection, with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 47%.

Relating Antimicrobial Resistance and Virulence in Surface-Water .

The role of the environment in the emergence and spread of antimicrobial resistance (AMR) is being increasingly recognized, raising questions about the public health risks associated with environmental AMR. Yet, little is known about pathogenicity among resistant bacteria in environmental systems. Existing studies on the association between AMR and virulence are contradictory, as fitness costs and genetic co-occurrence can be opposing influences.

An Adapted Optical Density-Based Microplate Assay for Characterizing Actinobacteriophage Infection.

Bacteriophages are a key part of natural environments, and they have a powerful ability to shape bacterial populations. To understand how individual phages interact with slow-growing bacterial hosts such as actinomycetes, an easy and reliable method for quantifying long-term bacterial growth in the presence of phages is needed. Spectrophotometric microplate readers allow for high-throughput repeated measurements, but incubating a small volume for an extended time can present technical challenges.

Colorectal cancer in patients of advanced age is associated with increased incidence of p.V600E mutation and mismatch repair deficiency.

Introduction: The highest incidence of colorectal cancer (CRC) is in patients diagnosed at 80 years or older highlighting a need for understanding the clinical and molecular features of these tumors. Methods. In this retrospective cohort study, 544 CRCs underwent next generation sequencing and mismatch repair (MMR) evaluation.

Complete Genome Sequences of Chop, DelRio, and GrandSlam, Three Phages Isolated from Soil in Central Arkansas.

Chop, DelRio, and GrandSlam are phage with a morphotype isolated from soil in Arkansas using the host Gordonia terrae 3612. All three are temperate, and their genomes share at least 96% nucleotide identity. These phage are assigned to cluster DI based on gene content similarity to other sequenced actinobacteriophage.

Cell-free DNA Predicts Prolonged Response to Multi-agent Chemotherapy in Pancreatic Ductal Adenocarcinoma.

Unlabelled: The treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) is frequently characterized by significant toxicity and rapid development of resistance to current approved therapies. More reliable biomarkers of response are needed to guide clinical decision making. We evaluated cell-free DNA (cfDNA) using a tumor-agnostic platform and traditional biomarkers (CEA and CA19-9) levels in 12 patients treated at Johns Hopkins University on NCT02324543 "Study of Gemcitabine/Nab-Paclitaxel/Xeloda (GAX) in Combination With Cisplatin and Irinotecan in Subjects With Metastatic Pancreatic Cancer.

Insurance barriers to substance use disorder treatment after passage of mental health and addiction parity laws and the affordable care act: A qualitative analysis.

Introduction: People who use drugs (PWUDs) in the United States historically have had a higher probability of being uninsured. Passage of the Affordable Care Act, the Paul Wellstone and Pete Domenici Health Parity and Addiction Equity was expected to increase access to treatment for substance use disorder. Few studies to date have conducted qualitative research with substance use disorder (SUD) treatment providers regarding Medicaid and other insurance coverage of SUD treatment following passage of the ACA and parity laws.

Solid Organ Transplantation Is Associated with an Increased Rate of Mismatch Repair Deficiency and PIK3CA Mutations in Colorectal Cancer.

Solid organ transplants are associated with a modestly increased risk of colorectal cancers (CRC). However, the molecular profile of these cancers has not been described. We hypothesized that transplant-related immunosuppression may promote development of more immunogenic tumors as suggested by a high tumor mutation burden or mismatch repair deficiency.

Post-operative ctDNA monitoring in stage I colon cancer: A case report.

Circulating tumor DNA (ctDNA) level monitoring after surgery for colon cancer has been studied in stage II and III colon cancer to risk-stratify patients for adjuvant therapy. However, there is less data regarding the role of this diagnostic tool in the management of stage I disease, where current recommended surveillance is limited to screening colonoscopy at one year. In this report, we describe the case of a 57-year-old man with stage I colon cancer who underwent complete resection with adequate lymph node surgical sampling, normal preoperative CEA and no evidence of metastatic disease on initial imaging.

Impact of the COVID-19 Pandemic on Liver Cancer Staging at a Multidisciplinary Liver Cancer Clinic.

Unlabelled: To compare liver cancer resectability rates before and during the COVID-19 pandemic.

Background: Liver cancers usually present with nonspecific symptoms or are diagnosed through screening programs for at-risk patients, and early detection can improve patient outcomes. In 2020, the COVID-19 pandemic upended medical care across all specialties, but whether the pandemic was associated with delays in liver cancer diagnosis is not known.

1000 Hometown Heroes: Mobilising community social influencers for COVID-19 prevention, care and coping.

Coronavirus disease 2019 (COVID-19) created life-disrupting stressors that disproportionately burden disadvantaged communities with devastating impacts that extend far beyond the burden of the disease itself, including joblessness, housing and food insecurity, educational system upheavals, isolation due to disrupted relationships, worsened mental health and substance use and violence. Socially interconnected community members are resources whose efforts can be mobilised to improve COVID-19 coping within their social networks. This research examined the feasibility, acceptability, and reach of a social media-based peer influencer intervention for COVID-19 coping.

A qualitative examination of naloxone access in three states: Connecticut, Kentucky, and Wisconsin.

Background: Prevention of opioid-involved overdose deaths remains a public health priority in the United States. While expanding access to naloxone is a national public health strategy, it is largely implemented at the state and local level, where significant variability in policies, resources, and norms exist. The aims of the current study were to examine the social context of naloxone access in three different states (Connecticut, Kentucky, Wisconsin) from the perspectives of key informants (first responders, harm reduction personnel, and pharmacists), who play some role in dispensing or administering naloxone within their communities.

Is PD-1 Inhibitor Monotherapy a New Standard Treatment for MMR-Deficient Locally Advanced Rectal Cancer?

Treatment of locally advanced rectal cancer with multimodal treatment courses can result in significant morbidity. Nonoperative management is feasible for patients with clinical complete response to neoadjuvant therapies. Several recent reports have evaluated the use of immunotherapy with checkpoint inhibition for patients with mismatch repair-deficient rectal and colon cancers, with striking results.

Nonoperative Management Following Complete Response in Rectal Cancer After Short-course Radiation Therapy and Consolidation Chemotherapy: Clinical Outcomes and Quality of Life Measures.

Purpose: The purpose of his study was to report on a cohort of patients managed with nonoperative management (NOM) with a watch-and-wait strategy after achieving complete response (CR) to sequential short-course radiation therapy (SCRT) and consolidation chemotherapy.

Methods: This was a retrospective study of patients treated SCRT and chemotherapy who achieved a CR and were managed with NOM. Bowel function was assessed with European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30, EORTC Quality of Life Questionnaire-Colorectal Cancer 29, and the low anterior resection syndrome (LARS) questionnaires.

A watershed study assessing effects of commercial hog operations on microbial water quality in North Carolina, USA.

Commercial Hog Operations (CHOs) produce large amounts of fecal waste, which is often treated in lagoons and sprayed onto fields as fertilizer. The effects of these systems on proximal water quality compared to ambient conditions have not been well-studied, and are particularly important for understanding the dissemination of fecal bacteria and antimicrobial resistance. A longitudinal, case-control watershed study was designed to study effects of CHOs on microbial water quality among watersheds with similar soil, land use, human population, and area.