Trends in minimally invasive and open inguinal hernia repair: an analysis of ACGME general surgery case logs.

BACKGROUND: Groin hernia repair is one of the most commonly performed surgical procedures and is often performed by surgical interns and junior residents. While traditionally performed open, minimally invasive (MIS) groin hernia repair has become an increasingly popular approach. The purpose of this study was to determine the trends in MIS and open inguinal and femoral hernia repair in general surgery residency training over the past two decades. METHODS: Accreditation Council for Graduate Medical Education (ACGME) national case log data of general surgery residents from 1999 through 2022 were reviewed. We collected means and standard deviations of open and MIS inguinal and femoral hernia repairs. Linear regression and ANOVA were used to identify trends in the average annual number of open and MIS hernia repairs logged by residents. Cases were distinguished between level of resident trainees: surgeon-chief (SC) and surgeon-junior (SJ). RESULTS: From July 1999 to June 2022, the average annual MIS inguinal and femoral hernia repairs logged by general surgery residents significantly increased, from 7.6 to 47.9 cases (p < 0.001), and the average annual open inguinal and femoral hernia repairs logged by general surgery residents significantly decreased, from 51.9 to 39.7 cases (p < 0.001). SJ resident results were consistent with this overall trend. For SC residents, the volume of both MIS and open hernia repairs significantly increased (p < 0.001). CONCLUSIONS: ACGME case log data indicates a trend of general surgery residents logging overall fewer numbers of open inguinal and femoral hernia repairs, and a larger proportion of open repairs by chief residents. This trend warrants attention and further study as it may represent a skill or knowledge gap with significant impact of surgical training.

Role of Race and Insurance Status in Prostate Cancer Diagnosis-to-Treatment Interval.

INTRODUCTION: Numerous studies have shown that both race and insurance status may affect prostate cancer (PCa) workup and treatment. Preliminary investigations have shown that these factors may be associated with treatment delays, which may indicate inequitable care and increase risk of tumor progression. This investigation aimed to assess whether race and insurance impacted the interval between multiparametric MRI (mpMRI)-to-biopsy, and biopsy-to-prostatectomy. MATERIALS AND METHODS: A single-institution analysis of 261 patients with recorded race and insurance data was performed using an Institutional Review Board-compliant database with information spanning from 2016 to 2022. Race was self-reported during intake, and insurance status was retrieved from the electronic medical record. Insurance was sub-divided into private, Medicare, and Medicaid. Diagnostic or treatment latency was defined as time between mpMRI-to-biopsy, or biopsy-to-surgery. RESULTS: Stratified by race, there was no difference in either latency period when comparing African American (AA) and white patients. Stratified by insurance status, there was no difference in time from mpMRI-to-biopsy (P = .50), but there was a significantly longer interval from biopsy-to-prostatectomy for patients with Medicaid insurance (P = .02). Patients with Medicaid waited on average 168 days to receive surgery, in contrast to 92 days for private and 87 for Medicare. Notably, 82% of Medicaid patients were AA. CONCLUSION: Insurance status, which is inherently linked to race and social determinants of health, portended a significantly increased interval between biopsy and surgery. Physicians should be aware of the relationship between insurance status and treatment delay, as well as its potential downstream consequences.

Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy.

Recent advances in cancer therapeutics clearly demonstrate the need for innovative multiplex therapies that attack the tumour on multiple fronts. Oncolytic or "cancer-killing" viruses (OVs) represent up-and-coming multi-mechanistic immunotherapeutic drugs for the treatment of cancer. In this study, we perform an in-vitro screen based on virus-encoded artificial microRNAs (amiRNAs) and find that a unique amiRNA, herein termed amiR-4, confers a replicative advantage to the VSVΔ51 OV platform. Target validation of amiR-4 reveals ARID1A, a protein involved in chromatin remodelling, as an important player in resistance to OV replication. Virus-directed targeting of ARID1A coupled with small-molecule inhibition of the methyltransferase EZH2 leads to the synthetic lethal killing of both infected and uninfected tumour cells. The bystander killing of uninfected cells is mediated by intercellular transfer of extracellular vesicles carrying amiR-4 cargo. Altogether, our findings establish that OVs can serve as replicating vehicles for amiRNA therapeutics with the potential for combination with small molecule and immune checkpoint inhibitor therapy.

Personalized oncology and BRAFK601N melanoma: model development, drug discovery, and clinical correlation.

PURPOSE: Mutations in BRAF are the most prominent activating mutations in melanoma and are increasingly recognized in other cancers. There is currently no accepted treatment regimen for patients with mutant BRAFK601N melanoma, and the study of melanoma driven by BRAF mutations at the 601 locus is lacking due to a paucity of cellular model systems. Therefore, we sought to better understand the treatment and clinical approach to patients with mutant BRAFK601N melanoma and subsequently develop a novel personalized oncology platform for rare or treatment-refractory cancers. METHODS: We developed and characterized the first patient-derived, naturally occurring BRAFK601N melanoma model, described herein as OHRI-MEL-13, and assessed efficacy using the Prestwick Chemical Library and select targeted therapeutics. RESULTS: OHRI-MEL-13 exhibits loss of heterozygosity of BRAF, closely mimics the original tumor's gene expression profile, is tumorigenic in immune-deficient murine models, and is available for public accession through American Type Culture Collection. We present in silico modeling data, which illustrates the therapeutic failure of BRAFV600E-targeted therapies in BRAFK601N mutants. Our platform elucidated a unique role for MEK inhibition with cobimetinib, which resulted in short-term clinical success by reducing the metastatic burden. CONCLUSION: Our model of BRAFK601N-activated melanoma was developed, thoroughly characterized, and made available for public accession. This model served to demonstrate the feasibility of a novel personalized oncology platform that could be optimized at an institutional level for rare variant or treatment-refractory cancers. We also demonstrate the clinical utility of monotherapy MEK inhibition in a case of BRAFK601N melanoma.

The effects of atrazine on the microbiome of the eastern oyster: Crassostrea virginica.

Long-standing evidence supports the importance of maintaining healthy populations of microbiota for the survival, homeostasis, and complete development of marine mollusks. However, the long-term ecological effects of agricultural runoff on these populations remains largely unknown. Atrazine (6-Chloro-n-ethyl-n'-(1-methylethyl)-triazine-2,4-diamine), a prevalent herbicide in the United States, is often used along tributaries of the Chesapeake Bay where oyster breeding programs are concentrated. To investigate any potential effects atrazine maybe having on mollusk-prokaryote interactions, we used 16S rRNA gene amplicons to evaluate how microbial compositions shift in response to exposure of environmentally relevant concentrations of atrazine previously found within the Chesapeake Bay. The dominant bacterial genera found within all groups included those belonging to Pseudoalteromonas, Burkholderia, Bacteroides, Lactobacillis, Acetobacter, Allobaculum, Ruminococcus, and Nocardia. Our results support previously published findings of a possible core microbial community in Crassostrea virginica. We also report a novel finding: oysters exposed to atrazine concentrations as low as 3 µg/L saw a significant loss of a key mutualistic microbial species and a subsequent colonization of a pathogenic bacteria Nocardia. We conclude that exposure to atrazine in the Chesapeake Bay may be contributing to a significant shift in the microbiomes of juvenile oysters that reduces fitness and impedes natural and artificial repopulation of the oyster species within the Bay.