Human soft tissue sarcomas harbor an intratumoral viral microbiome which is linked with natural killer cell infiltrate and prognosis.

BACKGROUND: Groundbreaking studies have linked the gut microbiome with immune homeostasis and antitumor immune responses. Mounting evidence has also demonstrated an intratumoral microbiome, including in soft tissue sarcomas (STS), although detailed characterization of the STS intratumoral microbiome is limited. We sought to characterize the intratumoral microbiome in patients with STS undergoing preoperative radiotherapy and surgery, hypothesizing the presence of a distinct intratumoral microbiome with potentially clinically significant microbial signatures. METHODS: We prospectively obtained tumor and stool samples from adult patients with non-metastatic STS using a strict sterile collection protocol to minimize contamination. Metagenomic classification was used to estimate abundance using genus and species taxonomic levels across all classified organisms, and data were analyzed with respect to clinicopathologic factors. RESULTS: Fifteen patients were enrolled. Most tumors were located at an extremity (67%) and were histologic grade 3 (87%). 40% were well-differentiated/dedifferentiated liposarcoma histology. With a median follow-up of 24 months, 4 (27%) patients developed metastases, and 3 (20%) died. Despite overwhelming human DNA (>99%) intratumorally, we detected a small but consistent proportion of bacterial DNA (0.02-0.03%) in all tumors, including Proteobacteria, Bacteroidetes, and Firmicutes, as well as viral species. In the tumor microenvironment, we observed a strong positive correlation between viral relative abundance and natural killer (NK) infiltration, and higher NK infiltration was associated with superior metastasis-free and overall survival by immunohistochemical, flow cytometry, and multiplex immunofluorescence analyses. CONCLUSIONS: We prospectively demonstrate the presence of a distinct and measurable intratumoral microbiome in patients with STS at multiple time points. Our data suggest that the STS tumor microbiome has prognostic significance with viral relative abundance associated with NK infiltration and oncologic outcome. Additional studies are warranted to further assess the clinical impact of these findings.

Objective Methodology to Assess Meaningful Research Productivity by Orthopaedic Residency Departments: Validation Against Widely Distributed Ranking Metrics and Published Surrogates.

The mission of any academic orthopaedic training program can be divided into 3 general areas of focus: clinical care, academic performance, and research. Clinical care is evaluated on clinical volume, patient outcomes, patient satisfaction, and becoming increasingly focused on data-driven quality metrics. Academic performance of a department can be used to motivate individual surgeons, but objective measures are used to define a residency program. Annual in-service examinations serve as a marker of resident knowledge base, and board pass rates are clearly scrutinized. Research productivity, however, has proven harder to objectively quantify. In an effort to improve transparency and better account for conflicts of interest, bias, and self-citation, multiple bibliometric measures have been developed. Rather than using individuals' research productivity as a surrogate for departmental research, we sought to establish an objective methodology to better assess a residency program's ability to conduct meaningful research. In this study, we describe a process to assess the number and quality of publications produced by an orthopaedic residency department. This would allow chairmen and program directors to benchmark their current production and make measurable goals for future research investment. The main goal of the benchmarking system is to create an "h-index" for residency programs. To do this, we needed to create a list of relevant articles in the orthopaedic literature. We used the Journal Citation Reports. This publication lists all orthopaedic journals that are given an impact factor rating every year. When we accessed the Journal Citation Reports database, there were 72 journals included in the orthopaedic literature section. To ensure only relevant, impactful journals were included, we selected journals with an impact factor greater than 0.95 and an Eigenfactor Score greater than 0.00095. After excluding journals not meeting these criteria, we were left with 45 journals. We performed a Scopus search over a 10-year period of these journals and created a database of articles and their affiliated institutions. We performed several iterations of this to maximize the capture of articles attributed to institutions with multiple names. Based off of this extensive database, we were able to analyze all allopathic US residency programs based on their quality research productivity. We believe this as a novel methodology to create a system by which residency program chairmen and directors can assess progress over time and accurate comparison with other programs.

Impaired blood pressure recovery to hemorrhage in obese Zucker rats with orthopedic trauma.

We have shown that obese Zucker rats with orthopedic trauma (OZT) exhibit a loss of arteriolar tone in skeletal muscle. We hypothesize that the loss of arteriolar tone in OZT blunts vasoconstrictor responses to hemorrhage, resulting in an impaired blood pressure recovery. Orthopedic trauma was induced with soft tissue injury and local injection of bone components in both hindlimbs in lean (LZT) and OZT (11-13 wk). One day after the orthopedic trauma, blood pressure responses following hemorrhage were measured in conscious control lean, control obese, LZT, and OZT. In another set of experiments, the spinotrapezius muscle of control and trauma animals was prepared for microcirculatory observation. Arteriolar responses to phenylephrine (PE) or hemorrhage were determined. Hemorrhage resulted in similar blood pressure responses in control animals and LZT, but the blood pressure recovery following hemorrhage was blunted in the OZT. In the spinotrapezius, OZT exhibited decreased arteriolar tone and blunted vasoconstrictor responses to PE and hemorrhage. Treatment with glibenclamide improved the blood pressure recovery in the conscious OZT and improved the arteriolar tone, and PE induced vasoconstriction in the spinotrapezius of the OZT. Thus, ATP-dependent K(+) channel-mediated loss of arteriolar tone in OZT blunts the arteriolar constriction to hemorrhage, resulting in impaired blood pressure recovery.