Association of Matrix Metalloproteinase 7 Expression With Pathologic Response After Neoadjuvant Treatment in Patients With Resected Pancreatic Ductal Adenocarcinoma.

Importance: The use of neoadjuvant therapy (NAT) in resectable pancreatic ductal adenocarcinoma (PDAC) remains controversial. A favorable pathologic response (complete or marked tumor regression) to NAT is associated with better outcomes in patients with resected PDAC. The role of NAT for early systemic control compared with immediate surgical resection for PDAC is under investigation. In the era of precision medicine, biomarkers for patient selection and prediction of therapy response are crucial. Objective: To evaluate the use of assessment for protein expression on fine-needle aspiration (FNA) biopsy specimens in predicting pathologic response to NAT in treatment-naive patients. Design, Setting, and Participants: This was a single-institution prognostic study from a high-volume center for pancreatic cancer. All specimens were obtained between January 1, 2009, and December 31, 2018, with a median (SE) follow-up of 20.2 (1.4) months. Analysis of the data was performed from October 1, 2019, to April 30, 2021. Targeted RNA sequencing of frozen FNA biopsy specimens from a discovery cohort of 23 patients was performed to identify genes with aberrant expression that was associated with patients' pathologic response to NAT. Immunohistochemical staining was performed on an additional 80 FNA biopsy specimens to assess expression of matrix metalloproteinase 7 (MMP-7) and its association with pathologic response. Receiver operating characteristic curves for prediction of favorable pathologic response were determined. Results: In the discovery cohort (12 [52.1%] male; 3 [13.0%] Black and 20 [86.9%] White), RNA sequencing showed that lower MMP-7 expression was associated with favorable pathologic response (College of American Pathologists system scores of 0 [complete response] and 1 [marked response]). In the validation cohort (40 [50.0%] female; 9 [11.3%] Black and 71 [88.7%] White), patients with negative MMP-7 expression were significantly more likely to have a favorable pathologic response (odds ratio, 21.25; 95% CI, 6.19-72.95; P = .001). Receiver operating characteristic curves for prediction of favorable pathologic response from multivariable Cox proportional hazards regression modeling showed that MMP-7 expression increased the area under the curve from 0.726 to 0.906 (P < .001) even after stratifying by resectability status. The positive predictive value and negative predictive value of MMP-7 protein expression on FNA biopsy specimens in predicting unfavorable pathologic response (scores of 2 [partial response] or 3 [poor or no response]) were 88.2% and 73.9%, respectively. Conclusions and Relevance: Assessment of MMP-7 expression on FNA biopsy specimens at the time of diagnosis may help identify patients who would benefit the most from NAT.

Have Students Used Techniques to Stop the Bleed?

INTRODUCTION: The Stop the Bleed course was initiated in response to the Hartford Consensus and over 1 million people have been taught basic bleeding control techniques. Our study sought to determine the extent to which this training has been utilized. METHODS: Surveys were sent by email to students that had taken the Stop the Bleed course through our institution in 2017 or 2018. Data were collected utilizing the REDCap system and statistical calculations were performed. RESULTS: 2505 surveys were sent with 445 (18%) responses. The mean age of respondents was 48 years of age, 343 (77%) were female, and 230 (52%) were in the medical field. There were 17 respondents (3.8%) that stated they had utilized the techniques taught in the course; 16 out of 17 put pressure on a wound, 7 packed a wound, and 6 used a tourniquet. Patients had been injured by a variety of mechanisms including gunshot wound, stabbing, accidental laceration, and motor vehicle collision. Patients had good outcomes with 3 out of 17 surviving to emergency medical services arrival without known final outcome and the remaining 14 were known to do well. CONCLUSION: The Stop the Bleed course is important to enable bystanders to provide hemorrhage control. Our study shows that the techniques have been utilized with 17 treated patients having a good outcome and while a utilization rate of 3.8% may appear low, it is similar to the utilization rate of cardiopulmonary resuscitation instruction of 2%.

Superior Mesenteric Artery Stenosis Due to Disseminated Tuberculosis in a Pediatric Patient.

Disseminated tuberculosis (TB) associated with mesenteric arteritis has not been established in children. We present the case of an 8-year-old woman who presented with TB and superior mesenteric artery stenosis. Although rare, large vessel involvement from Takayasu arteritis can occur in TB. Evaluation for mesenteric vessel involvement should be considered in pediatric patients presenting with widely disseminated TB and abdominal pain.

Integrating Endovascular and Operative Intervention in Trauma.

BACKGROUND: Patterns of utilization of the hybrid operating room (hybrid-OR) in trauma have not been described. The aim of this study was to describe the sequencing and integration of endovascular and operative interventions in trauma using a hybrid-OR. MATERIALS AND METHODS: This is a single-center, retrospective cohort study of trauma patients who underwent both endovascular and operative intervention (2013-2019). Patients were separated into four groups based on procedure patterns: concomitant-linked (C-L), concomitant-independent, serial-linked (S-L) and serial-independent (S-I). The groups were defined as follows: C-L - related endovascular and operative interventions in the same OR; concomitant-independent - unrelated interventions in the same OR; S-L - related interventions in separate ORs; S-I - unrelated interventions in separate ORs. Patient characteristics, procedures performed and time to angiography in each group were analyzed. RESULTS: Out of 202 patients, most procedures utilizing the hybrid-OR were for hemorrhage control (84.1%) and were performed in a C-L manner (36.1%). Patients in the C-L group were most likely to undergo lower extremity revascularization and received the most transfusions. Patients in the S-L and S-I groups were more severely injured, had greater severe abdominal injury and were more likely to undergo damage control surgery and solid organ interventions, respectively. The C-L group had the highest percentage of patients to undergo angiography within 12 h (77%, P = 0.053). CONCLUSION: The hybrid-OR is an ideal space for hemorrhage control in trauma, but there is room for improvement in the triage of patients with non-compressible torso hemorrhage. Current practice patterns prioritize the hybrid-OR for management of lower extremity injury and are not optimal. Use of the hybrid-OR could be improved by concomitant management of patients with severe abdominal injury requiring damage control surgery.

Measuring Lateral Screw Protuberance Is a Clinically Accurate Method for Quantifying Femoral Neck Shortening.

OBJECTIVES: The purpose of this study is to compare the reliability and accuracy of the screw protuberance method (SPM) and overlay method (OM) for measuring femoral neck shortening on anterior-posterior (AP) radiographs. The secondary aim is to investigate the changes in reliability and accuracy with varying femoral rotation. METHODS: Radio-opaque femur sawbone models were fitted with either 3 cancellous screws or a sliding hip screw implant. Anterior-posterior radiographs were obtained using C-arm fluoroscopy with femoral neck shortening up to 15 mm and with the femoral shaft in 30 degrees of internal rotation to 30 degrees of external rotation (ER). Four observers measured femoral neck shortening at 2 time points. Intraobserver and interobserver reliability were calculated using the intraclass coefficient. Accuracy was analyzed through a Bland-Altman agreement statistic stratified by femoral rotation. RESULTS: Both measurement techniques displayed excellent reliability, regardless of femoral rotation or implant. There was a significant difference in femoral neck shortening measurements with rotation for both the OM (P < 0.001) and SPM (P < 0.001). Both methods are accurate within 1 mm of the actual magnitude of shortening from 30-degree internal rotation to 15-degree ER. At 30-degree ER, shortening was underestimated by -2.10 mm using the OM (95% confidence interval, -2.43 to -1.76; P < 0.01) and by -1.64 mm using the SPM (95% confidence interval, -1.83 to -1.45; P < 0.01). CONCLUSION: This study demonstrates that both the OM and SPM are accurate and reliable assessments for femoral neck shortening; however, both methods are sensitive to extreme ER. Given the simplicity of the SPM technique, it may have increased utility for pragmatic research studies.

Radial versus femoral arterial access for trauma endovascular interventions: A noninferiority study.

BACKGROUND: The majority of endovascular interventions for trauma are performed using transfemoral access (TFA). Transradial access (TRA) is a recently integrated alternative at the authors' institution. This noninferiority study compares the technical success and complication rate of TRA compared with TFA. METHODS: All patients undergoing emergent endovascular interventions between March 2016 and March 2019 were identified from a prospectively maintained database. Data were collected on access type, complications, and procedural success. A noninferiority margin was established from previous randomized trials for technical success (0.475) and complications (0.015). RESULTS: Over 3 years, 96 patients underwent TRA and 335 patients received TFA. The overall technical success rate was 98.1%, without significance based on access strategy (p = 0.078). All femoral arteries and 97.9% (n = 94) of radial arteries were accessed as intended. Complications occurred in 1.0% of TRA and 9.9% of TFA groups (p = 0.002). In the TFA group, complications included access site bleeding, hematoma, pseudoaneurysm, lower limb ischemia, and femoral artery thrombosis (n = 6, 14, 3, 3, and 4, respectively). In the TRA group, complications included radial artery thrombosis (n = 1). Transradial access procedural success and complication rate fell within the lower bound confidence interval of the noninferiority margin, demonstrated the noninferiority of TRA in this data set. CONCLUSION: Transradial access in a cohort of trauma patients undergoing endovascular intervention does not appear to be inferior to TFA in relation to technical success and complications. For patients where groin access may be challenging, TRA is a useful, efficacious, and safe alternative. Longer-term study is required to fully characterize the advantages and disadvantages of TRA compared with TFA. LEVEL OF EVIDENCE: Therapeutic V.

Tourniquets USA: A Review of the Current Literature for Commercially Available Alternative Tourniquets for Use in the Prehospital Civilian Environment.

The American College of Surgeons' "Stop the Bleed" (STB) campaign emphasizes how to apply the Combat Application Tourniquet (CAT), a device adopted by the military to control extremity hemorrhage. However, multiple commercially available alternatives to the CAT exist, and it would be helpful for instructors to be knowledgeable about how these other models compare. A PubMed search from January 2012 to January 2020 cross-referenced with a Google search for "tourniquet" was performed for commercially available tourniquets that had been trialed against the CAT. Windlass-type models included the Special Operations Forces Tactical Tourniquet (SOFT-T), the SOFT-T Wide (SOFFT-W), the SAM-XT tourniquet, the Military Emergency Tourniquet (MET), and the Tactical Medical Tourniquet (TMT). Elastic-type tourniquets included were the Stretch, Wrap, And Tuck Tourniquet (SWAT-T), the Israeli Silicone Tourniquet (IST), and the Rapid Activation Tourniquet System (RATS). Ratchet-type tourniquets included were the Ratcheting Medical Tourniquet (RMT) and TX2/TX3 tourniquets, and pneumatic-type tourniquets were the Emergency and Military Tourniquet (EMT) and Tactical Pneumatic Tourniquet (TPT). This review aims to describe the literature surrounding these models so that instructors can help laypeople make more informed purchases, stop the bleed, and save a life.

Cone-beam computed tomography for trauma.

Radiographic imaging is critical in helping guide treatment of critically injured patients. Cone-beam computed tomography is an axial imaging technique available from fixed imaging systems found in hybrid operating rooms. It can be used to provide focused studies of specific anatomical regions, where patients cannot undergo conventional multidetector computed tomography. This includes non-contrast-enhanced evaluation of the intracranial contents and vascular imaging throughout the body. There are a number of advantages and disadvantages to cone-beam computed tomography, but these are not widely discussed within the trauma literature. This narrative review article presents the initial practical experience of this novel imaging modality. LEVEL OF EVIDENCE: Review article, level III.

A Comparison of Transradial and Transfemoral Access for Splenic Angio-Embolisation in Trauma: A Single Centre Experience.

OBJECTIVE: The study compared transradial access (TRA) and transfemoral access (TFA) for splenic angio-embolisation (SAE), with a focus on technical success, intra-operative adjuncts, and complications. METHODS: This was a retrospective comparative study of all trauma patients undergoing SAE by TRA or TFA between February 2015 and February 2019 at a single institution. The medical records were queried for procedural and post-operative data, with comparisons made based on access site. Continuous variables were compared using a two tailed t test and categorical variables were compared using a chi square test. RESULTS: Over a four year period, there were 47 cases of SAE via TRA and 127 via TFA. Technical success was 95.7% during TRA and 98.4% during TFA (p = .30). Technical failures were a result of failed splenic artery cannulation after successful radial or femoral access. Time to splenic cannulation was shorter in the TRA group (19 min vs. 30 min; p = .008). Two or fewer catheters were used during TRA, whereas more than two catheters were needed during TFA (p < .001). There were no statistically significant differences in procedure length, fluoroscopy time, radiation dose, or contrast volume between groups. Nine patients (5.2%) developed access related complications, all in the TFA group (p = .12). Mortality rate was 2.3% (n = 4), with no statistical significance between groups (p = .71). CONCLUSION: While TFA is the conventional strategy for SAE, TRA is a safe and efficacious modality for SAE in trauma patients. Although larger studies are needed to establish the full efficacy of TRA for SAE at the multi-institutional level, this single centre study demonstrates the legitimacy of an alternative means for SAE in the trauma population.

Oxidized low-density and high-density lipoproteins regulate the production of matrix metalloproteinase-1 and -9 by activated monocytes.

Monocytes/macrophages are prominent in atherosclerotic plaques where the vascular remodeling and plaque rupture may be influenced by the lipids and cytokines at these sites. Therefore, we evaluated the effects of factors found within the vascular wall, such as cytokines, oxidized low-density lipoprotein (ox-LDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), on monocyte-derived matrix metalloproteinase-1 (MMP-1) and -9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1). ox-LDL, LDL, and HDL alone had no effect on MMP-1, MMP-9, or TIMP-1 production. However, in the presence of tumor necrosis factor (TNF)-alpha and GM-CSF, ox-LDL enhanced MMP-1 significantly by two- to threefold, increased MMP-9 slightly, and had no effect on TIMP-1 production. In contrast, HDL suppressed the induction of MMP-1 by TNF-alpha and GM-CSF as well as the ox-LDL-mediated increase in MMP-1 production. The enhancement of MMP-1 production by ox-LDL occurred through, in part, a prostaglandin E2 (PGE2)-dependent pathway as indomethacin suppressed and PGE2 restored MMP-1 production. This conclusion was supported further by ox-LDL-mediated increases in PGE2 and cyclooxygenase-2 (COX-2) production. These data suggest that the interaction of primary monocytes with ox-LDL and proinflammatory cytokines may contribute to vascular remodeling and plaque rupture.