Comparative Experience of Short-wavelength Versus Long-wavelength Fluorophores for Intraoperative Molecular Imaging of Lung Cancer.

BACKGROUND: Intraoperative molecular imaging (IMI) using tumor-targeted optical contrast agents can improve cancer resections. The optimal wavelength of the IMI tracer fluorophore has never been studied in humans and has major implications for the field. To address this question, we investigated 2 spectroscopically distinct fluorophores conjugated to the same targeting ligand. METHODS: Between December 2011 and November 2021, patients with primary lung cancer were preoperatively infused with 1 of 2 folate receptor-targeted contrast tracers: a short-wavelength folate-fluorescein (EC17; λ em =520 nm) or a long-wavelength folate-S0456 (pafolacianine; λ em =793 nm). During resection, IMI was utilized to identify pulmonary nodules and confirm margins. Demographic data, lesion diagnoses, and fluorescence data were collected prospectively. RESULTS: Two hundred eighty-two patients underwent resection of primary lung cancers with either folate-fluorescein (n=71, 25.2%) or pafolacianine (n=211, 74.8%). Most tumors (n=208, 73.8%) were invasive adenocarcinomas. We identified 2 clinical applications of IMI: localization of nonpalpable lesions (n=39 lesions, 13.8%) and detection of positive margins (n=11, 3.9%). In each application, the long-wavelength tracer was superior to the short-wavelength tracer regarding depth of penetration, signal-to-background ratio, and frequency of event. Pafolacianine was more effective for detecting subpleural lesions (mean signal-to-background ratio=2.71 vs 1.73 for folate-fluorescein, P <0.0001). Limit of signal detection was 1.8 cm from the pleural surface for pafolacianine and 0.3 cm for folate-fluorescein. CONCLUSIONS: Long-wavelength near-infrared fluorophores are superior to short-wavelength IMI fluorophores in human tissues. Therefore, future efforts in all human cancers should likely focus on long-wavelength agents.

Outcomes in Post-operative Delirium Following Bowel Resection: A Single Center Retrospective Review.

INTRODUCTION: Delirium is associated with adverse post-operative outcomes, long-term cognitive dysfunction, and prolonged hospitalization. Risk factors for its development include longer surgical duration, increased operative complexity and invasiveness, and medical comorbidities. This study aims to further evaluate the incidence of delirium and its impact on outcomes among patients undergoing both elective and emergency bowel resections. METHODS: This is a retrospective cohort study using an institutional patient registry. All patients undergoing bowel resection over a 3.5-year period were included. The study measured the incidence of post-operative delirium via the nursing confusion assessment method. This incidence was then compared to patient age, emergency versus elective admission, length of stay, mortality, discharge disposition, and hospital cost. RESULTS: A total of 1934 patients were included with an overall delirium incidence of 8.8%. Compared to patients without delirium, patients with delirium were more likely to have undergone emergency surgery, be greater than 70 y of age, have a longer length of stay, be discharged to a skilled nursing facility, and have a more expensive hospitalization. In addition, the overall mortality was 14% in patients experiencing delirium versus 0.1% in those that did not. Importantly, when broken down between elective and emergency groups, the mortality of those experiencing delirium was similar (11 versus 13%). CONCLUSIONS: The development of delirium following bowel resection is an important risk factor for worsened outcomes and mortality. Although the incidence of delirium is higher in the emergency surgery population, the development of delirium in the elective population infers a similar risk of mortality.

Using State Data to Predict a Single Institution Mortality for Patients That Fall.

BACKGROUND: Falls are the most common cause of injury-related death for patients older than 45.  We hypothesized that a machine learning algorithm developed from state-level registry data could make accurate outcome predictions at a level 1 trauma hospital. METHODS: Data for all patients admitted for fall injury during 2009 - 2019 in the state of Pennsylvania were derived from the state trauma registry.  Thirteen variables that were immediately available upon patient arrival were used for prediction modeling.  Data for the test institution were withheld from model creation.  Algorithms assessed included logistic regression (LR), random forest (RF), and extreme gradient boost (XGB).  Model discrimination for mortality was assessed with area under the curve (AUC) for each algorithm at our level 1 trauma center. RESULTS: 180,284 patients met inclusion criteria.  The mean age was 69 years ± 18.5 years with a mortality rate of 4.0%.  The AUC for predicting mortality in patients that fall for LR, RF, and XGB were 0.797, 0.876, and 0.880, respectively.  The variables which contributed to the prediction in descending order of importance for XGB were respiratory rate, pulse, systolic blood pressure, ethnicity, weight, sex, age, temperature, Glasgow Coma Scale (GCS) eye, race, GCS voice, GCS motor, and blood alcohol level. CONCLUSIONS: An extreme gradient boost model developed using state-wide trauma data can accurately predict mortality after fall at a single center within the state.  This machine learning model can be implemented by local trauma systems within the state of Pennsylvania to identify patients injured by fall that require greater attention, transfer to a higher level of care, and higher resource allocation.

A clinical trial of intraoperative near-infrared imaging to assess tumor extent and identify residual disease during anterior mediastinal tumor resection.

BACKGROUND: The management of most solid tumors of the anterior mediastinum involves complete resection. Because of their location near mediastinal structures, wide resection is not possible; therefore, surgeons must use subjective visual and tactile cues to determine disease extent. This clinical trial explored intraoperative near-infrared (NIR) imaging as an approach to improving tumor delineation during mediastinal tumor resection. METHODS: Twenty-five subjects with anterior mediastinal lesions suspicious for malignancy were enrolled in an open-label feasibility trial. Subjects were administered indocyanine green (ICG) at a dose of 5 mg/kg, 24 hours before resection (via a technique called TumorGlow). The NIR imaging systems included Artemis (Quest, Middenmeer, the Netherlands) and Iridium (VisionSense Corp, Philadelphia, Pennsylvania). Intratumoral ICG uptake was evaluated. The clinical value was determined via an assessment of the ability of NIR imaging to detect phrenic nerve involvement or incomplete resection. Clinical and histopathologic variables were analyzed to determine predictors of tumor fluorescence. RESULTS: No drug-related toxicity was observed. Optical imaging added a mean of 10 minutes to case duration. Among the subjects with solid tumors, 19 of 20 accumulated ICG. Fluorescent tumors included thymomas (n = 13), thymic carcinomas (n = 4), and liposarcomas (n = 2). NIR feedback improved phrenic nerve dissection (n = 4) and identified residual disease (n = 2). There were no false-positives or false-negatives. ICG preferentially accumulated in solid tumors; this was independent of clinical and pathologic variables. CONCLUSIONS: NIR imaging for anterior mediastinal neoplasms is safe and feasible. This technology may provide a real-time tool capable of determining tumor extent and specifically identify phrenic nerve involvement and residual disease.

Intraoperative near-infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large-animal model.

BACKGROUND: Complete tumor resection is the most important predictor of patient survival with non-small cell lung cancer. Methods for intraoperative margin assessment after lung cancer excision are lacking. This study evaluated near-infrared (NIR) intraoperative imaging with a folate-targeted molecular contrast agent (OTL0038) for the localization of primary lung adenocarcinomas, lymph node sampling, and margin assessment. METHODS: Ten dogs with lung cancer underwent either video-assisted thoracoscopic surgery or open thoracotomy and tumor excision after an intravenous injection of OTL0038. Lungs were imaged with an NIR imaging device both in vivo and ex vivo. The wound bed was re-imaged for retained fluorescence suspicious for positive tumor margins. The tumor signal-to-background ratio (SBR) was measured in all cases. Next, 3 human patients were enrolled in a proof-of-principle study. Tumor fluorescence was measured both in situ and ex vivo. RESULTS: All canine tumors fluoresced in situ (mean Fluoptics SBR, 5.2 [range, 2.7-8.1]; mean Karl Storz SBR 1.9 [range, 1.4-2.6]). In addition, the fluorescence was consistent with tumor margins on pathology. Three positive lymph nodes were discovered with NIR imaging. Also, a positive retained tumor margin was discovered upon NIR imaging of the wound bed. Human pulmonary adenocarcinomas were also fluorescent both in situ and ex vivo (mean SBR, > 2.0). CONCLUSIONS: NIR imaging can identify lung cancer in a large-animal model. In addition, NIR imaging can discriminate lymph nodes harboring cancer cells and also bring attention to a positive tumor margin. In humans, pulmonary adenocarcinomas fluoresce after the injection of the targeted contrast agent. Cancer 2017;123:1051-60. © 2016 American Cancer Society.

Intraoperative Molecular Imaging Combined With Positron Emission Tomography Improves Surgical Management of Peripheral Malignant Pulmonary Nodules.

OBJECTIVE: To determine if intraoperative molecular imaging (IMI) can improve detection of malignant pulmonary nodules. BACKGROUND: 18-Fluorodeoxyglucose positron emission tomography (PET) is commonly utilized in preoperative assessment of patients with solid malignancies; however, false negatives and false positives remain major limitations. Using patients with pulmonary nodules as a study model, we hypothesized that IMI with a folate receptor targeted near-infrared contrast agent (OTL38) can improve malignant pulmonary nodule identification when combined with PET. METHODS: Fifty patients with pulmonary nodules with imaging features suspicious for malignancy underwent preoperative PET. Patients then received OTL38 before pulmonary resection. During resection, IMI was utilized to evaluate known pulmonary nodules and identify synchronous lesions. Tumor size, PET standardized uptake value, and IMI tumor-to-background ratios were compared for known and synchronous nodules via paired and unpaired t tests, when appropriate. Test characteristics of PET and IMI with OTL38 were compared. RESULTS: IMI identified 56 of 59 (94.9%) malignant pulmonary nodules identified by preoperative imaging. IMI located an additional 9 malignant lesions not identified preoperatively. Nodules only detected by IMI were smaller than nodules detected preoperatively (0.5 vs 2.4 cm; P < 0.01), but displayed similar fluorescence (tumor-to-background ratio 3.3 and 3.1; P = 0.50). Sensitivity of IMI and PET were 95.6% and 73.5% (P = 0.001), respectively; and positive predictive values were 94.2% and 89.3%, respectively (P > 0.05). Additionally, utilization of IMI clinically upstaged 6 (12%) subjects and improved management of 15 (30%) subjects. CONCLUSIONS: These data suggest that combining IMI with PET may provide superior oncologic outcomes for patients with resectable lung cancer.

Intraoperative Molecular Diagnostic Imaging Can Identify Renal Cell Carcinoma.

PURPOSE: Margin status can often be difficult to assess intraoperatively, particularly during partial nephrectomy given the time constraints related to renal hilar clamping. We hypothesized that a targeted molecular imaging approach could be used during surgery to identify tumor margins and confirm disease clearance. MATERIALS AND METHODS: EC17, a novel tracer targeting FRα, was used in murine models of renal cell carcinoma to identify positive margins after surgery. Positive margins were detected due to elevated tumor-to-background ratios of the tumor compared to surrounding normal tissues. We performed a pilot study in 4 patients using EC17 preoperatively with intraoperative imaging during the operation. RESULTS: FRα was highly expressed in 65% of clear cell renal cell carcinomas harvested from the operating room. In the murine model intraoperative imaging of renal cell carcinoma revealed a mean ± SD tumor-to-background ratio of 8.2 ± 1.1 in the RCC10, 11.2 ± 1.1 in the 786-0 and 4.3 ± 1.1 in the UMRC2 cell line. Compared to visual inspection intraoperative imaging of the surgical resection bed identified residual disease in 24% more animals. In the human pilot study targeted molecular imaging identified 2 of 4 renal cell carcinomas and had no false-positive results. In these 2 cases the tumor-to-background ratio was 3.7 and 4.6, respectively. In each case we confirmed disease clearance and tumor fluorescence did not correlate with nodule size or tumor grade. CONCLUSIONS: To our knowledge this is the first demonstration in humans of identifying renal cell carcinoma during surgery using a targeted molecular contrast agent. This approach may lead to a superior method of identifying malignancy and tumor borders in the intraoperative setting.

Clinical implications of positive margins following non-small cell lung cancer surgery.

Positive margins following pulmonary resection of non-small cell lung cancer (NSCLC) occur in approximately 5-15% of patients undergoing a curative procedure. The presence of positive margins negatively impacts long-term outcomes by setting the stage for local and potentially distant disease recurrence. Despite major clinical ramifications, there are very few dedicated reports that examine the implications of positive margins following surgery for NSCLC. Furthermore, published series are typically retrospective studies from single institutions. In this review we analyze published data with special consideration of four pertinent questions: (i) what are the long term outcomes of a positive margin following pulmonary resection?, (ii) is intraoperative margin assessment by frozen section reliable?, (iii) what is the optimal distance of the tumor margin to the surgical margin?, and (iv) should adjuvant chemotherapy and/or radiation therapy be used in the setting of a positive surgical margin?

Identification of breast cancer margins using intraoperative near-infrared imaging.

BACKGROUND AND OBJECTIVES: Current methods of intraoperative breast cancer margin assessment are labor intensive, not fully reliable, and time consuming; therefore novel strategies are necessary. We hypothesized that near infrared (NIR) intraoperative molecular imaging using systemic indocyanine green (ICG) would be helpful in discerning tumor margins. METHODS: A mammary cancer cell line, 4T1, was used to establish tumors in mouse flanks (n = 60). Tumors were excised 24 hr after intravenous ICG. Assessment of residual tumor in the wound bed was performed using a combination of NIR imaging and traditional method (by visual inspection and palpation) versus traditional method alone. Next we performed a clinical trial to evaluate the role of NIR imaging after systemic ICG for the margin assessment of 12 patients undergoing breast-conserving surgery. RESULTS: Traditional margin assessment identified 30% of positive margins while NIR imaging identified 90% of positive margins. In our clinical trial, all tumors were detected by NIR imaging and there was fluorescent evidence of residual tumor in the tumor bed in 6 of the 12 patients. None of these patients had positive margins on pathology. CONCLUSIONS: Systemic ICG reliably accumulates in breast cancers in murine models as well as human breast cancer. While NIR imaging is helpful for detection of retained tumor margins in our animal model, intraoperative imaging for precise margin detection will need further refinement before clinical value can be obtained. J. Surg. Oncol. 2016;113:508-514. © 2016 Wiley Periodicals, Inc.

Near-infrared operating lamp for intraoperative molecular imaging of a mediastinal tumor.

BACKGROUND: Near-Infrared (NIR) intraoperative molecular imaging is a new diagnostic modality utilized during cancer surgery for the identification of tumors, metastases and lymph nodes. Surgeons typically use headlamps during an operation to increase visible light; however, these light sources are not adapted to function simultaneously with NIR molecular imaging technology. Here, we design a NIR cancelling headlamp and utilize it during surgery to assess whether intraoperative molecular imaging of mediastinal tumors is possible. METHODS: A NIR cancelling headlamp was designed and tested using NIR spectroscopy preoperatively. Next, a 46 year-old-female was referred to the thoracic surgery clinic for a 5.8 cm mediastinal mass noted on chest x-ray. Prior to surgery, she was given intravenous indocyanine green (ICG). Then, the prototype headlamp was used in conjunction with our intraoperative molecular imaging device. The tumor was imaged both in vivo and following resection prior to pathological examination. RESULTS: NIR spectroscopy confirmed NIR light excitation of the unfiltered headlamp and the absence of NIR emitted light after addition of the filter. Next, in vivo imaging confirmed fluorescence of the tumor, but also demonstrated a significant amount of NIR background fluorescence emanating from the unfiltered headlamp. During imaging with the filtered headlamp, we again demonstrated a markedly fluorescent tumor but with a reduced false positive NIR signal. Final pathology was well-differentiated thymoma with negative surgical margins. CONCLUSIONS: NIR intraoperative molecular imaging using a systemic injection of intravenous ICG was successful in localizing a thymoma. Additionally, a simple design and implementation of a NIR cancelling headlamp reduces false positive NIR fluorescence.

The Optical Biopsy: A Novel Technique for Rapid Intraoperative Diagnosis of Primary Pulmonary Adenocarcinomas.

BACKGROUND: With increasing use of chest computed tomography scans, indeterminate pulmonary nodules are frequently detected as an incidental finding and present a diagnostic challenge. Tissue biopsy followed by histological review and immunohistochemistry is the gold standard to obtain a diagnosis and the most common malignant finding is a primary lung adenocarcinoma. Our objective was to determine whether an intraoperative optical biopsy (molecular imaging) may provide an alternative approach for determining if a pulmonary nodule is a primary lung adenocarcinoma. METHODS: Before surgery, 30 patients with an indeterminate pulmonary nodule were intravenously administered a folate receptor-targeted fluorescent contrast agent specific for primary lung adenocarcinomas. During surgery, the nodule was removed and the presence of fluorescence (optical biopsy) was assessed in the operating room to determine if the nodule was a primary pulmonary adenocarcinoma. Standard-of-care frozen section and immunohistochemical staining on permanent sections were then performed as the gold standard to validate the results of the optical biopsy. RESULTS: Optical biopsies identified 19 of 19 (100%) primary pulmonary adenocarcinomas. There were no false positive or false negative diagnoses. An optical biopsy required 2.4 minutes compared to 26.5 minutes for frozen section (P < 0.001) and it proved more accurate than frozen section in diagnosing lung adenocarcinomas. CONCLUSIONS: An optical biopsy has excellent positive predictive value for intraoperative diagnosis of primary lung adenocarcinomas. With refinement, this technology may prove to be an important supplement to standard pathology for examining close surgical margins, identifying lymph node involvement, and determining whether suspicious nodules are malignant.

Effect of Blood Product Resuscitation on Cefazolin Pharmacokinetics in Trauma Patients.

Background: Antibiotics are frequently administered prophylactically to trauma patients with various injury patterns to prevent infectious complications. Trauma patients may also require large volume resuscitation with blood products. Limited data are available to support antibiotic dosing recommendations in this population. We hypothesized that we would be able to develop a population pharmacokinetic model of cefazolin, a frequently used antibiotic in the trauma scenario, from remnant blood samples by pharmacokinetic analysis of trauma patients. Methods: Remnant plasma from standard of care chemistry/hematology assessments was retrieved within 48 h of collection and assayed to determine cefazolin concentrations. Population pharmacokinetic analyses were conducted in Pmetrics using R. Linear regression was conducted to assess the effect of blood product resuscitation volume on cefazolin pharmacokinetic parameters. Results: Cefazolin concentrations best fitted a two-compartment model (Akaike information criterion: 443.9). The mean ± standard deviation parameters were total body clearance (4.3 ± 1.9L), volume of the central compartment (Vc: 7.7 ± 6.9L), and intercompartment transfer constants (k12: 1.3 ± 0.98 h-1, k21: 0.6 ± 0.45 h-1). No statistical relationships were observed between blood products, volume of blood products, and cefazolin clearance or Vc (R2: 0.0004-0.21, p = 0.08-0.95). Using a 5,000-patient Monte Carlo simulation, 2 g with repeated dosing every 2 h until end of surgery was required to achieve 93.2% probability of 100% free time above the minimum inhibitory concentration (MIC) (fT > MIC) at the ECOFF value for Staphylococcus aureus (2 mg/L). Conclusions: In these 15 trauma patients receiving blood transfusion, no relationship with blood volume resuscitation and cefazolin pharmacokinetics was observed. On the basis of this pharmacokinetic model, frequent cefazolin doses are required to maintain 100% fT > MIC.

Stop the Bleed® in medical schools: Early advocacy and promising results.

OBJECTIVE: We hypothesized that medical students would be empowered by hemorrhage-control training and would support efforts to include Stop the Bleed® (STB) in medical education. DESIGN: This is a multi-institution survey study. Surveys were administered immediately following and 6 months after the course. SETTING: This study took place at the Association of American Medical Colleges-accredited medical schools in the United States. PARTICIPANTS: Participants were first-year medical students at participating institutions. A total of 442 students completed post-course surveys, and 213 students (48.2 percent) also completed 6-month follow-up surveys. INTERVENTION: An 1-hour, in-person STB course. MAIN OUTCOMES MEASURES: Student empowerment was measured by Likert-scale scoring, 1 (Strongly Disagree) to 5 (Strongly Agree). The usage of hemorrhage-control skills was also measured. RESULTS: A total of 419 students (95.9 percent) affirmed that the course taught the basics of bleeding control, and 169 (79.3 percent) responded positively at follow-up, with a significant decrease in Likert response (4.65, 3.87, p < 0.001). Four hundred and twenty-three students (97.0 percent) affirmed that they would apply bleeding control skills to a patient, and 192 (90.1 percent) responded positively at follow-up (4.61, 4.19, p < 0.001). Three hundred and sixty-one students (82.8 percent) believed that they were able to save a life, and 109 (51.2 percent) responded positively at follow-up (4.14, 3.56, p < 0.001). Four hundred and twenty-five students (97.0 percent) would recommend the course to another medical student, and 196 (92.0 percent) responded positively at follow-up (4.68, 4.31, p < 0.001). Six students (2.8 percent) used skills on live patients, with success in five of the six instances. CONCLUSIONS: Medical students were empowered by STB and have used hemorrhage-control skills on live victims. Medical students support efforts to include STB in medical education.

Tranexamic Acid and Pulmonary Complications: A Secondary Analysis of an EAST Multicenter Trial.

BACKGROUND: Anti-inflammatory effects of tranexamic acid (TXA) in reducing trauma endotheliopathy may protect from acute lung injury. Clinical data showing this benefit in trauma patients is lacking. We hypothesized that TXA administration mitigates pulmonary complications in penetrating trauma patients. MATERIALS AND METHODS: This is a post-hoc analysis of a multicenter, prospective, observational study of adults (18+ years) with penetrating torso and/or proximal extremity injury presenting at 25 urban trauma centers. Tranexamic acid administration in the prehospital setting or within three hours of admission was examined. Participants were propensity matched to compare similarly injured patients. The primary outcome was development of pulmonary complication (ARDS and/or pneumonia). RESULTS: A total of 2382 patients were included, and 206 (8.6%) received TXA. Of the 206, 93 (45%) received TXA prehospital and 113 (55%) received it within three hours of hospital admission. Age, sex, and incidence of massive transfusion did not differ. The TXA group was more severely injured, more frequently presented in shock (SBP < 90 mmHg), developed more pulmonary complications, and had lower survival (P < 0.01 for all). After propensity matching, 410 patients remained (205 in each cohort) with no difference in age, sex, or rate of shock. On logistic regression, increased emergency department heart rate was associated with pulmonary complications. Tranexamic acid was not associated with different rate of pulmonary complications or survival on logistic regression. Survival was not different between the groups on logistic regression or propensity score-matched analysis. CONCLUSIONS: Tranexamic acid administration is not protective against pulmonary complications in penetrating trauma patients.

The Implementation of a Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) Program at a Level 1 New England Trauma Center: Feasibility and Early Outcomes.

OBJECTIVES: We evaluated the feasibility of implementing a Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) program at our urban level 1 trauma center and evaluated early outcomes. DESIGN: A multidisciplinary committee including physicians (trauma surgery, emergency medicine, vascular surgery, and interventional radiology) and nurses created clinical practice guidelines for the placement of REBOA at our institution. All trauma surgeons and critical care board certified emergency medicine physicians were trained in placement and nurses received management training. A formal review process was implemented to identify areas for improvement. Finally, we instituted refresher training to maintain REBOA competency. Trauma patients with noncompressible torso hemorrhage from blunt or penetrating injuries who were partial or nonresponders to blood product resuscitation were included. Pregnant patients, children, or patients with significant hemothorax or suspected aortic or cardiac injury were excluded. RESULTS: Over seven months, eight catheters were successfully placed, all on the first attempt, including six in Zone 3 and two in Zone 1. All Zone 3 catheters were placed for pelvic fracture-related bleeding which were subsequently embolized. The Zone 1 catheters were placed immediately preoperatively for intraabdominal bleeding. Upon committee review, one critique was made regarding zone selection. One patient developed an arteriovenous fistula after placement which resolved without intervention. There were no other complications and all patients survived to discharge. CONCLUSIONS: An REBOA program is feasible and safe following a comprehensive multidisciplinary effort. The efforts described here can be utilized by similar trauma programs for adaptation of this endovascular approach to bleeding control.

Dispelling Dogma: American Association for Surgery of Trauma Prospective, Multicenter Trial of Index vs Delayed Fasciotomy after Extremity Trauma.

BACKGROUND: Surgical dogma states that "if you think about doing a fasciotomy, you do it," yet the benefit of this approach remains unclear. We hypothesized that early fasciotomy during index operative procedures for extremity vascular trauma would be associated with improved patient outcomes. STUDY DESIGN: This prospective, observational multicenter (17 level 1, 1 level 2) analysis included patients ≥15 years old with extremity vascular injury requiring operative management. Clinical variables were analyzed with respect to fasciotomy timing for correlation with outcomes, including muscle necrosis and limb amputation. Associated variables (p < 0.05) were input into multivariable logistic regression models evaluating these endpoints. RESULTS: Of 436 study patients, most were male (87%) with penetrating (57%), lower extremity (77%), arterial (73%), vein (40%), and bony (53%) injury with prolonged hospital length of stay (11 days). Patients who had index fasciotomy (66%) were compared with those who did not (34%), and no differences were appreciated with respect to age, initial systolic blood pressure, tourniquet time, "hard" signs of vascular injury, massive transfusion protocol activation, or Injury Severity Score (all p < 0.05). Of the 289 patients who underwent index fasciotomy, 49% had prophylactic fasciotomy, 11% developed muscle necrosis, 4% required an additional fasciotomy, and 8% required amputation, although only 28 of 147 (19%) required delayed fasciotomy in those without index fasciotomy. Importantly, forgoing index fasciotomy did not correlate (p > 0.05) with additional muscle necrosis or amputation risk in the delayed fasciotomy group. After controlling for confounders, index surgery fasciotomy was not associated with either muscle necrosis or limb salvage in multivariable models. CONCLUSIONS: Routine, index operation fasciotomy failed to demonstrate an outcome benefit in this prospective, multicenter analysis. Our data suggest that a careful observation and fasciotomy-when-needed approach may limit unnecessary surgery and its resulting morbidity in extremity vascular trauma patients.

Single-institution experience of 500 pulmonary resections guided by intraoperative molecular imaging.

OBJECTIVE: Intraoperative molecular imaging (IMI) using tumor-targeted optical contrast agents can improve thoracic cancer resections. There are no large-scale studies to guide surgeons in patient selection or imaging agent choice. Here, we report our institutional experience with IMI for lung and pleural tumor resection in 500 patients over a decade. METHODS: Between December 2011 and November 2021, patients with lung or pleural nodules undergoing resection were preoperatively infused with 1 of 4 optical contrast tracers: EC17, TumorGlow, pafolacianine, or SGM-101. Then, during resection, IMI was used to identify pulmonary nodules, confirm margins, and identify synchronous lesions. We retrospectively reviewed patient demographic data, lesion diagnoses, and IMI tumor-to-background ratios (TBRs). RESULTS: Five hundred patients underwent resection of 677 lesions. We found that there were 4 types of clinical utility of IMI: detection of positive margins (n = 32, 6.4% of patients), identification of residual disease after resection (n = 37, 7.4%), detection of synchronous cancers not predicted on preoperative imaging (n = 26, 5.2%), and minimally invasive localization of nonpalpable lesions (n = 101 lesions, 14.9%). Pafolacianine was most effective for adenocarcinoma-spectrum malignancies (mean TBR, 2.84), and TumorGlow was most effective for metastatic disease and mesothelioma (TBR, 3.1). False-negative fluorescence was primarily seen in mucinous adenocarcinomas (mean TBR, 1.8), heavy smokers (>30 pack years; TBR, 1.9), and tumors greater than 2.0 cm from the pleural surface (TBR, 1.3). CONCLUSIONS: IMI may be effective in improving resection of lung and pleural tumors. The choice of IMI tracer should vary by the surgical indication and the primary clinical challenge.

Rethinking protocolized completion angiography following extremity vascular trauma: A prospective observational multicenter trial.

BACKGROUND: Completion angiography (CA) is commonly used following repair of extremity vascular injury and is recommended by the Eastern Association for the Surgery of Trauma practice management guidelines for extremity trauma. However, it remains unclear which patients benefit from CA because only level 3 evidence exists. METHODS: This prospective observational multicenter (18LI, 2LII) analysis included patients 15 years or older with extremity vascular injuries requiring operative management. Clinical variables and outcomes were analyzed with respect to with our primary study endpoint, which is need for secondary vascular intervention. RESULTS: Of 438 patients, 296 patients required arterial repair, and 90 patients (30.4%) underwent CA following arterial repair. Institutional protocol (70.9%) was cited as the most common reason to perform CA compared with concern for inadequate repair (29.1%). No patients required a redo extremity vascular surgery if a CA was performed per institutional protocol; however, 26.7% required redo vascular surgery if the CA was performed because of a concern for inadequate repair. No differences were observed in hospital mortality, length of stay, extremity ischemia, or need for amputation between those who did and did not undergo CA. CONCLUSION: Completion angiogram following major extremity injury should be considered in a case-by-case basis. Limiting completion angiograms to those patients with concern for an inadequate vascular repair may limit unnecessary surgery and morbidity. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

An overview of a successful COVID-19 vaccination campaign at a prominent Connecticut healthcare system.

The coronavirus disease 2019 (COVID-19) pandemic has required healthcare systems to adapt, innovate, and collaborate to protect public health through treatment, testing, and vaccination initiatives related to the virus. As the pandemic evolved, lessons learned early on through testing and treatment were applied to vaccination efforts. Hartford HealthCare (HHC) is one of the largest healthcare systems in New England and took an integral role in vaccinating patients throughout the region, thus providing one of the largest vaccination campaigns in Connecticut. Early planning for equipment and personnel, in addition to effective communication between providers and patients, was critical in accomplishing HHC's goal of rapidly providing access to COVID-19 vaccines. The efficient and effective response to the pandemic at HHC was led by the Office of Emergency Management, which worked to ensure continuity of patient care and physician excellence in the face of disaster. Initially, resources were directed to testing and treatment of the disease; as vaccine clinical trials announced successful outcomes, these efforts shifted to preparing for the storage and distribution of a mass number of vaccines. This manuscript details the factors that enabled success in HHC's vaccination campaign and serves to provide a useful template for similar healthcare systems for future pandemic response.

Infection and Antibiotic Agents in Bleeding Trauma Patients: A Review of Available Literature.

Background: Antibiotic prophylaxis is a common, established practice at trauma centers worldwide for patients presenting with various forms of serious injury. Many patients simultaneously present with hemorrhage. The current guidelines by the Eastern Association for the Surgery of Trauma recommend re-dosing prophylactic antibiotic agents for every 10 units of blood products administered. However, these guidelines are only mildly supported by dated research. Methods: A literature search was completed through Medline EBSCO Host using antibiotic prophylaxis and transfusion as keywords. Articles judged to be relevant to the study question were selected for full-text review. Case studies were not included. Altogether, 18 articles were cited in our results through this process. Results: Risk of infection increases in patients resuscitated with large volume of blood products. Animal models of trauma offered conflicting findings on whether blood loss and blood resuscitation altered tissue antibiotic concentrations compared with controls. Studies focused on antibiotic pharmacokinetics in non-trauma human patients revealed agreement surrounding reported decreases in serum and tissue concentrations, although there was discrepancy surrounding the clinical relevancy of the reported decreases. Conclusions: Trauma, hemorrhage, and transfusion impair the immune response resulting in increased incidence of infection. Both animal and human models of antibiotic pharmacokinetics show decreased serum and tissue concentrations during hemorrhage. However, available data are insufficient to conclude that trauma patients experiencing hemorrhage are at elevated risk of infection and thus require more frequent redosing of antibiotic agents than the current guidelines suggest. An upcoming, prospective study by our institution seeks to evaluate this question.