TXA combined with whole blood transfusion in trauma patients does not increase the risk of VTE but shock index does.

INTRODUCTION: Previous studies have demonstrated the benefits of tranexamic acid (TXA) administration in combination with packed red blood cell (PRBC) transfusion in trauma patients without increasing the risk of venous thromboembolism (VTE). However, the effect of TXA in combination with whole blood (WB) has not been studied. Injury, abbreviated injury severity scores (ISS and AIS) and the need for blood transfusions are historically associated with VTE. The objective of this study was to determine the relationship between VTE and the combination of TXA administration and transfusion of PRBCs vs. WB. METHODS: Our institutional trauma registry was queried for trauma patients between 2015 and 2022 who received either WB â€‹+ â€‹TXA or PRBC â€‹+ â€‹TXA either prehospital or within 4 â€‹h of arrival. Multivariate analysis was utilized to determine independent risk factors for VTE, which were defined as either a deep vein thrombosis (DVT) or a pulmonary embolism (PE). Model covariates included age, mechanism of injury (MOI), ISS, lower extremity AIS, comorbid conditions, and shock index (SI). Additional outcomes analyzed were hospital length of stay (LOS), ICU LOS, and ventilator days. RESULTS: Three hundred and five patients had complete data and were included in the analysis. Of those, 251 received WB â€‹+ â€‹TXA and 54 received PRBC â€‹+ â€‹TXA. A total of 34 patients were found to have VTE event (11.1 â€‹%); 28 (11.2 â€‹%) and 6 (11.1 â€‹%) from the WB â€‹+ â€‹TXA and PRBC â€‹+ â€‹TXA groups, respectively. An elevated pre-hospital SI was independently associated with increased VTE rate (OR 1.85, 95 â€‹% CI 1.07-3.20). WB transfusion, TXA administration, ISS, and MOI did not influence the rate of VTE. CONCLUSION: These data demonstrate that the combination of WB â€‹+ â€‹TXA administered to trauma patients has no higher risk of VTE than patients who receive PRBC â€‹+ â€‹TXA, a comparison that has not been studied clinically to date. Despite the pro thrombotic state enhanced by TXA and the decreased dilutional coagulopathy seen in WB resuscitation, there was no increased risk of VTE compared to TXA â€‹+ â€‹PRBC. There is no evidence that TXA combined with whole blood transfusion is associated with an increased risk of VTE. However, higher pre-hospital SI was associated with an elevated rate of VTE. These clinical features provide insight into patients who may be at an increased risk of developing VTE and may benefit from targeted prevention strategies.

Emergency preparedness for mass casualty events: South Texas commentary on the development of a statewide emergency response system.

Mass casualty incidents (MCIs) are on the rise in the USA, and hemorrhage is the leading cause of preventable death in trauma. The need for rapid access to life-saving blood and blood products is essential for preventing death due to hemorrhage. It is well established that most major cities in the USA are underprepared to meet blood transfusion requirements in the event of an MCI. The South Texas Whole Blood Consortium sought to rectify this and vowed to be prepared to provide low-titer type O-positive whole blood (LTOWB) and blood components to the people who need it, where and when they need it. This system was able to transport 25 units of LTOWB and packed red blood cells almost 100 miles away to Uvalde Memorial Hospital within just 67 minutes after notification of an active shooter. The regional consortium has created a pool of dedicated LTOWB donors affectionately called Heroes in Arms who can be called on to instantly augment locoregional blood supply. Previously pregnant women have historically been excluded from donating plasma and LTOWB due to the increased rates of human leukocyte antigen (HLA) antibody (Ab) positivity, which is associated with transfusion-related acute lung injury. However, the South Texas Blood and Tissue Center in San Antonio had a large number of qualified, previously pregnant females desire to join the Heroes in Arms program prompting them to assess the feasibility of providing HLA Ab testing for this demographic and the results were promising. This is the first report of previously pregnant women being included in the pool for donation of LTOWB.

Diagnosis of Pancreatic Cancer after Cholecystectomy in the Elderly.

BACKGROUND: Previous studies evaluating whether recent cholecystectomy is associated with a pancreas cancer diagnosis are limited. We aimed to examine if cholecystectomy was performed more frequently in the year prior to cancer diagnosis than would be expected in a similar non-cancer population. METHODS: SEER-Medicare linked files were used to identify patients with pancreatic adenocarcinoma. Cancer diagnoses were considered to be "timely" if within 2 months of cholecystectomy or "delayed" if 2-12 months after cholecystectomy. Clinical factors and survival outcomes were compared using chi-square and Kaplan-Meier analyses. RESULTS: Rate of cholecystectomy in the year prior to diagnosis of cancer was 1.9% for the cancer group, compared to .4% in the non-cancer group (OR = 4.7, 95% CI 4.4-5.1). Differences in the cancer vs non-cancer cohorts at the time of cholecystectomy included a higher age (74 vs 70, P < .0001), more males (49.9% vs 41.7%, P < .0001), and more frequent open technique (21.0% vs 9.4%, P < .0001). Acute pancreatitis was nearly twice as common in the cancer cohort (19.1%) vs the non-cancer cohort (10.7%), P < .0001. There were no differences between patients who had a timely diagnosis after cholecystectomy compared to a delayed diagnosis with regard to age, gender, comorbidity index, race, or rural/urban designation. The rates of localized disease and subsequent resection were also similar between the delayed and timely groups. Overall unadjusted survival was no different between timely and delayed diagnoses, P = .96. DISCUSSION: Elderly patients diagnosed with pancreatic adenocarcinoma are more likely to have had a recent cholecystectomy compared to those without.

Stereo-EEG-guided network modulation for psychiatric disorders: Surgical considerations.

BACKGROUND: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders. OBJECTIVE: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field. METHODS: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators. RESULTS: Intraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°). CONCLUSION: This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders.

Transfusion-related cost comparison of trauma patients receiving whole blood versus component therapy.

INTRODUCTION: With the emergence of whole blood (WB) in trauma resuscitation, cost-related comparisons are of significant importance to providers, blood banks, and hospital systems throughout the country. The objective of this study was to determine if there is a transfusion-related cost difference between trauma patients who received low titer O+ whole blood (LTO+WB) and component therapy (CT). METHODS: A retrospective review of adult and pediatric trauma patients who received either LTO+WB or CT from time of injury to within 4 hours of arrival was performed. Annual mean cost per unit of blood product was obtained from the regional blood bank supplier. Pediatric and adult patients were analyzed separately and were compared on a cost per patient (cost/patient) and cost per patient per milliliter (cost/patient/mL) basis. Subgroup analysis was performed on severely injured adult patients (Injury Severity Score, >15) and patients who underwent massive transfusion. RESULTS: Prehospital LTO+WB transfusion began at this institution in January 2018. After the initiation of the WB transfusion, the mean annual cost decreased 17.3% for all blood products, and the average net difference in cost related to component blood products and LTO+WB was more than $927,000. In adults, LTO+WB was associated with a significantly lower cost/patient and cost/patient/mL compared with CT at 4 hours ( p < 0.001), at 24 hours ( p < 0.001), and overall ( p < 0.001). In the severely injured subgroup (Injury Severity Score, >15), WB was associated with a lower cost/patient and cost/patient/mL at 4 hours ( p < 0.001), 24 hours ( p < 0.001), and overall ( p < 0.001), with no difference in the prehospital setting. Similar findings were true in patients meeting massive transfusion criteria, although differences in injury severity may account for this finding. CONCLUSION: With increased use of LTO+WB for resuscitation, cost comparison is of significant importance to all stakeholders. Low titer O+ WB was associated with reduced cost in severely injured patients. Ongoing analyses may improve resource utilization and benefit overall healthcare cost. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Tumor infiltrating lymphocytes as an endpoint in cancer vaccine trials.

Checkpoint inhibitors have invigorated cancer immunotherapy research, including cancer vaccination. Classic early phase trial design and endpoints used in developing chemotherapy are not suited for evaluating all forms of cancer treatment. Peripheral T cell response dynamics have demonstrated inconsistency in assessing the efficacy of cancer vaccination. Tumor infiltrating lymphocytes (TILs), reflect the local tumor microenvironment and may prove a superior endpoint in cancer vaccination trials. Cancer vaccines may also promote success in combination immunotherapy treatment of weakly immunogenic tumors. This review explores the impact of TILs as an endpoint for cancer vaccination in multiple malignancies, summarizes the current literature regarding TILs analysis, and discusses the challenges of providing validity and a standardized implementation of this approach.

Depression in association with neutrophil-to-lymphocyte, platelet-to-lymphocyte, and advanced lung cancer inflammation index biomarkers predicting lung cancer survival.

Lung cancer is a product of inflammation and a dysfunctional immune system, and depression has similar dysregulation. Depression disproportionately affects lung cancer patients, having the highest rates of all cancers. Systemic inflammation and depression are both predictive of non-small cell lung cancer (NSCLC) survival, but the existence and extent of any co-occurrence is unknown. Studied is the association between systemic inflammation ratio (SIR) biomarker levels and patients' depressive symptoms, with the hypothesis that depression severity would be significantly associated with prognostically poor inflammation. Newly diagnosed stage-IV non-small cell lung cancer (NSCLC; N = 186) patients were enrolled (ClinicalTrials.gov Identifier: NCT03199651) and blood draws and depression self-reports (Patient Health Questionnaire-9) were obtained. For SIRs, cell counts of neutrophils (N), lymphocytes (L), and platelets (P) were abstracted for ratio (R) calculations for NLR, PLR, and the Advanced Lung cancer Inflammation Index (ALI). Patients were followed and biomarkers were tested as predictors of 2-year overall survival (OS) to confirm their relevance. Next, multivariate linear regressions tested associations of depression with NLR, PLR, and ALI. Overall 2-year mortality was 61% (113/186). Cox model analyses confirmed higher NLR [hazard ratio (HR) = 1.91; p = 0.001] and PLR (HR = 2.08; p<0.001), along with lower ALI (HR = 0.53; p = 0.005), to be predictive of worse OS. Adjusting for covariates, depression was reliably associated with biomarker levels (p ≤ 0.02). Patients with moderate/severe depressive symptoms were 2 to 3 times more likely to have prognostically poor biomarker levels. Novel data show patients' depressive symptoms were reliably associated with lung-relevant systemic inflammation biomarkers, all assessed at diagnosis/pretreatment. The same SIRs were found prognostic for patients' 2-year OS. Intensive study of depression, combined with measures of cell biology and inflammation is needed to extend these findings to discover mechanisms of depression toxicity for NSCLC patients' treatment responses and survival.

Safety and utility of modified ultrafiltration in pediatric cardiac surgery.

INTRODUCTION: Modified ultrafiltration (MUF) is employed at the termination of cardiopulmonary bypass (CPB) in pediatric and neonatal patients undergoing congenital heart surgery to reduce the accumulation of total body water thus increasing the concentration of red blood cells and the other formed elements in the circulation. Modified ultrafiltration has been reported to remove circulating pro-inflammatory mediators that result in systemic inflammatory response syndrome (SIRS) postoperatively. METHODS: Four hundred patients undergoing cardiac surgery requiring cardiopulmonary bypass and weighing less than or equal to 12 kg were retrospectively evaluated for the effectiveness of MUF. After the termination of CPB, blood was withdrawn through the aortic cannula and passed through a hemoconcentrator attached to the blood cardioplegia set and returned to the patient through the venous cannula. The entire CPB circuit volume in addition to the patient's circulating blood volume were concentrated until the hematocrit value displayed on the CDI cuvette within the MUF circuit reached 45% or there was no more volume to safely remove. At the same time a full unit of FFP can be infused as water is being removed, thus maintaining euvolemia. RESULTS: MUF was performed in all 400 patients with no MUF-related complications. Following the conclusion of MUF, anecdotal observations included improved surgical hemostasis, improved hemodynamic parameters, decreased transfusion requirements, and decreased ventilator times. CONCLUSIONS: Complete MUF enables the clinician to safely raise the post-CPB hematocrit to at least 40% while potentially removing mediators that could result in SIRS. In addition a full unit of FFP can be administered while maintaining euvolemia.

The effects of pulsatile versus nonpulsatile flow on cerebral pulsatility index, mean flow velocity at the middle cerebral artery, regional cerebral oxygen saturation, cerebral gaseous microemboli counts, and short-term clinical outcomes in patients undergoing congenital heart surgery.

Objective: The objective of this retrospective review was to evaluate whether or not pulsatile flow improves cerebral hemodynamics and clinical outcomes in pediatric congenital cardiac surgery patients. Methods: This retrospective study included 284 pediatric patients undergoing congenital cardiac surgery with cardiopulmonary bypass support utilizing nonpulsatile (n = 152) or pulsatile (n = 132) flow. Intraoperative cerebral gaseous microemboli counts, pulsatility index, and mean blood flow velocity at the right middle cerebral artery were assessed using transcranial Doppler ultrasound. Clinical outcomes were compared between groups. Results: Patient demographics and cardiopulmonary bypass characteristics between groups were similar. Although the pulsatility index during aortic crossclamping was consistently higher in the pulsatile group (P < .05), a significant degree of pulsatility was also observed in the nonpulsatile group. No significant differences in mean cerebral blood flow velocity, regional cerebral oxygen saturation, or gaseous microemboli counts were observed between the perfusion modality groups. Clinical outcomes, including intubation duration, intensive care unit and hospital length of stay, and mortality within 180 days were similar between groups. Conclusions: Although the pulsatility index was greater in the pulsatile group, other measures of intraoperative cerebral perfusion and short-term outcomes were similar to the nonpulsatile group. These findings suggest that while pulsatile perfusion represents a safe modality for cardiopulmonary bypass support, its use may not translate into detectably superior clinical outcomes.

AAST multicenter prospective analysis of prehospital tourniquet use for extremity trauma.

BACKGROUND: Tourniquet use for extremity hemorrhage control has seen a recent increase in civilian usage. Previous retrospective studies demonstrated that tourniquets improve outcomes for major extremity trauma (MET). No prospective study has been conducted to date. The objective of this study was to evaluate outcomes in MET patients with prehospital tourniquet use. We hypothesized that prehospital tourniquet use in MET decreases the incidence of patients arriving to the trauma center in shock. METHODS: Data were collected prospectively for adult patients with MET at 26 Level I and 3 Level II trauma centers from 2015 to 2020. Limbs with tourniquets applied in the prehospital setting were included in the tourniquet group and limbs without prehospital tourniquets were enrolled in the control group. RESULTS: A total of 1,392 injured limbs were enrolled with 1,130 tourniquets, including 962 prehospital tourniquets. The control group consisted of 262 limbs without prehospital tourniquets and 88 with tourniquets placed upon hospital arrival. Prehospital improvised tourniquets were placed in 42 patients. Tourniquets effectively controlled bleeding in 87.7% of limbs. Tourniquet and control groups were similarly matched for demographics, Injury Severity Score, and prehospital vital signs (p > 0.05). Despite higher limb injury severity, patients in the tourniquet group were less likely to arrive in shock compared with the control group (13.0% vs. 17.4%, p = 0.04). The incidence of limb complications was not significantly higher in the tourniquet group (p > 0.05). CONCLUSION: This study is the first prospective analysis of prehospital tourniquet use for civilian extremity trauma. Prehospital tourniquet application was associated with decreased incidence of arrival in shock without increasing limb complications. We found widespread tourniquet use, high effectiveness, and a low number of improvised tourniquets. This study provides further evidence that tourniquets are being widely and safely adopted to improve outcomes in civilians with MET. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Nanobubbles are Non-Echogenic for Fundamental-Mode Contrast-Enhanced Ultrasound Imaging.

Microbubbles (1-10 µm diameter) have been used as conventional ultrasound contrast agents (UCAs) for applications in contrast-enhanced ultrasound (CEUS) imaging. Nanobubbles (<1 µm diameter) have recently been proposed as potential extravascular UCAs that can extravasate from the leaky vasculature of tumors or sites of inflammation. However, the echogenicity of nanobubbles for CEUS remains controversial owing to prior studies that have shown very low ultrasound backscatter. We hypothesize that microbubble contamination in nanobubble formulations may explain the discrepancy. To test our hypothesis, we examined the size distributions of lipid-coated nanobubble and microbubble suspensions using multiple sizing techniques, examined their echogenicity in an agar phantom with fundamental-mode CEUS at 7 MHz and 330 kPa peak negative pressure, and interpreted our results with simulations of the modified Rayleigh-Plesset model. We found that nanobubble formulations contained a small contamination of microbubbles. Once the contribution from these microbubbles is removed from the acoustic backscatter, the acoustic contrast of the nanobubbles was shown to be near noise levels. This result indicates that nanobubbles have limited utility as UCAs for CEUS.

A Randomized Clinical Trial of Perfusion Modalities in Pediatric Congenital Heart Surgery Patients.

BACKGROUND: The objective of this randomized clinical trial was to investigate the effects of perfusion modalities on cerebral hemodynamics, vital organ injury, quantified by the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) Score, and clinical outcomes in risk-stratified congenital cardiac surgery patients. METHODS: This randomized clinical trial included 159 consecutive congenital cardiac surgery patients in whom pulsatile (n = 83) or nonpulsatile (n = 76) perfusion was used. Cerebral hemodynamics were assessed using transcranial Doppler ultrasound. Multiple organ injury was quantified using the PELOD-2 score at 24, 48, and 72 hours. Clinical outcomes, including intubation time, intensive care unit length of stay (LOS), hospital LOS, and mortality, were also evaluated. RESULTS: The Pulsatility Index at the middle cerebral artery and in the arterial line during aortic cross-clamping was consistently better maintained in the pulsatile group. Demographics and cardiopulmonary bypass characteristics were similar between the 2 groups. While risk stratification with The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Mortality Categories was similar between the groups, Mortality Categories 1 to 3 demonstrated more patients than Mortality Categories 4 and 5. There were no differences in clinical outcomes between the groups. The PELOD-2 scores showed a progressive improvement from 24 hours to 72 hours, but the results were not statistically different between the groups. CONCLUSIONS: The Pulsatillity Index for the pulsatile group demonstrated a more physiologic pattern compared with the nonpulsatile group. While pulsatile perfusion did not increase plasma-free hemoglobin levels or microemboli delivery, it also did not demonstrate any improvements in clinical outcomes or PELOD-2 scores, suggesting that while pulsatile perfusion is a safe method, it not a "magic bullet" for congenital cardiac operations.

Pacemaker Lead Placement via Transmural Approach in an Adult With Palliated Single Ventricle Heart Disease.

Given the lack of systemic venous return to the heart, palliated single ventricle patients frequently require epicardial pacemaker implantation for management of dysrhythmias including sinus node dysfunction, atrial arrhythmias, and heart block. Repeated device hardware replacement, frequently required due to high lead thresholds or other device failure, is a challenging and significant problem for this population. 3-dimensional imaging can assist in delineating the cardiac anatomy allowing for novel approaches to intervention. We review a patient with extracardiac Fontan circulation who underwent placement of an endocardial atrial pacemaker lead via a transmural approach with a 3D-printed model used for procedural guidance.

Antipsychotic Medications for Low-Income Preschoolers: Long Duration and Psychotropic Medication Polypharmacy.

OBJECTIVE: This study aimed to evaluate prescribing patterns of antipsychotic medication and factors that predict duration of use among low-income, preschool-age children. METHODS: State Medicaid claims from 2012 to 2017 were used to identify antipsychotic medication use for children <6 years old. ICD-9 and ICD-10 codes were used to describe child diagnoses. Descriptive and multivariable analyses were used to determine patterns of antipsychotic medication use and factors that predicted duration of use. RESULTS: In 2012, 316 children <6 years of age started an antipsychotic medication in a southeastern state. Most were non-Hispanic White (N=202, 64%) and boys (N=231, 73%). Diagnoses included attention-deficit hyperactivity disorder (N=288, 91%), neurodevelopmental disorders (N=208, 66%), anxiety and trauma-related diagnoses (N=202, 64%), and autism spectrum disorders (ASDs) (N=137, 43%). The mean±SD duration of exposure to antipsychotic medication for children in the cohort was 2.6±1.7 years, but 86 children (27%) had >4 years of exposure. Almost one-third (N=97, 31%) received polypharmacy of four or more medication classes, and 42% (N=131) received metabolic screening. Being male, being in foster care, and having a diagnosis of ASD or disruptive mood dysregulation disorder were significantly associated with duration of use of antipsychotic medications; race-ethnicity was not significantly associated with duration of use. Emergency department visits (N=277, 88%) and inpatient hospitalizations (N=107, 34%) were observed during the study period. CONCLUSIONS: Many preschoolers received antipsychotic medications for substantial periods. Further research is needed to identify evidence-based practices to reduce medication use and improve outcomes.

Multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: A subgroup analysis.

BACKGROUND: Checkpoint inhibitors (CPI) in combination with cell-based vaccines may produce synergistic antitumor immunity. The primary analysis of the randomized and blinded phase IIb trial in resected stage III/IV melanoma demonstrated TLPLDC is safe and improved 24-month disease-free survival (DFS) in the per treatment (PT) analysis. Here, we examine efficacy within pre-specified and exploratory subgroups. METHODS: Stage III/IV patients rendered disease-free by surgery were randomized 2:1 to TLPLDC vaccine versus placebo. The pre-specified PT analysis included only patients completing the primary vaccine/placebo series at 6 months. Kaplan-Meier analysis was used to compare 24-month DFS among subgroups. RESULTS: There were no clinicopathologic differences between subgroups except stage IV patients were more likely to receive CPI. In stage IV patients, 24-month DFS was 43% for vaccine versus 0% for placebo (p = 0.098) in the ITT analysis and 73% versus 0% (p = 0.002) in the PT analysis. There was no significant difference in 24-month DFS when stratified by use of immunotherapy or CPI. For patients with resected recurrent disease, 24-month DFS was 88.9% versus 33.3% (p = 0.013) in the PT analysis. All benefit from vaccination was in the PT analysis; no benefit was found in patients receiving up to three doses. CONCLUSION: The TLPLDC vaccine improved DFS in patients completing the primary vaccine series, particularly in the resected stage IV patients. The efficacy of the TLPLDC vaccine will be confirmed in a phase III study evaluating adjuvant TLPLDC + CPI versus Placebo + CPI in resected stage IV melanoma patients.

Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence.

PURPOSE: AE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year overall disease-free survival (DFS) but possible benefit in subgroups. Here, we present the final landmark analysis. METHODS: In this 4-arm, prospective, randomized, single-blinded, multi-center phase II trial, disease-free node positive and high-risk node negative breast cancer patients enrolled after standard of care therapy. Six monthly inoculations of vaccine (VG) vs. control (CG) were given as the primary vaccine series with 4 boosters at 6-month intervals. Demographic, safety, immunologic, and DFS data were evaluated. RESULTS: 456 patients were enrolled; 154 patients in the VG and 147 in CG for AE37, 89 patients in the VG and 91 in CG for GP2. The AE37 arm had no difference in DFS as compared to CG, but pre-specified exploratory subgroup analyses showed a trend towards benefit in advanced stage (p = 0.132, HR 0.573 CI 0.275-1.193), HER2 under-expression (p = 0.181, HR 0.756 CI 0.499-1.145), and triple-negative breast cancer (p = 0.266, HR 0.443 CI 0.114-1.717). In patients with both HER2 under-expression and advanced stage, there was significant benefit in the VG (p = 0.039, HR 0.375 CI 0.142-0.988) as compared to CG. The GP2 arm had no significant difference in DFS as compared to CG, but on subgroup analysis, HER2 positive patients had no recurrences with a trend toward improved DFS (p = 0.052) in VG as compared to CG. CONCLUSIONS: This phase II trial reveals that AE37 and GP2 are safe and possibly associated with improved clinical outcomes of DFS in certain subgroups of breast cancer patients. With these findings, further evaluations are warranted of AE37 and GP2 vaccines given in combination and/or separately for specific subsets of breast cancer patients based on their disease biology.

Validating clinical threshold values for a dashboard view of the compensatory reserve measurement for hemorrhage detection.

BACKGROUND: Compensatory reserve measurement (CRM) is a novel noninvasive monitoring technology designed to assess physiologic reserve using feature interrogation of arterial pulse waveforms. This study was conducted to validate clinically relevant CRM values with a simplified color-coded dashboard view. METHODS: We performed a prospective observational study of 300 injured patients admitted to a level I trauma center. Compensatory reserve measurement was recorded upon emergency department admission. Data collected to complement the analysis included patient demographics, vital signs, lifesaving interventions, Injury Severity Score (ISS), and outcomes. Threshold values of CRM were analyzed for predictive capability of hemorrhage. RESULTS: A total of 285 patients met the inclusion criteria. Mean age of the population was 47 years, and 67% were male. Hemorrhage was present in 32 (11%), and lifesaving intervention was performed in 40 (14%) patients. Transfusion of packed red blood cells was administered in 33 (11.6%) patients, and 21 (7.4%) were taken to the operating room for surgical or endovascular control of hemorrhage. Statistical analyses were performed to identify optimal threshold values for three zones of CRM to predict hemorrhage. Optimal levels for red, yellow, and green areas of the dashboard view were stratified as follows: red if CRM was less than 30%, yellow if CRM was 30% to 59%, and green if CRM was 60% or greater. Odds of hemorrhage increased by 12-fold (odds ratio, 12.2; 95% confidence interval, 3.8-38.9) with CRM less than 30% (red) and 6.5-fold (odds ratio, 6.5; 95% confidence interval, 2.7-15.9) with CRM of equal to 30% to 59% (yellow) when compared with patients with CRM of 60% or greater. The area under the receiver operating characteristic curve for three-zone CRM was similar to that of continuous CRM (0.77 vs. 0.79) but further increased the ability to predict hemorrhage after adjusting for ISS (area under the receiver operating characteristic curve, 0.87). CONCLUSION: A three-zone CRM could be a potentially useful predictor of hemorrhage in trauma patients with added capabilities of continuous monitoring and a real-time ISS assessment. These data substantiate easily interpretable threshold dashboard values for triage with potential to improve injury outcomes. LEVEL OF EVIDENCE: Diagnostic, level II.

Final analysis of a phase I/IIa trial of the folate-binding protein-derived E39 peptide vaccine to prevent recurrence in ovarian and endometrial cancer patients.

BACKGROUND: E39, an HLA-A2-restricted, immunogenic peptide derived from the folate-binding protein (FBP), is overexpressed in multiple malignancies. We conducted a phase I/IIa trial of the E39 + GM-CSF vaccine with booster inoculations of either E39 or E39' (an attenuated version of E39) to prevent recurrences in disease-free endometrial and ovarian cancer patients(pts). Here, we present the final 24-month landmark analysis. PATIENTS AND METHODS: HLA-A2 + patients receiving E39 + GM-CSF were included in the vaccine group (VG), and HLA-A2- pts (or HLA-A2 + patients refusing vaccine) were followed as the control group (CG). VG group received 6 monthly inoculations as the primary vaccine series (PVS) and were randomized to receive either E39 or E39' booster inoculations. Demographic, safety, immunologic, and disease-free survival (DFS) data were collected and evaluated. RESULTS: Fifty-one patients were enrolled; 29 in the VG and 22 in the CG. Fourteen patients received <1000 µg and 15 received 1000 µg of E39. There were no clinicopathologic differences between VG and CG or between dose groups. E39 was well tolerated. At the 24 months landmark, DFS was 55.5% (VG) vs 40.0% (CG), P = 0.339. Patients receiving 1000 µg and boosted patients also showed improved DFS (P < 0.03). DFS was improved in the 1000 µg group after treatment of primary disease (90.0% vs CG:42.9%, P = 0.007), but not in recurrent patients. In low-FBP expressing patients, DFS was 100.0% (1000 µg), 50.0% (<1000 µg), and 25.0% (CG), P = 0.029. CONCLUSIONS: This phase I/IIa trial reveals that E39 + GM-CSF is safe and may be effective in preventing recurrence in high-risk ovarian and endometrial cancer when optimally dosed (1000 µg) to FBP low patients being treated for primary disease.

Patient Experience Factors and Health-Related Quality of Life in Hospitalized Individuals.

PURPOSE: To identify a relationship between patient satisfaction with the hospital experience and health-related quality of life (HRQOL), as well as determine predictors of each variable. PARTICIPANTS & SETTING: 50 patients with cancer in two adult oncology units in an academic health sciences center. METHODOLOGIC APPROACH: A descriptive, cross-sectional design was used. Patient satisfaction was measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) and HRQOL was assessed using the Quality of Life Patient/Cancer Survivor (QOL-CS) version. FINDINGS: Patients who were single, diagnosed for 6-10 years, and diagnosed for 11 years or longer had significantly lower patient satisfaction scores. Patients with public insurance, diagnosed for 6-10 years, and diagnosed for 11 years or longer had lower QOL-CS scores. Physical and social well-being scores were associated with higher HCAHPS scores. There was a positive relationship between patient satisfaction and physical and social functioning. Patient demographics were related to patient satisfaction and HRQOL. IMPLICATIONS FOR NURSING: Nurses should have measurable goals to provide high-quality care to patients with cancer, including satisfaction during hospitalization and promotion of HRQOL.

The World Database for Pediatric and Congenital Heart Surgery "A Call to Service for North American Congenital Heart Surgery Programs".

The World Society for Pediatric and Congenital Heart Surgery has endorsed the establishment of an international platform for the exchange of knowledge and experience for those that treat patients with a congenital heart defect. On January 1, 2017, the release of the World Database for Pediatric and Congenital Heart Surgery opened a new era in evaluation of treatment with congenital heart defects. The contribution of data from countries with established congenital surgical databases will greatly enhance the efforts to provide the most accurate measure of overall surgical outcomes across the globe.