Courtesy Authorship Practices Among First and Senior Authors: Evaluation of Motivations, Gender Bias, and Inequities.

OBJECTIVES: A courtesy author is an individual who has not met authorship criteria but is listed as an author. This practice is common and often seen as victimless. Because publications are used for funding and promotion decisions, it is critical to understand biases in this practice. METHODS: An anonymous survey was conducted from March to October 2020 of first and senior authors of publications from 2014 to 2015 in 8 surgical journals. Authors were surveyed about demographic data, practice setting, and courtesy author practices. RESULTS: Three hundred forty-one authors responded (16% response rate). 75% were from academic practice settings. 14% reported adding courtesy authors 5 or more times in the past year. Courtesy authors were more often male (80%, P = 0.023), older (75%), and of higher academic rank (65%) than first/senior authors. All author groups were >75% white. When a reason was reported, 46% added a courtesy author due to avoid retaliation; 64% to avoid awkwardness. 26% expected reciprocal authorship offers. 92% of respondents acknowledge understanding International Committee of Medical Journal Editors authorship criteria. Women were less common among those added from goodwill than those added from fear (P = 0.039.) When courtesy authors were of a lower rank than first/senior authors, they were nearly twice as likely to be female (P = 0.0056) or non-white (P = 0.0184.). CONCLUSION: Courtesy authors were more often male, older, and higher rank than first/senior authors. Fear of career consequences was a major motivator for including courtesy authors. Understanding the motivations and pressures leading to courtesy authorship will help to correct this practice.

Rotational thromboelastometry predicts transfusion and disability in pediatric trauma.

BACKGROUND: Trauma-induced coagulopathy seen on rotational thromboelastometry (ROTEM) is associated with poor outcomes in adults; however, this relationship is poorly understood in the pediatric population. We sought to define thresholds for product-specific transfusion and evaluate the prognostic efficacy of ROTEM in injured children. METHODS: Demographics, ROTEM, and clinical outcomes from severely injured children (age, < 18 years) admitted to a Level I trauma center between 2014 and 2018 were retrospectively analyzed. Receiver operating characteristic curves were plotted and Youden indexes were calculated against the endpoint of packed red blood cell transfusion to identify thresholds for intervention. The ROTEM parameters were compared against the clinical outcomes of mortality or disability at discharge. RESULTS: Ninety subjects were reviewed. Increased tissue factor-triggered extrinsic pathway (EXTEM) clotting time (CT) >84.5 sec (p = 0.049), decreased EXTEM amplitude at 10 minutes (A10) <43.5 mm (p = 0.025), and decreased EXTEM maximal clot firmness (MCF) <64.5 mm (p = 0.026) were associated with need for blood product transfusion. Additionally, EXTEM CT longer than 68.5 seconds was associated with mortality or disability at discharge. CONCLUSION: Coagulation dysregulation on thromboelastometry is associated with disability and mortality in children. Based on our findings, we propose ROTEM thresholds: plasma transfusion for EXTEM CT longer than 84.5 seconds, fibrinogen replacement for EXTEM A10 less than 43.5 mm, and platelet transfusion for EXTEM MCF less than 64.5 mm. LEVEL OF EVIDENCE: Prognostic, Level III; Therapeutic, Level IV.

Surgical resection of breast cancers: Molecular analysis of cancer stem cells in residual disease.

BACKGROUND: Approximately 70% of breast cancer patients have residual disease after neoadjuvant chemotherapy. This study was designed to determine whether breast cancer cells with stemlike properties are present in residual disease after neoadjuvant chemotherapy and whether they exhibit oncogenic mutations. The presence of breast cancer cells with stemlike properties with specific mutations may help explain the poor prognosis associated with residual disease. METHODS: A total of 68 breast cancer specimens were collected at the time of mastectomy or lumpectomy. A total of 44 were chemotherapy naïve and 24 were collected as residual disease after neoadjuvant chemotherapy. Tumor cells were collected by fluorescence-activated cell sorting, with breast cancer cells with stemlike properties specifically identified using breast stem cell associated antibodies. Whole tumor specimens and fluorescence-activated cell sorting breast cancer cells with stemlike properties were analyzed for genetic mutations, including PIK3CA. RESULTS: Breast cancer cells with stemlike properties, demonstrating EpCAM-positive, CD44-positive, CD49f±, CD24± expression were present in chemotherapy-naïve tumors and residual disease. In both chemotherapy-naïve and residual disease specimens the highest frequency of PIK3CA mutations were detected in CD49f-CD24+ BCSCs (39% and 33%, respectively). PIK3CA mutations were detected in all stages of breast cancer (35%), in both chemotherapy naïve (39%) and residual disease (29%) and in both estrogen receptor positive (41%) and negative tumors (14%) (P = ns). Various PIK3CA mutations were identified in chemotherapy-naïve specimens versus residual disease specimens in both patient-paired and unpaired breast cancers. CONCLUSION: Breast cancer cells with stemlike properties with mutations in PIK3CA were present in chemotherapy-naïve breast cancers and residual disease after neoadjuvant chemotherapy. These results demonstrate that neoadjuvant chemotherapy does not completely eradicate PIK3CA-defective breast cancer cells with stemlike properties. Although these findings may help explain the poor clinical outcomes in patients with residual disease, they also identify breast cancer cells with stemlike-property targets for therapies.

Β-Adrenergic agonist administration is not associated with secondary carcinoid crisis in patients with carcinoid tumor.

BACKGROUND: Patients with carcinoid tumors are at risk for profound intraoperative hypotension known as carcinoid crisis, which catecholamines are traditionally believed to trigger. However, data supporting this are lacking. METHODS: Anesthesia records were retrospectively reviewed for carcinoid patients treated with vasopressors. Hemodynamics for those with crisis were compared between those who received ß-adrenergic agonists (B-AA) versus those who did not. RESULTS: Among 293 consecutive operations, 58 were marked by 161 crises. There was no significant difference in the incidence of paradoxical hypotension with B-AA compared to non-B-AA (p = 0.242). The maximum percent decrease in mean arterial pressure following drug administration was significantly greater in those patients treated with non-B-AA than with B-AA (31.6% vs. 12.5%, p < 0.0001). There were no differences in crisis duration (p = 0.257) or postoperative complication rate (p = 0.896). CONCLUSIONS: ß-Adrenergic agonist use was not associated with paradoxical hypotension, prolonged carcinoid crisis, or postoperative complications in patients with intraoperative carcinoid crisis.

A prospective study of the pathophysiology of carcinoid crisis.

BACKGROUND: Sudden massive release of serotonin, histamine, kallikrein, and bradykinin is postulated to cause an intraoperative carcinoid crisis. The exact roles of each of these possible agents, however, remain unknown. Optimal treatment will require an improved understanding of the pathophysiology of the carcinoid crisis. METHODS: Carcinoid patients with liver metastases undergoing elective abdominal operations were studied prospectively, using intraoperative, transesophageal echocardiography, pulmonary artery catheterization, and intraoperative blood collection. Serotonin, histamine, kallikrein, and bradykinin levels were analyzed by enzyme-linked immunosorbent assay. RESULTS: Of 46 patients studied, 16 had intraoperative hypotensive crises. Preincision serotonin levels were greater in patients who had crises (1,064 vs 453 ng/mL, P = .0064). Preincision hormone profiles were otherwise diverse. Cardiac function on transesophageal echocardiography during the crisis was normal, but intracardiac hypovolemia was observed consistently. Pulmonary artery pressure decreased during crises (P = .025). Linear regression of preincision serotonin levels showed a positive relationship with mid-crisis cardiac index (r = 0.73, P = .017) and a negative relationship with systemic vascular resistance (r=-0.61, P = .015). There were no statistically significant increases of serotonin, histamine, kallikrein, or bradykinin levels during the crises. CONCLUSION: The pathophysiology of carcinoid crisis appears consistent with distributive shock. Hormonal secretion from carcinoid tumors varies widely, but increased preincision serotonin levels correlate with crises and with hemodynamic parameters during the crises. Statistically significant increases of serotonin, histamine, kallikrein, or bradykinin during the crises were not observed.

Massive transfusion of low-titer cold-stored O-positive whole blood in a civilian trauma setting.

BACKGROUND: Based on the improved outcomes achieved with fresh whole blood in cases of military trauma as well as with 1:1:1 transfusion strategies for massive traumatic hemorrhage in civilian settings, there has been resurgent interest in using whole blood for civilian trauma patients. There have been reports of giving up to 4 units of low-titer cold-stored O-positive to these patients. This is the first modern report of a massive transfusion with unrestricted low-titer group O whole blood (LTOWB) use in a civilian trauma patient. STUDY DESIGN AND METHODS: This is a case report describing the resuscitation and massive transfusion of LTOWB of a 69-year-old man struck by an automobile. RESULTS: While working to achieve hemorrhage control, the patient received 38 units of LTOWB, 13 units of RBCs, 12 units of fresh frozen plasma, 2 packs of platelets, and 2 units of cryoprecipitate. No evidence of hemolytic reaction was observed. The patient was O positive. Monitoring by thrombelastography revealed adequate clot initiation and propagation, but decreased clot strength (49.6 and 50.2) and a drop in fibrinogen (from 207 to 141) during the resuscitation. CONCLUSION: This is the first report of a massive transfusion for civilian trauma based on cold-stored whole blood in the recent era. While this patient suffered a tremendous burden of traumatic injury and his recovery is not yet complete, his LTOWB resuscitation was successful. Frequent monitoring of coagulation status with thrombelastography during utilization of LTOWB is indicated because the efficacy of its components (particularly platelets) is not yet fully understood.

The procoagulant molecule plasminogen activator inhibitor-1 is associated with injury severity and shock in patients with and without traumatic brain injury.

BACKGROUND: Traumatic injury is associated with an increased risk of coagulopathy and venous thrombosis. plasminogen activator inhibitor-1 (PAI-1) is a procoagulant molecule that inhibits tPA/uPA, thrombomodulin, and activated protein C. We hypothesized that elevated PAI-1 levels would be associated with increased Injury Severity Score (ISS) in injured patients with and without traumatic brain injury and that PAI-1 levels would vary with injury type. METHODS: We retrospectively analyzed demographic, ISS, and hemodynamic data from a prospectively collected database. Patients with traumatic injury requiring intensive care unit admission (n = 268) were classified as multiple injuries, isolated body, or isolated head based on Abbreviated Injury Severity score. Admission PAI-1 levels were quantified using a Luminex analyte platform. Univariate tests for association informed the construction of a multivariate model of the relationship between PAI-1 and ISS. RESULTS: Plasminogen activator inhibitor-1 positively associated with ISS (p < 0.0001) and was highest in patients with ISS greater than 35 (p < 0.0001). Plasminogen activator inhibitor-1 was significantly different between multiple injuries, isolated body, and isolated head patients (p < 0.0001). On univariate analysis, age (p = 0.0011), hypotension (p = 0.0076), and alcohol intoxication (p = 0.0024) were all positively associated with PAI-1 level. Admission international normalized ratio was not associated with PAI-1 level (p = 0.638). After adjusting for age, sex, hypotension, and alcohol intoxication, higher PAI-1 levels were associated with higher ISS (p < 0.0001). CONCLUSION: Elevated PAI-1 at admission is associated with higher ISS. This association is more pronounced in patients with hypotension. These findings suggest that PAI-1 levels may reflect the burden of endothelial damage and platelet activation after injury. LEVEL OF EVIDENCE: Prognostic, level III.

Continuous infusion of octreotide combined with perioperative octreotide bolus does not prevent intraoperative carcinoid crisis.

BACKGROUND: Operations and anesthesia in carcinoid patients can provoke carcinoid crises, which can have serious sequelae, including death. Prophylactic octreotide is recommended to prevent crises. Recommended prophylaxis regimens vary from octreotide long-acting repeatable to preoperative bolus to continuous octreotide infusion; however, efficacy data are lacking. We have shown previously that crises correlated with major complications and that octreotide long-acting repeatable and preoperative bolus failed to prevent crises. This study examines the impact of continuous octreotide infusion. METHODS: A total of 127 patients (71% with liver metastases, 74% with carcinoid syndrome) who underwent 150 operations with continuous octreotide infusions were enrolled in this prospective case series. Our main outcome measures were the occurrence of intraoperative carcinoid crises and post-operative complications. RESULTS: Crises occurred at a rate of 30% as compared with 24% in our previous series, which examined the impact of preoperative octreotide bolus. Crises were significantly associated with the presence of hepatic metastases (P = .02) or history of carcinoid syndrome (P = .006), although neither was required for crises. Prompt vasopressor treatment shortened the mean duration of hypotension to 8.7 minutes, compared with 19 minutes in our prior series. Crises no longer correlated with major complications (P = .481) unless instability persisted for greater than 10 minutes (P = .011). CONCLUSION: Octreotide infusions do not prevent intraoperative crises. Patients without liver metastases or carcinoid syndrome can have intraoperative crises. Postoperative complications can be decreased by reducing the duration of crises. Further study is needed to determine how best to shorten hemodynamic instability during crises.

Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism.

INTRODUCTION: Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response. METHODS: Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test. RESULTS: While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression. CONCLUSIONS: The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.