Search

We sought to characterize if prehospital transfer origin from the scene of injury (SCENE) or from a referral emergency department (REF) alters the survival benefit attributable to prehospital plasma resuscitation in patients at risk of hemorrhagic shock.We performed a secondary analysis of data from a recently completed prehospital plasma clinical trial. All of the enrolled patients from either the SCENE or REF groups were included. The demographics, injury characteristics, shock severity and resuscitation needs were compared. The primary outcome was a 30-day mortality. Kaplan-Meier analysis and Cox-hazard regression were used to characterize the independent survival benefits of prehospital plasma for transport origin groups.Of the 501 enrolled patients, the REF group patients (n = 111) accounted for 22% with the remaining (n = 390) originating from the scene. The SCENE group patients had higher injury severity and were more likely intubated prehospital. The REF group patients had longer prehospital times and received greater prehospital crystalloid and blood products. Kaplan-Meier analysis revealed a significant 30-day survival benefit associated with prehospital plasma in the SCENE group (P.01) with no difference found in the REF group patients (P = .36). The Cox-regression verified after controlling for relevant confounders that prehospital plasma was independently associated with a 30-day survival in the SCENE group patients (hazard ratio 0.59; 95% confidence interval 0.39-0.89; P = .01) with no significant relationship found in the REF group patients (hazard ratio 1.03, 95% confidence interval 0.4-3.0).Important differences across the SCENE and REF cohorts exist that are essential to understand when planning prehospital studies. Prehospital plasma is associated with a survival benefit primarily in SCENE group patients. The results are exploratory but suggest transfer origin may be an important determinant of prehospital plasma benefit.

Mutations of the JAK2 gene are frequent aberrations in the aging hematopoietic system and in myeloid neoplasms. While JAK-inhibitors efficiently reduce hyperinflammation induced by the constitutively active mutated JAK2 kinase, the malignant clone and abundance of mutated cells remains rather unaffected. Here, we sought to assess for genetic vulnerabilities of JAK2-mutated clones. We identified lysine-specific demethylase KDM4C as a selective genetic dependency that persists upon JAK-inhibitor treatment. Genetic inactivation of KDM4C in human and murine JAK2-mutated cells resulted in loss of cell competition and reduced proliferation. These findings led to reduced disease penetrance and improved survival in xenograft models of human JAK2-mutated cells. KDM4C deleted cells showed alterations in target histone residue methylation and target gene expression, resulting in induction of cellular senescence. In summary, these data establish KDM4C as a specific dependency and therapeutic target in JAK2-mutated cells that is essential for oncogenic signaling and prevents induction of senescence.

Background Rib fracture (RF) pain management provides analgesia while reducing opioids. We postulated: (1) Prescriber factors affect opiate duration, and (2) lidocaine infusion curtails dependency. Materials and Methods Retrospective study of RF patients undergoing multimodal analgesia at ACS-verified Level 1 Trauma Center April 2018-February 2020. Exclusions: ageResults 153 patients included – 113 (74%) stopped opiates by 30 days post-discharge (NORx30), 40 (26%) continued beyond 30 days (Rx+). No significant differences in age, gender, ISS, number of RF, bilaterality, flail chest, and discharge disposition. Significant differences included hospital LOS (7.62 NORx30 vs. 10.22 Rx+, p = .02), number of prescribers (1.73 NORx30 vs. 2.98 Rx+, p < .01), average MME/day during initial 30 days post-discharge (36.7 ± 17 NORx30 vs. 45.4 ± 30.2 Rx+, p = .03), and number of pills (49 ± 38 NORx30 vs. 120 ± 85 Rx+, p < .01). Patients who received lidocaine infusion (LIDO+) had lower MME/day prescribed (32.24 ± 19.9, p = .03), were younger (61.2 vs. 65.6, p < .01), had more RFs (7.1 vs. 6.05, p = .03), and shorter LOS (7.71 vs 10.2, p = .01). Discussion Prescriber attention to MME/day and number of pills dispensed affects opioid dependency. We recommend 35–40 MME/day with 50 pill/month limit prescribed by a single provider monitoring patient and CSMD. Early LI offers post-discharge opioid cessation advantage.

Background and Objectives: The Accreditation Council for Graduate Medical Education (ACGME) has implemented milestones for progression of residents. Career academic physicians would benefit from similar concrete guidance for scholarly activity and faculty development. After developing milestones across six recognized competencies among our family medicine academicians, we acknowledged the potential benefit of expanding the development of milestones throughout the academic medical center. Methods: Milestones that we previously developed were modified by departmental leaders within our institution reflecting levels of career development based on benchmarks in each field. These objective measures for guiding maturation of clinical and academic skill sets were then circulated to clinicians in five residency programs throughout our academic medical center for self-evaluation. We analyzed the completed surveys to determine if an association exists between years in academics and rank across each area of competency. Results: We received fifty-three responses from the 91 faculty invited. We noted a significant association in the competency of medical knowledge with progression from assistant to full professor, and we noted a trend toward significance in professionalism and progression from assistant to full professor. These objective measures of clinician development and competency suggest association with levels of academic career development by rank within the institution. Conclusions: This rubric can be helpful for directing faculty development and faculty mentorship. These milestones are general enough that other physician specialties may be able to adopt them for their own needs.

In 816 patients with 2016 World Health Organization-defined polycythemia vera (PV) enrolled in a multicenter retrospective study, we investigated the predictive value of Charlson comorbidity index (CCI) and body mass index (BMI) on thrombosis, progression to post-PV myelofibrosis (PPV-MF) and survival. Patients were subgrouped according to CCI=0 (58.1%, no comorbidities) or CCI≥1 (41.9%) and according to normal/underweight (BMI&nbsp

Introduction: From the perspective of social determinants, homelessness perpetuates poor health and creates barriers to effective chronic disease management, necessitating frequent use of emergency department (ED) services. In this study we developed a screening algorithm (checklist) from common comorbidities observed in the homeless population in the United States. The result was a theoretical screening tool (checklist) to aid healthcare workers in the ED, including residents, medical students, and other trainees, to provide more efficacious treatment and referrals for discharge. Methods: In this retrospective cohort study we used the Nationwide Emergency Department Sample (NEDS) to investigate comorbidities and ED utilization patterns relating to 23 injury-related, psychiatric, and frequent chronic medical conditions in the US adult (≥18 years of age) homeless population. Cases were identified from the NEDS database for 2014–2017 using International Classification of Diseases, 9th and 10 revisions, and Clinical Classification Software diagnosis codes. We performed a two-step cluster analysis including pathologies with ≥10% prevalence in the sample to identify shared comorbidities. We then compared the clusters by sociodemographic and ED-related characteristics, including age, gender, primary payer, and patient disposition from the ED. Chi-square analysis was used to evaluate categorical variables (ie, gender, primary payer, patient disposition from the ED), and analysis of variance for continuous variables (age). Results: The study included 1,715,777 weighted cases. The two-step cluster analysis identified nine groups denominated by most prevalent disease: 1) healthy; 2) mixed psychiatric; 3) major depressive disorder (MDD); 4) psychosis; 5) addiction; 6) essential hypertension; 7) chronic obstructive pulmonary disease (COPD); 8) infectious disease; and (9) injury. The MDD, COPD, infectious disease, and Injury clusters demonstrated the highest prevalence of co-occurring disease, with the MDD cluster displaying the highest proportion of comorbidities. Although the addiction cluster existed independently, substance use was pervasive in all except the healthy cluster (prevalence 36-100%). We used the extracted screening algorithm to establish a screening tool (checklist) for ED healthcare workers, with physicians as the first point of contact for the initial use of the screening tool. Conclusion: Healthcare workers in the ED, including residents, medical students, and other trainees, provide services for homeless ED users. Screening tools (checklists) can help coordinate care to improve treatment, referrals, and follow-up care to reduce hospital readmissions. The screening tool may expedite targeted interventions for homeless patients with commonly occurring patterns of disease.

To construct and validate a scale of emotional intelligence (EI) for the medical field, n = 80 resident physicians responded to a 69-item self-report measure during the pilot phase of development of the Scale of Emotional Functioning: Medicine (SEF:MED). Based on multiple-phase item and structural analyses, a final 36-item version was created based on data from n = 321 respondent residents. Initially exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) supported the expected three-factor solution as did additional CFA from a second sample of n = 113 participants. Internal consistency reliabilities obtained from the original n = 321 residents for the three SEF:MED subscales of Interpersonal Skills (IS), Emotional Awareness (EA), and Emotional Management (EM) were 0.81, 0.82, and 0.84, respectively. Alphas for the second CFA data set were 0.89, 0.87, and 0.88 for IS, EM, and EA, respectively. In addition, the SEF:MED was validated by comparing it to related measures (i.e., the Profile of Emotional Competence (PEC) and the Maslach Burnout Inventory-Human Services Survey for Medical Personnel [MBI-HSS (MP)]); Correlation coefficients between the Total EI composite on the SEF:MED and the PEC global scales ranged from r = 0.64 to 0.68. Finally, correlation coefficients from the Total EI composite on the SEF:MED significantly related to the MBI-HSS (MP) Emotional Exhaustion (EE), Depersonalization (DP), and Personal Accomplishment (PA) scales (r = −0.50, −0.44, and 0.52, respectively). The SEF:MED may provide useful data to physicians and other medical professionals as they consider their own well-being and how it may affect care of their patients.

Purpose Head and neck cancer is often associated with pain and perineural invasion (PNI). The purpose of this study was to determine the association of pain complaints and the microscopic identification of PNI in patients with oropharyngeal squamous cell carcinoma (OPSCC). Patients and Methods A retrospective cohort study was performed including patients diagnosed with OPSCC from 2010 to 2019. Patients diagnosed and operated on with curative intent at 2 institutions were included. The primary predictor variable was pain (measured as no pain, ear pain, throat pain, or simultaneous pain). Other variables were patient demographics, p16 status, and TNM staging. The primary outcome variable was the histologic presence of PNI. Chi-square analysis was performed to test for any significant associations between pain, T stage, overall stage, and p16 status in relation to PNI outcome. Multivariate logistic regression analysis was used to control for cancer staging variables when testing the association between pain and PNI. Results The final sample was composed of 157 subjects of whom 126 were men. The mean age was 59.7 years. Seventy-seven (49.0%) presented with no pain, while 35 (22.3%), 39 (24.8%), and 6 (3.8%) presented with both throat/ear pain, throat pain only, and ear pain only, respectively. Patients with simultaneous pain had 3.41 times higher odds of PNI compared to the no pain group (P = .02), although only pathologic T stage 4 and a diagnosis on the base of the tongue were independent postoperative predictors of PNI (P Conclusions Our study demonstrates that otalgia is a preoperative predictor of PNI in OPSCC and also demonstrates a trend of increasing pain complaints with PNI.

Emotional intelligence (EI) is associated with job success in multiple fields, in part, because EI may mitigate stress and burnout. Research suggests these relationships may include teaching. Our purpose is to further explore the relationships between EI, burnout, and teaching for faculty surgeons.With IRB approval, surgical faculty were offered the opportunity to complete personal demographics, the Maslach Burnout Inventory, the SETQ-SMART assessment of teaching ability, and the SEF:MED self-assessment of emotional intelligence. Surgical residents rated faculty teaching ability using the SETQ-SMART SETTING: A medium-sized academic medical center in the Southeast approved to graduate 6 residents per year.ACGME surgical faculty and general surgical residents PGY1 to PGY5 including preliminary residents, were given the opportunity to participate.Faculty self-assessed teaching scores were significantly different from resident scores for nine (60%) faculty; three (33%) overrated their and 6 (67%) under rated their overall teaching ability, relative to resident ratings. The 3 SEF:MED scales correlated low-moderate to strongly with the SETQ-OTS: IS (r = 0.41, p = 0.13), EM (r = 0.67, p0.01), and EA (r = 0.43, p = 0.11). Overall, 8(53%) faculty scored moderate to high on at least 1 of the 3 MBI subscales. Overall self-rated faculty teaching scores correlated negatively with higher EE and DP and positively with PA (r = -0.08, -0.21, and 0.52, p = 0.047; respectively). EI negatively correlated with MBI-EE and DP and positively with PA (r = -0.31, -0.18, 0.45, respectively), though due to the small sample none reach statistical significance with alpha set to 0.05.In this pilot study, EI is positively correlated to surgical faculty members' teaching ability. Burnout was less strongly correlated with resident-assessed faculty teaching scores, but with similar trends. Finally, EI was correlated with MBI EE, DP, and PA as expected given the literature in other fields. Expanded study is warranted.

Objective. Team-based learning is widely used in pharmacy education. In this context, students need to be incentivized to do preclass preparation, thus ensuring they are ready for team-based learning, via graded readiness assurance tests (RATs). The purpose of this study was to determine the effect of graded versus ungraded RATs on examination performance in an ambulatory care elective course for third-year student pharmacists. Methods. For the course offered in spring 2020 and 2021, a standard team-based learning framework was employed. In 2020 the RATs were graded and contributed to the overall course grade (graded RAT cohort), but in 2021 RAT grades did not contribute to the course grade (ungraded RAT cohort). For the ungraded RAT cohort, at the end of the course students completed an online anonymous survey regarding class preparation and perceived team accountability. Results. No significant difference was found between the graded RAT (n=47) and ungraded RAT cohorts (n=36) in the overall mean percentage score on individual RATs (76% vs 74%) and individual examinations (82% vs 80%). Most students (69%-91%) in the ungraded RAT cohort reported completing preclass preparation assignments. In the postcourse survey, 94% of students agreed or strongly agreed that RATs contributed to team members’ learning, and 86% agreed or strongly agreed that they were proud of their ability to assist in the team’s learning. Conclusion. Ungraded RATs did not significantly impact students’ examination performance in an elective course. Removing the grading of this test, whereby grading promotes the performance approach to learning, may have shifted the students’ motivation to the mastery approach in the context of preclass preparation. This challenges a widely held belief that grades are necessary incentives for preclass preparation within team-based learning.

Myeloproliferative disease Enfermedad mieloproliferativa Malaltia mieloproliferativa The study was supported by a research grant by the COVID “3 × 1 project”, BREMBO S.p.A., Bergamo, Italy (T.B.) and by AIRC 5 × 1000 call “Metastatic disease: the key unmet need in oncology” to MYNERVA project, #21267 (MYeloid NEoplasms Research Venture AIRC). A detailed description of the MYNERVA project is available at https://progettomynerva.it (A.M.V., P.G.). The study was also supported by HARMONY PLUS, which is funded through the Innovative Medicines Initiative (IMI), Europe’s largest public–private initiative aiming to speed up the development of better and safer medicines for patients. The HARMONY Alliance has received funding from IMI 2 Joint Undertaking and is listed under grant agreement No. 945406. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). IMI supports collaborative research projects and builds networks of industrial and academic experts in order to boost pharmaceutical innovation in Europe.

Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression.

PURPOSE: Approximately 3-15% of COVID-19 patients will require prolonged mechanical ventilation thereby requiring consideration for tracheotomy. Guidelines for tracheotomy in this cohort of patients are therefore required with assessed outcomes of tracheotomies. PATIENTS AND METHODS: A retrospective chart review was performed of COVID-19 patients undergoing tracheotomy. Inclusion criteria were the performance of a tracheotomy in COVID-19 positive patients between March 11 and December 31, 2020. Exclusion criteria were lack of consent, extubation prior to the performance of a tracheotomy, death prior to the performance of the tracheotomy, and COVID-19 patients undergoing tracheotomy who tested negative twice after medical treatment. The primary predictor variable was the performance of a tracheotomy in COVID-19 positive patients and the primary outcome variable was the time to cessation of mechanical ventilation with the institution of supplemental oxygen via trach mask. RESULTS: Seventeen tracheotomies were performed between 4-25 days following intubation (mean = 17 days). Seven patients died between 4 and 16 days (mean = 8.7 days) following tracheotomy and 10 living patients realized cessation of mechanical ventilation from 4 hours to 61 days following tracheotomy (mean = 19.3 days). These patients underwent tracheotomy between 4 and 22 days following intubation (mean = 14 days). The 7 patients who died following tracheotomy underwent the procedure between 7 and 25 days following intubation (mean = 18.2 days). Seven patients underwent tracheotomy on or after 20 days of intubation and 3 survived (43%). Ten patients underwent tracheotomy before 20 days of intubation and 7 patients survived (70%). Significant differences between the mortality groups were detected for age (P = .006), and for P/F ratio at time of consult (P = .047) and the time of tracheotomy (P = .03). CONCLUSIONS: Tracheotomies are safely performed in COVID-19 patients with a standardized protocol. The timing of tracheotomy in COVID-19 patients is based on ventilator parameters, P/F ratio, patient prognosis, patient advanced directives, and family wishes.

Background Delirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population. Methods The study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events. Results The incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002). Conclusions The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

Rationale: Health outcomes of people with coronavirus disease (COVID-19) range from no symptoms to severe illness and death. Asthma, a common chronic lung disease, has been considered likely to increase the severity of COVID-19, although data addressing this hypothesis have been scarce until very recently. Objectives: To review the epidemiologic literature related to asthma’s potential role in COVID-19 severity. Methods: Studies were identified through the PubMed (MEDLINE) and medRxiv (preprint) databases using the search terms “asthma,” “SARS-CoV-2” (severe acute respiratory syndrome coronavirus 2), and “COVID-19,” and by cross-referencing citations in identified studies that were available in print or online before December 22, 2020. Measurements and Main Results: Asthma prevalence data were obtained from studies of people with COVID-19 and regional health statistics. We identified 150 studies worldwide that allowed us to compare the prevalence of asthma in patients with COVID-19 by region, disease severity, and mortality. The results of our analyses do not provide clear evidence of increased risk of COVID-19 diagnosis, hospitalization, severity, or mortality due to asthma. Conclusions: These findings could provide some reassurance to people with asthma regarding its potential to increase their risk of severe morbidity from COVID-19.

Medical comorbidities may contribute to falls and thus require identification for education and prevention. We hypothesized that the epidemiology and injuries seen will be similar to the literature, with most falls that result in injury occurring in the elderly, to prominent facial structures, and are associated with specific comorbidities.A retrospective review was performed of patients evaluated by the Trauma and Oral and Maxillofacial Surgery services after sustaining traumatic facial injury from July 2015 to June 2016 as a result of a fall. Associations between injury patterns, previous falls, and medical comorbidities were analyzed, and descriptive and bivariate statistics were reported.Of 152 patients included, 53.3% were females with a mean age of 61.2 years. Soft tissue laceration was seen in 59.9% of patients. The 3 most common fracture patterns seen were nasal fracture in 30.9%, orbital fracture in 30.3%, and zygoma fracture in 20.4%. Cardiovascular disease (53.3%) was the most common comorbidity. No major comorbidity was seen in 32.9% of patients. There was a significant association between orbital fracture and neurologic disease (P = .04). Patients with neurologic disease had a significantly longer length of stay (P .001), and those without any major comorbidities had a significantly shorter length of stay (P = .02). Patients with previous emergency department visits for falls were significantly older (P = .03), had more comorbidities (P = .005), and were more likely to have cardiovascular disease and associated comorbidities (P = .001).The results are consistent with the literature, with the most fall-related trauma occurring in the elderly with injury to prominent facial structures. The most common comorbidity was cardiovascular disease, which was associated with previous falls. There is a significant association between neurologic disease and orbital fractures. Future studies should focus on recurrent falls after receiving appropriate education to reduce risk based on their specific comorbidities.

Introduction To compare changes in muscle size, strength, and power between free-weight and machine-based exercises. Evidence acquisition The online databases of Pubmed, Scopus, and Web of Science were each searched using the following terms: ""free weights" OR barbells OR dumbbells AND machines" up until September 15, 2020. A three-level random effects meta-analytic model was used to compute effect sizes. Evidence synthesis When strength was tested using a free-weight exercise, individuals training with free-weights gained more strength than those training with machines [ES: 0.655; (95% CI: 0.269, 1.041)]. When strength was tested a machine-based exercise incorporated as part of the machine-based training program, individuals training with machines gained more strength than those training with free-weights [ES: -0.784 (95% CI: -1.223, -0.344)]. When strength was tested using a neutral device, machines and free-weight exercises resulted in similar strength gains [ES: 0.128 (95% CI: -0303, 0.559)]. There were no differences in the change in power [ES: -0.049 (95% CI: -0.557, 0.460)] or muscle hypertrophy [ES: -0.01 (95% CI: -0.525, 0.545)] between exercise modes. Conclusions Individuals looking to increase strength and power should take into account the specificity of exercise, and how their strength and power will be tested and applied. Individuals looking to increase general strength and muscle mass to maintain health may choose whichever activity they prefer and are more likely to adhere to.

Background Anecdotal experience demonstrates the existence of patients with superiorly located carotid stenosis, neoplasms, or aneurysms where the mandible obstructs effective surgical access using standard techniques. As carotid pathology extends anatomically beyond the limits of standard operative technique, additional exposure becomes paramount to safely and effectively address the lesion. Double mandibular osteotomy (DMO) is one of several techniques to obtain additional exposure to high-carotid pathology; however, there is no large series to address the outcomes of patients undergoing this procedure. Methods A retrospective case series was performed for all patients undergoing surgery for carotid pathology from 2011–2019 that could not be approached with standard cervical incision. The primary predictor variable was high–anatomic carotid pathology necessitating DMO. The primary outcome variable was early and late complications sustained by patients. Results Fifteen patients met study criteria and underwent 16 DMOs to access high-carotid pathology including carotid stenosis (n = 8 patients), carotid aneurysm (n = 2 patients), and carotid body tumor (n = 8 patients). Two patients had dual ipsilateral pathology with one patient having both carotid artery stenosis and aneurysm, and the other patient diagnosed with carotid artery stenosis and carotid body tumor. One patient had bilateral carotid artery stenosis, each requiring high anatomic exposure for treatment. Early complications occurred in 8 patients. Five patients experienced significant dysphagia requiring enteral feeding, and 2 patients developed malocclusion directly related to the double mandibular osteotomy. One patient experienced contralateral cortical watershed infarcts. Late complications included one patient developing osteomyelitis of the mandible, and this patient also developed distal mandibular segment screw exposure. The comparison of the outcome groups for categorical predictor variables using Fisher's exact test detected no statistically significant differences for gender, hypertension, hyperlipidemia, type 2 diabetes, chronic obstructive pulmonary disease, tobacco use, chronic kidney disease, or cerebrovascular disease. For the continuous variable comparisons, independent-samples t-tests detected no difference between the complication groups for age, operative time, or years of follow-up. No significant differences were found between the groups for body mass index or intraoperative blood loss. Conclusions The double mandibular osteotomy provides excellent exposure and surgical access to the distal internal carotid artery for repair of vascular pathology with acceptable outcomes and long-term complications compared with previously reported techniques. Because of the early complications realized with the DMO, we recommend the procedure for symptomatic patients with a high risk of failing medical therapy alone and not appropriate for endovascular treatment as well as those patients with tumors requiring surgical intervention.

Janus kinases (JAKs) mediate responses to cytokines, hormones and growth factors in haematopoietic cells1,2. The JAK gene JAK2 is frequently mutated in the ageing haematopoietic system3,4 and in haematopoietic cancers5. JAK2 mutations constitutively activate downstream signalling and are drivers of myeloproliferative neoplasm (MPN). In clinical use, JAK inhibitors have mixed effects on the overall disease burden of JAK2-mutated clones6,7, prompting us to investigate the mechanism underlying disease persistence. Here, by in-depth phosphoproteome profiling, we identify proteins involved in mRNA processing as targets of mutant JAK2. We found that inactivation of YBX1, a post-translationally modified target of JAK2, sensitizes cells that persist despite treatment with JAK inhibitors to apoptosis and results in RNA mis-splicing, enrichment for retained introns and disruption of the transcriptional control of extracellular signal-regulated kinase (ERK) signalling. In combination with pharmacological JAK inhibition, YBX1 inactivation induces apoptosis in JAK2-dependent mouse and primary human cells, causing regression of the malignant clones in vivo, and inducing molecular remission. This identifies and validates a cell-intrinsic mechanism whereby differential protein phosphorylation causes splicing-dependent alterations of JAK2–ERK signalling and the maintenance of JAK2V617F malignant clones. Therapeutic targeting of YBX1-dependent ERK signalling in combination with JAK2 inhibition could thus eradicate cells harbouring mutations in JAK2. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

An important limitation of FLT3 tyrosine kinase inhibitors (TKIs) in FLT3-ITD positive AML is the development of resistance. To better understand resistance to FLT3 inhibition, we examined FLT3-ITD positive cell lines which had acquired resistance to midostaurin or sorafenib. In 6 out of 23 TKI resistant cell lines we were able to detect a JAK1 V658F mutation, a mutation that led to reactivation of the CSF2RB-STAT5 pathway. Knockdown of JAK1, or treatment with a JAK inhibitor, resensitized cells to FLT3 inhibition. Out of 136 patients with FLT3-ITD mutated AML and exposed to FLT3 inhibitor, we found seven different JAK family mutations in six of the cases (4.4%), including five bona fide, activating mutations. Except for one patient, the JAK mutations occurred de novo (n = 4) or displayed increasing variant allele frequency after exposure to FLT3 TKI (n = 1). In vitro each of the five activating variants were found to induce resistance to FLT3-ITD inhibition, which was then overcome by dual FLT3/JAK inhibition. In conclusion, our data characterize a novel mechanism of resistance to FLT3-ITD inhibition and may offer a potential therapy, using dual JAK and FLT3 inhibition.

Pregnancies in women with essential thrombocythemia (ET) are at a higher risk for obstetrical complications. Acetylsalicylic acid (ASA) and low-molecular weight heparin (LMWH) are common options to prevent miscarriages and maternal complications, whereas interferon alpha (IFN) seems to be the cytoreductive therapy of choice. This retrospective study analyzes the largest number of IFN pregnancies to date in terms of outcome and safety. Data of 34 high-risk pregnancies in 23 women presenting at the University hospitals of Minden and Jena from 01-Jun-2007 to 01-Jun-2020 were collected. Reasons defining high-risk ET pregnancy in all 23 patients were: Thrombosis (n = 9) or severe hemorrhage (n = 2) in history, platelet count ≥ 1500 × 103/µl (n = 8) or severe microcirculatory disturbances not completely responding to ASA (n = 4). Without the use of IFN, live birth rate was 60% (6/10), however, after the use of IFN live birth rate increased to 73.5% (25/34 pregnancies). Nine pregnancies ended in miscarriages (9/34; 26.5%); all of them spontaneous abortions. Live birth rate significantly improved with ASA (90% versus 50%, p = 0.0168), however, if ASA and LMWH was added (n = 14), live birth rate was 100%. IFN compound (PEGylated versus standard IFN) and JAK2-driver mutation had no impact on pregnancy outcome. One major maternal complication occurred as a major peripartal bleeding after abortion curettage. IFN was associated with an encouraging live birth rate of 73.5% with no fatal maternal events and manageable side effects.

Mutant KRAS modulates the metabolic plasticity of cancer cells to confer a growth advantage during hypoxia, but the molecular underpinnings are largely unknown. Using a lipidomic screen, we found that PLCγ1 is suppressed during hypoxia in KRAS-mutant human lung adenocarcinoma cancer cell lines. Suppression of PLCγ1 in hypoxia promotes a less oxidative cancer cell metabolism state, reduces the formation of mitochondrial reactive oxygen species and switches tumour bioenergetics towards glycolysis by impairing Ca2+ entry into the mitochondria. This event prevents lipid peroxidation, antagonizes apoptosis and increases cancer cell proliferation. Accordingly, loss of function of Plcg1 in a mouse model of KrasG12D-driven lung adenocarcinoma increased the expression of glycolytic genes, boosted tumour growth and reduced survival. In patients with KRAS-mutant lung adenocarcinomas, low PLCγ1 expression correlates with increased expression of hypoxia markers and predicts poor patient survival. Thus, our work reveals a mechanism of cancer cell adaptation to hypoxia with potential therapeutic value.

Background Enhanced recovery after surgery (ERAS) protocols are widely utilized for elective colorectal surgery to improve outcomes and decrease costs, but few studies have evaluated the impact of ERAS protocols on cost with respect to anatomic site of resection. This study evaluated the impact of ERAS protocol on elective colon resections by site and longitudinal impact over time. Methods A single-center retrospective cohort study of 598 consecutive patients undergoing elective colorectal resection before and after implementation of ERAS protocol from 2013 to 2017 was performed. The primary outcomes were length of stay (LOS) and cost. Comparative and multivariate inferential statistics were used to assess additional outcomes. Results A total of 598 patients (100 pre-ERAS vs 498 post-ERAS) were evaluated with an overall median LOS of 4 days for right and left colectomies and 3 days for transverse colectomies. When comparing type of resection before and after ERAS protocol introduction, an increased LOS for left hemicolectomies from 3.09 to 4.03 days ( P = .047) was noted, with all other comparisons failing to reach statistical significance. Over time, an initial decrease in LOS for MIS approach after protocol introduction was observed; however, this effect diminished in the ensuing years and had no significant effect overall. Total cost of care was significantly increased post-ERAS for all cohorts except transverse colectomies. No further statistically significant differences were found. Conclusion After an initial improvement in outcomes, continued utilization of ERAS protocols demonstrated no improvement in LOS compared to pre-ERAS data and increased cost overall for patients regardless of site of resection.

Purpose Tongue cancer is often associated with pain and perineural invasion. The purpose of the present study was to determine the association between tongue pain and otalgia and the microscopic identification of perineural invasion (PNI) in patients with squamous cell carcinoma of the tongue (SCCOT). Patients and Methods A retrospective cohort study was performed of patients with a diagnosis of SCCOT from January 2013 through June 2019. Patients without a history of head and neck cancer, who had SCCOT diagnosed and treated surgically by a single surgeon, were included in the present study. The primary predictor variables were tongue pain and otalgia (presence vs absence of both). Other variables included patient demographic data and TNM stage. The primary outcome variable was the histologic presence of PNI. A χ2 analysis was performed to test for any significant associations between pain, T stage, and overall stage in relation to PNI outcome. Multivariate logistic regression analysis was used to control for cancer staging variables when testing the association between pain and PNI. Results The sample included 128 subjects, of whom 76 were men. Their mean age was 60 years. Most patients (n = 97; 75.8%) complained of tongue pain and a few (n = 50; 39.1%) complained of otalgia. The patients with otalgia had a 3.15 times greater odds of PNI when controlling for T stage (P = .016) and 3.68 times greater odds of PNI when controlling for overall stage (P = .007). Increasing T stage and overall stage—with the exception of stage II—were also significantly associated with PNI (P ≤ .05). Conclusions Our study has demonstrated a statistically significant association between preoperative otalgia and PNI in a consecutive group of patients presenting with newly diagnosed SCCOT.

Background: Neuromuscular blockers (NMBs) used during surgery have historically been reversed with acetylcholinesterase inhibitors and anticholinergic agents, which can slow gastrointestinal motility. Sugammadex (SUG) provides NMB reversal with minimal effects on gastrointestinal motility. Objective: The purpose of this study was to determine if SUG for reversal of NMB is associated with decreased time to first bowel movement (BM) following laparoscopic colorectal surgery. Methods: A retrospective cohort analysis divided 224 patients undergoing laparoscopic colorectal surgeries based on whether they received SUG or a combination of neostigmine and glycopyrrolate (NG) for NMB reversal. The primary outcome was time (in hours) from NMB reversal until first recorded BM. Secondary end points were postoperative ileus, postoperative nausea and vomiting, prevalence of residual NMB, and hospital length of stay. The relationship between NMB reversal agent and outcomes were analyzed using multivariable linear regression and Cox proportional hazards model. Results: There were 128 patients who received NG and 96 who received SUG. Time to first BM was faster in the SUG group by 11.7 hours ( P = 0.004). SUG maintained the effect in a multiple regression model ( P = 0.012). A Cox Proportional Hazards regression model found 50% increased odds of a BM across time for the SUG group ( P = 0.003). No adverse effects were noted. Conclusion and Relevance: This represents the first report demonstrating faster return of BM following colorectal surgery with SUG when compared with NG. Application of these data may add another tool to enhance recovery after colorectal surgery.

Clonal hematopoiesis is frequently observed in elderly people. To investigate the prevalence and dynamics of genetic alterations among healthy elderly individuals, a cohort of 50 people >80 years was genotyped for commonly mutated leukemia-associated genes by targeted deep next-generation sequencing. A total of 16 somatic mutations were identified in 13/50 (26%) individuals. Mutations occurred at low variant allele frequencies (median 11.7%) and remained virtually stable over 3 years without development of hematologic malignancies in affected individuals. With DNMT3A mutations most frequently detected, another cohort of 160 healthy people spanning all age groups was sequenced specifically for DNMT3A revealing an overall mutation rate of 6.2% (13/210) and an age-dependent increase of mutation prevalence. A significant difference (p = 0.017) in the DNMT3A expression pattern was detected between younger and healthy elderly people as determined by qRT-PCR. To evaluate the selection of clonal hematopoietic stem cells (HSCs), bone marrow of two healthy individuals with mutant DNMT3A was transplanted in a humanized mouse model. Xenografts displayed stable kinetics of DNMT3A mutations over 8 months. These findings indicate that the appearance of low-level clones with leukemia-associated mutations is a common age-associated phenomenon, but insufficient to initiate clonal selection and expansion without the additional influence of other factors.

To compare clonidine versus phenobarbital as adjunctive therapy in infants who failed monotherapy with morphine for neonatal abstinence syndrome (NAS). Prospective, randomized, open-label study of infants ≥ 35 weeks’ gestation. Infants received clonidine or phenobarbital per protocol. Primary outcome was morphine treatment days. Secondary outcomes were inpatient adjunctive days, length of stay (LOS), triple therapy, safety, and readmission rates. A total of 25 infants were treated with clonidine (n = 14) or phenobarbital (n = 11). Mean morphine treatment duration was significantly longer with clonidine (34.4 days, SD = 10.6) compared with phenobarbital (25.5 days, SD = 7.3, p = 0.026). The clonidine group also had higher inpatient adjunctive days (mean: 33.8 days [SD = 14.3] vs. 22 days [SD = 12.6], p = 0.042) and LOS (mean: 41.8 days [SD = 10.9] vs. 31 days [SD = 10]; p = 0.018) compared with phenobarbital. Phenobarbital, as adjunctive therapy, led to significantly shorter duration of morphine therapy, inpatient adjunctive days, and length of stay compared with clonidine.

Bleeding remains a complication during dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). Some data suggest a link between bleeding and worsened vascular outcomes. However, this association is unclear, due to omitting of minor bleedings when applying conservative scales. In contrast, the Platelet Inhibition and Outcomes (PLATO) trial classification used broad realistic capturing of all bleedings.Access was gained to the Food and Drug Administration-issued adjudication data set on which post hoc analyses of bleeding, myocardial infarction (MI), stroke, and death were conducted. Bleeding was defined as minimal, minor, major, and life-threatening or fatal (LTOF) as per the original PLATO scale.Among 18,624 enrollees, 10,705 adjudicated events occurred across 7171 patients. There were 618 minimal, 1412 minor, 1216 major, and 536 LTOF bleedings for the total of 3782 events reported in 3387 patients. There were 938 deaths, 2751 MIs and 359 strokes. The overall bleeding was 20.3%, exhibited in 19.2% patients. Total bleeds were associated with less deaths (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.47-0.63) and MI (OR: 0.47, 95% CI: 0.41-0.54; P.001 for both). There were no differences in deaths (OR: 1.11, 95% CI: 0.93-1.34; P = .24), but less MIs (OR: 0.72. 95% CI: 0.59-0.86; P.001), and more strokes (OR: 2.17, 95% CI: 1.64-2.88; P.001) after LTOF. Major, minor, and minimal bleeds were associated with less deaths and MI but not strokes.These large uniformly adjudicated data reveal that within 12 months of dual antiplatelet therapy, 1 out of 5 patients experiences bleeding. Overall, bleeding was associated with diminished incidence of death and MI but not strokes.

Dialysis access creation is a common outpatient procedure that can be completed using general, regional, or local anesthetic techniques. There are few endorsed guidelines regarding opioid-based pain control following fistula creation. The purpose of this study was to determine whether utilization of regional anesthesia (RA) is associated with the decreased use of narcotics postoperatively.We performed a prospective cohort study including all patients undergoing arteriovenous fistula creation with one vascular surgeon from August 2019 to February 2020. Patients were selected for regional versus general anesthesia. Selection for anesthesia type was determined by the primary anesthesiologist. Patients selected for RA underwent supraclavicular brachial plexus block with 30 cmIn the study period, 52 patients underwent arteriovenous fistula creation and completed the follow-up questionnaire. Forty patients received RA. Seventy-five percent of patients sent home with a narcotic prescription filled the prescription. There was a significant difference in postoperative opioid use between the two study groups. Patients who received regional block took on average 3.3 pills totaling 16.5 morphine milligram equivalents, whereas patients who received general anesthesia took on average 6.64 pills totaling 33.2 morphine milligram equivalents (Morbidity and mortality related to opiate use continues to be a public health issue in the United States. This study demonstrates that regional anesthetic techniques in comparison to general anesthesia can result in a significant decrease in postoperative opiate consumption.

In an effort to identify novel drugs targeting fusion-oncogene–induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE)-driven AML, we uncovered a deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein that is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO+ leukemic stem cells.

Background Aortic stenosis (AS) can cause acquired von Willebrand syndrome (AVWS) and valve replacement has been shown to lead to von Willebrand factor (vWF) recovery. The aim of the current study was to investigate the prevalence of AVWS in different severe AS phenotypes and its course after transcatheter aortic valve implantation (TAVI). Methods 143 patients with severe AS undergoing TAVI were included in the study. vWF function was assessed at baseline, 6 and 24 h after TAVI. AVWS was defined as a reduced vWF:Ac/Ag ratio ≤ 0.7. Phenotypes were classified by tricuspid (TAV) and bicuspid (BAV) valve morphology, mean transvalvular gradient (Pmean), stroke volume index (SVI), ejection fraction (EF) and indexed effective orifice area (iEOA). Results AVWS was present in 36 (25.2%) patients before TAVI. vWF:Ac/Ag ratio was significantly lower in high gradient compared to low-gradient severe AS [0.78 (IQR 0.67–0.86) vs. 0.83 (IQR 0.74–0.93), p p p Conclusions BAV morphology is a strong predictor for AVWS in severe AS. TAVI restores vWF function in most patients with severe AS independently of AS phenotype and valve morphology. Graphical abstract

Purpose Oxidative stress has been linked to initiation and progression of cancer and recent studies have indicated a potential translational role regarding modulation of ROS in various cancers, including acute myeloid leukemia (AML). Detailed understanding of the complex machinery regulating ROS including its producer elements in cancer is required to define potential translational therapeutic use. Based on previous studies in acute myeloid leukemia (AML) models, we considered NADPH oxidase (NOX) family members, specifically NOX4 as a potential target in AML. Methods Pharmacologic inhibition and genetic inactivation of NOX4 in murine and human models of AML were used to understand its functional role. For genetic inactivation, CRISPR-Cas9 technology was used in human AML cell lines in vitro and genetically engineered knockout mice for Nox4 were used for deletion of Nox4 in hematopoietic cells via Mx1-Cre recombinase activation. Results Pharmacologic NOX inhibitors and CRISPR-Cas9-mediated inactivation of NOX4 and p22-phox (an essential NOX component) decreased proliferative capacity and cell competition in FLT3-ITD-positive human AML cells. In contrast, conditional deletion of Nox4 enhanced the myeloproliferative phenotype of an FLT3-ITD induced knock-in mouse model. Finally, Nox4 inactivation in normal hematopoietic stem and progenitor cells (HSPCs) caused a minor reduction in HSC numbers and reconstitution capacity. Conclusion The role of NOX4 in myeloid malignancies appears highly context-dependent and its inactivation results in either enhancing or inhibitory effects. Therefore, targeting NOX4 in FLT3-ITD positive myeloid malignancies requires additional pre-clinical assessment.

Aim: To assess real-world ruxolitinib treatment patterns and outcomes in patients diagnosed with primary or secondary myelofibrosis. Materials & methods: Patient medical records were reviewed in six countries. Results: Eligible patients (n = 469) had a mean age of 63.5 years, and most were male (66.5%) with primary myelofibrosis (78.5%). Median duration of ruxolitinib treatment was 13.1 months; 40% of patients initiated treatment at the recommended dose. The Kaplan–Meier estimate of median survival from ruxolitinib initiation was 44.4 months (95% CI, 38.8–50.2 months). Approximately one quarter (23%) of patients continued ruxolitinib after progression. Conclusion: These results suggest an unmet need for more effective treatments for patients with myelofibrosis who failed ruxolitinib.

BACKGROUND: After ruxolitinib discontinuation, the outcome of patients with myelofibrosis (MF) is poor with scarce therapeutic possibilities. METHODS: The authors performed a subanalysis of an observational, retrospective study (RUX-MF) that included 703 MF patients treated with ruxolitinib to investigate 1) the frequency and reasons for ruxolitinib rechallenge, 2) its therapeutic effects, and 3) its impact on overall survival. RESULTS: A total of 219 patients (31.2%) discontinued ruxolitinib for ≥14 days and survived for ≥30 days. In 60 patients (27.4%), ruxolitinib was rechallenged for ≥14 days (RUX-again patients), whereas 159 patients (72.6%) discontinued it permanently (RUX-stop patients). The baseline characteristics of the 2 cohorts were comparable, but discontinuation due to a lack/loss of spleen response was lower in RUX-again patients (P =.004). In comparison with the disease status at the first ruxolitinib stop, at its restart, there was a significant increase in patients with large splenomegaly (P 10 mg twice daily predicted better spleen (P =.05) and symptom improvements (P =.02), the reasons for/duration of ruxolitinib discontinuation and the use of other therapies before rechallenge were not associated with rechallenge efficacy. At 1 and 2 years, 33.3% and 48.3% of RUX-again patients, respectively, had permanently discontinued ruxolitinib. The median overall survival was 27.9 months, and it was significantly longer for RUX-again patients (P =.004). CONCLUSIONS: Ruxolitinib rechallenge was mainly used in intolerant patients; there were clinical improvements and a possible survival advantage in many cases, but there was a substantial rate of permanent discontinuation. Ruxolitinib rechallenge should be balanced against newer therapeutic possibilities.

No abstract available

Comorbidities defined by the Charlson comorbidity index (CCI) and body mass index (BMI) are significantly associated with outcome in patients who receive continuous treatment with tyrosine kinase inhibitors. We evaluated the impact of CCI and BMI on responses, drug-related toxicities, and outcome in a cohort of 402 patients with myelofibrosis (MF) treated with ruxolitinib in 23 European Hematology Centers. Comorbidities were evaluable in all 402 patients. A higher (≥ 3) CCI did not correlate with a lower spleen reduction at any time (p = 0.68) or symptoms' response (p = 0.11), but influenced the onset of anemia during the first 3months of treatment and later (p = 0.02 and p = 0.03, respectively) in patients without anemia baseline. BMI was evaluable in 380 patients and did not correlate with differences in spleen and symptoms response (p = 0.57 and p = 0.49, respectively). A higher CCI and a lower BMI correlated also with a reduced overall survival (p

BACKGROUND: Pediatric heart transplant (PHT) patients have the highest waitlist mortality of solid organ transplants, yet more than 40% of viable hearts are unutilized. A tool for risk prediction could impact these outcomes. This study aimed to compare and validate the PHT risk score models (RSMs) in the literature. METHODS: The literature was reviewed to identify RSMs published. The United Network for Organ Sharing (UNOS) registry was used to validate the published models identified in a pediatric cohort ( 0.6]. Choudhry (AUC = 0.69) and SRTR (AUC = 0.71) remained the best predicting RSMs even after adjustment. CONCLUSION: Although the RSMs by SRTR and Choudhry provided the best prediction for 1-year mortality, none demonstrated a strong (AUC ≥ 0.8) concordance statistic. All published studies lacked advanced analytical approaches and were derived from an inherently limited dataset.

Objectives Hypothermia occurs in 30-50% of severely injured trauma patients and is associated with multiple metabolic derangements and worsened outcomes. However, hypothermia continues to be under-diagnosed which leads to inadequate triage and treatment in trauma patients. Our study set out to determine if hypothermia is an independent predictor of mortality in trauma patients. Methods We retrospectively reviewed data of all trauma activation patients over a 5-year period. Data were collected on patient demographics, initial core temperature, Glasgow Coma Scale (GCS) on presentation, and injury severity score (ISS). Patients were then stratified into groups based on presenting temperature, ISS, and GCS. Outcomes compared were mortality, blood products received, and intensive care unit (ICU) length of stay. Correlations and logistic regression were used to test the hypotheses. Results Survival and temperature data were reviewed on 15,567 patients. Initial temperature was not significantly associated with ICU length of stay or blood products transfused ( P = .21 and P = .08, respectively). However, odds ratio of mortality in hypothermic patients (Conclusions Hypothermia is an independent risk factor for mortality in trauma patients. It remains crucial to obtain accurate presenting temperatures in trauma patients in order to triage and treat hypothermia. Based on our data, obtaining core temperatures and rapidly treating hypothermia continues to be a vital part of the secondary survey of trauma patients.

Background Multimodal analgesia in rib fractures (RFs) is designed to maximize pain control while minimizing narcotics. Prior research with intravenous lidocaine (IVL) efficacy produced conflicting results. We hypothesized IVL infusion reduces opioid utilization and pain scores. Methods A retrospective review of RF patients at an ACS-verified Level I trauma center from April 2018 to 2/2020 was conducted. Patients (pts) stratified as receiving IVL vs no IVL. Initial lidocaine dose: 1 mg/kg/hr with a maximum of 3 mg/kg/hr. Duration of infusion: 48 h. Pain quantified by the Stanford Pain Score system (PS). Bivariate and multivariate analyses of variables were performed on SPSS, version 21 (IBM Corp). Results 414 pts met inclusion criteria: 254 males and 160 females. The average age for the non-IVL = 67.4 ± 15.2 years vs IVL = 58.3 ± 17.1 years ( P < .001). There were no statistically significant differences between groups for ISS, PS for initial 48 h, and ICU length of stay (LOS). There was a difference in morphine equivalents per hour: non-IVL = 1.25 vs IVL = 1.72 ( P = .004) and LOS non-IVL = 10.2+/−7.6 vs IVL = 7.82+/−4.94. By analyzing IVL pts in a crossover comparison before and after IVL, there was reduction in opiates: 3.01 vs 1.72 ( P < .001) and PS: 7.0 vs 4.9 ( P < .001). Stanford Pain Score system reduction in the IVL = 48.3 ± 23.9%, but less effective in narcotic dependency (27 ± 22.9%, P = .035); IVL pts had hospital cost reduction: $82,927 vs $118,202 ( P < .01). Discussion In a crossover analysis, IVL is effective for reduction of PS and opiate use and reduces hospital LOS and costs. Patient age may confound interpretation of results. Our data support IVL use in multimodal pain regimens. Future prospective study is warranted.