Time to Mobility Is Associated With Pulmonary Complications in Patients With Spine Fractures.

INTRODUCTION: Treatment of spine fractures may require periods of prolonged immobilization which prevents effective pulmonary toileting. We hypothesized that patients with longer time to mobilization, as measured by time to first physical therapy (PT) session, would have higher pulmonary complications. METHODS: We performed a retrospective review of all trauma patients with cervical and thoracolumbar spinal fractures admitted to a level 1 trauma center over a 12-month period. Demographic data collection included age, gender, BMI, pulmonary comorbidities, concomitant rib fractures, admission GCS, Injury Severity Score (ISS), GCS at 24 h, treatment with cervical or thoracolumbar immobilization, and time to first PT evaluation. The primary outcome was the presence of any one of the following complications: unplanned intubation, pneumonia, or mortality at 30 days. Multivariable logistic regression analysis was used to assess significant predictors of pulmonary complication. RESULTS: In total, 491 patients were identified. In terms of overall pulmonary complications, 10% developed pneumonia, 13% had unplanned intubation, and 6% died within 30 days. In total, 19% developed one or more complication. Overall, 25% of patients were seen by PT <48 h, 33% between 48 and 96 h, 19% at 96 h to 1 week, and 7% > 1 week. Multivariable logistic regression analysis showed that time to PT session (OR 1.010, 95% CI 1.005-1.016) and ISS (OR 1.063, 95% CI 1.026-1.102) were independently associated with pulmonary complication. CONCLUSION: Time to mobility is independently associated with pulmonary complications in patients with spine fractures.

A Single Hospital-Wide Antibiogram is Insufficient to Account for Differences in Antibiotic Resistance Patterns Across Multiple ICUs.

BACKGROUND: Infection is a common cause of mortality within intensive care units (ICUs). Antibiotic resistance patterns and culture data are used to create antibiograms. Knowledge of antibiograms facilitates guiding empiric therapies and reduces mortality. Most major hospitals utilize data collection to create hospital-wide antibiograms. Previous studies have shown significant differences in susceptibility patterns between hospital wards and ICUs. We hypothesize that institutional or combined ICU antibiograms are inadequate to account for differences in susceptibility for patients in individual ICUs. METHODS: Culture and susceptibility data were reviewed over a 1-year period for 13 bacteria in the following ICUs: Surgical/Trauma, Medical, Neuroscience, Burn, and Emergency department. Antibiotic management decisions are made by individual teams. RESULTS: Nine species had sufficient data for inclusion into an All-ICU antibiogram. E coli and S aureus were the most common isolates. Seven species had significant differences in susceptibility patterns between ICUs. E cloacae showed higher rates of resistance to multiple antibiotics in the STICU than other ICUs. P aeruginosa susceptibility rates in the NSICU and BICU were 88% and 92%, respectively, compared to 60% and 55% in the STICU and MICU. Cephalosporins and Aztreonam had reduced efficacy against E coli in the NSICU, however remain effective in other ICUs. CONCLUSIONS: The results of this study show that different ICUs do have variability in antibiotic susceptibility patterns within a single hospital. While this only represents a single institution, it shows that the use of hospital-wide antibiograms is inadequate for creating empiric antibiotic protocols within individual ICUs.

Monotherapy Antibiotic Prophylaxis of Lower Extremity Long Bone Type III Open Fractures.

Gustilo type III open fractures involve extensive soft tissue damage and wound contamination that pose significant infection risks. The historical standard for antibiotic prophylaxis has been cefazolin and gentamicin. We conducted a retrospective cohort study of lower extremity type III open fractures treated with ceftriaxone alone for prophylaxis. Eighty-six patients were identified. Nearly all (98%) were managed with appropriate antibiotics, but only 55 (64%) received prophylaxis within 1 hour. Overall, there were 12 infections. This infection rate was not statistically different than the reported literature (14% vs 19%, P = .20). The infection rate between those who received antibiotics within 1 hour was not statistically different from those who got it beyond 1 hour (15% vs 13%, P = .98). In conclusion, the use of ceftriaxone as monotherapy for antibiotic prophylaxis in lower extremity type III open fractures is not statistically different than the use of historic prophylactic regimens.

Effects of the COVID-19 Pandemic on the Trauma Population in a Level 1 Trauma Center.

In this study, we evaluated the effects of the pandemic on our trauma population. We performed a retrospective review of the trauma registry in the 2 years prior, and then 2 years during the pandemic. We evaluated age, race, gender, injury severity score (ISS), mechanism of trauma, rate of self-inflicted injury, rate of gunshot wounds (GSW), presence of EtOH, drug screen results, mortality, rate of burn traumas, and zip code of residence. Our query captured 5 054 patients before, and 5 731 during the pandemic. We found no statistical difference in age, gender, mechanism of trauma, rate of self-inflicted injuries, and mortality during the pandemic when compared to before. There were statistically significant differences in race, ISS, rate of GSWs, EtOH use, drug screen results, and burn traumas. Geospatial mapping found a rise in GSWs for zip code 36606. Gun violence and substance use rose in our trauma population during COVID-19.

Survey of venous thromboembolism prophylaxis in trauma patients: current prescribing practices and concordance with clinical practice guidelines.

Objectives: Pharmacological venous thromboembolism (VTE) prophylaxis is recommended in the vast majority of trauma patients. The purpose of this study was to characterize current dosing practices and timing of initiation of pharmacological VTE chemoprophylaxis at trauma centers. Methods: This was an international, cross-sectional survey of trauma providers. The survey was sponsored by the American Association for the Surgery of Trauma (AAST) and distributed to AAST members. The survey included 38 questions about practitioner demographics, experience, level and location of trauma center, and individual/site-specific practices regarding the dosing, selection, and timing of initiation of pharmacological VTE chemoprophylaxis in trauma patients. Results: One hundred eighteen trauma providers responded (estimated response rate 6.9%). Most respondents were at level 1 trauma centers (100/118; 84.7%) and had >10 years of experience (73/118; 61.9%). While multiple dosing regimens were used, the most common dose reported was enoxaparin 30 mg every 12 hours (80/118; 67.8%). The majority of respondents (88/118; 74.6%) indicated adjusting the dose in patients with obesity. Seventy-eight (66.1%) routinely use antifactor Xa levels to guide dosing. Respondents at academic institutions were more likely to use guideline-directed dosing (based on the Eastern Association of the Surgery of Trauma and the Western Trauma Association guidelines) of VTE chemoprophylaxis compared with those at non-academic centers (86.2% vs 62.5%; p=0.0158) and guideline-directed dosing was reported more often if the trauma team included a clinical pharmacist (88.2% vs 69.0%; p=0.0142). Wide variability in initial timing of VTE chemoprophylaxis after traumatic brain injury, solid organ injury, and spinal cord injuries was found. Conclusions: A high degree of variability exists in prescribing and monitoring practices for the prevention of VTE in trauma patients. Clinical pharmacists may be helpful on trauma teams to optimize dosing and increase prescribing of guideline-concordant VTE chemoprophylaxis.

Identifying Radiographic and Clinical Indicators to Reduce the Occurrence of Nontherapeutic Laparotomy for Blunt Bowel and Mesenteric Injury.

BACKGROUND: Roughly 5% of patients with blunt abdominal trauma (BAT) have a blunt bowel and/or mesenteric injury (BBMI). Determining the need for operative management in these patients can be challenging when hemodynamically stable. Single center studies have proposed scoring systems based on CT findings to guide management. Our study aimed to determine the predictability of abdominopelvic CT scan (CT A/P) findings in conjunction with clinical exam to determine the necessity of operative intervention for BBMI. METHODS: Patients presenting from 2017 to 2022 to the University of South Alabama Level 1 Trauma Center after motor vehicle collision were retrospectively reviewed. Patients with CT findings suggestive of BBMI were further analyzed, noting CT findings, Glasgow coma scale (GCS), shock index, abdominal exam, operative or nonoperative management, and intraoperative intervention. RESULTS: 1098 patients with BAT underwent CT A/P. 139 patients had ≥1 finding suggestive of BBMI. 38 patients underwent surgical exploration and 30 had surgically confirmed BBMI. 27 patients required intervention for BBMI. Univariate analysis indicated that pneumoperitoneum (p < 0.0001), active extravasation of contrast (p = 0.0001), hemoperitoneum without solid organ injury (SOI) (p < 0.0001), peritonitis (p < 0.0001), and mesenteric stranding(p < 0.05) were significantly associated with intervention. CONCLUSION: In total, 30 patients had surgically confirmed BBMI. Active extravasation, pneumoperitoneum, hemoperitoneum without SOI, mesenteric stranding, and peritonitis were significant indicators of BBMI requiring intervention. CT and clinical findings cannot reliably predict the need for surgical intervention without ≥1 of these findings. Initial nonoperative management with serial clinical exams should be strongly considered to reduce incidence of nontherapeutic laparotomies.

Aortic Injury From High-Speed Deceleration Against a Lap Belt in a 10-year-Old.

Traumatic aortic injuries in children and adolescents are rare, and even more rare are blunt traumatic injury to the abdominal aorta in this population. Therefore, there are few reports discussing the presentation and repair of such injuries, especially within the pediatric population. We report the successful repair of traumatic abdominal aortic transection in a 10-year-old female after a high speed MVC. She arrived in extremis with a seatbelt sign and was taken emergently for damage control laparotomy with subsequent postoperative CT findings of aortic transection/dissection at L3 with active extravasation. She immediately underwent open thrombectomy of the bilateral iliac arteries, and repair of her aortic injury with a 12 × 7 mm Hemashield interposition graft extending just distal to the IMA and 1 cm proximal to the aortic bifurcation. There are little data regarding long-term outcomes of pediatric patients undergoing different aortic repair techniques, and further research is needed.

Treatment of Chronic Hypertrophic Burn Scars With a Fractional CO 2 Laser Is Well Tolerated in an Outpatient Clinic Setting.

INTRODUCTION: The necessity of treating hypertrophic burn scars has expanded significantly with increased burn survivorship. Ablative lasers, such as carbon dioxide (CO 2 ) lasers, have been the most common nonoperative option for improving functional outcomes in severe recalcitrant hypertrophic burn scars. However, the overwhelming majority of ablative lasers used for this indication require a combination of systemic analgesia, sedation, and/or general anesthesia due to the painful nature of the procedure. More recently, the technology of ablative lasers has advanced and is more tolerable than their first-generation counterparts. Herein, we hypothesized that refractory hypertrophic burn scars can be treated by a CO 2 laser in an outpatient clinic. METHODS: We enrolled 17 consecutive patients with chronic hypertrophic burn scars that were treated with a CO 2 laser. All patients were treated in the outpatient clinic with a combination of a topical solution (23% lidocaine and 7% tetracaine) applied to the scar 30 minutes before the procedure, Cryo 6 air chiller by Zimmer, and some patients received a mixture of N 2 O/O 2 . Laser treatments were repeated every 4 to 8 weeks until the patient's goals were met. Each patient completed a standardized questionnaire to assess tolerability and patient satisfaction of functional results. RESULTS: All patients tolerated the laser well in the outpatient clinic setting, with 0% indicating "not tolerable," 70.6% "tolerable," and 29.4% "very tolerable." Each patient received more than 1 laser treatment for the following complaints: decreased range of motion (n = 16, 94.1%), pain (n = 11, 64.7%), or pruritis (n = 12, 70.6%). Patients were also satisfied with the results of the laser treatments ("no improvement or worsened" = 0%, "improved" = 47.1%, and "significant improvement" = 52.9%). The age of patient, type of burn, location of burn, presence of skin graft, or age of scar did not significantly affect the tolerability of treatment or satisfaction of outcome. CONCLUSIONS: The treatment of chronic hypertrophic burn scars with a CO 2 laser is well tolerated in an outpatient clinic setting in select patients. Patients reported a high level of satisfaction with notable improvement in functional and cosmetic outcomes.

Incidence and Severity of Medication Reconciliation Discrepancies in Trauma Patients.

Trauma patients are especially vulnerable to inadvertent medication reconciliation discrepancies. We conducted a prospective study to evaluate the USA Health University Hospital's incidence and type of inadvertent medication reconciliation discrepancies among trauma patients. Patients were interviewed for accuracy of their admission medication reconciliation (AMR). Eighty-nine patients were included in this study. Twenty-six patients (29%) never received an AMR. There were 107 inadvertent medication reconciliation errors identified from 30 separate patients (48%), for a rate of 3.6 errors per patient with any error. There was a significant difference in the frequency of inadvertent medication reconciliation discrepancies for patients with >5 medication compared to those with fewer (P = .00029). In conclusion, trauma centers must be adequately staffed to provide timely, accurate, and available medication lists so that patients can be appropriately cared for.

Social Determinants of Health Impact Physical Recovery After Blunt Injury.

As defined by the United States Department of Health and Human Services, the Social Determinants of Health (SDOH) are conditions in the environment that affect health function and outcomes. The SDOH are divided into the following categories: economic stability, education access and quality, health care access and quality, neighborhood and built environment, and social and community content. It is known that SDOH impact long-term health outcomes. The influence that SDOH have on physical recovery after acute injury is less understood, however. In this study, patients who suffered a traumatic blunt injury completed a survey 12-14 months post-injury to assess their SDOH and physical health before and after their injury. The results showed that for the cohort of patients studied SDOH was the greatest predictor of long-term recovery, having a stronger correlation with recovery than injury severity score (ISS) or hospital length of stay (HLOS).

Incidence and Outcomes of Undiagnosed and Untreated Diabetes Mellitus in Trauma Patients.

Diabetes is a major determinate for mortality in trauma patients. Many diabetics are undiagnosed or poorly controlled. Trauma patients disproportionately come from lower socioeconomic status, making missed diagnoses more likely. We aimed to quantify the incidence of undiagnosed or poorly controlled diabetics assessed at a Level 1 Trauma Center. We did a retrospective chart review of admitted trauma patients over a one-month period. Past Medical History, home medication lists, and Hemoglobin A1c on admission were recorded for each patient. We determined that 30 of 173 trauma patients qualifying for the study were diabetic. Furthermore, 30% of these diabetics were undiagnosed or had poorly controlled diabetes. Undiagnosed pre-diabetics made up 20% of the entire study group. Our data show that 26% of trauma patients would benefit from an intervention for improved glucose control. Trauma centers should consider creating routine clinical practice guidelines to identify at-risk patients and provide intervention for long-term management.

The Relationship between Serum Sodium, Serum Osmolality, and Intracranial Pressure in Patients with Traumatic Brain Injury Treated with Hyperosmolar Therapy.

BACKGROUND: Treatment of elevated intracranial pressure (ICP) in traumatic brain injury (TBI) is controversial. Hyperosmolar therapy is used to prevent cerebral edema in these patients. Many intensivists measure direct correlates of these agents-serum sodium and osmolality. We seek to provide context on the utility of using these measures to estimate ICP in TBI patients. MATERIALS AND METHODS: Patients admitted with TBI who required ICP monitoring from 2008 to 2012 were included. Intracranial pressure, serum sodium, and serum osmolality were assessed prior to hyperosmotic therapy then at 6, 12, 18, 24, 48, and 72 hours after admission. A linear regression was performed on sodium, osmolality, and ICP at baseline and serum sodium and osmolality that corresponded with ICP for 6-72-hour time points. RESULTS: 136 patients were identified. Patients with initial measures were included in the baseline analysis (n = 29). Patients who underwent a craniectomy were excluded from the 6-72-hour analysis (n = 53). Initial ICP and serum sodium were not significantly correlated (R2 .00367, P = .696). Initial ICP and serum osmolality were not significantly correlated (R2 .00734, P = .665). Intracranial pressure and serum sodium 6-72 hours after presentation were poorly correlated (R2 .104, P < .0001), as were ICP and serum osmolality at 6-72 hours after presentation (R2 .116, P < .0001). DISCUSSION: Our results indicate initial ICP is not correlated with serum sodium or osmolality suggesting these are not useful initial clinical markers for ICP estimation. The association between ICP and serum sodium and osmolality after hyperosmolar therapy was poor, thus may not be useful as surrogates for direct ICP measurements.

Two-year survival with nivolumab in previously treated advanced non-small-cell lung cancer: A real-world pooled analysis of patients from France, Germany, and Canada.

OBJECTIVES: Immune checkpoint inhibitors have become the standard of care for metastatic non-small-cell lung cancer (NSCLC) progressing during or after platinum-based chemotherapy. Real-world clinical practice tends to represent more diverse patient characteristics than randomized clinical trials. We sought to evaluate overall survival (OS) outcomes in the total study population and in key subsets of patients who received nivolumab for previously treated advanced NSCLC in real-world settings in France, Germany, or Canada. MATERIALS AND METHODS: Data were pooled from two prospective observational cohort studies, EVIDENS and ENLARGE, and a retrospective registry in Canada. Patients included in this analysis were aged ≥18 years, had stage IIIB/IV NSCLC, and received nivolumab after at least one prior line of systemic therapy. OS was estimated in the pooled population and in various subgroups using the Kaplan-Meier method. Timing of data collection varied across cohorts (2015-2019). RESULTS: Of the 2585 patients included in this analyses, 1235 (47.8 %) were treated in France, 881 (34.1 %) in Germany, and 469 (18.1 %) in Canada. Median OS for the total study population was 11.3 months (95 % CI: 10.5-12.2); this was similar across France, Germany, and Canada. The OS rate was 49 % at 1 year and 28 % at 2 years for the total study population. In univariable Cox analyses, the presence of epidermal growth factor receptor mutations in nonsquamous disease, liver, or bone metastases were associated with significantly shorter OS, whereas tumor programmed death ligand 1 expression and Eastern Cooperative Oncology Group performance status 0-1 were associated with significantly prolonged OS. Similar OS was noted across subgroups of age and prior lines of therapy. CONCLUSION: OS rates in patients receiving nivolumab for previously treated advanced NSCLC in real-world clinical practice closely mirrored those in phase 3 studies, suggesting similar effectiveness of nivolumab in clinical trials and clinical practice.

Smoking Behavior in Patients With Early-Stage NSCLC: A Report From ECOG-ACRIN 1505 Trial.

INTRODUCTION: Smoking cessation has been reported to benefit patients even after a diagnosis of lung cancer. We studied the smoking behavior of patients who participated in a phase 3 trial of adjuvant therapy following resection of stages IB-IIIA NSCLC. METHODS: The ECOG-ACRIN 1505 was conducted to determine whether the addition of bevacizumab to adjuvant chemotherapy would improve overall survival (OS) for patients with early-stage NSCLC. Studying the association between smoking status and OS was a secondary end point. Patients completed a questionnaire on their smoking habits at baseline, 3, 6, 9, and 12 months. RESULTS: A total of 1501 patients were enrolled, and 99.8%, 95%, 94%, 93%, and 93% responded to the questionnaire at baseline, 3, 6, 9, and 12 months, respectively. A total of 90% reported a current or previous history of cigarette smoking. In addition, 60% of nonsmokers at enrollment reported smoking after diagnosis (before randomization); however, 1% of them reported smoking at 12 months. Furthermore, 94% of the respondents smoked none/fewer cigarettes daily at 12 months. The incidence of grades 3-5 toxicity on treatment was 68%, 76%, and 72% in never, former, and current smokers, respectively (p = 0.05). The disease-free survival for never-smokers relative to current and former smokers was (hazard ratio [HR] 0.93, p = 0.64 and HR 1.05, p = 0.72), and OS was (adjusted HR for death 0.54, p = 0.005 and adjusted HR for death 0.68, p = 0.03), respectively. CONCLUSIONS: This is the first comprehensive, prospective report of smoking habits in patients with NSCLC patients from a phase III early-stage trial. There was a high rate of smoking reduction and cessation following study entry. The disease-free survival did not differ significantly between smokers and never smokers, though there were less grade 3-5 toxicities and more favorable OS in never-smokers.

Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non-Small-Cell Lung Cancer.

PURPOSE: Immunotherapy has revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). In two phase III trials (CheckMate 017 and CheckMate 057), nivolumab showed an improvement in overall survival (OS) and favorable safety versus docetaxel in patients with previously treated, advanced squamous and nonsquamous NSCLC, respectively. We report 5-year pooled efficacy and safety from these trials. METHODS: Patients (N = 854; CheckMate 017/057 pooled) with advanced NSCLC, ECOG PS ≤ 1, and progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg once every 2 weeks) or docetaxel (75 mg/m2 once every 3 weeks) until progression or unacceptable toxicity. The primary end point for both trials was OS; secondary end points included progression-free survival (PFS) and safety. Exploratory landmark analyses were investigated. RESULTS: After the minimum follow-up of 64.2 and 64.5 months for CheckMate 017 and 057, respectively, 50 nivolumab-treated patients and nine docetaxel-treated patients were alive. Five-year pooled OS rates were 13.4% versus 2.6%, respectively; 5-year PFS rates were 8.0% versus 0%, respectively. Nivolumab-treated patients without disease progression at 2 and 3 years had an 82.0% and 93.0% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression-free at 5 years, respectively. Treatment-related adverse events (TRAEs) were reported in 8 of 31 (25.8%) nivolumab-treated patients between 3-5 years of follow-up, seven of whom experienced new events; one (3.2%) TRAE was grade 3, and there were no grade 4 TRAEs. CONCLUSION: At 5 years, nivolumab continued to demonstrate a survival benefit versus docetaxel, exhibiting a five-fold increase in OS rate, with no new safety signals. These data represent the first report of 5-year outcomes from randomized phase III trials of a programmed death-1 inhibitor in previously treated, advanced NSCLC.

The Treatment of Rib Fractures : A Single-Center Comparison.

BACKGROUND: Rib fractures are a major problem characterized by pain, increased length of stay, and respiratory complications. Treatments include fixation, management with opiates, paraspinous local anesthetic pumps, and intercostal nerve blocks. The aim of this study was to evaluate the use of treatment options and compare clinically relevant outcomes. METHODS: Patients admitted to a Level 1 trauma center with multiple rib fractures between 2015 and 2019 were screened. We included all participants treated with surgical fixation and/or intercostal nerve block or local anesthetic pump. Patients were case-matched 1:2 by Injury Severity Score (ISS), Abbreviated Injury Scale (AIS) Chest and Head, age, and number of rib fractures. Outcomes assessed were hospital length of stay (LOS), intensive care unit (ICU) LOS, ventilator days, pneumonia, and tracheostomy rates. RESULTS: We identified 25 patients who received rib fixation and intercostal analgesia. Of these, 14 cases were treated with liposomal bupivaicaine nerve block and 11 by paraspinous catheter block. Fifty control cases treated with opiates were identified. All patients survived to discharge. Cases and controls were approximately equivalent in age, ISS, number of fractured ribs, chest AIS, and head AIS. Rib-plated patients had a lower rate of pneumonia (OR 0.2029, 95% CI 0.0242, 0.09718), decreased average ICU LOS (10.62 vs 6.64, P = .018), and decreased average ventilator days (5.44 vs 1.68, P = .003). DISCUSSION: Findings suggest more aggressive treatment of rib fractures may decrease ICU LOS, ventilator days, and pneumonia in patients with multiple rib fractures. These findings are in line with current literature; however, more research is needed in this area.

Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis.

BACKGROUND: Phase 3 clinical data has shown higher proportions of patients with objective response, longer response duration, and longer overall survival with nivolumab versus docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival. METHODS: We pooled data from four clinical studies of nivolumab in patients with previously treated NSCLC (CheckMate 017, 057, 063, and 003) to evaluate survival outcomes. Trials of nivolumab in the second-line or later setting with at least 4 years follow-up were included. Comparisons of nivolumab versus docetaxel included all randomised patients from the phase 3 CheckMate 017 and 057 studies. We did landmark analyses by response status at 6 months to determine post-landmark survival outcomes. We excluded patients who did not have a radiographic tumour assessment at 6 months. Safety analyses included all patients who received at least one dose of nivolumab. FINDINGS: Across all four studies, 4-year overall survival with nivolumab was 14% (95% CI 11-17) for all patients (n=664), 19% (15-24) for those with at least 1% PD-L1 expression, and 11% (7-16) for those with less than 1% PD-L1 expression. In CheckMate 017 and 057, 4-year overall survival was 14% (95% CI 11-18) in patients treated with nivolumab, compared with 5% (3-7) in patients treated with docetaxel. Survival subsequent to response at 6 months on nivolumab or docetaxel was longer than after progressive disease at 6 months, with hazard ratios for overall survival of 0·18 (95% 0·12-0·27) for nivolumab and 0·43 (0·29-0·65) for docetaxel; for stable disease versus progressive disease, hazard ratios were 0·52 (0·37-0·71) for nivolumab and 0·80 (0·61-1·04) for docetaxel. Long-term data did not show any new safety signals. INTERPRETATION: Patients with advanced NSCLC treated with nivolumab achieved a greater duration of response compared with patients treated with docetaxel, which was associated with a long-term survival advantage. FUNDING: Bristol-Myers Squibb.

Rapid atrophy of cardiac left ventricular mass in patients with non-small cell carcinoma of the lung.

BACKGROUND: Cancer is a systemic catabolic condition affecting skeletal muscle and fat. We aimed to determine whether cardiac atrophy occurs in this condition and assess its association with cardiac function, symptoms, and clinical outcomes. METHODS: Treatment naïve metastatic non-small cell lung cancer patients (n = 50) were assessed prior to and 4 months after commencement of carboplatin-based palliative chemotherapy. Methods included echocardiography for left ventricular mass (LVM) and LV function [LV ejection fraction, global longitudinal strain (GLS), diastolic function], computed tomography to quantify skeletal muscle and total adipose tissue, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), validated questionnaires for dyspnoea and fatigue, plasma biomarkers, tumour response to therapy, and overall survival. RESULTS: During 112 ± 6 days, the median change in LVM was -8.9% [95% confidence interval (95% CI) -10.8 to -4.8, P < 0.001]. Quartiles of LVM loss were -20.1%, -12.9%, -4.8%, and +5.5%. Losses of muscle, adipose tissue, and LVM were frequently concurrent; LVM loss > median value was associated with loss of skeletal muscle [odds ratio (OR) = 4.5, 95% CI: 1.4-14.8, P=0.01] and loss of total adipose tissue (OR = 10.0, 95% CI: 2.7-36.7, P < 0.001). LVM loss was associated with decreased GLS (OR = 6.6, 95% CI: 1.9-22.7, P=0.003) but not with LV ejection fraction or diastolic function. In the population overall, plasma levels of C-reactive protein (P=0.008), high sensitivity troponin T (hs-TnT) (P=0.03), and galectin-3 (P=0.02) increased over time, while N-terminal pro B-type natriuretic peptide and hs-cTnI did not change over time. C-reactive protein was the only biomarker associated with LVM loss but at the univariate level only. Independent predictors of LVM loss were prior weight loss (adjusted OR = 10.2, 95% CI: 2.2-46.9, P=0.003) and tumour progression (adjusted OR = 14.6, 95% CI: 1.4-153.9, P=0.02). LVM loss was associated with exacerbations of fatigue (OR = 6.6, 95% CI: 1.9-22.7, P=0.003), dyspnoea (OR = 9.3, 95% CI: 2.4-35.8, P<0.001), and deterioration of performance status (OR = 4.8, 95% CI: 1.3-18.3,P=0.02). Patients with concurrent loss of LVM, skeletal muscle, and fat were more likely to deteriorate in all three symptom domains and to have reduced survival (P=0.05). CONCLUSIONS: Intense LVM atrophy is associated with non-small cell lung cancer-induced cachexia. Loss of LVM was associated with emerging alterations of GLS, indicating subtle changes in left ventricular function. Longer term studies are needed to assess the full scope of cardiac atrophy and its impact. LVM atrophy arises in conjunction with losses of fat and skeletal muscle and is temporally associated with meaningful declines in performance status, worsening of fatigue, and dyspnoea, as well as poorer tumour response and decreased survival. The specific contribution of LVM atrophy to these outcomes requires further study.

Selumetinib in patients receiving standard pemetrexed and platinum-based chemotherapy for advanced or metastatic KRAS wildtype or unknown non-squamous non-small cell lung cancer: A randomized, multicenter, phase II study. Canadian Cancer Trials Group (CCTG) IND.219.

INTRODUCTION: Activation of the RAS/RAF/MEK/ERK pathway may confer resistance to chemotherapy in non-small cell lung cancer (NSCLC). Selumetinib (AZD6244, ARRY142886), a MEK1/2 inhibitor combined with chemotherapy in patients with NSCLC was evaluated in two schedules to evaluate efficacy and toxicity. METHODS: IND.219 was a three-arm study of first line pemetrexed/platinum chemotherapy with two schedules of selumetinib (Arm A: intermittent given on days 2-19; Arm B: continuous given on days 1-21) versus chemotherapy alone (Arm C). The primary endpoint was objective response rate (ORR); secondary objectives were tolerability, progression-free survival (PFS), overall survival (OS). The trial was stopped at the planned interim analysis. RESULTS: Arms A/B/C enrolled 20/21/21 patients, ORR was 35% (95% CI 15-59% median duration 3.8 months), 62% (95% CI 38-82%; median duration 6.3 months), 24% (95% CI 8-47%; median duration 11.6 months) respectively. The PFS (months Arm A, B, C) was 7.5, 6.7, 4.0 respectively (hazard ratio (HR) PFS Arm A over Arm C: 0.76 [95% CI, 0.38-1.51, 2-sided p = 0.42]; Arm B over Arm C 0.75 [95% CI 0.37-1.54, p = 0.43]. Skin and gastrointestinal adverse events were more common with the addition of selumetinib. A high incidence of venous thromboembolism was seen in all arms. CONCLUSIONS: Selumetinib combined with chemotherapy was associated with a higher response rate. Continuous selumetinib appeared to be superior to an intermittent schedule. PFS was prolonged with the addition of selumetinib, however this was not statistically significant.

Is lobectomy superior to sublobar resection for early-stage small-cell lung cancer discovered intraoperatively?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: Is lobectomy superior to sublobar resection (SLR) for early-stage (cT1/2N0) small-cell lung cancer (SCLC) discovered intraoperatively? Altogether, more than 360 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Surgical treatment was shown to be superior to non-surgical treatment for early-stage SCLC in 8 papers. Seven papers showed that among patients treated surgically, lobectomy is associated with improved survival compared to SLR. One paper demonstrated both improved survival and improved freedom from local recurrence. However, 1 paper showed no difference when lobectomy was compared to anatomical segmentectomy. Three papers demonstrated significant rates of upstaging in surgical patients. Although both lobectomy and SLR are associated with improved survival compared with non-surgical treatment in early-stage SCLC, lobectomy is superior. Lobectomy was associated with improved median and overall survival, better upstaging and decreased local recurrence compared to SLR, although there is potential for selection bias and stage migration. Lobectomy should be considered the optimal approach for patients with early-stage SCLC.