Citations

8008 Background: Morphology remains the best biomarker for chemotherapy selection in NSCLC. Both bevacizumab and pemetrexed (in first line) are FDA indicated for non-SC histology only, making precise diagnosis key, although data are few on the reproducibility of their categorization. The standard of care, consensus-based World Health Organization diagnostic classification system, Ed. 4 (WHOC) includes 44 diagnostic categories (DC), does not include immunohistochemical (IHC) data, and is not independently validated. In this study, we estimate the reproducibility of SC versus non-SC classification to be only moderately precise. Methods: Pathologists (P) assigned WHOC diagnoses to virtual H&E slides from an incident surgical cohort of 96 primary lung tumors. At a power of 80% we estimated 24 P reviewing 48 slides each would allow for a reproducibility measure in the clinically useful range kappa=0.7, standard error=0.09. In addition to the 44 DC, we also considered the reproducibility of a simplified 10 category system and a chemotherapy-directed 2 class system. Results: 12 self-identified “lung experts” (E) and 12 community (C) P scored slides based on the 44 possible WHOC DC totaling 222 pathologist-pairs and 7130 slides-pairs. P rated confidence in their choices as: high 53%, somewhat 38%, and not confident 8%. 92% of slides were rated as having sufficient quality. Distribution of DC included SC 30% and adenocarcinoma 36%. Conclusions: To our knowledge this is the largest study ever performed of the WHOC, the only one to consider all 44 DC and to distinguish E vs C P. Although this model tests the reproducibility of the WHOC, not clinical lung cancer diagnoses, it shows that reproducible diagnosis of SC based on H&E morphology alone is inadequate. In the era of histology guided therapy, it highlights the need for strict diagnostic criteria and confirmatory IHC stains in the diagnosis of SC. [Table: see text] No significant financial relationships to disclose.

4010 Background: Prior studies suggested that older and younger pts with colon cancer receive similar benefit from IV fluoropyrimidine (FU) adjuvant (adj) therapy (rx). Combination and/or oral FU rx are increasingly given as adj rx. We sought to determine the impact of pts age <70 v ≥70 yrs on colon cancer recurrence and mortality from adj rx with these newer options. Methods: We used data from 10,499 pts <70 yrs and 2,170 pts ≥70 yrs in 6 phase III adj rx trials comparing IV FU to combinations with irinotecan, oxaliplatin or oral FU (capecitabine and UFT/LV) in stage II/III colon cancer from the ACCENT database. Endpoints were overall survival (OS; time to death), disease-free survival (DFS; time to recurrence or death), and time to recurrence (TTR; censoring at last follow-up). Cox models were stratified by age and adjusted for gender and stage; interaction testing was used to explore the differential benefit by age. Results: Approximately 75% of pts had stage III disease (74% age<70, 77% age≥70). OS, DFS, and TTR were statistically significantly improved for those in the experimental v control arms among pts <70 but not those >70 ( table ); the interaction between age and rx was statistically significant for all endpoints (p=0.01 for OS, DFS, and TTR). These results were consistent whether experimental rx was oxaliplatin-based, irinotecan-based or oral FU. Deaths in first 6 month of adj rx were not statistically significantly different between experimental and control arm. Conclusions: Our results show conclusively that pts >70 do not receive the same benefit from combination and/or oral FU as those <70. Any benefit, if present, compared to IV FU/LV would not be clinically meaningful. Outcomes of experimental (combination or oral FU) vs control (IV 5-FU) by treatment and age [Table: see text] [Table: see text]

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.

Globally, diabetes mellitus is a leading cause of kidney disease, with a critical percent of patients approaching end-stage kidney disease. In the current era, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as phenomenal agents in halting the progression of kidney disease. Positive effects of SGLT2i are centered on multiple mechanisms, including glycosuric effects, tubule—glomerular feedback, antioxidant, anti-fibrotic, natriuretic, and reduction in cortical hypoxia, alteration in energy metabolism. Concurrently, multiple kidney and cardiovascular outcome studies have reported remarkable advantages of SGLT2i including mortality benefits. Additionally, the superiority of combination therapies (SGLT2I along with metformin/DDP-4 Inhibitors) in treatment-naïve diabetic patients is further looked into with potential signal towards glycemic and blood pressure control. Reported promising results initiate a gateway for future research targeting kidney outcomes with combination therapies as an initial approach. In the current paper, we summarize leading cardiovascular and kidney outcome trials in patients with type 2 diabetes, the role of SGLT2i in non-diabetic proteinuric kidney disease, and the potential mechanisms of action of SGLT2i with special focus on combination therapy as an initial therapeutic approach in treatment-naïve diabetic patients.

Abstract The pandemic of COVID-19 has presented several diagnostic challenges in both recognition of acute disease and also the temporal presentation of disease convalescence with return to normal activity. We present a case of delayed clinical progression of COVID-19 associated respiratory failure on day 25 after initial symptom onset and, notably, after initial full resolution of symptoms and negative RT-PCR nasopharyngeal testing. The patient’s delayed presentation of exertional dyspnea and the utilization of specific characteristics of chest radiography in confirmation with laboratory cytokine measurement allowed for clinical re-categorization of the patient’s status to active COVID-19 clinical disease and changed acute management. COVID-19 positive patients should be advised to continue to monitor for respiratory deterioration for a greatly extended period of time, even if RT-PCR testing is negative and initial clinical symptoms have resolved. Frontline healthcare workers, including first responders and primary care providers, also need to be aware to monitor for and recognize this delayed presentation.

Background: The objective of this study was to describe inpatient prevalence, characteristics, outcomes, and resource use for acute salicylate intoxication hospitalizations in the United States. Methods: A total of 13,805 admissions with a primary diagnosis of salicylate intoxication from 2003 to 2014 in the National Inpatient Sample database were analyzed. Prognostic factors for in-hospital mortality were determined using multivariable logistic regression. Results: The overall inpatient prevalence of salicylate intoxication among hospitalized patients was 147.8 cases per 1,000,000 admissions in the United States. The average age was 34 ± 19 years. Of these, 35.0% were male and 65.4% used salicylate for suicidal attempts. Overall, 6% required renal replacement therapy. The most common complications of salicylate intoxication were electrolyte and acid-base disorders, including hypokalemia (25.4%), acidosis (19.1%), and alkalosis (11.1%). Kidney failure (9.3%) was the most common observed organ dysfunction. In-hospital mortality was 1.0%. Increased in-hospital mortality was associated with age ≥30, Asian/Pacific Islander race, diabetes mellitus, hyponatremia, ventricular arrhythmia, kidney failure, respiratory failure, and neurological failure, while decreased in-hospital mortality was associated with African American and Hispanic race. Conclusion: hospitalization for salicylate intoxication occurred in 148 per 1,000,000 admissions in the United States. Several factors were associated with in-hospital mortality.

OBJECTIVE The goal of this study was to compare different recognized definitions of osteoporosis in patients with degenerative lumbar spine pathology undergoing elective spinal fusion surgery to determine which patient population should be considered for preoperative optimization. METHODS A retrospective review of patients in whom lumbar spine surgery was planned at 2 academic medical centers was performed, and the rate of osteoporosis was compared based on different recognized definitions. Assessments were made based on dual-energy x-ray absorptiometry (DXA), CT Hounsfield units (HU), trabecular bone score (TBS), and fracture risk assessment tool (FRAX). The rate of osteoporosis was compared based on different definitions: 1) the WHO definition (T-score ≤ −2.5) at total hip or spine; 2) CT HU of < 110; 3) National Bone Health Alliance (NBHA) guidelines; and 4) “expanded spine” criteria, which includes patients meeting NBHA criteria and/or HU < 110, and/or “degraded” TBS in the setting of an osteopenic T-score. Inclusion criteria were adult patients with a DXA scan of the total hip and/or spine performed within 1 year and a lumbar spine CT scan within 6 months of the physician visit. RESULTS Two hundred forty-four patients were included. The mean age was 68.3 years, with 70.5% female, 96.7% Caucasian, and the mean BMI was 28.8. Fracture history was reported in 53.8% of patients. The proportion of patients identified with osteoporosis on DXA, HUs, NBHA guidelines, and the authors’ proposed “expanded spine” criteria was 25.4%, 36.5%, 75%, and 81.9%, respectively. Of the patients not identified with osteoporosis on DXA, 31.3% had osteoporosis based on HU, 55.1% had osteoporosis with NBHA, and 70.4% had osteoporosis with expanded spine criteria (p < 0.05), with poor correlations among the different assessment tools. CONCLUSIONS Limitations in the use of DXA T-scores alone to diagnose osteoporosis in patients with lumbar spondylosis has prompted interest in additional methods of evaluating bone health in the spine, such as CT HU, TBS, and FRAX, to inform guidelines that aim to reduce fracture risk. However, no current osteoporosis assessment was developed with a focus on improving outcomes in spinal surgery. Therefore, the authors propose an expanded spine definition for osteoporosis to identify a more comprehensive cohort of patients with potential poor bone health who could be considered for preoperative optimization, although further study is needed to validate these results in terms of clinical outcomes.

Background: Limb salvage of the proximal tibia can be difficult due to the growth potential of and functional demands of the pediatric patients. Multiple reconstruction techniques exist, however, the ideal form of reconstruction is yet to be elucidated. The purpose of the current study is to evaluate outcomes in patients with an intercalary resection of the proximal tibia reconstructed with an allograft with or without a free vascularized fibula flap (FVF). Methods: Seventeen pediatric patients (9 males, 8 females) underwent lower extremity limb salvage with the use of intercalary cadaveric allograft at a mean age of 12±4 years. The most common diagnoses were osteosarcoma (n=6) and Ewing sarcoma (n=6). Patients were reconstructed with an allograft alone (n=6) or supplemented with an FVF (n=11). Results: All surviving patients had at least 2 years of clinical follow-up, with the mean follow-up of 12±7 years. The mean time to union of the allograft was 11±4 months, with 6 patients requiring additional bone grafting. There was no difference in the need for an additional bone graft (odds ratio=1.14, P=1.0) between patients with an FVF and those without. Four patients underwent an amputation, all with an allograft alone, due to disease recurrence (n=2) and due to infection (n=2). As such, there was a higher 10-year overall limb-salvage rate when the allograft was combined with an FVF compared with an allograft alone (100% vs. 33%, P=0.001). At last follow-up, the mean Mankin and Musculoskeletal Tumor Society rating was 86%, with a higher mean score in patients reconstructed with an FVF (94% vs. 70%, P=0.002). Conclusion: Use of an intercalary allograft supplemented with an FVF to reconstruct the proximal tibia provides a durable means of reconstruction with an excellent functional outcome following oncologic proximal tibia resection in a pediatric population. Level of Evidence: Level III—therapeutic level.

Objective: To evaluate the incidence of and characterize the presentation of neuropsychiatric symptoms and/or Parkinsonism as a presentation of central nervous system lymphoma (CNSL) in either its primary CNSL form or when it spreads to the brain in systemic diffuse large B-cell lymphoma (secondary CNSL). Patients and Methods: With Institutional Review Board approval we identified patients who had been treated at Mayo Clinic from 1998 to 2018 and were recorded to have a combination of ICD 9/10 codes for CNSL and various psychiatric diagnoses. Results: A total of 20 of the 232 patients (9%) were noted to have neuropsychiatric symptoms preceding diagnosis. The average age at diagnosis was 62, with even split for sex. The majority (85%) of patients had primary CNSL. The average duration of symptoms before the diagnosis was 4.8 months. Confusion (80%), depression (40%), apathy (30%), anxiety (30%), and agitation (30%) were the most common symptoms identified. The majority (65%) of patients had subcortical lesions followed by the frontal lobe (50%). Parkinsonism was identified in 5 of the 20 patients with 4 demonstrating resolution of symptoms with treatment of the lymphoma. Conclusions: Neuropsychiatric symptoms are a rare but notable symptom before the presentation of CNSL. There is an increasing awareness of neurological illness presenting as pure psychiatric disturbance, prompting the need to exclude organic and treatable diseases, particularly in elderly patients. Acknowledgment and diagnosis are important for an appropriate management as there is a significant impact on patient and caregiver quality of life.

Abstract Background Post-operative management of patients undergoing cardiac transplantation with an infected left ventricular assist device (LVAD) is unclear. Methods We retrospectively screened all adults with an LVAD who underwent cardiac transplantation at our institution from 2010 through 2018. We selected all cases of LVAD-specific and LVAD-related infections who were receiving antimicrobial therapy as initial treatment course or chronic suppression at the time of cardiac transplantation. Non-LVAD infections, superficial driveline-infection, or concurrent use of right ventricular assist device or extracorporeal membrane oxygenation device were excluded. Results A total of 54 cases met study criteria with 18/54 (33.6%) classified as LVAD- specific or related infections and 36/54 (66.6%) as non-infected. Cases of LVAD-infection had a higher median Charlson Comorbidity Index score at the time of transplantation compared to non-infected cases (P=.005). Of the 18 cases of infection, 13/18 (72.2%) were classified as LVAD-specific and 5/18 (27.8%) as LVAD-related. A total of 9/13 (69.2%) cases had proven LVAD-specific infections. Antimicrobial therapy was extended post-transplant to treat preceding LVAD-specific infection in all nine cases (9/13, 69.2%) with a median duration of 14 days (IQR 14-28). Following LVAD removal, antimicrobial treatment was not continued for preceding LVAD-related infections. Conclusions Patients with an LVAD-specific infection were treated with two weeks of pathogen-directed therapy post heart transplant without any relapses. For those without LVAD-specific infection or uncomplicated LVAD-related bacteremia who had completed antimicrobial therapy pre-transplant, antibiotics were discontinued after standard peri-operative prophylaxis and no relapses were observed.