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BackgroundMultiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard‐risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent.MethodsThis study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187).ResultsAfrican Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation–Comorbidity Index (HCT‐CI). Fewer African Americans with t(11;14) (21%) had a coexistent high‐risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression‐free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30‐0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT‐CI, and receipt of maintenance.ConclusionsRace may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.

BackgroundUpfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults.MethodsThe authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression‐free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori.ResultsAn increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2. On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1‐1.7 [P = .06]), REL (HR, 1.03; 99% CI, 0.9‐1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1‐1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1‐1.4 [P = .02]) compared with the reference group (those aged 60‐69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2, including day 100 NRM (1% [95% CI, 1%‐2%] vs 0% [95% CI, 0%‐1%]; P = .003]), 2‐year PFS (64% [95% CI, 60%‐67%] vs 69% [95% CI, 66%‐73%]; P = .003), and 2‐year OS (85% [95% CI, 82%‐87%] vs 89% [95% CI, 86%‐91%]; P = .01]), likely representing frailty.ConclusionsThe results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.

Trichorhinophalangeal syndrome (TRPS) is a genetic disorder that may pose anesthetic challenges. We present a case of airway management for urgent surgery in a 56-year-old female with TRPS and difficult airway (macroglossia, narrow glottic opening, and hypoplastic epiglottis). Intubation was successful with video laryngoscopy using a size 2.5 pediatric blade and size 5.0 endotracheal tube. During emergence, she experienced bronchospasm and persistent urosepsis, necessitating intensive care unit (ICU) admission. Her pulmonary reserve was hindered by a Morgagni hernia causing lung compression. Our case demonstrates challenges in TRPS including challenging airway, decreased pulmonary reserve, and joint laxity introducing potential for spinal cord injury.

Objectives: To describe the Children’s Hospital Association’s Improving Pediatric Sepsis Outcomes sepsis definitions and the identified patients; evaluate the definition using a published framework for evaluating sepsis definitions. Design: Observational cohort. Setting: Multicenter quality improvement collaborative of 46 hospitals from January 2017 to December 2018, excluding neonatal ICUs. Patients: Improving Pediatric Sepsis Outcomes Sepsis was defined by electronic health record evidence of suspected infection and sepsis treatment or organ dysfunction. A more severely ill subgroup, Improving Pediatric Sepsis Outcomes Critical Sepsis, was defined, approximating septic shock. Interventions: Participating hospitals identified patients, extracted data, and transferred de-identified data to a central data warehouse. The definitions were evaluated across domains of reliability, content validity, construct validity, criterion validity, measurement burden, and timeliness. Measurements and Main Results: Forty hospitals met data quality criteria across four electronic health record platforms. There were 23,976 cases of Improving Pediatric Sepsis Outcomes Sepsis, including 8,565 with Improving Pediatric Sepsis Outcomes Critical Sepsis. The median age was 5.9 years. There were 10,316 (43.0%) immunosuppressed or immunocompromised patients, 4,135 (20.3%) with central lines, and 2,352 (11.6%) chronically ventilated. Among Improving Pediatric Sepsis Outcomes Sepsis patients, 60.8% were admitted to intensive care, 26.4% had new positive-pressure ventilation, and 19.7% received vasopressors. Median hospital length of stay was 6.0 days (3.0–13.0 d). All-cause 30-day in-hospital mortality was 958 (4.0%) in Improving Pediatric Sepsis Outcomes Sepsis; 541 (6.3%) in Improving Pediatric Sepsis Outcomes Critical Sepsis. The Improving Pediatric Sepsis Outcomes Sepsis definitions demonstrated strengths in content validity, convergent construct validity, and criterion validity; weakness in reliability. Improving Pediatric Sepsis Outcomes Sepsis definitions had significant initial measurement burden (median time from case completion to submission: 15 mo [interquartile range, 13–18 mo]); timeliness improved once data capture was established (median, 26 d; interquartile range, 23–56 d). Conclusions: The Improving Pediatric Sepsis Outcomes Sepsis definitions demonstrated feasibility for large-scale data abstraction. The patients identified provide important information about children treated for sepsis. When operationalized, these definitions enabled multicenter identification and data aggregation, indicating practical utility for quality improvement.

Precision medicine (PM) is an emerging approach for disease treatment and prevention that accounts for the individual variability in the genes, environment, and lifestyle of each person. Lysosomal diseases (LDs) are a group of genetic metabolic disorders that include approximately 70 monogenic conditions caused by a defect in lysosomal function. LDs may result from primary lysosomal enzyme deficiencies or impairments in membrane-associated proteins, lysosomal enzyme activators, or modifiers that affect lysosomal function. LDs are heterogeneous disorders, and the phenotype of the affected individual depends on the type of substrate and where it accumulates, which may be impacted by the type of genetic change and residual enzymatic activity. LDs are individually rare, with a combined incidence of approximately 1:4000 individuals. Specific therapies are already available for several LDs, and many more are in development. Early identification may enable disease course prediction and a specific intervention, which is very important for clinical outcome. Driven by advances in omics technology, PM aims to provide the most appropriate management for each patient based on the disease susceptibility or treatment response predictions for specific subgroups. In this review, we focused on the emerging diagnostic technologies that may help to optimize the management of each LD patient and the therapeutic options available, as well as in clinical developments that enable customized approaches to be selected for each subject, according to the principles of PM.

AbstractBackgroundLow back pain is the leading cause of years lost to disability worldwide. Approximately 15% to 45% of chronic low back pain is due to facet joint arthropathy. Currently, no large‐scale retrospective studies have investigated long‐term clinical predictors of success in individuals receiving radiofrequency ablation (RFA) of the medial branches for facet joint arthropathy.ObjectiveTo determine the clinical factors associated with success and failure of RFA of lumbar facet joints at 1‐year follow‐up.MethodsClinical data were gathered from 500 consecutive patients with an International Classification of Diseases (ICD)‐10 diagnosis of lumbar spondylosis. VAS pain scores for patients undergoing lumbar medial branch RFA procedures were recorded at multiple time points, up to the 1‐year follow‐up visit. A responder was defined as having ≥30% improvement in VAS score from the pre‐procedural VAS score. For our primary analysis, regression analysis was conducted to identify associations between responder status and patient characteristics, including age, gender, body mass index (BMI), hormone use, opiate dose, and smoking history at multiple time points, up to the 1‐year follow‐up visit.ResultsA total of 500 patients were included in the study. At the 1‐year post‐RFA follow‐up visit, responder status was associated with a lower rate of prior opioid use (43.22% vs. 55.76%, odds ratio 0.60 [95% confidence interval (CI) 0.40 to 0.92], P = 0.018), lower pre‐procedural opioid consumption in oral morphine equivalents (10.16 ± 16.02 vs. 14.67 ± 20.65, β −4.50 [95% CI −8.57 to −0.44], P = 0.030), and a higher pre‐VAS pain score (6.36 ± 2.17 vs. 5.85 ± 2.17, β 0.50 [95% CI 0.06 to 0.95], P = 0.028). There were no significant associations between responder status and age, gender, BMI, hormone use, and smoking history at the 1‐year follow‐up visit.ConclusionsOur results suggest that patients prescribed opioids, particularly at higher dosages, may find less pain relief 1 year following RFA for facetogenic pain. Additionally, patients with higher pre‐procedural VAS pain scores may be more likely to have a positive response at 1 year.

Background: Black patients have higher rates of hospitalization for acute heart failure than other race/ethnic groups. We sought to determine whether diuretic efficiency is associated with racial differences in risk for rehospitalization after acute heart failure. Methods: A post hoc analysis was performed on 721 subjects (age, 68±13 years; 22% black) enrolled in 3 acute heart failure clinical trials: ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure), DOSE-AHF (Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure), and CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Repeated-measures ANOVA was used to test for a race×time effect on measures of decongestion. Diuretic efficiency was calculated as net fluid balance per total furosemide equivalents. In a subset of subjects, Cox regression was used to examine the association between race and rehospitalization according to plasma renin activity (PRA). Results: Compared with nonblack patients, black patients were younger and more likely to have nonischemic heart failure. During the first 72 to 96 hours, there was greater fluid loss ( P =0.001), decrease in NT-proBNP (N-terminal pro-B-type natriuretic peptide; P =0.002), and lower levels of PRA ( P <0.0001) in black patients. Diuretic efficiency was higher in black than in nonblack patients (403 [interquartile range, 221–795] versus 325 [interquartile range, 154–698]; P =0.014). However, adjustment for baseline PRA attenuated the association between black race and diuretic efficiency. Over a median follow-up of 68 (interquartile range, 56–177) days, there was an increased risk of all-cause and heart failure–specific rehospitalization in nonblack patients with increasing levels of PRA, while the risk of rehospitalization was relatively constant across levels of PRA in black patients. Conclusions: Higher diuretic efficiency in black patients with acute heart failure may be related to racial differences in activity of the renin-angiotensin-aldosterone system.

Venous air embolism (VAE) is a well-described phenomenon that may have life-threatening cardiopulmonary and neurological consequences. Accidental administration of air during resuscitation while using a rapid infuser is rare. Furthermore, there is a paucity of published data describing the intraoperative management of VAE during emergent nonseated neurological surgery. We report a 22-year-old previously healthy female who experienced a motor vehicle accident with severe facial and head trauma, and mixed subdural and epidural hematomas with an 8 mm midline shift. Computed tomography revealed significant air entrainment in the right heart and main pulmonary artery, with venous air tracking from the right axillary vein. Given her age, lack of preexisting cardiac comorbidities, hemodynamic stability, and critical cerebral herniation risk, further cardiac evaluation was deferred, and the patient was transferred to the operating room for emergent decompressive craniotomy. Intraoperatively, she experienced acute decrease in mean arterial pressure and end-expiratory carbon-dioxide with loss of pulse oximetry waveform concerning for obstructive VAE physiology. She was responsive to fluid resuscitation and epinephrine administration and did not experience any recurrence of obstructive VAE. This challenging case report describes positive neurologic and hemodynamic outcomes after resuscitation-associated VAE and cardiopulmonary collapse during emergency neurosurgery. Comprehensive evaluation of risk, urgency of procedure, and need for diagnostic monitoring and treatment should be personalized.

8515 Background: AL is a clonal plasma cell (PC) disorder causing multiorgan dysfunction from amyloid fibril deposition. While bortezomib (B) induction has been used prior to AHCT recently, AHCT without prior induction has been a common practice. The primary objective of this study was to compare outcomes of AL patients who proceeded to AHCT without induction to those receiving pre-AHCT induction with B. Methods: Outcomes of 426 systemic AL AHCT recipients between 2014-2018 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) were reviewed. Patients receiving induction with therapy other than B, AHCT occurring > 9 months after diagnosis, no documented AL end-organ involvement, myeloma-defining events and conditioning other than melphalan (MEL) monotherapy were excluded. Multivariate analysis (MVA) was conducted to identify prognostic factors associated with relapse, PFS and overall survival (OS). Results: 286 patients received B induction therapy vs 140 patients receiving no induction. Age, gender, number and type of organs involved, and AL AHCT center volume were similar between the groups. Patients receiving induction had greater PC burden compared with no induction (PC ≥ 10%, 41% vs 11%, p < 0.01). Induction was B, cyclophosphamide and dexamethasone (D) in 83% followed by B, lenalidomide and D (10%) or B+D (7%). Median follow-up was 24.9 months. At 2 years, B induction vs. no induction was associated with 13% (95% CI 10-17%) vs 22% (95% CI 15-30%) relapse risk (p = 0.03); 83% (95% CI 79-87%) vs 74% (95% CI 66-81%) PFS (p = 0.04); 93% (95% CI 90-95%) vs 94% (95% CI 89-97%) OS (p = 0.7). On MVA, the B induction group had improved PFS (HR 0.46, 95% CI 0.3-0.7, p < 0.001) with similar OS (HR 0.6, 95% CI 0.3-1.2, p = 0.1) compared with no induction. Creatinine < 2 mg/dl (HR 0.55, 95% CI 0.3-0.9, p = 0.02) and Karnofsky score ≥90 (HR 0.51, 95% CI 0.33-0.78, p < 0.01) were also associated with improved PFS. MEL dose < 180 mg/m2 was associated with inferior PFS (HR 2.17, 95% CI 1.31-3.61, p < 0.01) and OS (HR 3.6, 95% CI 1.5-8.6, p < 0.01). No deaths were seen in the first 100 days post-AHCT. At last follow-up, 32 deaths occurred, 26 (81%) due to AL. Conclusions: Compared with prior CIBMTR analyses, B induction use has increased in AL AHCT recipients and a higher PC burden was the only clinical determinant. Furthermore, B induction was associated with lower relapse and improved PFS at 2 years with no OS difference despite higher proportion of patients with > 10% PC, which has been associated with poor outcomes.