Near-universal hospitalization of US emergency department patients with cancer and febrile neutropenia

IMPORTANCE: Febrile neutropenia (FN) is the most common oncologic emergency and is among the most deadly. Guidelines recommend risk stratification and outpatient management of both pediatric and adult FN patients deemed to be at low risk of complications or mortality, but our prior single-center research demonstrated that the vast majority (95%) are hospitalized. OBJECTIVE: From a nationwide perspective, to determine the proportion of cancer patients of all ages hospitalized after an emergency department (ED) visit for FN, and to analyze variability in hospitalization rates. Our a priori hypothesis was that >90% of US cancer-associated ED FN visits would end in hospitalization. DESIGN: Analysis of data from the Nationwide Emergency Department Sample, 2006-2014. SETTING: Stratified probability sample of all US ED visits. PARTICIPANTS: Inclusion criteria were: (1) Clinical Classification Software code indicating cancer, (2) diagnostic code indicating fever, and (3) diagnostic code indicating neutropenia. We excluded visits ending in transfer. EXPOSURE: The hospital at which the visit took place. MAIN OUTCOMES AND MEASURES: Our main outcome is the proportion of ED FN visits ending in hospitalization, with an a priori hypothesis of >90%. Our secondary outcomes are: (a) hospitalization rates among subsets, and (b) proportion of variability in the hospitalization rate attributable to which hospital the patient visited, as measured by the intra-class correlation coefficient (ICC). RESULTS: Of 348,868 visits selected to be representative of all US ED visits, 94% ended in hospitalization (95% Confidence Interval [CI] 93-94%). Each additional decade of age conferred 1.23x increased odds of hospitalization. Those with private (92%), self-pay (92%), and other (93%) insurance were less likely to be hospitalized than those with public insurance (95%, odds ratios [OR] 0.74-0.76). Hospitalization was least likely at non-metropolitan hospitals (84%, OR 0.15 relative to metropolitan teaching hospitals), and was also less likely at metropolitan non-teaching hospitals (94%, OR 0.64 relative to metropolitan teaching hospitals). The ICC adjusted for hospital random effects and patient and hospital characteristics was 26% (95%CI 23-29%), indicating that 26% of the variability in hospitalization rate was attributable to which hospital the patient visited. CONCLUSIONS AND RELEVANCE: Nearly all cancer-associated ED FN visits in the US end in hospitalization. Inter-hospital variation in hospitalization practices explains 26% of the limited variability in hospitalization decisions. Simple, objective tools are needed to improve risk stratification for ED FN patients

Prelamination of Neourethra with Uterine Mucosa in Radial Forearm Osteocutaneous Free Flap Phalloplasty in the Female-to-Male Transgender Patient

Radial forearm free flap phalloplasty is the most commonly performed flap for neophallus construction in the female-to-male (FtM) transgender patient. Urological complications, however, can arise quite frequently and can prevent the patient from urinating in the standing position, an important postsurgical goal for many. Using mucosa to construct the fixed urethra and to prelaminate the penile urethra has been successful in reducing urologic complications, particularly strictures and fistulas. Until now, only buccal, vaginal, colonic, and bladder sites have been described as sources for these mucosal grafts. We present the successful use of uterine mucosa for prelamination of the neourethra in an FtM patient who underwent hysterectomy and vaginectomy at the prelamination stage of a radial forearm phalloplasty. Three months postoperatively, the patient was able to void while standing and showed no evidence of stricture or fistula on retrograde cystogram. These results suggest that uterine mucosa may be used for prelamination of the penile neourethra in patients undergoing phalloplasty

Vitamin D Status and Community-Acquired Pneumonia: Results from the Third National Health and Nutrition Examination Survey

Objective: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] level and history of community-acquired pneumonia (CAP). Patients and Methods We identified 16,975 individuals (≥17 years) from the third National Health and Nutrition Examination Survey (NHANES III) with documented 25(OH)D levels. To investigate the association of 25(OH)D with history of CAP in these participants, we developed a multivariable logistic regression model, adjusting for demographic factors (age, sex, race, poverty-to-income ratio, and geographic location), clinical data (body mass index, smoking status, asthma, chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, stroke, chronic kidney disease, neutropenia, and alcohol consumption), and season. Locally weighted scatterplot smoothing (LOWESS) was used to depict the relationship between increasing 25(OH)D levels and the cumulative frequency of CAP in the study cohort. Results: The median [interquartile range (IQR)] serum 25(OH)D level was 24 (IQR 18–32) ng/mL. 2.1% [95% confidence interval (CI): 1.9–2.3] of participants reported experiencing a CAP within one year of their participation in the national survey. After adjusting for demographic factors, clinical data, and season, 25(OH)D levels <30 ng/mL were associated with 56% higher odds of CAP [odds ratio 1.56; 95% confidence interval: 1.17–2.07] compared to levels ≥30 ng/mL. LOWESS analysis revealed a near linear relationship between vitamin D status and the cumulative frequency of CAP up to 25(OH)D levels around 30 ng/mL. Conclusion: Among 16,975 participants in NHANES III, 25(OH)D levels were inversely associated with history of CAP. Randomized controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of CAP

Understanding cytoskeletal avalanches using mechanical stability analysis

Eukaryotic cells are mechanically supported by a polymer network called the cytoskeleton, which consumes chemical energy to dynamically remodel its structure. Recent experiments in vivo have revealed that this remodeling occasionally happens through anomalously large displacements, reminiscent of earthquakes or avalanches. These cytoskeletal avalanches might indicate that the cytoskeleton's structural response to a changing cellular environment is highly sensitive, and they are therefore of significant biological interest. However, the physics underlying "cytoquakes" is poorly understood. Here, we use agent-based simulations of cytoskeletal self-organization to study fluctuations in the network's mechanical energy. We robustly observe non-Gaussian statistics and asymmetrically large rates of energy release compared to accumulation in a minimal cytoskeletal model. The large events of energy release are found to correlate with large, collective displacements of the cytoskeletal filaments. We also find that the changes in the localization of tension and the projections of the network motion onto the vibrational normal modes are asymmetrically distributed for energy release and accumulation. These results imply an avalanche-like process of slow energy storage punctuated by fast, large events of energy release involving a collective network rearrangement. We further show that mechanical instability precedes cytoquake occurrence through a machine learning model that dynamically forecasts cytoquakes using the vibrational spectrum as input. Our results provide the first connection between the cytoquake phenomenon and the network's mechanical energy and can help guide future investigations of the cytoskeleton's structural susceptibility.Comment: 35 pages, 18 figure