A Review of COVID-19-Related Publications and Lag Times During the First Six Months of the Year 2020.

INTRODUCTION: Considering the need for information regarding approaches to prevention and treatment of coronavirus disease 2019 (COVID-19), we sought to determine publication lag times of COVID-19-related original research articles published in top general medicine and emergency medicine (EM) journals. We further sought to characterize the types of COVID-19 publications within these journals. METHODS: We reviewed 125 top-ranked general medicine journals and 20 top-ranked EM-specific journals for COVID-19-related publications. We abstracted article titles and manuscript details for each COVID-19-related article published between January 1-June 30, 2020, and categorized articles as one of the following: original research; case report; review; or commentary. We abstracted data for preprint publications over the same time period and determined whether articles from the general medicine and EM journals had been previously published as preprint articles. Our primary outcomes were the following: 1) lag time (days) between global cumulative World Health Organization (WHO)-confirmed cases of COVID-19 and publications; 2) lag times between preprint article publication and peer-reviewed journal publication; and 3) lag times between submission and publication in peer-reviewed journals. Our secondary outcome was to characterize COVID-19-related publications. RESULTS: The first original research publications appeared in a general medicine journal 20 days and in an EM journal 58 days after the first WHO-confirmed case of COVID-19. We found median and mean lag times between preprint publications and journal publications of 32 days (19, 49) and 36 days (22) for general medicine journals, and 26 days (16, 36) and 25 days (13) for EM journals. Median and mean lag times between submission and publication were 30 days (19, 45) and 35 days (13) for general medicine journals, and 23 days (11, 39) and 27 days (19) for EM journals. Of 2530 general medicine journal articles and 351 EM journal articles, 28% and 23.6% were original research. We noted substantial closing of the preprint to peer-reviewed publication (160 days pre-pandemic) and peer-reviewed journal submission to publication (194 days pre-pandemic) lag times for COVID-19 manuscripts. CONCLUSION: We found a rapid and robust response with shortened publication lag times to meet the need for the publication of original research and other vital medical information related to COVID-19 during the first six months of 2020.

Relationship Between Sever Disease and Skeletal Maturity.

BACKGROUND: Sever disease is a common condition in active, growing children. This condition presents as pain in the heel and is thought to be an overuse condition of the calcaneal apophysis. There are currently no defined radiographic diagnostic criteria for evaluation of Sever disease, with radiographs generally showing normal appearance of the calcaneal apophysis. A better understanding of the relationship of Sever disease and skeletal maturity may allow for improved interpretation of radiographs when trying to diagnose this condition. METHODS: ICD-9 code 732.5 was used to search for patients diagnosed with Sever disease from 2007 to 2015 at a single hospital. For every patient with Sever disease with available calcaneal imaging within 40 days of diagnosis, heel x-rays were staged for calcaneal maturity score using a previously described calcaneal skeletal maturity assessment system. Controls matched by age, race, and sex were evaluated for calcaneal stage to compare with the Sever patients. RESULTS: The chart review yielded 78 patients diagnosed with Sever disease by the orthopaedic attending, 39 of which have x-rays around the time of diagnosis. Calcaneal scores averaged 2.2±0.8 for all patients, 2.1±0.9 for male individuals, and 2.3±0.8 for female individuals. The average age for male individuals was 10.4±1.9 years and for female individuals, 9.2±2.2 years. The ages of diagnosis were similar for patients with and without x-rays. Twenty-two of 39 patients with Sever disease were calcaneal stage 2, and 37 of 39 were stages 1, 2, or 3. We calculated the absolute difference from stage 2 for the Sever and control groups. Mean difference from stage 2 was 0.51±0.68 for the Sever patients and 0.95±0.79 for control patients (P=0.01). CONCLUSION: Sever disease occurs in a very narrow range of skeletal maturity, as measured by the calcaneal skeletal maturity assessment system and our observations with chronological age. When compared with age-matched and race-matched controls, stage 2 was seen more frequently in the Sever patients. If a child is not within calcaneal stages 1, 2, or 3, then a different diagnosis should be considered. LEVEL OF EVIDENCE: Level III-retrospective case-control study.

Evaluation of Skeletal Maturity Using the Distal Femoral Physeal Central Peak Is Not Significantly Affected by Radiographic Projection.

BACKGROUND: Accurate estimation of skeletal maturity is important in several pediatric orthopaedic conditions. The current gold standard for estimating skeletal maturity using the Greulich and Pyle Bone Atlas is complex and shown to have significant interobserver variability. Recent data have shown peak height velocity to occur on average at 90% of final adult height, providing an improved gold standard to quantify skeletal maturity, facilitating the investigation of different skeletal maturity systems. Measurement of topographical changes to the developing distal femoral physis on anteroposterior (AP) radiographs allow for calculation of the central peak value (CPV), a quantitative method shown to provide accurate prediction of 90% of final adult height. The purpose of this study was to assess the clinical tolerance of the CPV method to varying beam angles by comparing measurement reliability between AP radiographs of the knee versus standing hip-to-ankle leg-length radiographs. METHODS: We searched our institution's pediatric orthopaedic clinical database for skeletally immature patients evaluated with both standard AP radiographs of the knee as well as standing hip-to-ankle radiographs. Patients included female individuals aged 7 to 16 years and male individuals aged 7 to 18 years with both radiographs within 6 months. CPV was measured using a previously published method. Intraclass correlation coefficient was calculated to determine the level of agreement between observers in all available radiographs. CPVs between AP radiographs of the knee and standing hip-to-ankle radiographs were compared using a paired t test to determine if there is a significant difference between radiographic projection and sex. RESULTS: A total of 78 subjects meeting appropriate inclusion and exclusion criteria were identified. intraclass correlation coefficient value was 0.873, indicating excellent interobserver reliability for CPV measurements. The mean time between radiographs was 0.30 years for male and 0.27 years for female patients. CPV values between the 2 radiographic projections were not significantly different in male (P=0.37), female (P=0.22) or male+female patients (P=0.17). CPV values were significantly higher in male patients on both AP radiographs (P<0.001) and standing hip-to-ankle radiographs (P<0.001) when compared with female patients. CONCLUSIONS: The CPV is a quick, quantitative method for estimating skeletal maturity. CPVs are not significantly different between standard AP radiographs of the knee versus standing hip-to-ankle leg-length radiographs, expanding the potential to utilize this method without the need for additional expense or radiation. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Perioperative Considerations When Treating Isolated Periprosthetic Distal Femur Fractures.

BACKGROUND: Periprosthetic distal femur (PPDF) fractures occur most frequently via low energy mechanisms in elderly patients. This population is often frail and ill-suited to the physiologic burden of trauma and surgery. Here, we describe the perioperative and early hospital course for patients with PPDF fractures, and identify risk factors for poor outcomes. METHODS: Consecutive patients with isolated PPDF fractures from 2005 - 2015 were treated operatively at a Level I trauma center. Perioperative records were reviewed. Complications included wound complications, cardiac complications, pneumonia, thromboembolic events, urinary tract infections (UTIs), sepsis, multiple organ failure, death, and 90-day readmissions. RESULTS: Thirty-nine patients were treated operatively for isolated PPDF fractures. Mean age was 75.1 years old, 87.2% were women, and 92.3% occurred after falls from standing. Average American Society of Anesthesiologists score was 3.0. Thirty-six patients underwent open reduction and internal fixation with a mean operative time of 108 minutes. Excluding outliers, mean LOS was 4.6 days. Patients admitted to the ICU had longer LOS (p=0.03). Complications occurred in 17.9% of patients, including cardiac events (12.8%) and (5.1%) deaths. CONCLUSIONS: Patients with PPDF fractures frequently have underlying medical comorbidities. A complicated and/or protracted hospital course is not uncommon. Further study to optimize treatment appears warranted. Level of evidence: Prognostic, level 4.

The Cardioplastic Approach to the Treatment of Infected Aortic Grafts.

BACKGROUND: Aortic graft infection (AGI) is a rare complication following reconstructive aortic surgery, yet it represents a significant source of morbidity and mortality. There is no consensus regarding the optimal surgical management, due in part to the small cohorts of patient reports. Pedicled muscle or omental flap coverage of AGI has been shown to improve outcomes, making them a valuable consideration in the treatment algorithm. Thus, we aim to compile and evaluate cases of autologous vascularized tissue (AVT) in the treatment of infected aortic grafts, summarizing location specific trends, treatments, and outcomes. METHODS: A comprehensive review of peer-reviewed literature regarding the management of AGI was performed. Data collected included patient characteristics, original procedure, pathogen, infection location, tissue utilized, technique of tissue isolation and delivery, staging, outcome, length of follow-up, and level of evidence. RESULTS: Ninety-four cases of AGI managed with AVT transfer were identified. Infection of ascending aorta grafts accounted for 59% of cases, followed by a combination of ascending aorta and aortic arch (21%), the descending thoracic aorta (18%), and the thoracoabdominal aorta (2%). The infected graft was preserved in 81% of cases, followed by debridement and AVT coverage. The omentum was the most commonly applied flap (69%) for all divisions of the aorta followed by the pectoralis major (19%), the rectus abdominis (5%), and latissimus dorsi (4%). Mortality was limited, and the Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation overall survival was 93% (7 deaths), with a mean follow-up of 33.5 months. CONCLUSIONS: Autologous vascularized tissue coverage has proven to be a successful approach for treatment of infected aortic grafts. Although the incidence of AGI is rare, it represents an area of scarce evidence-based literature that warrants increased attention and surgical refinement. These results, which show a remarkably low infection-related mortality rate (3%), should encourage interdisciplinary collaboration with the plastic surgeon, cardiothoracic surgeon, and infectious disease specialists with the goal of improving outcomes in the treatment of infected aortic grafts.

Chemotherapy-Induced Inflammatory Gene Signature and Protumorigenic Phenotype in Pancreatic CAFs via Stress-Associated MAPK.

UNLABELLED: Pancreatic ductal adenocarcinoma (PDAC) has a characteristically dense stroma comprised predominantly of cancer-associated fibroblasts (CAF). CAFs promote tumor growth, metastasis, and treatment resistance. This study aimed to investigate the molecular changes and functional consequences associated with chemotherapy treatment of PDAC CAFs. Chemoresistant immortalized CAFs (R-CAF) were generated by continuous incubation in gemcitabine. Gene expression differences between treatment-naïve CAFs (N-CAF) and R-CAFs were compared by array analysis. Functionally, tumor cells (TC) were exposed to N-CAF- or R-CAF-conditioned media and assayed for migration, invasion, and viability in vitro Furthermore, a coinjection (TC and CAF) model was used to compare tumor growth in vivo R-CAFs increased TC viability, migration, and invasion compared with N-CAFs. In vivo, TCs coinjected with R-CAFs grew larger than those accompanied by N-CAFs. Genomic analysis demonstrated that R-CAFs had increased expression of various inflammatory mediators, similar to the previously described senescence-associated secretory phenotype (SASP). In addition, SASP mediators were found to be upregulated in response to short duration treatment with gemcitabine in both immortalized and primary CAFs. Inhibition of stress-associated MAPK signaling (P38 MAPK or JNK) attenuated SASP induction as well as the tumor-supportive functions of chemotherapy-treated CAFs in vitro and in vivo These results identify a negative consequence of chemotherapy on the PDAC microenvironment that could be targeted to improve the efficacy of current therapeutic regimens. IMPLICATIONS: Chemotherapy treatment of pancreatic cancer-associated fibroblasts results in a proinflammatory response driven by stress-associated MAPK signaling that enhances tumor cell growth and invasiveness. Mol Cancer Res; 14(5); 437-47. ©2016 AACR.