Genomic analysis of atypical fibroxanthoma

Atypical fibroxanthoma (AFX), is a rare type of skin cancer affecting older individuals with sun damaged skin. Since there is limited genomic information about AFX, our study seeks to improve the understanding of AFX through whole-exome and RNA sequencing of 8 matched tumor-normal samples. AFX is a highly mutated malignancy with recurrent mutations in a number of genes, including COL11A1, ERBB4, CSMD3, and FAT1. The majority of mutations identified were UV signature (C>T in dipyrimidines). We observed deletion of chromosomal segments on chr9p and chr13q, including tumor suppressor genes such as KANK1 and CDKN2A, but no gene fusions were found. Gene expression profiling revealed several biological pathways that are upregulated in AFX, including tumor associated macrophage response, GPCR signaling, and epithelial to mesenchymal transition (EMT). To further investigate the presence of EMT in AFX, we conducted a gene expression meta-analysis that incorporated RNA-seq data from dermal fibroblasts and keratinocytes. Ours is the first study to employ high throughput sequencing for molecular profiling of AFX. These data provide valuable insights to inform models of carcinogenesis and additional research towards tumor-directed therapy

Non-Invasive Venous waveform Analysis (NIVA) for volume assessment during complex cranial vault reconstruction: A proof-of-concept study in children.

BACKGROUND:Non-Invasive Venous waveform Analysis (NIVA) is novel technology that captures and analyzes changes in venous waveforms from a piezoelectric sensor on the wrist for hemodynamic volume assessment. Complex cranial vault reconstruction is performed in children with craniosynostosis and is associated with extensive blood loss, potential life-threatening risks, and significant morbidity. In this preliminary study, we hypothesized that NIVA will provide a reliable, non-invasive, quantitative assessment of intravascular volume changes in children undergoing complex cranial vault reconstruction. OBJECTIVE:To present proof-of-concept results of a novel technology in the pediatric population. METHODS:The NIVA prototype was placed on each subject's wrist, and venous waveforms were collected intraoperatively. Estimated blood loss and fluid/blood product administration were recorded in real time. Venous waveforms were analyzed into a NIVA value and then correlated, along with mean arterial pressure (MAP), to volume changes. Concordance was quantified to determine if the direction of change in volume was similar to the direction of change in MAP or change in NIVA. RESULTS:Of 18 patients enrolled, 14 had usable venous waveforms, and there was a significant correlation between change in NIVA value and change in volume. Change in MAP did not correlate with change in volume. The concordance between change in MAP and change in volume was less than the concordance between change in NIVA and change in volume. CONCLUSION:NIVA values correlate more closely to intravascular volume changes in pediatric craniofacial patients than MAP. This initial study suggests that NIVA is a potential safe, reliable, non-invasive quantitative method of measuring intravascular volume changes for children undergoing surgery

Feasibility of refreezing human spermatozoa through the technique of liquid nitrogen vapor

OBJECTIVE: To assess the feasibility of refreezing human semen using the technique of liquid nitrogen vapor with static phases. MATERIALS AND METHODS: Twenty samples from 16 subjects who required disposal of their cryopreserved semen were thawed, corresponding to 6 cancer patients and 10 participants in the assisted reproduction (AR) program. Samples were refrozen using the technique of liquid nitrogen vapor with static phases, identical to the one used for the initial freezing, and thawed again after 72 hours. We assessed the concentration of motile spermatozoa, total and progressive percent motility and spermatic vitality, according to criteria of the World Health Organization (WHO), as well as spermatic morphology according to the strict Kruger criterion, after the first and after the second thawing. RESULTS: We observed a significant decrease in all the parameters evaluated between the first and the second thawing. Median values for the concentration of motile spermatozoa decreased from 2.0x10(6)/mL to 0.1x10(6)/mL (p < 0.01); total percent motility from 42% to 22.5% (p < 0.01); progressive percent motility from 34% to 9.5% (p < 0.01); vitality from 45% to 20% (p < 0.01); and morphology from 5% to 5% (p = 0.03). There was no significant difference in the spermatic parameters between the cancer and assisted reproduction groups, both after the first and after the second thawing. We observed that in 100% of cases there was retrieval of motile spermatozoa after the second thawing. CONCLUSIONS: Refreezing of human semen by the technique of liquid nitrogen vapor allows the retrieval of viable spermatozoa after thawing

Postoperative Respiratory Complications in SARS-CoV-2 Positive Pediatric Patients Across 20 United States Hospitals: A Cohort Study

IntroductionData examining rates of postoperative complications among SARS-CoV-2 positive children are limited. The purpose of this study was to evaluate the impact of symptomatic and asymptomatic SARS-CoV-2 positive status on postoperative respiratory outcomes for children.MethodsThis retrospective cohort study included SARS-CoV-2 positive pediatric patients across 20 hospitals who underwent general anesthesia from March to October 2020. The primary outcome was frequency of postoperative respiratory complications, including: high-flow nasal cannula/non invasive ventilation, reintubation, pneumonia, Extracorporeal Membrane Oxygenation (ECMO), and 30-day respiratory-related readmissions or emergency department (ED) visits. Univariate analyses were used to evaluate associations between patient and procedure characteristics and stratified analyses by symptoms were performed examining incidence of complications.ResultsOf 266 SARS-CoV-2 positive patients, 163 (61.7%) were male, and the median age was 10 years (interquartile range 4-14). The majority of procedures were emergent or urgent (n&nbsp;=&nbsp;214, 80.5%). The most common procedures were appendectomies (n&nbsp;=&nbsp;78, 29.3%) and fracture repairs (n&nbsp;=&nbsp;40,15.0%). 13 patients (4.9%) had preoperative symptoms including cough or dyspnea. 26 patients (9.8%) had postoperative respiratory complications, including 15 requiring high-flow oxygen, 8 with pneumonia, 4 requiring non invasive ventilation, 3 respiratory ED visits, and 2 respiratory readmissions. Respiratory complications were more common among symptomatic patients than asymptomatic patients (30.8% vs. 8.7%, p&nbsp;=&nbsp;0.01). Higher ASA class and comorbidities were also associated with postoperative respiratory complications.ConclusionsPostoperative respiratory complications are less common in asymptomatic versus symptomatic SARS-COV-2 positive children. Relaxation of COVID-19-related restrictions for time-sensitive, non urgent procedures in selected asymptomatic patients may be reasonably considered. Additionally, further research is needed to evaluate the costs and benefits of routine testing for asymptomatic patients.Level of evidenceIii, Respiratory complications

Resistance of human spermatozoa to cryoinjury in repeated cycles of thaw-refreezing

Objective: To study the resistance of human spermatozoa to cryoinjury in repeated cycles of thaw-refreezing by using the fast liquid nitrogen vapor method. Material and Methods: Semen specimens were obtained from sixteen normal and oligozoospermic individuals who required disposal at the sperm bank. Five of them had testicular cancer. Specimens were thawed and an aliquot was removed for analysis. The remaining specimens were refrozen without removing the cryomedia. Repeated freeze-thaw cycles were performed until no motile sperm were observed. Sperm motility, number of motile spermatozoa and viability were determined after thawing. Resistance to cryoinjury was compared between groups and also after each refreezing cycle within groups. Results: Motile spermatozoa were recovered after five and two refreeze-thawing cycles in normozoospermic and oligozoospermic specimens, respectively. There were no significant differences in the recovery of motile spermatozoa between thaws within each group of normal and oligozoospermic specimens, but percentage motility and total number of motile spermatozoa were significantly lower in the oligozoospermic one. Specimens from men with cancer were exposed to six refreeze-thawing cycles. Although recovery of motile spermatozoa was significantly impaired after each thawing, there were no significant differences in the recovery of motile sperm between thaws in cancer and non-cancer groups. Conclusions: Human spermatozoa resist repeated cryopreservation using the fast liquid nitrogen vapor method. Normozoospermic specimens withstand refreezing for an average two cycles longer than oligozoospermic ones. Specimens from cancer patients seem to resist repeated cryoinjury similarly to non-cancer counterparts. Resistance to repeated cryoinjury was related to the initial semen quality

Incidence and management of pleural effusions in patients with Wilms tumor: A Pediatric Surgical Oncology Research Collaborative study

Wilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi-institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P < .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event-free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage-specific treatment regimens.What’s new?Some Wilms tumor (WT) patients have fluid around the lungs, or pleural effusion, at diagnosis, but its effect on outcomes is not well known. Here, the authors evaluated data from 1259 children with WT from 21 hospitals in North America. Pleural effusion was present in 7.5% of patients, higher than the previously reported rate of 4.3%, and management was not standardized among different hospitals. The authors also report that patients with pleural effusion were more likely to present with advanced stage tumors and to have their preoperative tumor rupture, but their outcomes were not significantly worse than other patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/174970/1/ijc34188_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/174970/2/ijc34188.pd