Insights into the mechanisms and structure of breakage-fusion-bridge cycles in cervical cancer using long-read sequencing.

Cervical cancer is caused by human papillomavirus (HPV) infection, has few approved targeted therapeutics, and is the most common cause of cancer death in low-resource countries. We characterized 19 cervical and four head and neck cancer cell lines using long-read DNA and RNA sequencing and identified the HPV types, HPV integration sites, chromosomal alterations, and cancer driver mutations. Structural variation analysis revealed telomeric deletions associated with DNA inversions resulting from breakage-fusion-bridge (BFB) cycles. BFB is a common mechanism of chromosomal alterations in cancer, and our study applies long-read sequencing to this important chromosomal rearrangement type. Analysis of the inversion sites revealed staggered ends consistent with exonuclease digestion of the DNA after breakage. Some BFB events are complex, involving inter- or intra-chromosomal insertions or rearrangements. None of the BFB breakpoints had telomere sequences added to resolve the dicentric chromosomes, and only one BFB breakpoint showed chromothripsis. Five cell lines have a chromosomal region 11q BFB event, with YAP1-BIRC3-BIRC2 amplification. Indeed, YAP1 amplification is associated with a 10-year-earlier age of diagnosis of cervical cancer and is three times more common in African American women. This suggests that individuals with cervical cancer and YAP1-BIRC3-BIRC2 amplification, especially those of African ancestry, might benefit from targeted therapy. In summary, we uncovered valuable insights into the mechanisms and consequences of BFB cycles in cervical cancer using long-read sequencing.

Insights into the Mechanisms and Structure of Breakage-Fusion-Bridge Cycles in Cervical Cancer using Long-Read Sequencing.

Cervical cancer is caused by human papillomavirus (HPV) infection, has few approved targeted therapeutics, and is the most common cause of cancer death in low-resource countries. We characterized 19 cervical and four head and neck cell lines using long-read DNA and RNA sequencing and identified the HPV types, HPV integration sites, chromosomal alterations, and cancer driver mutations. Structural variation analysis revealed telomeric deletions associated with DNA inversions resulting from breakage-fusion-bridge (BFB) cycles. BFB is a common mechanism of chromosomal alterations in cancer, and this is one of the first analyses of these events using long-read sequencing. Analysis of the inversion sites revealed staggered ends consistent with exonuclease digestion of the DNA after breakage. Some BFB events are complex, involving inter- or intra-chromosomal insertions or rearrangements. None of the BFB breakpoints had telomere sequences added to resolve the dicentric chromosomes and only one BFB breakpoint showed chromothripsis. Five cell lines have a Chr11q BFB event, with YAP1/BIRC2/BIRC3 gene amplification. Indeed, YAP1 amplification is associated with a 10-year earlier age of diagnosis of cervical cancer and is three times more common in African American women. This suggests that cervical cancer patients with YAP1/BIRC2/BIRC3-amplification, especially those of African American ancestry, might benefit from targeted therapy. In summary, we uncovered new insights into the mechanisms and consequences of BFB cycles in cervical cancer using long-read sequencing.

Preoperative Prevention of Surgical-Site Infection in Spine Surgery.

Surgical-site infections (SSI) contribute to increased hospital length of stay, readmission rates, cost, and morbidity and mortality rates. The spine service line at a suburban Level II trauma center encountered 2 SSIs among the spine fusion population within a 6-month period. This did not meet the organization's internal benchmark of zero. A pilot quasi-experimental design was used to determine whether preoperative cleansing with 2% chlorhexidine gluconate (CHG)-impregnated cloths versus current practice of bathing with 4% CHG solution would reduce SSIs. Infection rates were measured using simple percentages. Level of significance was p < .05. Outcome data showed a reduction in SSIs from 3.9% to 1.9% with use of 2% CHG-impregnated cloths. There was no significant difference found between the use of 2% CHG-impregnated cloths and 4% CHG solution (p = .524). This quality improvement change, combined with a strengthened preoperative bundle approach, has permanently been adopted within the spine service line. From October 2017 to March 2021, the spine service line has had zero SSIs within the spine fusion population.

Fluid Resuscitation of the Adult Trauma Patient: Where Have We Been and Where Are We Going?

The resuscitation of an adult trauma patient has been researched and written about for the past century. Throughout those discussions, 2 major controversies persist when discussing resuscitation methods: (1) the ideal choice of fluid type to use during the initial resuscitation period, and (2) the ideal fluid volume to infuse during the initial resuscitation period. This article presents a brief historical perspective of fluids used during a trauma resuscitation, along with the latest research findings as they relate to the 2 stated issues.