Implementation of a health system intervention to reduce time from presentation to surgical intervention for pediatric testicular torsion.

PURPOSE: Testicular salvage rates for torsion are time-dependent1. Door to detorsion time has been identified as an independent testicular survival factor2. We describe an initiative to reduce door to incision (DTI) time for pediatric testicular torsion. MATERIALS AND METHODS: An institutional multidisciplinary quality improvement initiative with a primary outcome of reducing DTI time for pediatric testicular torsion was developed with multidisciplinary stakeholders. Several process and balancing measures were used as secondary outcomes to help interpret and verify the observed change in DTI time. Interventions were implemented in cycles. Initial interventions standardized assessment of suspected torsion by Emergency Medicine utilizing a validated scoring system. A threshold Testicular Workup for Ischemia and Suspected Torsion (TWIST) score led to parallel notification of essential services for rapid assessment and case prioritization3. Subsequently, bedside ultrasound in the Emergency Department was implemented. Progress was tracked in a live dashboard and analyzed with X-mR process control charts and Nelson rules. These tools are used in quality improvement and process control to demonstrate the significance of changes as they are being implemented, prior to when traditional hypothesis testing would be able to do so. We aimed to increase the proportion of cases with DTI times under 4 h from 64% to >90% within one year. RESULTS: We observed 22 torsion cases prior to and 62 following initial implementation. The percentage of cases with DTI times under 4 h improved from 64% to 95%. At week 29, a shift identified a significant change on the X chart, with reduction in mean DTI time from 221 to 147 min. At the same time, a shift on the mR chart identified reduction in patient-to-patient variation. Mean time from arrival to Urology evaluation decreased from 140 to 56 min, mean time from arrival to scrotal ultrasound decreased from 70 to 36 min, and mean time from scrotal ultrasound to surgical incision decreased from 128 to 80 min. These improvements highlight the two key successes of our project: application of the TWIST score and bedside ultrasound for rapid assessment of suspected testicular torsions, and parallel processing of the evaluation and management. CONCLUSIONS: Implementation of a protocol for pediatric testicular torsion increased the proportion of cases with DTI time <4 h to 95%, decreased mean DTI time, and decreased variation. Our protocol provides a model to improve timeliness of care in treating pediatric testicular torsion.

A conserved signaling pathway activates bacterial CBASS immune signaling in response to DNA damage.

To protect themselves from the constant threat of bacteriophage (phage) infection, bacteria have evolved diverse immune systems including restriction-modification, CRISPR-Cas, and many others. Here, we describe the discovery of a two-protein transcriptional regulator module associated with hundreds of CBASS immune systems and demonstrate that this module drives the expression of its associated CBASS system in response to DNA damage. We show that the helix-turn-helix transcriptional repressor CapH binds the promoter region of its associated CBASS system to repress transcription until it is cleaved by the metallopeptidase CapP. CapP is activated in vitro by single-stranded DNA, and in cells by DNA-damaging drugs. Together, CapH and CapP drive increased expression of their associated CBASS system in response to DNA damage. We identify CapH- and CapP-related proteins associated with diverse known and putative bacterial immune systems including DISARM and Pycsar antiphage operons. Overall, our data highlight a mechanism by which bacterial immune systems can sense and respond to a universal signal of cell stress, potentially enabling multiple immune systems to mount a coordinated defensive response against an invading pathogen.

Control of bacterial immune signaling by a WYL domain transcription factor.

Bacteria use diverse immune systems to defend themselves from ubiquitous viruses termed bacteriophages (phages). Many anti-phage systems function by abortive infection to kill a phage-infected cell, raising the question of how they are regulated to avoid cell killing outside the context of infection. Here, we identify a transcription factor associated with the widespread CBASS bacterial immune system, that we term CapW. CapW forms a homodimer and binds a palindromic DNA sequence in the CBASS promoter region. Two crystal structures of CapW suggest that the protein switches from an unliganded, DNA binding-competent state to a ligand-bound state unable to bind DNA. We show that CapW strongly represses CBASS gene expression in uninfected cells, and that phage infection causes increased CBASS expression in a CapW-dependent manner. Unexpectedly, this CapW-dependent increase in CBASS expression is not required for robust anti-phage activity, suggesting that CapW may mediate CBASS activation and cell death in response to a signal other than phage infection. Our results parallel concurrent reports on the structure and activity of BrxR, a transcription factor associated with the BREX anti-phage system, suggesting that CapW and BrxR are members of a family of universal defense signaling proteins.

The Medical Community's Evolving Focus on Physician and Surgeon Pregnancy: Thematic Trends From a Scoping Review.

PURPOSE: The authors aimed to chronicle the evolution of the medical community's study of physician and surgeon pregnancy by investigating thematic trends in the literature in the context of pertinent sociopolitical events. METHOD: A scoping review was conducted in Cochrane Library, Google Scholar, Ovid MEDLINE, Ovid Embase, Scopus, and Web of Science Core Collection from inception through August 11, 2020, using vocabulary and terms for physicians (including surgeons), pregnancy, and family leave. Study populations were categorized by all physician specialties or exclusively surgical specialties as well as by all career levels or exclusively trainees. Subthemes and themes were based on a priori assumptions of physician pregnancy and extrapolated from previously published reviews, respectively. Thematic trends were analyzed by plotting the total number of publications and the frequency of themes and subthemes by publication year. RESULTS: After title and abstract and full-text reviews, 407 manuscripts met inclusion criteria. Publications on physician pregnancy first emerged in the 1960s and surged from 1988 to 1996 and again from 2010 to 2019. The first known manuscript exclusively on surgeon pregnancy was published in 1991; subsequent publication frequency trends for surgeon pregnancy generally paralleled those for all physician pregnancy publications albeit in reduced quantities. Four major themes were found: impact of pregnancy on the physician and her colleagues, pregnant physician work productivity, physician maternity leave policies, and physician maternal-fetal health outcomes. CONCLUSIONS: As the number of women physicians increased and the sociopolitical environment progressed, the thematic focus of the literature on physician pregnancy evolved. Multi-institutional prospective observational studies are needed to develop definitive evidence-based recommendations that will positively impact physician pregnancy.

Pregnancy in physicians: A scoping review.

BACKGROUND: The personal health and professional impact of physician pregnancy requires further study. We performed a comprehensive scoping review of physician pregnancy to synthesize and assess the evidence to aid decision-making for relevant stakeholders. METHODS: A search of 7 databases resulted in 3733 citations. 407 manuscripts were included and scored for evidence level. Data were extracted into themes using template analysis. RESULTS: Physician pregnancy impacted colleagues through perceived increased workload and resulted in persistent stigmatization and discrimination despite work productivity and academic metrics being independent of pregnancy events. Maternity leave policies were inconsistent and largely unsatisfactory. Women physicians incurred occupational hazard risk and had high rates of childbearing delay, abortion, and fertility treatment; obstetric and fetal complication rates compared to controls are conflicting. CONCLUSIONS: Comprehensive literature review found that physician pregnancy impacts colleagues, elicits negative perceptions of productivity, and is inadequately addressed by current parental leave policies. Data are poor and insufficient to definitively determine the impact of physician pregnancy on maternal and fetal health. Prospective risk-matched observational studies of physician pregnancy should be pursued.

The role of metastatic burden in cytoreductive/consolidative radical cystectomy.

PURPOSE: To describe our institutional experience with cytoreductive/consolidative radical cystectomy (CCRC) for metastatic urothelial carcinoma (UC) and to investigate clinicopathologic features predicting prolonged cancer specific survival (CSS) following CCRC. METHODS: We performed IRB-approved review of our cystectomy database, and identified 43 patients with metastatic UC who underwent CCRC. Baseline demographics, chemotherapy regimen, clinicopathologic features, and perioperative complications were collected. Progression-free survival (PFS) and CSS were estimated from the time of CCRC. Univariate and multivariate Cox regression models were used to identify predictors of improved CSS after CCRC. RESULTS: Of the 43 patients, 32 (74.4%) had clinical evidence of distant metastases, while 11 harbored occult metastases on the surgical specimen. The most common site of metastasis was the retroperitoneal lymph nodes, found in 30 patients. Solitary metastases were found in 22 patients (51.1%). Forty-one (95%) patients received chemotherapy prior to CCRC. Disease progression was detected in 35 patients after CCRC (median PFS 5.9 months), and 34 died of metastatic cancer (median CSS 12.3 months). On multivariate analysis, patients with solitary metastases were found to have improved CSS compared to those with multiple metastases (HR 2.62, 95% CI 1.16-5.90, p = 0.02), with median CSS of 26.0 months vs. 7.9 months (p < 0.001). Median postoperative length of stay was 10 days. Overall, 56% suffered postoperative complications, including one perioperative mortality. CONCLUSIONS: CCRC is feasible in the setting of metastatic UC. Patients with solitary metastasis demonstrated longer CSS than those with multiple metastases, and should be considered candidates for future trials evaluating the role of CCRC for metastatic UC.