Risk of Bleeding Versus Venous Thromboembolism After Surgery for Breast Cancer: A National Surgical Quality Improvement Program Analysis.

INTRODUCTION: Patients who undergo surgery for breast cancer are at risk for venous thromboembolism (VTE) and bleeding, which can lead to significant consequences on outcomes. This study examined factors related to VTE and bleeding risk in breast cancer surgery, with and without reconstruction. We also investigated the relationship between operative time and resident involvement on bleeding and VTE risk. METHODS: Using the ACS-NSQIP database, patients who underwent mastectomy, implant, pedicled, or free flap reconstruction from 2005 to 2021 were identified. Resident involvement was available from 2007 to 2010. We fitted two logistic regressions to model the log odds of bleeding occurrence and VTE as linear functions of procedure type, controlling for age, body mass index, and comorbidities. RESULTS: Implant reconstruction had significantly reduced 30-d incidence of bleeding, compared to those who underwent transverse rectus abdominus muscle flap (P < 0.001). Free flap was associated with a significant increase in bleeding but not VTE risk (P < 0.001; P = 0.132). Increase in operative time significantly increased the risk of bleeding and VTE (P < 0.001). For surgeries with resident involvement coded, there was no significantly increased risk of bleeding or VTE (P = 0.600; P = 0.766). CONCLUSIONS: Implant reconstruction remains the procedure with the lowest risk of both bleeding and VTE. Free flap reconstruction did not show a significantly increased risk of VTE, potentially expanding reconstruction options for patients previously excluded from autologous reconstruction. Surgeons should be mindful of operative time, with re-evaluation of risk factors with each additional hour of surgery, irrespective of reconstruction type. Resident involvement in surgeries should continue to be encouraged by faculty.

Trends in minimally invasive and open inguinal hernia repair: an analysis of ACGME general surgery case logs.

BACKGROUND: Groin hernia repair is one of the most commonly performed surgical procedures and is often performed by surgical interns and junior residents. While traditionally performed open, minimally invasive (MIS) groin hernia repair has become an increasingly popular approach. The purpose of this study was to determine the trends in MIS and open inguinal and femoral hernia repair in general surgery residency training over the past two decades. METHODS: Accreditation Council for Graduate Medical Education (ACGME) national case log data of general surgery residents from 1999 through 2022 were reviewed. We collected means and standard deviations of open and MIS inguinal and femoral hernia repairs. Linear regression and ANOVA were used to identify trends in the average annual number of open and MIS hernia repairs logged by residents. Cases were distinguished between level of resident trainees: surgeon-chief (SC) and surgeon-junior (SJ). RESULTS: From July 1999 to June 2022, the average annual MIS inguinal and femoral hernia repairs logged by general surgery residents significantly increased, from 7.6 to 47.9 cases (p < 0.001), and the average annual open inguinal and femoral hernia repairs logged by general surgery residents significantly decreased, from 51.9 to 39.7 cases (p < 0.001). SJ resident results were consistent with this overall trend. For SC residents, the volume of both MIS and open hernia repairs significantly increased (p < 0.001). CONCLUSIONS: ACGME case log data indicates a trend of general surgery residents logging overall fewer numbers of open inguinal and femoral hernia repairs, and a larger proportion of open repairs by chief residents. This trend warrants attention and further study as it may represent a skill or knowledge gap with significant impact of surgical training.

Operation time effect on rates of perioperative complications after operative treatment of distal radius fractures.

PURPOSE: The purpose is to identify the impact of operation time length on complications for patients undergoing operative treatment of distal radius fracture. METHODS: Patients who underwent operative treatments for distal radius fractures were identified in a national database. Data collected include patient demographic information, comorbidities, and complications. RESULTS: Operation time was found to be an independent predictor for return to the operating room. Operation time was not found to be a predictor of other postoperative complications. CONCLUSION: Surgeons should work to shorten procedure duration whenever possible to minimize the risks that longer operative times can have on patient outcomes.

Diabetes mellitus effect on rates of perioperative complications after operative treatment of distal radius fractures.

PURPOSE: This study focuses on distal radius fractures that require surgical treatment. Patients with diabetes mellitus (DM) are at increased risk of bone fracture despite normal areal bone mineral density. The aim of this study is to identify the impact of DM on perioperative complications for patients undergoing operative treatment of distal radius fracture. METHODS: A retrospective cohort study was conducted using data collected through the National Surgical Quality Improvement Program database. All patients who underwent operative treatments for distal radius fractures from 2007 through 2018 were identified. Data collected include demographic information, comorbidities, and complications occurring within 30 days of initial surgical intervention. The incidence of adverse events following surgery was evaluated with univariate and multivariate analyses where appropriate. RESULTS: Patients with DM were found to have a low rate of complications postsurgical repair of distal radius fractures. Preoperative comorbidity analysis showed that the diabetic group had significantly higher rates of chronic obstructive pulmonary disease, hypertension, congestive heart failure, renal failure, steroid use, bleeding disorders, dyspnea, and poorer functional status. Diabetes was found to be an independent predictor for unplanned intubation, sepsis, and septic shock. Diabetes was not found to be an independent predictor of other postoperative complications. CONCLUSION: Complications after surgical repair of distal radius fracture are low except when it comes to reintubation, sepsis, and septic shock. While the risks of independent complications remain relatively low, diabetes remains an important factor to consider when selecting surgical candidates and to ensure appropriate pre-operative risk assessment.

Improving intraoperative administration of surgical antimicrobial prophylaxis: a quality improvement report.

Despite widespread adoption of the Surgical Care Improvement Programme, the incidence of surgical site infections (SSIs) remains high. It is possible that lapses in appropriate administration of antimicrobial prophylaxis may play a role. We noted significant discordance with national guidelines with regards to intraoperative antibiotic administration at our institution, leading to implementation of a quality improvement initiative using multidisciplinary education and reminder-based interventions to improve prescribing practices and increase compliance with national guidelines. We observed a significant improvement in adherence to all aspects of antibiotic administration guidelines as a result of such interventions. Targeted multidisciplinary interventions may help improve prescribing practices of surgical antimicrobial prophylaxis and provide an opportunity to potentially decrease the burden of SSI and the related morbidity and mortality.

CDK4/6 Therapeutic Intervention and Viable Alternative to Taxanes in CRPC.

Resistance to second-generation androgen receptor (AR) antagonists and CYP17 inhibitors in patients with castration-resistant prostate cancer (CRPC) develops rapidly through reactivation of the androgen signaling axis and has been attributed to AR overexpression, production of constitutively active AR splice variants, or the selection for AR mutants with altered ligand-binding specificity. It has been established that androgens induce cell-cycle progression, in part, through upregulation of cyclin D1 (CCND1) expression and subsequent activation of cyclin-dependent kinases 4 and 6 (CDK4/6). Thus, the efficacy of the newly described CDK4/6 inhibitors (G1T28 and G1T38), docetaxel and enzalutamide, was evaluated as single agents in clinically relevant in vitro and in vivo models of hormone-sensitive and treatment-resistant prostate cancer. CDK4/6 inhibition (CDK4/6i) was as effective as docetaxel in animal models of treatment-resistant CRPC but exhibited significantly less toxicity. The in vivo effects were durable and importantly were observed in prostate cancer cells expressing wild-type AR, AR mutants, and those that have lost AR expression. CDK4/6i was also effective in prostate tumor models expressing the AR-V7 variant or the AR F876L mutation, both of which are associated with treatment resistance. Furthermore, CDK4/6i was effective in prostate cancer models where AR expression was lost. It is concluded that CDK4/6 inhibitors are a viable alternative to taxanes as therapeutic interventions in endocrine therapy-refractory CRPC.Implications: The preclinical efficacy of CDK4/6 monotherapy observed here suggests the need for near-term clinical studies of these agents in advanced prostate cancer. Mol Cancer Res; 15(6); 660-9. ©2017 AACR.

PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation.

Therapies that efficiently induce apoptosis are likely to be required for durable clinical responses in patients with solid tumors. Using a pharmacological screening approach, we discovered that combined inhibition of B cell lymphoma-extra large (BCL-XL) and the mammalian target of rapamycin (mTOR)/4E-BP axis results in selective and synergistic induction of apoptosis in cellular and animal models of PIK3CA mutant breast cancers, including triple-negative tumors. Mechanistically, inhibition of mTOR/4E-BP suppresses myeloid cell leukemia-1 (MCL-1) protein translation only in PIK3CA mutant tumors, creating a synthetic dependence on BCL-XL This dual dependence on BCL-XL and MCL-1, but not on BCL-2, appears to be a fundamental property of diverse breast cancer cell lines, xenografts, and patient-derived tumors that is independent of the molecular subtype or PIK3CA mutational status. Furthermore, this dependence distinguishes breast cancers from normal breast epithelial cells, which are neither primed for apoptosis nor dependent on BCL-XL/MCL-1, suggesting a potential therapeutic window. By tilting the balance of pro- to antiapoptotic signals in the mitochondria, dual inhibition of MCL-1 and BCL-XL also sensitizes breast cancer cells to standard-of-care cytotoxic and targeted chemotherapies. Together, these results suggest that patients with PIK3CA mutant breast cancers may benefit from combined treatment with inhibitors of BCL-XL and the mTOR/4E-BP axis, whereas alternative methods of inhibiting MCL-1 and BCL-XL may be effective in tumors lacking PIK3CA mutations.

Uncoupling phototoxicity-elicited neural dysmorphology and death by insidious function and selective impairment of Ran-binding protein 2 (Ranbp2).

Morphological disintegration of neurons is coupled invariably to neural death. In particular, disruption of outer segments of photoreceptor neurons triggers photoreceptor death regardless of the pathological stressors. We show that Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) mice with mutations in SUMO-binding motif (SBM) of cyclophilin-like domain (CLD) of Ran-binding protein 2 (Ranbp2) expressed in a null Ranbp2 background lack untoward effects in photoreceptors in the absence of light-stress. However, compared to wild type photoreceptors, light-stress elicits profound disintegration of outer segments of Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) with paradoxical age-dependent resistance of photoreceptors to death and genotype-independent activation of caspases. Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) exhibit photoreceptor death-independent changes in ubiquitin-proteasome system (UPS), but death-dependent increase of ubiquitin carrier protein 9(ubc9) levels. Hence, insidious functional impairment of SBM of Ranbp2's CLD promotes neuroprotection and uncoupling of photoreceptor degeneration and death against phototoxicity.