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Background: It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-2/Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. We designed the BH3 α-helix mimetic JY-1-106 to engage the hydrophobic BH3-binding grooves on the surfaces of both Bcl-xL and Mcl-1. Methods: JY-1-106-protein complexes were studied using molecular dynamics (MD) simulations and the SILCS methodology. We have evaluated the in vitro effects of JY-1-106 by using a fluorescence polarization (FP) assay, an XTT assay, apoptosis assays, and immunoprecipitation and western-blot assays. A preclinical human cancer xenograft model was used to test the efficacy of JY-1-106 in vivo. Results: MD and SILCS simulations of the JY-1-106-protein complexes indicated the importance of the aliphatic side chains of JY-1-106 to binding and successfully predicted the improved affinity of the ligand for Bcl-xL over Mcl-1. Ligand binding affinities were measured via an FP assay using a fluorescently labeled Bak-BH3 peptide in vitro. Apoptosis induction via JY-1-106 was evidenced by TUNEL assay and PARP cleavage as well as by Bax-Bax dimerization. Release of multi-domain Bak from its inhibitory binding to Bcl-2/Bcl-xL and Mcl-1 using JY-1-106 was detected via immunoprecipitation (IP) western blotting. At the cellular level, we compared the growth proliferation IC50s of JY-1-106 and ABT-737 in multiple cancer cell lines with various Bcl-xL and Mcl-1 expression levels. JY-1-106 effectively induced cell death regardless of the Mcl-1 expression level in ABT-737 resistant solid tumor cells, whilst toxicity toward normal human endothelial cells was limited. Furthermore, synergistic effects were observed in A549 cells using a combination of JY-1-106 and multiple chemotherapeutic agents. We also observed that JY-1-106 was a very effective agent in inducing apoptosis in metabolically stressed tumors. Finally, JY-1-106 was evaluated in a tumor-bearing nude mouse model, and was found to effectively repress tumor growth. Strong TUNEL signals in the tumor cells demonstrated the effectiveness of JY-1-106 in this animal model. No significant side effects were observed in mouse organs after multiple injections. Conclusions: Taken together, these observations demonstrate that JY-1-106 is an effective pan-Bcl-2 inhibitor with very promising clinical potential. [ABSTRACT FROM AUTHOR]

Transforming growth factor (TGF)-β-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. Previously, we have shown that TGF-β inhibits the growth of rat intestinal epithelial (RIE)-1 cells. However, RIE-1 cells are relatively resistant to TGF-β-induced apoptosis due to a low endogenous Smad3-to-Akt ratio. Overexpression of Smad3 sensitizes RIE-1 cells (RIE-1/Smad3) to TGF-β-induced apoptosis by altering the Smad3-to-Akt ratio in favor of apoptosis. In this study, we utilized a genomic approach to identify potential downstream target genes that are regulated by TGF-β/Smad3. Total RNA samples were analyzed using Affymetrix oligo- nucleotide microarrays. We found that TGF-β regulated 518 probe sets corresponding to its target genes. Interestingly, among the known apoptotic genes included in the microarray analyses, only caspase-3 was induced, which was confirmed by real-time RT-PCR. Further- more, TGF-β activated caspase-3 through protein cleavage. Upstream of caspase-3, TGF-β induced mitochondrial depolarization, cytochrome c release, and cleavage of caspase-9, which suggests that the intrinsic apoptotic pathway mediates TGF-β-induced apoptosis in RIE-1/Smad3 cells. [ABSTRACT FROM AUTHOR]

PURPOSE: Immunosuppression used in transplantation is associated with an increased incidence of various cancers. Although the incidence of colorectal cancer in transplant patients seems to be equal to nontransplant population, the effects of immunosuppression on patients who develop colorectal cancer are not well defined. The purpose of this study was to define the characteristics and survival patterns of transplant patients developing tie novo colorectal cancer. METHODS: The Israel Penn International Transplant Tumor Registry was queried for patients with cob rectal cancer. Analysis included patient demographics, age at transplantation and colorectal cancer diagnosis, tumor stage, and survival. Age and survival rates were compared to United States population-based cob rectal cancer statistics using the National Cancer Institute Surveillance Epidemiology and End Results database. RESULTS: A total of 150 transplant patients with de novo colorectal cancer were identified: 93 kidney, 29 heart, 27 liver, and 1 lung. Mean age at transplantation was 53 years. Age at transplantation and coborectab cancer diagnosis was not significant for gender, race, or stage of disease. Compared to National Cancer Institute Surveillance Epidemiology and End Results database, transplantation patients had a younger mean age at colorectal cancer diagnosis (58 vs. 70 years; P < 0.001), and a worse five-year survival (overall, 44 vs. 62 percent, P < 0.001; Dukes A&B, 74 vs. 90 percent, P < 0.001; Dukes C, 20 vs. 66 percent, P < 0.001; and Dukes D, 0 vs. 9 percent, P = 0.08). CONCLUSIONS: Transplant patients develop colorectal cancer at a younger age and exhibit worse five-year survival rates than the general population. These data suggest that chronic immunosuppression results in a more aggressive tumor biology. Frequent posttransplantation colorectal cancer screening program may be warranted. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The World Health Organization Surgical Safety Checklist (SSC) has been shown to decrease surgical site infections (SSI). The Surgical Care Improvement Project (SCIP) SSI reduction bundle (SCIP Inf) contains elements to improve SSI rates. We wanted to determine if integration of SCIP measures within our SSC would improve SCIP performance and patient outcomes for SSI. Methods: An integrated SSC that included perioperative SCIP Inf measures (antibiotic selection, antibiotic timing, and temperature management) was implemented. We compared SCIP Inf compliance and patient outcomes for 1-y before and 1-y after SSC implementation. Outcomes included number of patients with initial post-anesthesia care unit temperature <98.6°F and SSI rates according to our National Surgical Quality Improvement Program data. Results: Implementation of a SCIP integrated SSC resulted in a significant improvement in antibiotic infusion timing (92.7% [670/723] versus 95.4% [557/584]; P < 0.05), antibiotic selection (96.2% [707/735] versus 98.7% [584/592]; P < 0.01), and temperature management (93.8% [723/771] versus 97.7% [693/709]; P < 0.001). Furthermore, we found a significant reduction in number of patients with initial post-anesthesia care unit temperature <98.6°F from 9.7% (982/10,126) to 6.9% (671/9676) (P < 0.001). Institutional SSI rates decreased from 3.13% (104/3319) to 2.96% (107/3616), but was not significant (P = 0.72). SSI rates according to specialty service were similar for all groups except colorectal surgery (24.1% [19/79] versus 11.5% [12/104]; P < 0.05). Conclusion: Implementation of an integrated SSC can improve compliance of SSI reduction strategies such as SCIP Inf performance and maintenance of normothermia. This did not, however, correlate with an improvement in overall SSI at our institution. Further investigation is required to determine other factors that may influence SSI at an institutional level. [Copyright &y& Elsevier]

Goal: Accurate prediction of operating room (OR) time is critical for effective utilization of resources, optimal staffing, and reduced costs. Currently, electronic health record (EHR) systems aid OR scheduling by predicting OR time for a specific surgeon and operation. On many occasions, the predicted OR time is subject to manipulation by surgeons during scheduling. We aimed to address the use of the EHR for OR scheduling and the impact of manipulations on OR time accuracy., Methods: Between April and August 2022, a pilot study was performed in our tertiary center where surgeons in multiple surgical specialties were encouraged toward nonmanipulation for predicted OR time during scheduling. The OR time accuracy within 5 months before trial (Group 1) and within the trial period (Group 2) were compared. Accurate cases were defined as cases with total length (wheels-in to wheels-out) within ±30 min or ±20% of the scheduled duration if the scheduled time is ≥ or <150 min, respectively. The study included single and multiple Current Procedural Terminology code procedures, while procedures involving multiple surgical specialties (combo cases) were excluded., Principal Findings: The study included a total of 8,821 operations, 4,243 (Group 1) and 4,578 (Group 2), (p < .001). The percentage of manipulation dropped from 19.8% (Group 1) to 7.6% (Group 2), (p < .001), while scheduling accuracy rose from 41.7% (Group 1) to 47.9% (Group 2), (p = .0001) with a significant reduction of underscheduling percentage (38.7% vs. 31.7%, p = .0001) and without a significant difference in the percentage of overscheduled cases (15% vs. 17%, p = .22). Inaccurate OR hours were reduced by 18% during the trial period (2,383 hr vs. 1,954 hr)., Practical Applications: The utilization of EHR systems for predicting OR time and reducing manipulation by surgeons helps improve OR scheduling accuracy and utilization of OR resources., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Foundation of the American College of Healthcare Executives.)

Background: Frailty is a recent multidimensional concept of a contemporary growing interest for understanding the complex health status of elderly population. We aimed to assess the impact of frailty scores on the outcome and complication rate of holmium laser enucleation of prostate (HoLEP). Methods: A 7-year data of HoLEP patients in a single tertiary referral center were reviewed. The preoperative, operative, early, and late postoperative outcome data were collected and compared according to the preoperative frailty scores. Frailty was assessed preoperatively using the Modified Hopkins frailty score. Results: The study included 837 patients categorized into two groups: group I included 533 nonfrail patients (frailty score = 0), whereas group II included 304 frail patients (frailty score ≥1). The median (interquartile range) age was 70 (11) and 75 (11) years for groups I and II, respectively (<0.001). The 30-day perioperative complication rate ( p  = 0.005), blood transfusion ( p  = 0.013), failed voiding trial ( p  = 0.0015), and 30-day postoperative readmission ( p  = 0.0363) rates were significantly higher in frail patients of group II. The two groups were statistically comparable regarding postoperative international prostate symptom score ( p  = 0.6886, 0.6308, 0.9781), incontinence rate ( p  = 0.475, 0.592, 0.1546), postvoid residual ( p  = 0.5801, 0.1819, 0.593) at 6 weeks and 3 months, and 1-year follow-up intervals, respectively. Conclusion: In elderly patients undergoing HoLEP, the preoperative frailty scores strongly correlate with the risk of perioperative complications. Frail patients should be counseled regarding their relative higher risk of early perioperative complications although they gain the same functional profit of HoLEP as nonfrail patients.

Objective: The leadership team invited surgical team members to participate in educational sessions that created self and other awareness as well as gathered baseline information about these topics: communication, conflict management, emotional intelligence, and teamwork., Design: Each educational session included an inventory that was completed to help participants understand their own characteristics and the characteristics of their team members. The results from these inventories were aggregated, relationships were identified, and the intervention was evaluated., Setting: A level 1 trauma center, Baylor Scott and White Health, in central Texas; a 636-bed tertiary care main hospital and an affiliated children's hospital., Participants: An open invitation for all surgical team members yielded 551 interprofessional OR team members including anesthesia, attending physicians, nursing, physician assistants, residents, and administration., Results: Surgeons' communication styles were individual focused, while other team members were group focused. The most common conflict management mode for surgical team members on average was avoiding, and the least common was collaborating. Surgeons primarily used competing mode for conflict management, with avoiding coming in a close second. Finally, the 5 dysfunctions of a team inventory revealed low accountability scores, meaning the participants struggled with holding team members accountable., Conclusions: Helping team members understand their own and others' strengths and blind spots will help create opportunity for more purposeful and clear communication. Additionally, this knowledge should improve efficiency and safety in the high-stakes environment of the operating room., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Psychological safety enables the interpersonal risk-taking necessary for providing safer patient care in the operating room (OR). Limited studies look at psychological safety in the OR from the perspectives of each highly specialized team member. Therefore, we investigated each member's perspective on the factors that influence psychological safety in the OR. Interviews were conducted with operative team members of a level 1 trauma center in central Texas. The interviews were transcribed, de-identified, and coded by two investigators independently, and thematic analysis was performed. Responses were collected from 21 participants representing all surgical team roles (attending surgeons, attending anesthesiologists, circulating nurses, nurse anesthetists, scrub techs, and residents). Circulating nurse responses were redacted for confidentiality (n = 1). Six major themes influencing psychological safety in the OR were identified. Psychological safety is essential to better, safer patient care. Establishing a climate of mutual respect and suspended judgment in an OR safe for learning will lay the foundation for achieving psychological safety in the OR. Team exercises in building rapport and mutual understanding are important starting points., (Copyright © 2022 Baylor University Medical Center.)

Whereas the advancement of minimally invasive surgical techniques and enhanced recovery after surgery (ERAS) pathways for partial colectomies has shortened postoperative length of stay, the ideal length of stay after partial colectomy with or without diverting loop ileostomy is still up for debate. This article examines the safety and efficacy of discharging select patients home from day surgery following partial colectomy. We performed a retrospective review of 7 patients who underwent partial colectomy at one tertiary care center from December 2020 to August 2021. None of our cases suffered complications such as anastomotic leak, surgical site infection, or bowel obstruction or required admission to the hospital. One patient was seen in the emergency department on postoperative day 1 for nausea and vomiting and was managed as an outpatient. A second patient required a fluid bolus in the clinic for high ileostomy output. In conclusion, our study suggests that appropriately selected patients can be successfully managed in the outpatient setting without increased complications following partial colectomy when preoperative preparation and education are put in place alongside our colon ERAS pathway and minimally invasive surgical techniques., (Copyright © 2021 Baylor University Medical Center.)

Background: The CDC reported in 2017 that the largest increments in probability of continued use were observed after days 5 and 31 on opioid therapy. This study demonstrates the correlation between a system-wide pain management and opioid stewardship effort with reductions in discharge prescriptions for elective surgical patients., Study Design: Discharge prescriptions were monitored through the electronic health record. Baseline prescribing patterns were established for the first quarter of 2018, preceding the first intervention in the multipronged opioid reduction initiative. Beginning in the second quarter of 2018, a series of pain management and opioid stewardship educational conferences were provided. Enhanced Recovery after Surgery protocols were simultaneously implemented system-wide. In the third quarter of 2018, a quality metric linked to compensation rewarded surgeons for limiting postoperative discharge prescriptions to 5 or fewer days. Opioid prescriptions were compared by quarter from January 2018 to March 2019 using chi-square and Kruskal-Wallis test with significance of p < 0.05., Results: There were 31,814 patients who underwent elective surgical procedures during the study period. At baseline, the rate of postoperative opioid prescriptions of 5 or fewer days was 81%. This rate increased to 82%, 86%, 89%, and 92% in each successive quarter (p < 0.0001 for quarters 3 to 5)., Conclusions: A system-wide, multipronged pain management and opioid reduction program significantly reduced opioid discharge prescriptions written for more than 5 days. This approach can serve as a model for other healthcare systems attempting to reduce opioid prescribing and combat the opioid crisis in the US., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Frailty is an emerging risk factor for surgical outcomes; however, its application across large populations is not well defined. We hypothesized that frailty affects postoperative outcomes in a large health care system., Study Design: Frailty was prospectively measured in elective surgery patients (January 2016 to June 2017) in a health care system (4 hospitals/901 beds). Frailty classifications-low (0), intermediate (1 to 2), high (3 to 5)-were assigned based on the modified Hopkins score. Operations were classified as inpatient (IP) vs outpatient (OP). Outcomes measured (30-day) included major morbidity, discharge location, emergency department (ED) visit, readmission, length of stay (LOS), mortality, and direct-cost/patient., Results: There were 14,530 elective surgery patients (68.1% outpatient, 31.9% inpatient) preoperatively assessed (cardiothoracic 4%, colorectal 4%, general 29%, oral maxillofacial 2%, otolaryngology 8%, plastic surgery 13%, podiatry 6%, surgical oncology 5%, transplant 3%, urology 24%, vascular 2%). High frailty was found in 3.4% of patients (5.3% IP, 2.5% OP). Incidence of major morbidity, readmission, and mortality correlated with frailty classification in all patients (p < 0.05). In the IP cohort, length of stay in days (low 1.6, intermediate 2.3, high 4.1, p < 0.0001) and discharge to facility increased with frailty (p < 0.05). In the OP cohort, ED visits increased with frailty (p < 0.05). Frailty was associated with increased direct-cost in the IP cohort (low, $7,045; intermediate, $7,995; high, $8,599; p < 0.05)., Conclusions: Frailty affects morbidity, mortality, and health care resource use in both IP and OP operations. Additionally, IP cost increased with frailty. The broad applicability of frailty (across surgical specialties) represents an opportunity for risk stratification and patient optimization across a large health care system., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

The American Recovery and Reinvestment Act mandates "meaningful use" of an electronic health record (EHR) to receive current financial incentives and to avoid future financial penalties. Surgeons' ongoing adoption of an EHR nationally will be influenced by the early experiences of institutions that have made the transition from paper to electronic records. We conducted a survey to query surgeons at our institution regarding their perception of the EHR 3 months after institutional implementation. A total of 59 surveys were obtained from 24 senior staff and 35 residents. Results showed that surgeons believed the EHR was more effective as a billing tool than as a form of clinical documentation and believed the billing was more complete and accurate with the EHR. Surgeons also expressed concern that the EHR would negatively impact patient satisfaction, but in spite of this, they indicated that their personal quality of life was not negatively impacted.

Background: Increased focus on reducing patient harm has led to surgical safety initiatives, including time-out, surgical safety checklists, and debriefings. The perception of the lay public of the surgical safety process is largely unknown., Methods: A 20-question survey focused on perceptions of surgical safety practice was distributed to a random sample of patients following elective operations requiring hospitalization. Responses were measured by a 7-point Likert scale. Qualitative feedback was obtained through nonphysician-moderated sessions. Participation was voluntary and anonymous., Results: Surveys were distributed to 345 patients of whom 102 (29.5%) responded. Overall, patients felt safe as evidenced by scores for the questions "I felt safe the day of my surgery" (6.53 ± 0.72) and "Mistakes rarely happen during surgery" (5.39 ± 1.51). Patients undergoing their first surgery and patients with higher income levels were associated with a significant decrease in specific safety perceptions. Qualitative feedback sessions identified the physician-patient relationship as the most important factor positively influencing patient safety perceptions., Conclusion: Current surgical safety practice is perceived positively by our patients; however, patients still identify physician-patient interactions, relationships, and trust as the most positive factors influencing their perception of the safety environment.

Health care is evolving into a value-based reimbursement system focused on quality and outcomes. Reported outcomes from national databases are used for quality improvement projects and public reporting. This study compared reported outcomes in cardiac and thoracic surgery from two validated reporting databases-the Society of Thoracic Surgeons (STS) database and the National Surgical Quality Improvement Program (NSQIP)-from January 2011 to June 2012. Quality metrics and outcomes included mortality, wound infection, prolonged ventilation, pneumonia, renal failure, stroke, and cardiac arrest. Comparison was made by chi-square analysis. A total of 737 and 177 cardiac surgery cases and 451 and 105 thoracic surgery cases were captured by the STS database and NSQIP, respectively. Within cardiac surgery, there was a statistically significant difference in the reported rates of prolonged ventilation, renal failure, and mortality. No significant differences were found for the thoracic surgery data. In conclusion, our data indicated a significant discordance in quality reporting for cardiac surgery between the NSQIP and the STS databases. The disparity between databases and duplicate participation strongly indicates that a unified national quality reporting program is required. Consolidation of reporting databases and standardization of morbidity definitions across all databases may improve participation and reduce hospital cost.

Background: The World Health Organization (WHO) surgical safety checklist has been shown to decrease mortality and complications and has been adopted worldwide. However, system flaws and human errors persist. Identifying provider perspectives of patient safety initiatives may identify strategies for improvement. The purpose of this study was to determine provider perspectives of surgical safety checklist implementation in an effort to improve initiatives that enhance surgical patients' safety., Methods: In September 2010, a WHO-adapted surgical safety checklist was implemented at our institution. Surgical teams were invited to complete a checklist-focused questionnaire 1 month before and 1 year after implementation. Baseline and follow-up results were compared., Results: A total of 437 surgical care providers responded to the survey: 45% of providers responded at baseline and 64% of providers responded at follow-up. Of the total respondents, 153 (35%) were nurses, 104 (24%) were anesthesia providers, and 180 (41%) were surgeons. Overall, we found an improvement in the awareness of patient safety and quality of care, with significant improvements in the perception of the value of and participation in the time-out process, in surgical team communication, and in the establishment and clarity of patient care needs. Some discordance was noted between surgeons and other surgical team members, indicating that barriers in communication still exist. Overall, approximately 65% of respondents perceived that the checklist improved patient safety and patient care; however, we found a strong negative perception of operating room efficiency., Conclusion: Implementation of a surgical safety checklist improves perceptions of surgical safety. Barriers to implementation exist, but staff feedback may be used to enhance the sustainability and success of patient safety initiatives.

Background: Isolated perineal endometrioma is a rare entity and often causes diagnostic uncertainty., Cases: Three premenopausal women, none with a prior history of endometriosis, presented with vague perineal pain 3-6 months following obstetric delivery with episiotomy. The latency periods between the onset of symptoms and definitive diagnosis were 3 months, 18 months and 3 years despite multiple physician evaluations in the interim. Patient presentation and management were virtually identical in all cases. Detailed questioning revealed that the pain was located adjacent to the episiotomy incision and waxed and waned with menses. Physical examination revealed a vague fullness adjacent to the episiotomy incision. Endoanal ultrasound revealed a mass of mixed echogenicity adjacent to the external anal sphincter. Transperineal exploration revealed a tumor with the gross appearance of an endometrioma, which was confirmed histologically. Excision of the mass with preservation of the anal sphincter muscle resulted in resolution of symptoms in all patients without the need for hormonal manipulation. No patient suffered diminution of fecal continence., Conclusion: Occult perineal endometriosis should be considered when a woman presents with cyclic pain in the perineum following delivery and episiotomy. Endoanal ultrasound can assist with the diagnosis. Transperineal excision with sparing of the anal sphincter can be curative, without compromising continence.