A Randomized, Controlled Trial Evaluating Perioperative Risk-Stratification and Risk-Based, Protocol-Driven Management After Elective Major Cancer Surgery.

OBJECTIVE: We evaluated the efficacy of risk-based, protocol-driven management versus (vs) usual management after elective major cancer surgery to reduce 30-day rates of postoperative death or serious complications (DSC) . SUMMARY BACKGROUND DATA: Major cancer surgery is associated with significant perioperative risks which result in worse long-term outcomes. METHODS: Adults scheduled for elective major cancer surgery were stratified/randomized to risk-based escalating levels of care, monitoring, and co-management vs usual management. The primary study outcome was 30-day rate of DSC. Additional outcomes included complications, adverse events, health care utilization, health-related quality of life (HRQOL), and disease-free and overall survival (DFS and OS). RESULTS: Between August 2014 and June 2020, 1529 patients were enrolled and randomly allocated to the study arms; 738 patients in the Intervention Arm and 732 patients in the Control Arm were eligible for analysis. 30-day rate of DSC with the intervention was 15.0% (95% CI, 12.5-17.6%) vs 14.1%, (95% CI, 11.6-16.6%) with usual management (P=0.65). There were no differences in 30-day rates of complications or adverse events (including return to the operating room); postoperative length of stay; rate of discharge to home; or 30, 60, or 90-day HRQOL or rates of hospital readmission or receipt of anti-neoplastic therapy between the study arms. At median follow-up of 48 months, OS (P=0.57) and DFS (P=0.91) were similar. CONCLUSIONS: Risk-based, protocol-driven management did not reduce 30-day rate of DSC after elective major cancer surgery compared to usual management, nor improve postoperative health care utilization, HRQOL, or cancer outcomes. Trials are needed to identify cost-effective, tailored perioperative strategies to optimize outcomes after major cancer surgery.

Preoperative CA 19-9 Predicts Disease Progression in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: An Analysis from the US HIPEC Collaborative.

INTRODUCTION: Patients with colorectal peritoneal metastases (CRPM) are increasingly treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, data identifying preoperative risk factors for poor oncologic outcomes after this procedure are limited. We aimed to determine the prognostic value of preoperative CEA, CA 125, and CA 19-9 on disease progression after CRS/HIPEC. METHODS: Patients with CRPM treated with curative intent CRS/HIPEC from 12 participating sites in the United States from 2000 to 2017 were identified. Progression-free survival (PFS), defined as disease progression or recurrence, was the primary outcome. RESULTS: In 279 patients who met inclusion criteria, the rate of disease progression was 63.8%, with a median PFS of 11 months (interquartile range [IQR] 5-20). Elevated CA 19-9 was associated with dismal PFS at 2 years (8.9% elevated vs. 30% not elevated, p < 0.01). In 113 patients who underwent upfront CRS/HIPEC, CA 19-9 emerged as the sole tumor marker independently predictive of worse PFS (hazard ratio [HR] 2.88, p = 0.048). In the subgroup of patients who had received neoadjuvant therapy (NAT), no variable was independently predictive of PFS. CA 19-9 levels over 37 U/ml were highly specific for accelerated disease progression after CRS/HIPEC. Lastly, there was no association between PFS and elevated CEA or CA 125. CONCLUSIONS: Elevated CA 19-9 is associated with decreased PFS in patients with CRPM. While traditionally CEA is the main tumor marker assessed in colon cancer, we found that CA 19-9 may better inform preoperative risk stratification for poor oncologic outcomes in patients with CRPM. However, prospective studies are required to confirm this association.

Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Contemporary Outcomes of Grade-C Postoperative Pancreatic Fistula in a Nationwide Database.

INTRODUCTION: Grade-C postoperative pancreatic fistulas (POPFs) are dreaded complications following pancreaticoduodenectomy. The aim of this study was to quantify the incidence and risk factors associated with grade C POPF in a national database. METHODS: The National Surgical Quality Improvement Program targeted user files were queried for patients who underwent elective pancreaticoduodenectomy (2014-2020). Outcomes were compared between clinically relevant (CR) grade B POPF and grade C POPF. RESULTS: Twenty-six thousand five hundred fifty-two patients were included, of which 90.1% (n = 23,714) had No CR POPF, 8.7% (n = 2287) suffered grade B POPF, and 1.2% (n = 327) suffered grade C POPF. There was no change in the rate Grade-C fistula overtime (m = 0.06, P = 0.63), while the rate of Grade-B fistula significantly increased (m = +1.40, P < 0.01). Fistula Risk Scores were similar between grade B and C POPFs (high risk: 34.9% versus 31.2%, P = 0.21). Associated morbidity was increased with grade C POPF, including delayed gastric emptying, organ space infections, wound dehiscence, respiratory complications, renal complications, myocardial infarction, and bleeding. On multivariate logistic regression, diabetes mellitus (odds ratio: 1.41 95% confidence interval: 1.06-1.87, P = 0.02) was associated with grade C POPF. CONCLUSIONS: This study represents the largest contemporary series evaluating grade C POPFs. Of those suffering CR POPF, the presence of diabetes mellitus was associated with grade C POPF. While modern management has led to grade C POPF in 1% of cases, they remain associated with alarmingly high morbidity and mortality, requiring further mitigation strategies to improve outcomes.

Routine Infectious Diseases Consultations on a Pediatric Cardiac Unit to Improve Positive Blood Culture Management.

Bacteremia can be life-threatening, and highly medicalized patients, such as those with complex congenital heart disease, are at high risk. Infectious diseases (ID) consultation is associated with improved outcomes in bacteremia. We noted an opportunity for improvement in management of positive blood cultures in our cardiac care unit (CCU). We completed a quality improvement project that included a single plan-do-study-act cycle consisting of a policy of routine ID consultation for all positive blood cultures events in the CCU. Our outcome measure of interest was percentage of appropriately managed blood culture events, the process measure was percentage of blood culture events for which the ID service was formally consulted, and the balancing measure was number of individual patients for whom the ID service was formally consulted. Appropriate antimicrobial management was determined via chart review by an ID physician. Data were analyzed via run chart and simple statistics. Following the intervention, the rate of appropriately managed positive blood culture events increased from a baseline of 86% to 98%, and the rate of ID consultation for these events increased from 75% to 98%. A shift was noted in run charts for both the outcome and process measures. There was an increase in patients for whom the ID service was consulted throughout the entire study period. We successfully implemented mandatory ID consultations in a CCU to increase proportion of appropriately managed blood cultures. While this intervention cannot be universally applied, others may find it useful in selected scenarios.

Percutaneous Drainage of Pediatric Pulmonary Abscesses: An Effective Therapy.

INTRODUCTION: Pulmonary abscess is a complication of lung infection with localized necrosis and purulent cavity formation. Pulmonary abscesses are typically managed using antibiotic therapy with anatomic surgical resection reserved as a rescue. Percutaneous drainage is considered relatively contraindicated in some centers due to perceived risk of bronchopleural fistula. However, drain placement has been frequently employed at our institution. The purpose of this study was to review and describe our longitudinal experience. METHODS: Medical records of children diagnosed with lung abscess and treated with percutaneous drainage from 2005 through 2023 were reviewed. Patient clinical parameters, follow-up imaging, and clinical outcomes were evaluated. RESULTS: Percutaneous drainage (n = 24) or aspiration alone (n = 4) under imaging guidance was performed by interventional radiologists for 28 children with lung abscesses. A single catheter (8-12 Fr) was deployed in the pulmonary abscess cavity and remained for a median of 6 days (IQR: 6-8 days). The median hospital stay was 10 days (IQR: 8.8-14.8 days). The technical success rate for percutaneous drainage or aspiration of primary pulmonary abscesses was 100% (26/26). Two children were later diagnosed with secondarily infected congenital pulmonary airway malformations that were both successfully drained and ultimately surgically resected. The abscess cavities resolved in all patients and catheters were removed upon clinical, radiographic, and laboratory improvement. Complications included the presence of two bronchopleural fistula, both of which were treated with immediate pleural drain placement. CONCLUSION: Percutaneous drainage of pulmonary abscesses is an effective therapeutic option in children and can be considered alongside antibiotics as part of the initial treatment for pulmonary abscesses. Bronchopleural fistula can occur, but at a lower frequency than previously reported. LEVEL OF EVIDENCE: Level V.

Chimeric versus Multiple Flaps for Composite Oral Cavity Defects: A Systematic Review and Meta-Analysis.

OBJECTIVES: Complex head and neck defects involving composite defects can be reconstructed using chimeric flaps or multiple flaps with separate anastomoses. Limited comparisons exist between chimeric and multiple flap reconstructions. We compare outcomes between chimeric and multiple flap reconstructions in oral cavity reconstruction. DATA SOURCES: PubMed (NLM), Embase (Elsevier), Web of Science (Clarivate Analytics), and Cochrane CENTRAL (Wiley). METHODS: A systematic review was conducted, including English articles reporting outcomes of oral cavity reconstruction with either chimeric flaps or multiple flaps. Data extraction included patient characteristics, flap type, and outcomes such as flap survival, partial flap loss, operating room time, hospital length of stay, and postoperative complications. RESULTS: Forty-seven articles comprising 1435 patients were included. Notably, 552 patients underwent multiple flaps, while 883 received chimeric flaps. Meta-analysis revealed no statistically significant difference in flap survival between chimeric and multiple flap patients (98% vs. 99%, p = 0.198). Multiple flap patients had higher rates of operating room take-backs for anastomotic issues and longer hospital stays compared with chimeric flap patients. There were no significant differences in partial flap failure, resumption of diet and speech, need for subsequent flaps, fistula formation, or general complications. CONCLUSION: This large-scale meta-analysis demonstrates equivalent flap survival between chimeric and multiple flaps in the reconstruction of composite oral cavity defects. Both approaches appear to be safe and acceptable, with comparable outcomes in terms of diet and speech resumption, rates of fistulization, and general postoperative complications. Multiple flap patients had higher rates of operating room take-backs and longer hospital stays. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

The Critical Blood-Sparing Effect of Tranexamic Acid (TXA) in Liposuction: A Systematic Review and Meta-Analysis.

Introduction: Tranexamic acid (TXA) has been used to improve bleeding outcomes in many surgical procedures. However, its blood-sparing effect in liposuction is not well established. Methods: A systematic literature search was performed using PubMed, Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central, ClinicalTrials.gov, and WorldWideScience.org databases from their inception to October 8, 2021, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors focused on 3 main topics: 1) TXA, 2) liposuction, and 3) complications. We included articles evaluating the potential blood-sparing effects of TXA in liposuction. Studies were excluded if they were systematic review articles or protocol papers, animal studies, conference abstracts, survey studies, or non-English publications. Results: A total of 711 articles were identified, with 1 retrospective and 4 prospective (3 randomized) studies meeting our inclusion criteria. TXA was used in various forms: administered intravenously either on induction or after the procedure, mixed into the tumescent solution, or infiltrated into the liposuction sites after lipoaspiration. A significantly smaller reduction in hematocrit was noted in the TXA group compared with that in the non-TXA group (p<0.001) despite a significantly greater amount of lipoaspirate removed in the TXA group (p<0.001). Patients in non-TXA cohorts experienced adverse effects (such as seroma and need for transfusion) that were not seen in TXA cohorts. Conclusion: TXA use in patients undergoing liposuction seems to be associated with a beneficial blood-sparing effect, which may enhance safety in this population. Future studies should aim to determine the optimal route and dosing for TXA in liposuction. Evidence Based Medicine: Level IV.

Sphingosine is involved in PAPTP-induced death of pancreas cancer cells by interfering with mitochondrial functions.

Pancreas ductal adenocarcinoma belongs to the most common cancers, but also to the tumors with the poorest prognosis. Here, we pharmacologically targeted a mitochondrial potassium channel, namely mitochondrial Kv1.3, and investigated the role of sphingolipids and mutated Kirsten Rat Sarcoma Virus (KRAS) in Kv1.3-mediated cell death. We demonstrate that inhibition of Kv1.3 using the Kv1.3-inhibitor PAPTP results in an increase of sphingosine and superoxide in membranes and/or membranes associated with mitochondria, which is enhanced by KRAS mutation. The effect of PAPTP on sphingosine and mitochondrial superoxide formation as well as cell death is prevented by sh-RNA-mediated downregulation of Kv1.3. Induction of sphingosine in human pancreas cancer cells by PAPTP is mediated by activation of sphingosine-1-phosphate phosphatase and prevented by an inhibitor of sphingosine-1-phosphate phosphatase. A rapid depolarization of isolated mitochondria is triggered by binding of sphingosine to cardiolipin, which is neutralized by addition of exogenous cardiolipin. The significance of these findings is indicated by treatment of mutated KRAS-harboring metastasized pancreas cancer with PAPTP in combination with ABC294640, a blocker of sphingosine kinases. This treatment results in increased formation of sphingosine and death of pancreas cancer cells in vitro and, most importantly, prolongs in vivo survival of mice challenged with metastatic pancreas cancer. KEY MESSAGES: Pancreatic ductal adenocarcinoma (PDAC) is a common tumor with poor prognosis. The mitochondrial Kv1.3 ion channel blocker induced mitochondrial sphingosine. Sphingosine binds to cardiolipin thereby mediating mitochondrial depolarization. Sphingosine is formed by a PAPTP-mediated activation of S1P-Phosphatase. Inhibition of sphingosine-consumption amplifies PAPTP effects on PDAC in vivo.

Contemporary Prophylactic Antibiotic Practices and Adjunct Therapies in Autologous Fat Grafting Procedures: A Survey of The Aesthetic Society Members.

Background: Autologous fat grafting (AFG) is a widely used surgical technique that involves extracting a patient's own adipose tissue and transferring it to different areas of the body. This practice is still evolving. Guidelines for antibiotic prophylaxis and use of adjuncts in plastic surgery are currently limited, with a notable absence of standardized guidelines for AFG. Objectives: In this survey, we assess contemporary antibiotic practices and adjuncts in AFG procedures. Methods: A 52-question survey was emailed to 3106 active members of The Aesthetic Society. Two hundred and ninety-three responses were recorded, representing a 9% response rate. Results: We analyzed 288 responses. The most common AFG procedures were facial (38%), gluteal (34%), and breast (27%) augmentation. Preoperative antibiotics were used by 84.0% overall, with rates of 74.3%, 88.0%, and 92.7% in face, breast, and gluteal AFG, respectively. Lipoaspirate-antibiotic mixing was reported by 19.8%, mainly during gluteal AFG (46.9%), and less so in face (2.8%) and breast (8%) AFG. Notably, 46.9% of surgeons administered prolonged prophylaxis for 72 h or more. Tranexamic acid was utilized by 39.9% of the surveyed surgeons. Platelet-rich plasma was used by 5.6%. Doppler ultrasound was incorporated by 16.7% in AFG, with 21.5% in gluteal AFG, 14% in the face, and 19% in breast procedures. Conclusions: In this survey, we offer insights into antibiotic practices and adjunct therapies in AFG, especially intraoperative antibiotic mixing. Practices among members of The Aesthetic Society vary from guidelines. It is crucial to standardize practices and conduct further research to pave the way for evidence-based guidelines in AFG.

Ambulatory amoxicillin use for common acute respiratory infections during a national shortage: Results from the SHARPS-OP benchmarking collaborative.

We quantified antibiotic prescribing for ambulatory pediatric acute respiratory illness at 22 institutions in "pre-shortage" (Jan 2019-Sep 2022) and "shortage" (Oct 2022-Mar 2023) periods for amoxicillin. While acute respiratory illness prescribing increased across settings, the proportion of amoxicillin prescriptions decreased. Variation was seen within and between institutions.

Bard Versus the 2022 American Society of Plastic Surgeons In-Service Examination: Performance on the Examination in Its Intern Year.

Background: Bard is a conversational generative artificial intelligence (AI) platform released by Google (Mountain View, CA) to the public in May 2023. Objectives: This study investigates the performance of Bard on the American Society of Plastic Surgeons (ASPS) In-Service Examination to compare it to residents' performance nationally. We hypothesized that Bard would perform best on the comprehensive and core surgical principles portions of the examination. Methods: Google's 2023 Bard was used to answer questions from the 2022 ASPS In-Service Examination. Each question was asked as written with the stem and multiple-choice options. The 2022 ASPS Norm Table was utilized to compare Bard's performance to that of subgroups of plastic surgery residents. Results: A total of 231 questions were included. Bard answered 143 questions correctly corresponding to an accuracy of 62%. The highest-performing section was the comprehensive portion (73%). When compared with integrated residents nationally, Bard scored in the 74th percentile for post-graduate year (PGY)-1, 34th percentile for PGY-2, 20th percentile for PGY-3, 8th percentile for PGY-4, 1st percentile for PGY-5, and 2nd percentile for PGY-6. Conclusions: Bard outperformed more than half of the first-year integrated residents (74th percentile). Its best sections were the comprehensive and core surgical principle portions of the examination. Further analysis of the chatbot's incorrect questions might help improve the overall quality of the examination's questions.

Validation of the CREST model & Comparison with SCAI Shock Classification for Prediction of Circulatory Death in Resuscitated Out of Hospital Cardiac Arrest.

OBJECTIVE: We validated the CREST model, a 5 variable score for stratifying risk of circulatory etiology death (CED) following out of hospital cardiac arrest (OHCA), and compared its discrimination with the SCAI shock classification. BACKGROUND: CED occurs in approximately a third of patients admitted after resuscitated OHCA. There is an urgent need for improved stratification of the OHCA patient on arrival to a cardiac arrest centre to improve patient selection for invasive interventions. METHODS: The CREST model and SCAI shock classification were applied to a dual-centre registry of 723 patients with cardiac etiology OHCA, both with and without ST-elevation myocardial infarction, between May 2012 to December 2020. The primary endpoint was 30-day CED. RESULTS: Of 509 patients included (62.3 years, 75.4% male), 125 patients had CREST=0 (24.5%), 162 were CREST=1 (31.8%), 140 were CREST=2 (27.5%), 75 were CREST=3 (14.7%), 7 were CREST of 4 (1.4%) and no patients were CREST=5. CED was observed in 91 (17.9%) patients at 30 days [STEMI - 51/289 (17.6%); NSTEMI - 40/220 (18.2%)]. For the total population, and both NSTEMI & STEMI subpopulations, increasing CREST score was associated with increasing CED (all p<0.001). CREST score and SCAI classification had similar discrimination for the total population (AUC=0.72/calibration slope=0.95), NSTEMI cohort (AUC=0.75/calibration slope=0.940) and STEMI cohort (AUC=0.69 and calibration slope=0.925). AUC meta-analyses demonstrated no significant differences between the two classifications. CONCLUSIONS: The CREST model and SCAI shock classification have similar prediction for the development of CED after OHCA.

Distribution of NADPH-diaphorase in rat mesencephalon: a light and electron microscopical study

NADPH-diaphorase is a useful technique to reveal NO producing neurons at light microscopic level (LM). A modification of the technique using the tetrazolium salt BSPT as substrate, is useful to study the ultrastructure of NO neurons. The aim of this work was to perform a detailed analysis of NADPH-diaphorase reactive neurons in rat mesencephalon both at light and electron microscopic levels. NADPH-diaphorase reactive neurons were observed in superior colliculus, in central gray matter, in dorsal and medial raphe and in the pedunculopontine tegmental nucleus using two histochemical techniques at LM. Electron microscopy showed deposits on membranes of the endoplasmic reticulum, Golgi apparatus and nuclear envelope of dorsal raphe neurons. Presynaptic and postsynaptic terminals showed deposits on membranous elements but postsynaptic terminals also showed deposits on the inner surface of their membranes. Further physiological studies are needed to clarify the meaning of the ultrastructural findings such as the putative interaction of NOS with postsynaptic proteins, receptors or membranous channels.