Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty.

BACKGROUND: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. METHODS: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. RESULTS: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83). CONCLUSIONS: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.).

Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

Prognostic performance of the IABP-SHOCK II Risk Score among cardiogenic shock subtypes in the critical care cardiology trials network registry.

BACKGROUND: Risk stratification has potential to guide triage and decision-making in cardiogenic shock (CS). We assessed the prognostic performance of the IABP-SHOCK II score, derived in Europe for acute myocardial infarct-related CS (AMI-CS), in a contemporary North American cohort, including different CS phenotypes. METHODS: The critical care cardiology trials network (CCCTN) coordinated by the TIMI study group is a multicenter network of cardiac intensive care units (CICU). Participating centers annually contribute ≥2 months of consecutive medical CICU admissions. The IABP-SHOCK II risk score includes age > 73 years, prior stroke, admission glucose > 191 mg/dl, creatinine > 1.5 mg/dl, lactate > 5 mmol/l, and post-PCI TIMI flow grade < 3. We assessed the risk score across various CS etiologies. RESULTS: Of 17,852 medical CICU admissions 5,340 patients across 35 sites were admitted with CS. In patients with AMI-CS (n = 912), the IABP-SHOCK II score predicted a >3-fold gradient in in-hospital mortality (low risk = 26.5%, intermediate risk = 52.2%, high risk = 77.5%, P < .0001; c-statistic = 0.67; Hosmer-Lemeshow P = .79). The score showed a similar gradient of in-hospital mortality in patients with non-AMI-related CS (n = 2,517, P < .0001) and mixed shock (n = 923, P < .001), as well as in left ventricular (<0.0001), right ventricular (P = .0163) or biventricular (<0.0001) CS. The correlation between the IABP-SHOCK II score and SOFA was moderate (r2 = 0.17) and the IABP-SHOCK II score revealed a significant risk gradient within each SCAI stage. CONCLUSIONS: In an unselected international multicenter registry of patients admitted with CS, the IABP- SHOCK II score only moderately predicted in-hospital mortality in a broad population of CS regardless of etiology or irrespective of right, left, or bi-ventricular involvement.

Effectiveness of Prehabilitation Modalities on Postoperative Outcomes Following Colorectal Cancer Surgery: A Systematic Review of Randomised Controlled Trials.

BACKGROUND: Postoperative morbidity in patients undergoing curative colorectal cancer surgery is high. Prehabilitation has been suggested to reduce postoperative morbidity, however its effectiveness is still lacking. OBJECTIVE: The aim of this study was to investigate the effectiveness of prehabilitation in reducing postoperative morbidity and length of hospital stay in patients undergoing colorectal cancer surgery. METHODS: A comprehensive electronic search was conducted in the CINAHL, Cochrane Library, Medline, PsychINFO, AMED, and Embase databases from inception to April 2023. Randomised controlled trials testing the effectiveness of prehabilitation, including exercise, nutrition, and/or psychological interventions, compared with usual care in patients undergoing colorectal cancer surgery were included. Two independent review authors extracted relevant information and assessed the risk of bias. Random-effect meta-analyses were used to pool outcomes, and the quality of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines. RESULTS: A total of 23 trials were identified (N = 2475 patients), including multimodal (3 trials), exercise (3 trials), nutrition (16 trials), and psychological (1 trial) prehabilitation. There was moderate-quality evidence that preoperative nutrition significantly reduced postoperative infectious complications (relative risk 0.65, 95% confidence interval [CI] 0.45-0.94) and low-quality evidence on reducing the length of hospital stay (mean difference 0.87, 95% CI 0.17-1.58) compared with control. A single trial demonstrated an effect of multimodal prehabilitation on postoperative complication. CONCLUSION: Nutrition prehabilitation was effective in reducing infectious complications and length of hospital stay. Whether other multimodal, exercise, and psychological prehabilitation modalities improve postoperative outcomes after colorectal cancer surgery is uncertain as the current quality of evidence is low. PROTOCOL REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/VW72N ).

Modes of Death in Patients with Cardiogenic Shock in the Cardiac Intensive Care Unit: A Report from the Critical Care Cardiology Trials Network.

BACKGROUND: There are limited data on how patients with cardiogenic shock (CS) die. METHODS: The Critical Care Cardiology Trials Network is a research network of cardiac intensive care units coordinated by the Thrombolysis In Myocardial Infarction (TIMI) Study Group (Boston, MA). Using standardized definitions, site investigators classified direct modes of in-hospital death for CS admissions (October 2021 to September 2022). Mutually exclusive categories included 4 modes of cardiovascular death and 4 modes of noncardiovascular death. Subgroups defined by CS type, preceding cardiac arrest (CA), use of temporary mechanical circulatory support (tMCS), and transition to comfort measures were evaluated. RESULTS: Among 1068 CS cases, 337 (31.6%) died during the index hospitalization. Overall, the mode of death was cardiovascular in 82.2%. Persistent CS was the dominant specific mode of death (66.5%), followed by arrhythmia (12.8%), anoxic brain injury (6.2%), and respiratory failure (4.5%). Patients with preceding CA were more likely to die from anoxic brain injury (17.1% vs 0.9%; P < .001) or arrhythmia (21.6% vs 8.4%; P < .001). Patients managed with tMCS were more likely to die from persistent shock (P < .01), both cardiogenic (73.5% vs 62.0%) and noncardiogenic (6.1% vs 2.9%). CONCLUSIONS: Most deaths in CS are related to direct cardiovascular causes, particularly persistent CS. However, there is important heterogeneity across subgroups defined by preceding CA and the use of tMCS.

Influence of hospital-level and surgeon factors on the outcomes after ileo-anal pouch surgery for inflammatory bowel disease: systematic review.

BACKGROUND: Ileal pouch-anal anastomosis ('pouch surgery') provides a chance to avoid permanent ileostomy after proctocolectomy, but can be associated with poor outcomes. The relationship between hospital-level/surgeon factors (including volume) and outcomes after pouch surgery is of increasing interest given arguments for increasing centralization of these complex procedures. The aim of this systematic review was to appraise the literature describing the influence of hospital-level and surgeon factors on outcomes after pouch surgery for inflammatory bowel disease. METHODS: A systematic review was performed of studies reporting outcomes after pouch surgery for inflammatory bowel disease. The MEDLINE (Ovid), Embase (Ovid), and Cochrane CENTRAL databases were searched (1978-2022). Data on outcomes, including mortality, morbidity, readmission, operative approach, reconstruction, postoperative parameters, and pouch-specific outcomes (failure), were extracted. Associations between hospital-level/surgeon factors and these outcomes were summarized. This systematic review was prospectively registered in PROSPERO, the international prospective register of systematic reviews (CRD42022352851). RESULTS: A total of 29 studies, describing 41 344 patients who underwent a pouch procedure, were included; 3 studies demonstrated higher rates of pouch failure in lower-volume centres, 4 studies demonstrated higher reconstruction rates in higher-volume centres, 2 studies reported an inverse association between annual hospital pouch volume and readmission rates, and 4 studies reported a significant association between complication rates and surgeon experience. CONCLUSION: This review summarizes the growing body of evidence that supports centralization of pouch surgery to specialist high-volume inflammatory bowel disease units. Centralization of this technically demanding surgery that requires dedicated perioperative medical and nursing support should facilitate improved patient outcomes and help train the next generation of pouch surgeons.

Comparison of urological outcomes and quality of life after pelvic exenteration: partial vs radical cystectomy.

OBJECTIVE: To compare perioperative morbidity, functional and quality-of-life (QoL) outcomes in patients with partial cystectomy vs radical cystectomy as part of pelvic exenteration. PATIENTS AND METHODS: Retrospective analysis of a prospectively maintained database of pelvic exenteration patients (1998-2021) was conducted in a single centre. Study outcomes included postoperative complications, quality-of-life, functional and stoma-related outcomes. The 36-item Short-Form Health Survey Physical and Mental Health Components, Functional Assessment of Cancer Therapy-Colorectal questionnaires and Distress Thermometer were available pre- and postoperatively. QoL outcomes were compared at the various time points. Stoma embarrassment and care scores were compared between patients with a colostomy, urostomy, and both. RESULTS: Urological complications were similar between both groups, but patients with partial cystectomy experienced less wound-related complications. Overall, 34/81 (42%) partial cystectomy patients reported one or more long-term voiding complication (i.e., incontinence [17 patients], frequency [six], retention [three], high post-voiding residuals [10], permanent suprapubic catheter/indwelling catheter [14], recurrent urinary tract infection [nine], percutaneous nephrostomy [three], progression to urostomy [three]). The QoL improved following surgery in both the partial and radical cystectomy groups, differences between cohorts were not significant. Patients with two stomas reported higher embarrassment scores than patients with one stoma, although this did not result in more difficulties in stoma care. CONCLUSIONS: Partial cystectomy patients have fewer postoperative wound-related complications than radical cystectomy patients, but often experience long-term voiding issues. The QoL outcomes are similar for both cohorts, with significant improvement following surgery.

Impact of Intraoperative Decision-Making on Pathological Margin Status in Patients Undergoing Pelvic Exenteration for Locally Recurrent Rectal Cancer.

BACKGROUND: A key component of preoperative preparation for pelvic exenteration surgery is development of an operative plan in a multidisciplinary setting, based on the extent of local tumor invasion on preoperative imaging. Changes to the extent of resection or operative plan may occur intraoperatively based on intraoperative findings. OBJECTIVE: To report the frequency and extent of intraoperative deviation from the planned extent of resection during pelvic exenteration for locally recurrent rectal cancer, and whether this resulted in a more or less radical resection. DESIGN: Retrospective observational study. SETTINGS: A high-volume pelvic exenteration center. PATIENTS: Patients who underwent pelvic exenteration for locally recurrent rectal cancer between January 2015 and December 2020. MAIN OUTCOME MEASURES: Frequency and extent of intraoperative deviation from the planned extent of resection, R0 resection rate. RESULTS: 136 patients underwent pelvic exenteration for locally recurrent rectal cancer, of which 110 (81%) had R0 resection margins. 12 patients were excluded due to missing information and 49 patients (40%) had a change to the operative plan. Operative changes were major in 30 patients (61%), more radical in 40 patients (82%), and margin relevant in 24 patients (49%). In patients where there was a change to the operative plan and R0 resection was achieved, the median distance to a relevant margin was 2.5 mm (range, 0.1-10mm). Of eight patients with a change in operative plan and R1 resection, three were margin relevant of which all were considered major, and two were more radical and one was less radical. LIMITATIONS: Generalizability outside of specialist units may be limited. CONCLUSIONS: Intraoperative changes to the planned extent of resection occur commonly and most often results in an unanticipated major, more radical resection. Such changes may contribute to high rates of R0 resection margins in specialist PE units that employ an ultra-radical approach in these patients. See Video Abstract.

Trajectories of Quality of Life After Pelvic Exenteration: A Latent Class Growth Analysis.

BACKGROUND: Information on the course of quality of life after surgery for advanced cancers within the pelvis is important to guide patient decision-making; however, the current evidence is limited. OBJECTIVE: To identify quality-of-life trajectory classes and their predictors after pelvic exenteration. DESIGN: Prospective cohort study. SETTINGS: Highly specialized quaternary pelvic exenteration referral center. PATIENTS: Patients undergoing pelvic exenteration due to advanced/recurrent cancers within the pelvis between July 2008 and July 2022. MAIN OUTCOME MEASURES: Quality-of-life data included the 36-item Short-Form Survey (physical and mental component scores) and the Functional Assessment of Cancer Therapy-Colorectal instruments, which were collected at 11 distinct points from baseline to 5 years postoperatively. Predictors included patient characteristics and surgical outcomes. Latent class analysis was used to identify the likelihood of a better quality-of-life class, and logistic regression models were used to identify predictors of the identified classes. RESULTS: The study included 565 participants. Two distinct quality-of-life trajectory classes were identified for the Physical Component Score (class 1: high stable and class 2: high decreasing). Three distinct classes were identified for the Mental Component Score (class 1: high increasing, class 2: moderate stable, and class 3: moderate decreasing) and for Functional Assessment of Cancer Therapy-Colorectal total score (class 1: high increasing, class 2: high decreasing, and class 3: low decreasing). Across the 3 quality-of-life domains, overall survival probabilities were also higher in class 1 ( p < 0.0001). Age, repeat exenteration, neoadjuvant therapy, surgical margin, length of operation, and hospital stay were significant predictors of quality-of-life classes. LIMITATIONS: This study was conducted at a single highly specialized quaternary pelvic exenteration referral center, and findings may not apply to other centers. CONCLUSIONS: This study demonstrates that quality of life after pelvic exenteration diverges into distinct trajectories, with most patients reporting an optimal course. See Video Abstract . TRAYECTORIAS EN LA CALIDAD DE VIDA DESPUS DE EXENTERACIN PLVICA ANLISIS DE CRECIMIENTO DE CLASES LATENTES: ANTECEDENTES:La información sobre la evolución en la calidad de vida después de cirugía en cánceres avanzados situados en la pelvis es importante para guiar la toma de decisiones sobre el paciente; sin embargo, la evidencia actual es muy limitada.OBJETIVO:Identificar las clases de trayectorias en la calidad de vida y sus factores pronóstico después de la exenteración pélvica.DISEÑO:Estudio de cohortes prospectivo.AJUSTES:Centro de referencia altamente especializado en la exenteración pélvica cuaternaria.PACIENTES:Todos aquellos sometidos a exenteración pélvica por cáncer avanzados/recurrentes situados en la pelvis entre Julio de 2008 y Julio de 2022.PRINCIPALES MEDIDAS DE RESULTADO:Los datos sobre la calidad de vida incluyeron el Cuestionario de Salud SF-36 (puntuaciones de componentes físicos y mentales) y la evaluación funcional entre la terapia del cáncer/-herramientas colorrectales, recopilados en 11 puntos distintos desde el diagnóstico hasta los 5 años después de la operación.Los predictores incluyeron las características de los pacientes y los resultados quirúrgicos. Se utilizó el análisis de clases latentes para identificar la probabilidad de una mejor calidad de vida y se utilizaron modelos de regresión logística para identificar predictores de las clases identificadas.RESULTADOS:El estudio incluyó a 565 participantes. Se identificaron dos clases distintas de trayectorias de calidad de vida para la puntuación del componente físico (clase 1: alta estable y clase 2: alta decreciente), se identificaron tres clases distintas para la puntuación del componente mental (clase 1: alta creciente; clase 2: moderadamente estable; y clase 3: moderada disminución) y para la evaluación funcional de la terapia contra el cáncer-puntuación total colorrectal (clase 1: aumento alto; clase 2: disminución alta; y clase 3: disminución baja). En los tres dominios de calidad de vida, las probabilidades de supervivencia general también fueron mayores en las clases 1 (p <0,0001). La edad, las exenteraciones pélvicas repetidas, la terapia neoadyuvante, el margen quirúrgico, la duración de la operación y la estadía hospitalaria fueron predictores significativos en las clases de calidad de vida.LIMITACIONES:El presente estudio fué realizado en un único centro de referencia altamente especializado en exenteración pélvica cuaternaria y es posible que los hallazgos no se apliquen a otros centros.CONCLUSIONES:Demostramos con nuestro estudio que la calidad de vida después de la exenteración pélvica diverge en trayectorias distintas, y que la mayoría de los pacientes nos reportaron de una évolución óptima. (Traducción-Dr. Xavier Delgadillo ).

Outcomes Following Pelvic Exenteration for Locally Recurrent Rectal Cancer With and Without En Bloc Sacrectomy.

BACKGROUND: Extended radical resection is often the only chance of cure for locally recurrent rectal cancer. Recurrence in the posterior compartment often necessitates en bloc sacrectomy as part of pelvic exenteration to obtain clear resection margins and provide survival benefit. OBJECTIVE: To compare oncological outcomes, morbidity, and quality-of-life outcomes following pelvic exenteration with and without en bloc sacrectomy for recurrent rectal cancer. DESIGN: Comparative cohort study with retrospective analysis of prospectively collected data. SETTING: This study was conducted at a high-volume pelvic exenteration center. PATIENTS: Patients who underwent pelvic exenteration for locally recurrent rectal cancer between 1994 and 2022. MAIN OUTCOME MEASURES: Overall survival, postoperative morbidity, R0 resection margin, and quality-of-life outcomes. RESULTS: Of 965 patients, 305 (31.6%) underwent pelvic exenteration for locally recurrent rectal cancer. Among these patients, 64.3% were men and the median age was 62 years (range, 29-86). One hundred eighty-five patients (60.7%) underwent en bloc sacrectomy, 65 (35.1%) underwent high transection, and 119 (64.3%) had sacrectomy below S2. R0 resection was achieved in 80% of patients with sacrectomy and 72.5% of patients without sacrectomy. Sacrectomy patients experienced more postoperative complications without increased mortality. The median overall survival was 52 months; median survival was 47 months with sacrectomy and 73 months without ( p = 0.059). Quality-of-life scores were not significantly different across physical component ( p = 0.346), mental component ( p = 0.787), or Functional Assessment of Cancer Therapy-Colorectal ( p = 0.679) scores at 24-month follow-up. LIMITATIONS: The generalizability of these findings may be limited outside of subspecialist exenteration units. Selection bias exists in a retrospective analysis. CONCLUSIONS: Patients undergoing pelvic exenteration with and without en bloc sacrectomy for locally recurrent rectal cancer experience similar rates of R0 resection, survival, and quality-of-life outcomes. As R0 remains the most important predictor of survival, the requirement of sacral resection should prompt referral to a subspecialist center that performs sacrectomy routinely. See Video Abstract . RESULTADOS DESPUS DE LA EXENTERACIN PLVICA PARA EL CNCER DE RECTO CON RECURRENCIA LOCAL, CON Y SIN SACRECTOMA EN BLOQUE: ANTECEDENTES:La resección radical ampliada es generalmente la única posibilidad de curación para el cáncer de recto con recurrencia local. La recurrencia en el compartimento posterior generalmente requiere sacrectomía en bloque como parte de la exenteración pélvica para obtener márgenes de resección claros y proporcionar un beneficio de supervivencia.OBJETIVO:Comparar los resultados oncológicos, de morbilidad y de calidad de vida después de la exenteración pélvica con y sin sacrectomía en bloque para el cáncer de recto recurrente.DISEÑO:Estudio de cohorte comparativo con análisis retrospectivo de datos recopilados prospectivamente.AMBIENTE AJUSTE:Estudio realizado en un centro de exenteración pélvica de alto volumen.PACIENTES:Aquellos sometidos a exenteración pélvica por cáncer de recto con recurrencia local entre 1994 y 2022.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general, morbilidad posoperatoria, margen de resección R0 y resultados de calidad de vida.RESULTADOS:305 (31,6%) de 965 pacientes se sometieron a exenteración pélvica por cáncer de recto con recurrencia local. El 64,3% de los pacientes eran hombres con una mediana de edad de 62 años (rango 29-86). 185 pacientes (60,7%) fueron sometidos a sacrectomía en bloque, 65 (35,1%) fueron sometidos a transección alta, 119 (64,3%) tuvieron sacrectomía por debajo de S2. La resección R0 se logró en el 80% de los pacientes con sacrectomía y en el 72,5% sin ella. Los pacientes de sacrectomía experimentaron más complicaciones postoperatorias sin aumento de la mortalidad. La mediana de supervivencia global fue de 52 meses, 47 meses con sacrectomía y 73 meses sin sacrectomía ( p = 0,059). Las puntuaciones de calidad de vida no fueron significativamente diferentes entre las puntuaciones del componente físico ( p = 0,346), componente mental ( p = 0,787) o la evaluación funcional de la terapia contra el cáncer - colorrectal ( p = 0,679) a los 24 meses de seguimiento.LIMITACIONES:La generalización de estos hallazgos puede estar limitada fuera de las unidades de exenteración de subespecialistas. Existe un sesgo de selección en un análisis retrospectivo.CONCLUSIONES:Los pacientes sometidos a exenteración pélvica con y sin sacrectomía en bloque por cáncer de recto con recurrencia local experimentan tasas similares de resección R0, supervivencia y resultados de calidad de vida. Como R0 sigue siendo el predictor más importante de supervivencia, la necesidad de resección sacra debe provocar la derivación a un centro subespecialista que realice sacrectomía de forma rutinaria. (Traducción-Dr. Fidel Ruiz Healy ).

Outcome Heterogeneity in Prehabilitation Trials-Are We Comparing Apples and Oranges?

INTRODUCTION: Over the last decade, the number of prehabilitation randomised controlled trials (RCTs) has increased significantly. Therefore, this review aimed to describe the outcomes reported in prehabilitation RCTs in patients undergoing cancer surgery. METHODS: A search was conducted in Embase, Allied and Complementary Medicine Database, The Cochrane Library, PsycINFO, MEDLINE, and Cumulated Index to Nursing and Allied Health Literature from inception to July 2021. We included RCTs evaluating the effectiveness of preoperative exercise, nutrition, and psychological interventions on postoperative complications and length of hospital stay in adult oncology patients who underwent thoracic and gastrointestinal cancer surgery. The verbatim outcomes reported in each article were extracted, and each outcome was assessed to determine whether it was defined and measured using a validated tool. Verbatim outcomes were grouped into standardized outcomes and categorized into domains. The quality of outcome reporting in each identified article was assessed using the Harman tool (score range 0-6, where 0 indicated the poorest quality). RESULTS: A total of 74 RCTs were included, from which 601 verbatim outcomes were extracted. Only 110 (18.3%) of the verbatim outcomes were defined and 270 (44.9%) were labeled as either "primary" or "secondary" outcomes. Verbatim outcomes were categorized into 119 standardized outcomes and assigned into one of five domains (patient-reported outcomes, surgical outcomes, physical/functional outcomes, disease activity, and intervention delivery). Surgical outcomes were the most common outcomes reported (n = 71 trials, 95.9%). The overall quality of the reported outcomes was poor across trials (median score: 2.0 [IQR = 0.00-3.75]). CONCLUSIONS: Prehabilitation RCTs display considerable heterogeneity in outcome reporting, and low outcome reporting quality. The development of standardized core outcome sets may help improve article quality and enhance the clinical utility of prehabilitation following cancer surgery.

The health-related quality of life of early-onset colorectal cancer patients: an Australian cross-sectional study.

AIM: Early-onset colorectal cancer (EOCRC) patients are more likely to have advanced disease and undergo more aggressive treatment modalities. However, current literature investigating the health-related quality of life (HRQoL) of EOCRC patients is scarce. This study aimed to determine the HRQoL of an Australian cohort of EOCRC patients including a subset who underwent pelvic exenteration (PE) or cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: A cross-sectional study of EOCRC patients treated at the Royal Prince Alfred Hospital, Sydney Australia was performed. Patients were divided into groups based on the time interval from their index operation: ≤2 years and >2 years. HRQoL was evaluated using the SF-36v2 questionnaire. RESULTS: A total of 50 patients were included. For patients ≤2 years from surgery, the median physical component summary (PCS) and mental health component summary (MCS) scores were 53.3 (36.4-58.9) and 47.3 (37.5-55.7). In the >2 years group, the median PCS and MCS scores were 50.6 (43.3-57.7) and 50.2 (39.04-56.2), respectively. Stage I (vs. stage II) disease and emergency (vs. elective) surgery conferred poorer PCS scores in patients ≤2 years from surgery. No other variables impacted PCS or MCS scores in EOCRC patients in either group. CONCLUSIONS: HRQoL of EOCRC patients was equivocal to the Australian population. Having an earlier stage of diagnosis and emergency index operation was associated with poorer levels of physical functioning in patients ≤2 years from surgery. However, because of the limitations of this study, these findings require validation in future large-scale prospective research.

Unexpected variation in outcomes following total (procto)colectomies for ulcerative colitis in New South Wales, Australia: a population-based 19-year linked-data study.

AIM: Total (procto)colectomy for ulcerative colitis (UC) is associated with significant morbidity, which is increased in the emergency setting. This study aimed to evaluate the outcomes following total (procto)colectomies at a population level within New South Wales (NSW), Australia, and identify case mix and hospital factors associated with these outcomes. METHODS: A retrospective data linkage study of patients undergoing total (procto)colectomy for UC in NSW over a 19-year period (2001-2020) was performed. The primary outcome was 90-day mortality. The influence of hospital level factors (including annual volume) and patient demographic variables on outcomes was assessed using logistic regression. Temporal trends in annual volume and evidence for centralization were assessed. RESULTS: In all, 1418 patients (mean 47.0 years [SD 18.7], 58.7% male) underwent total (procto)colectomy during the study period. The overall 90-day mortality rate was 3.2% (emergency 8.6% and elective 0.8%). After adjusting for confounding, increasing age at total (procto)colectomy, higher comorbidity burden, public health insurance (Medicare) status, emergency operation and living outside a major city were significantly associated with increased mortality. Hospital volume was significantly associated with mortality at a univariate level, but this did not persist on multivariate modelling. CONCLUSIONS: Outcomes of UC patients undergoing total (procto)colectomy in NSW Australia are comparable to international experience. Whilst higher mortality rates are observed in low volume and public hospitals, this appears attributable to case mix and acuity rather than surgical volume alone. However, as inflammatory bowel disease surgery is not centralized in Australia, only one NSW hospital performed >10 UC total (procto)colectomies annually. Variation in mortality according to insurance status and across regional/remote areas may indicate inequality in the availability of specialist inflammatory bowel disease treatment, which warrants further research.

Variation in outcome measurement and reporting in studies of pelvic exenteration for locally advanced and recurrent rectal cancer: a systematic review.

AIM: There is increasing research interest in pelvic exenteration for locally advanced and recurrent rectal cancer. Heterogeneity in outcome reporting can prevent meaningful interpretation and valid synthesis of pooled data and meta-analyses. The aim of this study was to assess homogeneity in outcome measures in the current pelvic exenteration literature. METHOD: MEDLINE, Embase, CENTRAL, CINAHL and Scopus databases were searched from 1990 to 25 April 2023 to identify studies reporting outcomes of pelvic exenteration for locally advanced or recurrent rectal cancer. All reported outcomes were extracted, merged with those of similar meaning and assigned a domain. RESULTS: Of 4137 abstracts screened, 156 studies met the inclusion criteria. A total of 2765 outcomes were reported, of which 17% were accompanied by a definition. There were 1157 unique outcomes, merged into 84 standardized outcomes and assigned one of seven domains. The most reported domains were complications (147 studies, 94%), survival (127, 81%) and surgical outcomes (123, 79%). Resection margins were reported in 122 studies (78%): the definition of a clear resection margin was not provided in 45 studies (37%), it was unclear in 11 studies (9%) and not specified beyond microscopically 'clear' or 'negative' in 31 (28%). Measurements of 2, 1, 0.5 mm and any healthy tissue were all used to define R0 margins. CONCLUSION: There is significant heterogeneity in outcome measurement and reporting in the current pelvic exenteration literature, raising concerns about the validity of comparative or collaborative studies between centres and meta-analyses. Coordinated international collaboration is required to define core outcome sets and benchmarks.

Patients' and carers' views on research priorities in prehabilitation for cancer surgery.

INTRODUCTION: The views of patients and carers are important for the development of research priorities. This study aimed to determine and compare the top research priorities of cancer patients and carers with those of multidisciplinary clinicians with expertise in prehabilitation. MATERIALS AND METHODS: This cross-sectional study surveyed patients recovering from cancer surgery at a major tertiary hospital in Sydney, Australia, and/or their carers between March and July 2023. Consenting patients and carers were provided a list of research priorities according to clinicians with expertise in prehabilitation, as determined in a recent International Delphi study. Participants were asked to rate the importance of each research priority using a 5-item Likert scale (ranging from 1 = very high research priority to 5 = very low research priority). RESULTS: A total of 101 patients and 50 carers participated in this study. Four areas were identified as research priorities, achieving consensus of highest importance (> 70% rated as "high" or "very high" priority) by patients, carers, and clinical experts. These were "optimal composition of prehabilitation programs" (77% vs. 82% vs. 88%), "effect of prehabilitation on surgical outcomes" (85% vs. 90% vs. 95%), "effect of prehabilitation on functional outcomes" (83% vs. 86% vs. 79%), and "effect of prehabilitation on patient reported outcomes" (78% vs. 84% vs. 79%). Priorities that did not reach consensus of high importance by patients despite reaching consensus of highest importance by experts included "identifying populations most likely to benefit from prehabilitation" (70% vs. 76% vs. 90%) and "defining prehabilitation core outcome measures" (66% vs. 74% vs. 87%). "Prehabilitation during neoadjuvant therapies" reached consensus of high importance by patients but not by experts or carers (81% vs. 68% vs. 69%). CONCLUSION: This study delineated the primary prehabilitation research priorities as determined by patients and carers, against those previously identified by clinicians with expertise in prehabilitation. It is recommended that subsequent high-quality research and resource allocation be directed towards these highlighted areas of importance.

A review of patient recruitment in randomised controlled trials of preoperative exercise.

BACKGROUND: Randomised controlled trials (RCTs) are considered the gold standard design to determine the effectiveness of an intervention, as the only method of decreasing section bias and minimising random error. However, participant recruitment to randomised controlled trials is a major challenge, with many trials failing to recruit the targeted sample size accordingly to the planned protocol. Thus, the aim of this review is to detail the recruitment challenges of preoperative exercise clinical trials. METHODS: A comprehensive search was performed on MEDLINE, Embase, The Cochrane Library, CINAHL, AMED and PsycINFO from inception to July 2021. Randomised controlled trials investigating the effectiveness of preoperative exercise on postoperative complication and/or length of hospital stay in adult cancer patients were included. Main outcomes included recruitment rate, retention rate, number of days needed to screen and recruit one patient and trial recruitment duration. Descriptive statistics were used to summarise outcomes of interest. RESULTS: A total of 27 trials were identified, including 3656 patients screened (N = 21) and 1414 randomised (median recruitment rate (interquartile range) = 53.6% (25.2%-67.6%), N = 21). The sample size of the included trials ranged from 19 to 270 (median = 48.0; interquartile range = 40.0-85.0) and the duration of trial recruitment ranged from 3 to 50 months (median = 19.0 months; interquartile range = 10.5-34.0). Overall, a median of 3.6 days was needed to screen one patient, whereas 13.7 days were needed to randomise one participant. Over the trials duration, the median dropout rate was 7.9%. Variations in recruitment outcomes were observed across trials of different cancer types but were not statistically significant. CONCLUSION: The recruitment of participants to preoperative exercise randomised controlled trials is challenging, but patient retention appears to be less of a problem. Future trials investigating the effectiveness of a preoperative exercise programme following cancer surgery should consider the time taken to recruit patients. Strategies associated with improved recruitment should be investigated in future studies.

Evaluating geographical disparities on clinical outcomes following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Rural Australians typically encounter disparities in healthcare access leading to adverse health outcomes, delayed diagnosis and reduced quality of life (QoL) parameters. These disparities may be exacerbated in advanced malignancies, where treatment is only available at highly specialised centres with appropriate multidisciplinary expertise. Thus, this study aims to determine the association between patient residence on oncological, surgical and QoL outcomes following cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC). METHODS: A retrospective analysis was conducted on consecutive patients undergoing CRS and HIPEC at Royal Prince Alfred Hospital from January 2017 to March 2022. On the basis of their postcode of residence, patients were stratified into metropolitan and regional groups. Data encompassing demographics, oncological, surgical and QoL outcomes were compared. Statistical analysis included chi-square test, t-tests and Kaplan-Meier survival curves. RESULTS: Among the 317 patients, 228 (72%) were categorised as metropolitan and 89 (28%) as regional. Metropolitan patients presented higher rates of recurrence (61.8% versus 40.0%, p = 0.014) and shorter overall mean survival [3.8 years (95% CI: 3.44-4.09) versus 4.2 years (95% CI: 3.76-4.63), p = 0.019] compared with regional patients. No other statistically significant differences were observed in oncological, surgical and QoL outcomes. CONCLUSIONS: Most oncological, surgical and QoL parameters did not differ by geographical location of patients undergoing CRS and HIPEC for peritoneal malignancies at a high-volume quaternary referral centre. Observed differences in recurrence and survival may be attributed to the selective nature of surgical referrals and variable follow-up patterns. Future research should focus on characterising referral pathways and its influence on post-operative outcomes.

Enhancing outpatient anxiety treatment with mobile technology: A quality improvement study.

INTRODUCTION: Mobile mental health applications are a novel treatment method with unique qualities and capabilities for enhancing existing psychiatric treatments. Outpatient settings such as Mile Square Health Clinic have identified a need to leverage this new technology into their routine care. BACKGROUND: In the U.S., over 40 million people suffer from an anxiety disorder, however, only 1 in 4 responds to pharmacological treatment. Preliminary research indicates mental health apps are acceptable, feasible, and can improve patient outcomes for those with anxiety. METHODS: Participants from two different outpatient psychiatric clinics locations with generalized anxiety disorder were identified and recruited by participating nurse practitioners. Participants were instructed on how to download and use IntelliCare by the Project Lead. The Project Lead administered a semi-structured interview to collect qualitative data at three weeks and six weeks follow-up. RESULTS AND CONCLUSIONS: Survey responses at three and six weeks showed relevant themes of increased journaling, increased feelings of connectedness, positive associations with gamification, and IntelliCare being most useful for a moderate to severe level of anxiety. RECOMMENDATIONS: The results of this QI project demonstrate the clinical utility of incorporating the IntelliCare app into regular outpatient practice. IntelliCare should be used with those with moderate to severe anxiety and journaling features should follow research developments to incorporate best-practice guidelines.

Plasma Cell-Free DNA Predicts Survival and Maps Specific Sources of Injury in Pulmonary Arterial Hypertension.

BACKGROUND: Cell-free DNA (cfDNA) is a noninvasive marker of cellular injury. Its significance in pulmonary arterial hypertension (PAH) is unknown. METHODS: Plasma cfDNA was measured in 2 PAH cohorts (A, n=48; B, n=161) and controls (n=48). Data were collected for REVEAL 2.0 (Registry to Evaluate Early and Long-Term PAH Disease Management) scores and outcome determinations. Patients were divided into the following REVEAL risk groups: low (≤6), medium (7-8), and high (≥9). Total cfDNA concentrations were compared among controls and PAH risk groups by 1-way analysis of variance. Log-rank tests compared survival between cfDNA tertiles and REVEAL risk groups. Areas under the receiver operating characteristic curve were estimated from logistic regression models. A sample subset from cohort B (n=96) and controls (n=16) underwent bisulfite sequencing followed by a deconvolution algorithm to map cell-specific cfDNA methylation patterns, with concentrations compared using t tests. RESULTS: In cohort A, median (interquartile range) age was 62 years (47-71), with 75% female, and median (interquartile range) REVEAL 2.0 was 6 (4-9). In cohort B, median (interquartile range) age was 59 years (49-71), with 69% female, and median (interquartile range) REVEAL 2.0 was 7 (6-9). In both cohorts, cfDNA concentrations differed among patients with PAH of varying REVEAL risk and controls (analysis of variance P≤0.002) and were greater in the high-risk compared with the low-risk category (P≤0.002). In cohort B, death or lung transplant occurred in 14 of 54, 23 of 53, and 35 of 54 patients in the lowest, middle, and highest cfDNA tertiles, respectively. cfDNA levels stratified as tertiles (log-rank: P=0.0001) and REVEAL risk groups (log-rank: P<0.0001) each predicted transplant-free survival. The addition of cfDNA to REVEAL improved discrimination (area under the receiver operating characteristic curve, 0.72-0.78; P=0.02). Compared with controls, methylation analysis in patients with PAH revealed increased cfDNA originating from erythrocyte progenitors, neutrophils, monocytes, adipocytes, natural killer cells, vascular endothelium, and cardiac myocytes (Bonferroni adjusted P<0.05). cfDNA concentrations derived from erythrocyte progenitor cells, cardiac myocytes, and vascular endothelium were greater in patients with PAH with high-risk versus low-risk REVEAL scores (P≤0.02). CONCLUSIONS: Circulating cfDNA is elevated in patients with PAH, correlates with disease severity, and predicts worse survival. Results from cfDNA methylation analyses in patients with PAH are consistent with prevailing paradigms of disease pathogenesis.

Inflammation and DKK1-induced AKT activation contribute to endothelial dysfunction following NR2F2 loss.

NR2F2 is expressed in endothelial cells (ECs) and Nr2f2 knockout produces lethal cardiovascular defects. In humans, reduced NR2F2 expression is associated with cardiovascular diseases including congenital heart disease and atherosclerosis. Here, NR2F2 silencing in human primary ECs led to inflammation, endothelial-to-mesenchymal transition (EndMT), proliferation, hypermigration, apoptosis-resistance, and increased production of reactive oxygen species. These changes were associated with STAT and AKT activation along with increased production of DKK1. Co-silencing DKK1 and NR2F2 prevented NR2F2-loss-induced STAT and AKT activation and reversed EndMT. Serum DKK1 concentrations were elevated in patients with pulmonary arterial hypertension (PAH) and DKK1 was secreted by ECs in response to in vitro loss of either BMPR2 or CAV1, which are genetic defects associated with the development of PAH. In human primary ECs, NR2F2 suppressed DKK1, whereas its loss conversely induced DKK1 and disrupted endothelial homeostasis, promoting phenotypic abnormalities associated with pathologic vascular remodeling. Activating NR2F2 or blocking DKK1 may be useful therapeutic targets for treating chronic vascular diseases associated with EC dysfunction.NEW & NOTEWORTHY NR2F2 loss in the endothelial lining of blood vessels is associated with cardiovascular disease. Here, NR2F2-silenced human endothelial cells were inflammatory, proliferative, hypermigratory, and apoptosis-resistant with increased oxidant stress and endothelial-to-mesenchymal transition. DKK1 was induced in NR2F2-silenced endothelial cells, while co-silencing NR2F2 and DKK1 prevented NR2F2-loss-associated abnormalities in endothelial signaling and phenotype. Activating NR2F2 or blocking DKK1 may be useful therapeutic targets for treating vascular diseases associated with endothelial dysfunction.