Association between Complications and Death within 30 days after General Surgery: A Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) substudy.

OBJECTIVE: To determine the epidemiology of post-operative complications among general surgery patients, inform their relationships with 30-day mortality, and determine the attributable fraction of death of each postoperative complication. BACKGROUND: The contemporary causes of post-operative mortality among general surgery patients are not well characterized. METHODS: VISION is a prospective cohort study of adult non-cardiac surgery patients across 28 centres in 14 countries, who were followed for 30 days after surgery. For the subset of general surgery patients, a cox proportional hazards model was used to determine associations between various surgical complications and post-operative mortality. The analyses were adjusted for preoperative and surgical variables. Results were reported in adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 7950 patients included in the study, 240 (3.0%) patients died within 30 days of surgery. Five post-operative complications (myocardial injury after non-cardiac surgery [MINS], major bleeding, sepsis, stroke, and acute kidney injury resulting in dialysis) were independently associated with death. Complications associated with the largest attributable fraction (AF) of post-operative mortality (i.e., percentage of deaths in the cohort that can be attributed to each complication, if causality were established) were major bleeding (n=1454, 18.3%, HR 2.49 95%CI 1.87-3.33, P<0.001, AF 21.2%), sepsis (n=783, 9.9%, HR 6.52, 95%CI 4.72-9.01, P<0.001, AF 15.6%), and MINS (n=980, 12.3%, HR 2.00, 95%CI 1.50-2.67, P<0.001, AF 14.4%). CONCLUSION: The complications most associated with 30-day mortality following general surgery are major bleeding, sepsis, and MINS. These findings may guide the development of mitigating strategies, including prophylaxis for perioperative bleeding.

OMIP-109: 45-color full spectrum flow cytometry panel for deep immunophenotyping of the major lineages present in human peripheral blood mononuclear cells with emphasis on the T cell memory compartment.

The need for more in-depth exploration of the human immune system has moved the flow cytometry field forward with advances in instrumentation, reagent development and availability, and user-friendly implementation of data analysis methods. We developed a high-quality human 45-color panel, for comprehensive characterization of major cell lineages present in circulation including T cells, γδ T cells, NKT-like cells, B cells, NK cells, monocytes, basophils, dendritic cells, and ILCs. Assay optimization steps are described in detail to ensure that each marker in the panel was optimally resolved. In addition, we highlight the outstanding discernment of cell activation, exhaustion, memory, and differentiation states of CD4+ and CD8+ T cells using this 45-color panel. The panel enabled an in-depth description of very distinct phenotypes associated with the complexity of the T cell memory response. Furthermore, we present how this panel can be effectively used for cell sorting on instruments with a similar optical layout to achieve the same level of resolution. Functional evaluation of sorted specific rare cell subsets demonstrated significantly different patterns of immunological responses to stimulation, supporting functional and phenotypic differences within the T cell memory subsets. In summary, the combination of full spectrum profiling technology and careful assay design and optimization results in a high resolution multiparametric 45-color assay. This panel offers the opportunity to fully characterize immunological profiles present in peripheral blood in the context of infectious diseases, autoimmunity, neurodegeneration, immunotherapy, and biomarker discovery.

Fragility of Statistically Significant Outcomes in Colonic Diverticular Disease Randomized Trials: A Systematic Review.

BACKGROUND: The p value has been criticized as an oversimplified determination of whether a treatment effect exists. One alternative is the fragility index. It is a representation of the minimum number of nonevents that would need to be converted to events to increase the p value above 0.05. OBJECTIVE: To determine the fragility index of randomized controlled trials assessing the efficacy of interventions for patients with diverticular disease since 2010 to assess the robustness of current evidence. DESIGN: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to August 2022. SETTINGS: Articles were eligible for inclusion if they were randomized trials conducted between 2010 and 2022 with parallel, superiority designs evaluating interventions in patients with diverticular disease. Only randomized trials with dichotomous primary outcomes with an associated p value of <0.05 were considered for inclusion. PARTICIPANTS: Any surgical or medical intervention for patients with diverticular disease. MAIN OUTCOME MEASURES: The fragility index was determined by adding events and subtracting nonevents from the groups with the smaller number of events. Events were added until the p value exceeded 0.05. The smallest number of events required was considered the fragility index. RESULTS: After screening 1271 citations, 15 randomized trials met the inclusion criteria. Nine of the studies evaluated surgical interventions and 6 evaluated medical interventions. The mean number of patients randomly assigned and lost to follow-up per randomized controlled trial was 92 (SD 35.3) and 9 (SD 11.4), respectively. The median fragility index was 1 (range, 0-5). The fragility indices for the included studies did not correlate significantly with any study characteristics. LIMITATIONS: Small sample, heterogeneity, and lack of inclusion of studies with continuous outcomes. CONCLUSIONS: The randomized trials evaluating surgical and medical interventions for diverticular disease are not robust. Changing a single-outcome event in most studies was sufficient to make a statistically significant study finding not significant. See Video Abstract . FRAGILIDAD DE LOS RESULTADOS ESTADSTICAMENTE SIGNIFICATIVOS EN ENSAYOS ALEATORIOS DE ENFERMEDAD DIVERTICULAR DEL COLON UNA REVISIN SISTEMTICA: ANTECEDENTES:El valor p ha sido criticado por una determinación demasiado simplificada de si existe un efecto del tratamiento. Una alternativa es el Índice de Fragilidad. Es una representación del número mínimo de no eventos que deberían convertirse en eventos para aumentar el valor p por encima de 0,05.OBJETIVO:Determinar el IF de ensayos controlados aleatorios que evalúan la eficacia de las intervenciones para pacientes con enfermedad diverticular desde 2010 para evaluar la solidez de la evidencia actual.FUENTES DE DATOS:Se realizaron búsquedas en MEDLINE, Embase y CENTRAL desde el inicio hasta agosto de 2022.SELECCIÓN DE ESTUDIOS:Los artículos eran elegibles para su inclusión si eran ensayos aleatorizados realizados entre 2010 y 2022 con diseños paralelos de superioridad que evaluaran intervenciones en pacientes con enfermedad diverticular. Sólo se consideraron para su inclusión los ensayos aleatorizados con resultados primarios dicotómicos con un valor de p asociado menor que 0,05.INTERVENCIÓNES:Cualquier intervención quirúrgica o médica para pacientes con enfermedad diverticular.PRINCIPALES MEDIDAS DE VALORACIÓN:El índice de fragilidad se determinó sumando eventos y restando no eventos de los grupos con el menor número de eventos. Se agregaron eventos hasta que el valor p superó 0,05. El menor número de eventos requeridos se consideró índice de fragilidad.RESULTADOS:Después de examinar 1271 citas, 15 ensayos aleatorios cumplieron los criterios de inclusión. Nueve de los estudios evaluaron intervenciones quirúrgicas y seis evaluaron intervenciones médicas. El número medio de pacientes aleatorizados y perdidos durante el seguimiento por ECA fue 92 (DE 35,3) y 9 (DE 11,4), respectivamente. La mediana del índice de fragilidad fue 1 (rango: 0-5). Los índices de fragilidad de los estudios incluidos no se correlacionaron significativamente con ninguna característica del estudio.LIMITACIONES:Muestra pequeña, heterogeneidad y falta de inclusión de estudios con resultados continuos.CONCLUSIONES:Los ensayos aleatorios que evalúan las intervenciones quirúrgicas y médicas para la enfermedad diverticular no son sólidos. Cambiar un solo evento de resultado en la mayoría de los estudios fue suficiente para que un hallazgo estadísticamente significativo del estudio no fuera significativo. (Traducción- Dr. Ingrid Melo ).

Quality of life following perioperative optimization with nutritional supplements in patients undergoing gastrointestinal surgery for cancer: A randomized, placebo-controlled feasibility clinical trial.

BACKGROUND: Up to two thirds of patients presenting for abdominal cancer surgery are malnourished pre-operatively. Perioperative nutritional supplementation has been proposed to improve surgical outcomes, though its effect on quality of life (QoL) is not yet understood. METHODS: A randomized controlled feasibility trial for perioperative nutrition among patients undergoing major abdominal cancer surgery was conducted. Participants in the intervention group received supplements for 30 days before surgery. Participants completed two QoL questionnaires (EORTC-QLQ-C-30 and FACT-G) at baseline, then 4 and 12 weeks postoperatively. Participants were compared between and within groups at baseline, Weeks 4, and 12 using t tests. Minimal clinically important differences (MCIDs) were considered as a 10-point worsening from baseline. RESULTS: Sixty-six participants were available for analysis in this study, including 33 in the intervention and 30 in the control arms. Baseline demographics were balanced between groups except for different rates of pancreas cancer (36% intervention vs. 9% control) and colorectal cancer (19% intervention vs. 34% control). At baseline, participants in the intervention group had lower overall QoL (59% vs. 77%, p = 0.01), role functioning (72% vs 88%, p = 0.045), and cognitive functioning (79% vs 90%, p = 0.047). Following surgery, role and physical functioning worsened in the control group, without significant differences between groups. Role functioning was persistently worsened at 12 weeks in the control group. The rates of MCIDs were similar between both intervention and control groups. DISCUSSION: Perioperative nutrition was associated with preservation of QoL in the postoperative period following major abdominal cancer surgery compared to placebo. SUMMARY: Among patients undergoing surgery for cancer, the majority present at high risk for malnutrition. In this placebo-controlled randomized trial among patients undergoing major abdominal surgery for cancer, preoperative nutrition supplementation was associated with the preservation of QoL in the postoperative period.

Comparing cefazolin/ metronidazole, piperacillin-tazobactam, or c efoxitin as surgical antibiotic prophylaxis in patients undergoing pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. OBJECTIVE: To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). METHODS: Consecutive adult patients at one institution who underwent PD from November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. RESULTS: Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. CONCLUSION: PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PD at our center.

Short-term postoperative outcomes for obese versus non-obese inflammatory bowel disease patients undergoing bowel resection: a propensity score matched analysis.

PURPOSE: Up to 40% of patients with inflammatory bowel disease (IBD) are obese. Obesity is a well-known risk factor for increased perioperative morbidity, but this risk has never been quantified in IBD patients undergoing abdominal surgery using the United States National Inpatient Sample (NIS) database. This study aims to compare postoperative morbidity between obese and non-obese patients undergoing bowel resection for IBD using recent NIS data. METHODS: Adult patients who underwent bowel resection for IBD from 2015 to 2019 were identified in the NIS using ICD-10-CM coding. Patients were stratified into obese (BMI > 30 kg/m2) and non-obese groups, then propensity score matched (PSM) for demographic, operative, and hospital characteristics. The primary outcome was postoperative in-hospital morbidity. Secondary outcomes included postoperative in-hospital mortality, system-specific postoperative complications, total admission healthcare costs, and length of stay (LOS). Univariable and multivariable regressions were utilized. RESULTS: Overall, 6601 non-obese patients and 671 obese patients were identified. The PSM cohort included 659 patients per group. Obese patients had significantly increased odds of experiencing postoperative in-hospital morbidity (aOR 1.50, 95% CI 1.10-2.03, p = 0.010) compared to non-obese patients. Specifically, obese patients experienced increased gastrointestinal complications (aOR 1.49, 95% CI 1.00-2.24, p = 0.050), and genitourinary complications (aOR 1.71, 95% CI 1.12-2.61, p = 0.013). There were no differences in total admission healthcare costs (MD - $2256.32, 95% CI - 19,144.54-14,631.9, p = 0.79) or LOS (MD 0.16 days, 95% CI - 0.93-1.27, p = 0.77). CONCLUSIONS: Obese IBD patients are at greater risk of postoperative in-hospital morbidity than non-obese IBD patients. This supports targeted preoperative weight loss protocols for IBD patients to optimize surgical outcomes.

Associations of preoperative anaemia with healthcare resource use and outcomes after colorectal surgery: a population-based cohort study.

BACKGROUND: Preoperative anaemia is common in patient undergoing colorectal surgery. Understanding the population-level costs of preoperative anaemia will inform development and evaluation of anaemia management at health system levels. METHODS: This was a population-based cohort study using linked, routinely collected data, including residents from Ontario, Canada, aged ≥18 yr who underwent an elective colorectal resection between 2012 and 2022. Primary exposure was preoperative anaemia (haemoglobin <130 g L-1 in males; <120 g L-1 in females). Primary outcome was 30-day costs in 2022 Canadian dollars (CAD), from the perspective of a publicly funded healthcare system. Secondary outcomes included red blood cell transfusion, major adverse events (MAEs), length of stay (LOS), days alive at home (DAH), and readmissions. RESULTS: We included 54,286 patients, with mean 65.3 (range 18-102) years of age and 49.0% females, among which 21 264 (39.2%) had preoperative anaemia. There was an absolute adjusted cost increase of $2671 per person at 30 days after surgery attributable to preoperative anaemia (ratio of means [RoM] 1.05, 95% confidence interval [CI] 1.04-1.06). Compared with the control group, 30-day risks of transfusion (odds ratio [OR] 4.34, 95% CI 4.04-4.66), MAEs (OR 1.14, 95% CI 1.03-1.27), LOS (RoM 1.08, 95% CI 1.07-1.10), and readmissions (OR 1.16, 95% CI 1.08-1.24) were higher in the anaemia group, with reduced DAH (RoM 0.95, 95% CI 0.95-0.96). CONCLUSIONS: Approximately $2671 CAD per person in 30-day health system costs are attributable to preoperative anaemia after colorectal surgery in Ontario, Canada.

Primary localized cutaneous lichen myxedematosus with light chain-restricted plasma cells: A distinct variant of the localized form of lichen myxedematosus.

Lichen myxedematosus (LM) is a chronic cutaneous mucinosis that can present as a localized skin lesion or as a generalized systemic disease termed scleromyxedema. The differential diagnosis is determined by a combination of clinical presentation, serological studies, and histopathological examination. Currently, well-established and accepted histopathological features to distinguish localized LM from scleromyxedema have not been elucidated. Our recent publication, together with a retrospective literature review, suggests that the presence of groups of light chain-restricted plasma cells represents a distinct histopathological clue for the diagnosis of localized LM. In this report, we provide two additional cases of localized LM with lambda light chain-restricted plasma cells, together with clinical and histopathological findings that are similar to our previous publication. These cases support our theory that the light chain-restricted plasmacytic microenvironment is primarily attributed to the pathogenesis of localized LM. Therefore, we consider these cases to constitute a clinically and pathologically new variant of localized LM and name it primary localized cutaneous LM with light chain-restricted plasma cells.

Using preoperative C-reactive protein levels to predict anastomotic leaks and other complications after elective colorectal surgery: A systematic review and meta-analysis.

AIM: While postoperative C-reactive protein (CRP) is used routinely as an early indicator of anastomotic leak (AL), preoperative CRP remains to be established as a potential predictor of AL for elective colorectal surgery. The aim of this systematic review and meta-analysis is to examine the association between preoperative CRP and postoperative complications including AL. METHOD: MEDLINE, EMBASE, Web of Science, PubMed, Cochrane Library and CINAHL databases were searched. Studies with reported preoperative CRP values and short-term surgical outcomes after elective colorectal surgery were included. An inverse variance random effects meta-analysis was performed for all meta-analysed outcomes to determine if patients with or without complications and AL differed in their preoperative CRP levels. Risk of bias was assessed with MINORS and certainty of evidence with GRADE. RESULTS: From 1945 citations, 23 studies evaluating 7147 patients were included. Patients experiencing postoperative infective complications had significantly greater preoperative CRP values [eight studies, n = 2421 patients, mean difference (MD) 8.0, 95% CI 3.77-12.23, p < 0.01]. A significant interaction was observed with subgroup analysis based on whether patients were undergoing surgery for inflammatory bowel disease (X2 = 8.99, p < 0.01). Preoperative CRP values were not significantly different between patients experiencing and not experiencing AL (seven studies, n = 3317, MD 2.15, 95% CI -2.35 to 6.66, p = 0.35), nor were they different between patients experiencing and not experiencing overall postoperative morbidity (nine studies, n = 2958, MD 4.54, 95% CI -2.55 to 11.62, p = 0.31) after elective colorectal surgery. CONCLUSION: Higher preoperative CRP levels are associated with increased rates of overall infective complications, but not with AL alone or with overall morbidity in patients undergoing elective colorectal surgery.

Financial toxicity among patients undergoing resectional surgery for inflammatory bowel disease in the United States.

AIM: Financial toxicity describes the financial burden and distress that patients experience due to medical treatment. Financial toxicity has yet to be characterized among patients with inflammatory bowel disease (IBD) undergoing surgical management of their disease. This study investigated the risk of financial toxicity associated with undergoing surgery for IBD. METHODS: This study used a retrospective analysis using the National Inpatient Sample from 2015 to 2019. Adult patients who underwent IBD-related surgery were identified using the International Classification of Diseases (10th Revision) diagnostic and procedure codes and stratified into privately insured and uninsured groups. The primary outcome was risk of financial toxicity, defined as hospital admission charges that constituted 40% or more of patient's post-subsistence income. Secondary outcomes included total hospital admission cost and predictors of financial toxicity. RESULTS: The analytical cohort consisted of 6412 privately insured and 3694 uninsured patients. Overall median hospital charges were $21 628 (interquartile range $14 758-$35 386). Risk of financial toxicity was 86.5% among uninsured patients and 0% among insured patients. Predictors of financial toxicity included emergency admission, being in the lowest residential income quartile and having ulcerative colitis (compared to Crohn's disease). Additional predictors were being of Black race or male sex. CONCLUSION: Financial toxicity is a serious consequence of IBD-related surgery among uninsured patients. Given the pervasive nature of this consequence, future steps to support uninsured patients receiving surgery, in particular emergency surgery, related to their IBD are needed to protect this group from financial risk.

Osteonecrosis of the jaw after radiation followed by bevacizumab.

Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced minimal skin fibrosis following intensity-modulated radiation therapy. Subsequently, the patient developed rectal adenocarcinoma and encountered osteonecrosis of the jaw after receiving two cycles of bevacizumab. Close monitoring, accompanied by thorough examination to detect early signs of osteonecrosis of the jaw, should be considered for patients who have undergone radiation therapy in the head and neck region and are receiving bevacizumab or other medications known to be associated with osteonecrosis of the jaw.

Myocardial Injury After Noncardiac Surgery in Major General Surgical Patients a Prospective Observational Cohort Study.

OBJECTIVE: The objective of this study was to determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in major general surgery patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in major general surgical patients have not been described. METHODS: This was an international prospective cohort study of a representative sample of 22,552 noncardiac surgery patients 45 years or older, of whom 4490 underwent major general surgery in 24 centers in 13 countries. All patients had fifth-generation plasma high-sensitivity troponin T (hsTnT) concentrations measured during the first 3 postoperative days. MINS was defined as a hsTnT of 20-65 ng/L and absolute change >5 ng/L or hsTnT ≥65 ng/L secondary to ischemia. The objectives of the present study were to determine (1) whether MINS is prognostically important in major general surgical patients, (2) the clinical characteristics of major general surgical patients with and without MINS, (3) the 30-day outcomes for major general surgical patients with and without MINS, and (4) the proportion of MINS that would have gone undetected without routine postoperative monitoring. RESULTS: The incidence of MINS in the major general surgical patients was 16.3% (95% CI, 15.3-17.4%). Thirty-day all-cause mortality in the major general surgical cohort was 6.8% (95% CI, 5.1%-8.9%) in patients with MINS compared with 1.2% (95% CI, 0.9%-1.6%) in patients without MINS ( P <0.01). MINS was independently associated with 30-day mortality in major general surgical patients (adjusted odds ratio 4.7, 95% CI, 3.0-7.4). The 30-day mortality was higher both among MINS patients with no ischemic features (ie, no ischemic symptoms or electrocardiogram findings) (5.4%, 95% CI, 3.7%-7.7%) and among patients with 1 or more clinical ischemic features (10.6%, 95% CI, 6.7%-15.8%). The proportion of major general surgical patients who had MINS without ischemic symptoms was 89.9% (95% CI, 87.5-92.0). CONCLUSIONS: Approximately 1 in 6 patients experienced MINS after major general surgery. MINS was independently associated with a nearly 5-fold increase in 30-day mortality. The vast majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Laparoscopic ovarian transposition prior to pelvic radiation in young women with anorectal malignancies: a systematic review and meta-analysis of prevalence.

AIM: Young women undergoing radiotherapy (RT) for pelvic malignancies are at risk of developing premature ovarian insufficiency. Ovarian transposition (OT) aims to preserve ovarian function in these patients. However, its role in anorectal malignancy has yet to be firmly established. The aim of this review was to determine the effectiveness of laparoscopic OT in preserving ovarian function in premenopausal women undergoing neoadjuvant pelvic RT for anorectal malignancies. METHODS: MEDLINE, Embase and CENTRAL were systematically searched from inception through to May 2022. Articles were included if they evaluated ovarian function after OT in women with anorectal malignancies undergoing pelvic RT. The primary outcome was ovarian function preservation. The secondary outcome was 30-day postoperative morbidity following OT. RESULTS: From 207 citations, 10 studies with 133 patients with rectal or anal cancer who underwent OT prior to RT were included. Meta-analysis of pooled proportions of preserved ovarian function demonstrated an incidence of 66.9% (95% CI 55.0-79.0%, I2 = 43%). The 30-day postoperative morbidity rate was 1.2% (n = 1). There was heterogeneity in interventions and outcome reporting. CONCLUSIONS: Laparoscopic OT in premenopausal patients undergoing pelvic radiation for anorectal malignancies might be an effective technique at reducing ovarian exposure to RT. The meta-analyses must be interpreted within the context of clinical heterogeneity of the included studies. Further studies are required to fully investigate the outcomes of OT in patients undergoing pelvic radiation for anorectal malignancies.

Landiolol for the prevention of postoperative atrial fibrillation after cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery. Although the evidence suggests that beta blockers prevent POAF, they often cause hypotension. Landiolol, an ultra-short-acting ß1 blocker, may prevent POAF, without adverse hemodynamic consequences. SOURCE: We searched MEDLINE, CENTRAL, Embase, and trial registries between January 1970 and March 2022. We included randomized controlled trials (RCTs) that evaluated the effect of landiolol for the prevention of POAF after cardiac surgery. Two reviewers independently assessed eligibility, extracted data, and assessed risk of bias using the Risk of Bias 2.0 tool. We pooled data using random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess certainty of evidence. PRINCIPAL FINDINGS: Nine RCTs including 868 participants met the eligibility criteria. Patients randomized to landiolol (56/460) had less POAF compared with controls (133/408) with a relative risk (RR) of 0.40 (95% confidence interval [CI], 0.30 to 0.54; I2 = 0%;) and an absolute risk of 12.2% vs 32.6% (absolute risk difference, 20.4%; 95% CI, 15.0 to 25.0). Landiolol resulted in a shorter hospital length-of-stay (LOS) (268 patients; mean difference, -2.32 days; 95% CI, -4.02 to -0.57; I2 = 0%). We found no significant difference in bradycardia (RR, 1.11; 95% CI, 0.48 to 2.56; I2 = 0%). No hypotension was reported with landiolol. We judged the certainty of evidence as moderate for POAF (because of indirectness as outcomes were not clearly defined) and low for LOS (because of imprecision and concern of reporting bias). CONCLUSION: In patients undergoing cardiac surgery, landiolol likely reduces POAF and may reduce LOS. A definitive large RCT is needed to confirm these findings. STUDY REGISTRATION: PROSPERO (CRD42021262703); registered 25 July 2021.

RéSUMé: OBJECTIF: La fibrillation auriculaire postopératoire (FAPO) est une complication fréquente après une chirurgie cardiaque. Bien que les données probantes suggèrent que les bêta-bloqueurs préviennent la FAPO, ces agents provoquent souvent une hypotension. Le landiolol, un ß1-bloqueur à action ultra-courte, pourrait prévenir la FAPO sans conséquences hémodynamiques indésirables. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, CENTRAL et Embase, et dans les registres d'études publiées entre janvier 1970 et mars 2022. Nous avons inclus les études randomisées contrôlées (ERC) évaluant l'effet du landiolol pour la prévention de la FAPO après une chirurgie cardiaque. Deux personnes ont indépendamment révisé l'éligibilité, extrait les données et évalué le risque de biais à l'aide de l'outil Risque de biais 2.0. Nous avons regroupé les données à l'aide de modèles à effets aléatoires. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes. CONSTATATIONS PRINCIPALES: Neuf ERC incluant 868 personnes remplissaient les critères d'éligibilité. Les patient·es randomisé·es dans le groupe landiolol (56/460) présentaient moins de FAPO que les témoins (133/408), avec un risque relatif (RR) de 0,40 (intervalle de confiance [IC] à 95 %, 0,30 à 0,54; I2 = 0 %) et un risque absolu de 12,2 % vs 32,6 % (différence de risque absolue, 20,4 %; IC 95 % 95 %, 15,0 à 25,0). Le landiolol a entraîné une durée de séjour hospitalier plus courte (268 patient·es; différence moyenne, −2,32 jours; IC 95 %, −4,02 à −0,57; I2 = 0 %). Nous n'avons trouvé aucune différence significative en matière de bradycardie (RR, 1,11; IC 95 %, 0,48 à 2,56; I2 = 0 %). Aucune hypotension n'a été rapportée avec le landiolol. Nous avons jugé que la certitude des données probantes était modérée pour la FAPO (en raison du caractère indirect car les critères d'évaluation n'étaient pas clairement définis) et faible pour la durée de séjour hospitalier (en raison de l'imprécision et de questionnements concernant le biais de déclaration). CONCLUSION: Chez les patient·es bénéficiant d'une chirurgie cardiaque, le landiolol réduit probablement la FAPO et peut réduire la durée de séjour hospitalier. Une ERC définitive à grande échelle est nécessaire pour confirmer ces résultats. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021262703); enregistrée le 25 juillet 2021.

The impact of surgical randomised controlled trials on the management of FAI syndrome: a citation analysis.

PURPOSE: To identify and assess the clinical impact of randomised controlled trials (RCTs) assessing the surgical management of femoroacetabular impingement syndrome (FAIS) through a citation analysis. METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to April 22, 2023 for RCTs assessing the surgical management of FAIS. Study characteristics were directly abstracted from included trials and citation metrics were obtained from the Clarivate Web of Knowledge database on May 19, 2023. The continuous fragility index (CFI) was calculated for eligible outcomes. Univariate regression models were used to explore correlations between total citations per year and various study characteristics. RESULTS: Ten studies comprising one thousand two hundred ninetypatients were eligible for analysis. Studies were published from 2013 to 2023. Eight countries were represented across various trials with 91% being either North American or European. The mean journal impact factor of published studies was 39.684 (median 2.982; range 1.31-202.73). The mean citation density was 14.17 (range 0.33-48.67). The median CFI was 4.8 (range 1-32.2). Correlation analysis demonstrated strong and statistically significant correlations to study sample size (R = 0.75, p = 0.012), journal impact factor (R = 0.80, p = 0.006) and continuous fragility index (R = 0.95, p = 0.015). CONCLUSION: Trials assessing the surgical management of FAIS present with a wide range of clinical uptake based on citation density and are published in journals of broadly variable impact factor. Despite promising citation metrics, high-quality evidence on arthroscopy for FAIS is limited to the United States and Europe with an unclear international impact. Future knowledge translation efforts are warranted to maximise the international uptake of evidence regarding arthroscopic management of FAIS. LEVEL OF EVIDENCE: I.

Surgical techniques for medial Patellofemoral ligament reconstruction: a systematic review and meta-analysis of level I and II studies.

PURPOSE: To determine the most optimal surgical technique for medial patellofemoral ligament reconstruction (MPFLR). METHODS: Three databases MEDLINE, PubMed, and EMBASE were searched from inception to December 13th, 2022, for level I or II studies comparing MPFLR techniques. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Data on patient-reported outcome measures were recorded. Quality assessment was carried out using the MINORS and Cochrane Risk of Bias assessment tools. Certainty of evidence was carried out with the GRADE assessment tool. RESULTS: Ten studies comprising 723 patients (723 knees) were included in this review. The weighted mean difference in Kujala, Lysholm, and IKDC scores comparing single- and double-tunnel patellar drilling techniques was 2.66 (95% CI -1.05-6.37, p = 0.16, I2 = 0%) with moderate certainty, 0.78 (95% CI -9.02-10.58, p = 0.88, I2 = 87%) with low certainty, and 1.71 (95% CI -2.43-5.86, p = 0.42, I2 = 0%) with low certainty, respectively. Double-suture anchor patellar fixation demonstrated greater Kujala scores than transpatellar fixation (87.1 ± 2.8 vs 84.0 ± 3.8, p < 0.001) with moderate certainty. Y-shaped graft patellar fixation demonstrated superior Kujala scores to C-shaped graft patellar fixation (95.9 ± 4.7 vs 91.3 ± 9.7, p = 0.001) with moderate certainty. Augmentation of femoral fixation with polyester sutures demonstrated superior Kujala scores (97.8 ± 6.4. vs 88.0 ± 6.3, p < 0.005) with low certainty. Four-stranded grafts demonstrated greater Kujala scores than two-stranded grafts (93.5 ± 2.6 vs 91.6 ± 3.5, p = 0.01) with low certainty. CONCLUSION: The optimal MPFLR surgical technique is likely to utilize a four-stranded graft using either endobutton, double-suture anchor, or transosseous suture patellar fixation with polyester suture augmented interference screw femoral fixation. Orthopedic surgeons can consider employing such a technique to improve patient outcomes by conferring greater graft stability, strength, and function. Level of evidence Level II.

A Systematic Review and Meta-analysis of Randomized Controlled Trials Comparing Intraoperative Red Blood Cell Transfusion Strategies.

OBJECTIVE: The objective of this work was to carry out a meta-analysis of RCTs comparing intraoperative RBC transfusion strategies to determine their impact on postoperative morbidity, mortality, and blood product use. SUMMARY OF BACKGROUND DATA: RBC transfusions are common in surgery and associated with widespread variability despite adjustment for casemix. Evidence-based recommendations guiding RBC transfusion in the operative setting are limited. METHODS: The search strategy was adapted from a previous Cochrane Review. Electronic databases were searched from January 2016 to February 2021. Included studies from the previous Cochrane Review were considered for eligibility from before 2016. RCTs comparing intraoperative transfusion strategies were considered for inclusion. Co-primary outcomes were 30-day mortality and morbidity. Secondary outcomes included intraoperative and perioperative RBC transfusion. Meta-analysis was carried out using random-effects models. RESULTS: Fourteen trials (8641 patients) were included. One cardiac surgery trial accounted for 56% of patients. There was no difference in 30-day mortality [relative risk (RR) 0.96, 95% confidence interval (CI) 0.71-1.29] and pooled postoperative morbidity among the studied outcomes when comparing restrictive and liberal protocols. Two trials reported worse composite outcomes with restrictive triggers. Intraoperative (RR 0.53, 95% CI 0.43-0.64) and perioperative (RR 0.70, 95% CI 0.62-0.79) blood transfusions were significantly lower in the restrictive group compared to the liberal group. CONCLUSIONS: Intraoperative restrictive transfusion strategies decreased perioperative transfusions without added postoperative morbidity and mortality in 12/14 trials. Two trials reported worse outcomes. Given trial design and generalizability limitations, uncertainty remains regarding the safety of broad application of restrictive transfusion triggers in the operating room. Trials specifically designed to address intraoperative transfusions are urgently needed.

Prognostic factors of overall survival in patients with recurrent disease following liver resection for colorectal cancer metastases: A multicenter external validation study.

BACKGROUND: The clinical course of patients experiencing recurrence following hepatectomy for colorectal cancer metastases (CRM) is poorly defined. Previous studies associated shorter time to recurrence (TTR) in months, node-positive primary tumor, and more than one site of recurrence with worse outcomes. METHODS: We conducted a retrospective cohort study across four Canadian institutions to externally validate previously established prognostic factors of overall survival (OS). We included consecutive adult patients who had a recurrence following curative-intent liver resection for CRM. Prognostic factors were explored using a multivariable Cox regression model. Risk group cutoffs were identified through recursive partitioning. OS between low- and high-risk groups was compared using the Kaplan-Meier method. RESULTS: This study included 471 patients. Shorter TTR in months (hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.93-0.97), presence of extrahepatic disease at first hepatectomy (HR: 2.54, 95% CI: 1.18-5.50), and larger tumor size in millimetres (HR: 1.01, 95% CI: 1.00-1.02) were associated with worse OS. Median OS in the high- and low-risk groups were 40.5 (95% CI: 34.0-45.7 months) versus 64.7 months (95% CI: 57.9-72.3 months; p < 0.001), respectively. CONCLUSIONS: We externally validated the prognostic significance of shorter TTR (<8.5 months) as a predictor of worse OS in patients who recur the following hepatectomy for CRM.

Intravenous acetaminophen for postoperative pain control after open abdominal and thoracic surgery in pediatric patients: a systematic review and meta-analysis.

Pediatric opioid exposure increases short- and long-term adverse events (AE). The addition of intravenous acetaminophen (IVA) to pediatric pain regimes to may reduce opioids but is not well studied postoperatively. Our objective was to quantify the impact of IVA on postoperative pain, opioid use, and AEs in pediatric patients after major abdominal and thoracic surgery. Medline, Embase, CINAHL, Web of Science, and Cochrane Library were searched systematically for randomized controlled trials (RCTs) comparing IVA to other modalities. Five RCTs enrolling 443 patients with an average age of 2.12 years (± 2.81) were included. Trials comparing IVA with opioids to opioids alone were meta-analyzed. Low to very low-quality evidence demonstrated equivalent pain scores between the groups (-0.23, 95% CI -0.88 to 0.40, p 0.47) and a reduction in opioid consumption (-1.95 morphine equivalents/kg/48 h, 95% CI -3.95 to 0.05, p 0.06) and minor AEs (relative risk 0.39, 95% CI 0.11 to 1.43, p 0.15). We conclude that the addition of IVA to opioid-based regimes in pediatric patients may reduce opioid use and minor AEs without increasing postoperative pain. Given the certainty of evidence, further research featuring patient-important outcomes and prolonged follow-up is necessary to confirm these findings.

High Throughput 3D Cell Migration Assay Using Micropillar/Microwell Chips.

The 3D cell migration assay was developed for the evaluation of drugs that inhibit cell migration using high throughput methods. Wound-healing assays have commonly been used for cell migration assays. However, these assays have limitations in mimicking the in vivo microenvironment of the tumor and measuring cell viability for evaluation of cell migration inhibition without cell toxicity. As an attempt to manage these limitations, cells were encapsulated with Matrigel on the surface of the pillar, and an analysis of the morphology of cells attached to the pillar through Matrigel was performed for the measurement of cell migration. The micropillar/microwell chips contained 532 pillars and wells, which measure the migration and viability of cells by analyzing the roundness and size of the cells, respectively. Cells seeded in Matrigel have a spherical form. Over time, cells migrate through the Matrigel and attach to the surface of the pillar. Cells that have migrated and adhered have a diffused shape that is different from the initial spherical shape. Based on our analysis of the roundness of the cells, we were able to distinguish between the diffuse and spherical shapes. Cells in Matrigel on the pillar that were treated with migration-inhibiting drugs did not move to the surface of the pillar and remained in spherical forms. During the conduct of experiments, 70 drugs were tested in single chips and migration-inhibiting drugs without cell toxicity were identified. Conventional migration assays were performed using transwell for verification of the four main migration-inhibiting drugs found on the chip.