Age-Related Perioperative Neurocognitive Disorders: Experimental Models and Druggable Targets.

With the worldwide increase in life span, surgical patients are becoming older and have a greater propensity for postoperative cognitive impairment, either new onset or through deterioration of an existing condition; in both conditions, knowledge of the patient's preoperative cognitive function and postoperative cognitive trajectory is imperative. We describe the clinical utility of a tablet-based technique for rapid assessment of the memory and attentiveness domains required for executive function. The pathogenic mechanisms for perioperative neurocognitive disorders have been investigated in animal models in which excessive and/or prolonged postoperative neuroinflammation has emerged as a likely contender. The cellular and molecular species involved in postoperative neuroinflammation are the putative targets for future therapeutic interventions that are efficacious and do not interfere with the surgical patient's healing process.

Periprocedural Management and Multidisciplinary Care Pathways for Patients With Cardiac Implantable Electronic Devices: A Scientific Statement From the American Heart Association.

The rapid technological advancements in cardiac implantable electronic devices such as pacemakers, implantable cardioverter defibrillators, and loop recorders, coupled with a rise in the number of patients with these devices, necessitate an updated clinical framework for periprocedural management. The introduction of leadless pacemakers, subcutaneous and extravascular defibrillators, and novel device communication protocols underscores the imperative for clinical updates. This scientific statement provides an inclusive framework for the periprocedural management of patients with these devices, encompassing the planning phase, procedure, and subsequent care coordinated with the primary device managing clinic. Expert contributions from anesthesiologists, cardiac electrophysiologists, and cardiac nurses are consolidated to appraise current evidence, offer patient and health system management strategies, and highlight key areas for future research. The statement, pertinent to a wide range of health care professionals, underscores the importance of quality care pathways for patient safety, optimal device function, and minimization of hemodynamic disturbances or arrhythmias during procedures. Our primary objective is to deliver quality care to the expanding patient cohort with cardiac implanted electronic devices, offering direction in the era of evolving technologies and laying a foundation for sustained education and practice enhancement.

2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery" provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery. METHODS: A comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. STRUCTURE: Recommendations from the "2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery" have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.

Ultra-early navigated transcranial magnetic stimulation for perioperative stroke: anatomo-functional report.

Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12 hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice.

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD.

Discontinuation vs. continuation of renin-angiotensin system inhibition before non-cardiac surgery: the SPACE trial.

BACKGROUND AND AIMS: Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear. METHODS: From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin-angiotensin system inhibitors were withheld for different durations (2-3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy. RESULTS: Two hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45-1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16-1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)]. CONCLUSIONS: Discontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.

A Biodegradable Nanosuspension Locally Used for Inhibiting Postoperative Recurrence and Brain Metastasis of Breast Cancer.

Addressing the urgent need to prevent breast cancer postoperative recurrence and brain metastasis, Fe-metal organic framework (MOF)-coated hollow mesoporous organosilica nanoparticles (HMON) with tumor microenvironment dual-responsive degradability were prepared to encapsulate doxorubicin (DOX), formulating a tissue-adhesive nanosuspension for perioperative topical medication. This nanosuspension can not only retain the sustainably released drug in the postoperative residual tumor sites but also enhance the intracellular oxidative stress of tumors for remarkable tumor ferroptosis. Interestingly, the nanosuspension can act as an immune amplifier, which could not only stimulate DC cells to secrete chemokines for T cell recruitment but also elevate antigen exposure to facilitate the antigen presentation in lymph nodes. Thus, this nanosuspension could significantly activate antitumor immune responses in both in situ tumors and metastatic encephaloma for enhanced immunotherapy. In conjunction with the clinical PD-1 antibody, the locally administered nanosuspension could achieve an advanced therapeutic outcome for inhibiting postoperative recurrence and metastasis.

Existing Nongated CT Coronary Calcium Predicts Operative Risk in Patients Undergoing Noncardiac Surgeries (ENCORES).

BACKGROUND: Preoperative cardiovascular risk stratification before noncardiac surgery is a common clinical challenge. Coronary artery calcium scores from ECG-gated chest computed tomography (CT) imaging are associated with perioperative events. At the time of preoperative evaluation, many patients will not have had ECG-gated CT imaging, but will have had nongated chest CT studies performed for a variety of noncardiac indications. We evaluated relationships between coronary calcium severity estimated from previous nongated chest CT imaging and perioperative major clinical events (MCE) after noncardiac surgery. METHODS: We retrospectively identified consecutive adults age ≥45 years who underwent in-hospital, major noncardiac surgery from 2016 to 2020 at a large academic health system composed of 4 acute care centers. All patients had nongated (contrast or noncontrast) chest CT imaging performed within 1 year before surgery. Coronary calcium in each vessel was retrospectively graded from absent to severe using a 0 to 3 scale (absent, mild, moderate, severe) by physicians blinded to clinical data. The estimated coronary calcium burden (ECCB) was computed as the sum of scores for each coronary artery (0 to 9 scale). A Revised Cardiac Risk Index was calculated for each patient. Perioperative MCE was defined as all-cause death or myocardial infarction within 30 days of surgery. RESULTS: A total of 2554 patients (median age, 68 years; 49.7% women; median Revised Cardiac Risk Index, 1) were included. The median time interval from nongated chest CT imaging to noncardiac surgery was 15 days (interquartile range, 3-106 days). The median ECCB was 1 (interquartile range, 0-3). Perioperative MCE occurred in 136 (5.2%) patients. Higher ECCB values were associated with stepwise increases in perioperative MCE (0: 2.9%, 1-2: 3.7%, 3-5: 8.0%; 6-9: 12.6%, P<0.001). Addition of ECCB to a model with the Revised Cardiac Risk Index improved the C-statistic for MCE (from 0.675 to 0.712, P=0.018), with a net reclassification improvement of 0.428 (95% CI, 0.254-0.601, P<0.0001). An ECCB ≥3 was associated with 2-fold higher adjusted odds of MCE versus an ECCB <3 (adjusted odds ratio, 2.11 [95% CI, 1.42-3.12]). CONCLUSIONS: Prevalence and severity of coronary calcium obtained from existing nongated chest CT imaging improve preoperative clinical risk stratification before noncardiac surgery.

Transcarotid Arterial Revascularization of Symptomatic Internal Carotid Artery Disease: A Systematic Review and Study-Level Meta-Analysis.

BACKGROUND: Transcarotid artery revascularization (TCAR) is an interventional therapy for symptomatic internal carotid artery disease. Currently, the utilization of TCAR is contentious due to limited evidence. In this study, we evaluate the safety and efficacy of TCAR in patients with symptomatic internal carotid artery disease compared with carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: A systematic review was conducted, spanning from January 2000 to February 2023, encompassing studies that used TCAR for the treatment of symptomatic internal carotid artery disease. The primary outcomes included a 30-day stroke or transient ischemic attack, myocardial infarction, and mortality. Secondary outcomes comprised cranial nerve injury and major bleeding. Pooled odds ratios (ORs) for each outcome were calculated to compare TCAR with CEA and CAS. Furthermore, subgroup analyses were performed based on age and degree of stenosis. In addition, a sensitivity analysis was conducted by excluding the vascular quality initiative registry population. RESULTS: A total of 7 studies involving 24 246 patients were analyzed. Within this patient cohort, 4771 individuals underwent TCAR, 12 350 underwent CEA, and 7125 patients underwent CAS. Compared with CAS, TCAR was associated with a similar rate of stroke or transient ischemic attack (OR, 0.77 [95% CI, 0.33-1.82]) and myocardial infarction (OR, 1.29 [95% CI, 0.83-2.01]) but lower mortality (OR, 0.42 [95% CI, 0.22-0.81]). Compared with CEA, TCAR was associated with a higher rate of stroke or transient ischemic attack (OR, 1.26 [95% CI, 1.03-1.54]) but similar rates of myocardial infarction (OR, 0.9 [95% CI, 0.64-1.38]) and mortality (OR, 1.35 [95% CI, 0.87-2.10]). CONCLUSIONS: Although CEA has traditionally been considered superior to stenting for symptomatic carotid stenosis, TCAR may have some advantages over CAS. Prospective randomized trials comparing the 3 modalities are needed.

Microbiota-gut-brain axis in perioperative neurocognitive and depressive disorders: Pathogenesis to treatment.

An increasing number of people undergo anesthesia and surgery. Perioperative neurocognitive and depressive disorders are common central nervous system complications with similar pathogeneses. These conditions pose a deleterious threat to human health and a significant societal burden. In recent years, numerous studies have focused on the role of the gut microbiota and its metabolites in the central nervous system via the gut-brain axis. Its involvement in perioperative neurocognitive and depressive disorders has attracted considerable attention. This review aimed to elucidate the role of the gut microbiota and its metabolites in the pathogenesis of perioperative neurocognitive and depressive disorders, as well as the value of targeted interventions and treatments.

Top advances of the year: Perioperative therapy for lung cancer.

Emerging data supporting the rise of perioperative immune checkpoint inhibitors (ICIs) as a standard of care in the treatment of early stage, surgically resectable non-small cell lung cancer (NSCLC) dominated the NSCLC news in 2023. Adjuvant pembrolizumab became the second adjuvant ICI to receive US Food and Drug Administration approval in early 2023 after the 2021 approval of adjuvant atezolizumab and the 2022 approval of neoadjuvant nivolumab with chemotherapy. Subsequently in 2023, multiple phase 3 trials examining perioperative ICIs were positive and demonstrated clinically meaningful outcomes by prolonging event-free survival, improving pathologic complete response rates, and trending toward improved overall survival in most. Perioperative pembrolizumab became the first ICI to attain US Food and Drug Administration approval in this setting through the KEYNOTE-671 trial (ClinicalTrials.gov identifier NCT03425643), which also demonstrated a definitive overall survival benefit in the entire study population. However, questions remain regarding patient selection for either approach and how we can optimize biomarkers to determine who needs adjuvant therapy after surgery.

Perioperative extracorporeal membrane oxygenation in liver transplantation-bridge to transplantation, intraoperative salvage, and postoperative support: outcomes and predictors for survival in a large-volume liver transplant center.

Data on perioperative extracorporeal membrane oxygenation (ECMO) in liver transplantation (LT) are scarce. ECMO has been used preoperatively, intraoperatively, and postoperatively for a variety of indications at our center. This retrospective, single-center study of ECMO use peri-LT aimed to describe predictors for successful outcome in this highly select cohort of patients. Demographics, support method, and indication for LT were compared between survivors and nonsurvivors. Twenty-nine patients received venovenous (V-V; n = 20), venoarterial (V-A; n = 8), and venoarteriovenous (n = 1) ECMO. Twelve (41.4%) patients were bridged to emergency LT for acute liver failure, and emergency redo LT. Four (13.3%) patients required intraoperative V-A ECMO salvage, 2 necessitating extracorporeal cardiopulmonary resuscitation. Thirteen (43.3%) patients required ECMO support after LT: V-V ECMO (n = 9); V-A ECMO (n = 1); and extracorporeal cardiopulmonary resuscitation (n = 3) between postoperative days 2 to 30. Overall, 19 patients (65.5%) were successfully weaned off ECMO; 15 (51.7%) survived to intensive care unit discharge. All patients who underwent intraoperative salvage ECMO and all who were bridged to emergency redo LT died. Peri-LT ECMO is feasible. Post-LT ECMO outcomes are encouraging, in particular for V-V ECMO. Intraoperative ECMO salvage, uncontrolled sepsis, and graft failure are associated with poor outcomes.

Perioperative acute kidney injury: The renoprotective effect and mechanism of dexmedetomidine.

Dexmedetomidine (DEX) is a highly selective and potent α2-adrenoceptor (α2-AR) agonist that is widely used as a clinical anesthetic to induce anxiolytic, sedative, and analgesic effects. In recent years, a growing body of evidence has demonstrated that DEX protects against acute kidney injury (AKI) caused by sepsis, drugs, surgery, and ischemia-reperfusion (I/R) in organs or tissues, indicating its potential role in the prevention and treatment of AKI. In this review, we summarized the evidence of the renoprotective effects of DEX on different models of AKI and explored the mechanism. We found that the renoprotective effects of DEX mainly involved antisympathetic effects, reducing inflammatory reactions and oxidative stress, reducing apoptosis, increasing autophagy, reducing ferroptosis, protecting renal tubular epithelial cells (RTECs), and inhibiting renal fibrosis. Thus, the use of DEX is a promising strategy for the management and treatment of perioperative AKI. The aim of this review is to further clarify the renoprotective mechanism of DEX to provide a theoretical basis for its use in basic research in various AKI models, clinical management, and the treatment of perioperative AKI.

Long-term survivals of immune checkpoint inhibitors as neoadjuvant and adjuvant therapy in dMMR/MSI-H colorectal and gastric cancers.

BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.

Optimizing perioperative treatment for potentially resectable stage III squamous cell lung carcinoma: promising results of a condensed four-cycle regimen with tislelizumaband chemotherapy.

BACKGROUND: The standard care for resectable non-small cell lung cancer (NSCLC) involves perioperative therapy combining chemotherapy and immune checkpoint inhibitors, typically lasting 6 to 12 months. However, the optimal treatment strategies for potentially resectable squamous cell lung carcinoma (SCC) remain unclear. This Phase 2 trial aimed to assess the efficacy and safety of a condensed four-cycle perioperative treatment regimen with tislelizumab combined with chemotherapy in patients with potentially resectable stage III SCC. METHODS: Patients with potentially resectable stage IIIA-IIIB (N2) SCC received intravenous tislelizumab, albumin-bound paclitaxel, and carboplatin for up to four cycles. The primary endpoints were major pathologic response (MPR) and incidence of treatment-related adverse events. Safety and potential biomarkers for efficacy prediction were also assessed. RESULTS: Among 35 enrolled patients, 32 underwent surgery with R0 resection achieved in all cases. MPR was achieved in 24 patients and pathological complete response (pCR) in 14 patients. Radiographic objective response was observed in 31 patients. The 12-month and 24-month event-free survival rate was 85.7 and 61.0%, respectively. Four patients experienced grade 3 or 4 adverse events. Tumor tissue based next-generation sequencing revealed the potential associations between several biomarkers and pathological response, including tumor neoantigen burden score, 18-gene expression profile score, CD8 + T cells, M1/M2 macrophages ratio and interferon-gamma expression level. Besides, circulating tumor DNA (ctDNA) dynamics and concentration were also associated with pathological response and the presence of ctDNA at postoperative month 1 was a strong predictor for disease relapse. Furthermore, metagenomic sequencing in bronchoalveolar lavage fluid demonstrated Streptococcus was the most abundant genus in the pCR group. CONCLUSIONS: A condensed four-cycle perioperative treatment regimen of tislelizumab combined with chemotherapy demonstrated promising efficacy and manageable toxicities in potentially resectable stage III SCC. Specific biomarkers showed potential for predicting treatment efficacy and the mechanism of superior antitumor response of pCR patients was preliminarily and indirectly explored. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05024266. Registered August 27, 2021.

Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.

Anaphylaxis mortality in the perioperative setting: Epidemiology, elicitors, risk factors and knowledge gaps.

Perioperative anaphylaxis (PA) is a severe condition that can be fatal, but data on PA mortality are scarce. The aim of this article is to review the epidemiology, elicitors and risk factors for PA mortality and identify knowledge gaps and areas for improvement regarding the management of severe PA. PA affects about 100 cases per million procedures. Mortality is rare, estimated at 3 to 5 cases per million procedures, but the PA mortality rate is higher than for other anaphylaxis aetiologies, at 1.4% to 4.8%. However, the data are incomplete. Published data mention neuromuscular blocking agents and antibiotics, mainly penicillin and cefazolin, as the main causes of fatal PA. Reported risk factors for fatal PA vary in different countries. Most frequently occurring comorbidities are obesity, male gender, cardiovascular diseases and ongoing treatment with beta-blockers. However, there are no clues about how these factors interact and the impact of individual risk factors. The pathophysiology of fatal PA is still not completely known. Genetic factors such as deficiency in PAF-acetyl hydrolase and hereditary alpha-tryptasemia, have been reported as modulators of severe anaphylaxis and possible targets for specific treatments. Our review underlines unmet needs in the field of fatal PA. Although we confirmed the need for timely administration of an adequate dose of adrenaline and the proper infusion of fluids, there is no evidence-based data on the proper dose of intravenous titrated adrenaline and which clinical manifestations would flag the need for fluid therapy. There are no large clinical studies supporting the administration of alternative vasopressors, such as glucagon and methylene blue. Further research on pathophysiological mechanisms of PA and its severity may address these issues and help clinicians to define new therapeutic approaches.

Postoperative Adverse Events Following Neoadjuvant Therapy and Surgery for Borderline Resectable Pancreatic Cancer in a Phase 2 Clinical Trial (Alliance A021501).

BACKGROUND: Postoperative adverse events (AEs) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PC) treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. We conducted a preplanned secondary analysis of patients enrolled on the Alliance A021501 clinical trial to quantify perioperative AE rates. METHODS: The A021501 phase 2 trial randomized patients with BR-PC to receive 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX and hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (December 31, 2016 to May 31, 2019). Adverse events were assessed 90 days after pancreatectomy. RESULTS: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n = 32, Arm 1; n = 19, Arm 2) at 28 institutions. Five (10%) patients required reoperation within 90 days; 56% of patients (n = 27/48) experienced at least one grade 3 or higher AE (50% vs. 67%, p = 0.37). Ninety-day mortality was 2.0%. Readmission was less frequent in Arm 1 (16% vs. 42%, p = 0.05), but there were no differences between study arms in rates of reoperation (13% vs. 5%), pancreatic fistula or intra-abdominal abscess requiring drainage (9% vs. 16%), or wound infection (6% vs. 16%). Pancreatic fistula or intra-abdominal abscess requiring drainage was associated with receipt of adjuvant therapy (p = 0.012). No difference in overall survival was observed based on occurrence of postoperative AEs (hazard ratio = 1.1; 95% confidence interval 0.5-2.6). CONCLUSIONS: In this multicenter study, rates of postoperative AEs were consistent with those previously reported. Multimodality trials of preoperative therapy for BR-PC may be performed in the cooperative group setting with careful quality assurance and safety monitoring. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02839343.

Oncologic and Perioperative Outcomes of Robot-Assisted Versus Conventional Laparoscopy for the Treatment of Clinically Uterine-Confined High-Grade Adenocarcinoma.

OBJECTIVE: The aim of this study was to compare oncologic and perioperative outcomes of robot-assisted laparoscopy (RA) and conventional laparoscopy (LSC) in apparent clinically uterine-confined, high-grade adenocarcinoma. METHODS: A retrospective review was conducted to identify patients with newly diagnosed high-grade uterine adenocarcinoma treated at our institution between 1 January 2009 and 30 June 2021. Exclusion criteria included bulky extrauterine disease, no lymph node assessment, or synchronous tumors. Clinicopathologic details were obtained from medical records. Postoperative complications were classified using the Memorial Sloan Kettering Cancer Center Surgical Secondary Events system, and statistical analysis was performed using appropriate tests. RESULTS: Of 901 patients identified, 748 (83%) underwent RA and 153 (17%) underwent LSC. Median age was 65 years (range 25-92) and median body mass index was 30 kg/m2 (range 15-60). Overall, 650 patients (72%) had 2009 International Federation of Obstetrics and Gynecology (FIGO) stage I disease. Forty-one patients (4.6%) converted to laparotomy-26 (3.5%) from RA versus 15 (9.8%) from LSC (p = 0.02). Postoperative complications occurred in 81 patients (9.0%), with no significant differences in type or rate between groups. Median operative time was 192 mins (range 88-936) for RA versus 168 mins (range 90-372) for LSC (p = 0.002). Median follow-up was 52 months (range 1-163) for RA and 66 months (range 7-165) for LSC. Four-year progression-free survival (PFS) and disease-specific survival (DSS) were similar between groups. Multivariate analysis showed stage, histology, peritoneal cytology, and lymphovascular invasion predicated a decrease in PFS and DSS. CONCLUSIONS: RA demonstrated comparable oncologic outcomes to LSC in patients with high-grade endometrial carcinoma, with no significant difference in postoperative complications or long-term survival.

Robotic Versus Laparoscopic Pancreaticoduodenectomy for Pancreatic Cancer: Evaluation and Analysis of Surgical Efficacy.

BACKGROUND: Evidence is limited for the treatment of pancreatic cancer among minimally invasive pancreatoduodenectomy. METHODS: This retrospective analysis evaluated patients who underwent robotic pancreaticoduodenectomy (RPD) or laparoscopic pancreaticoduodenectomy (LPD) from April 2016 to April 2023. Their baseline and perioperative data, including operative time, R0 resection rates, and severe complications rates, were analyzed, and the follow-up data, such as disease-free survival (DFS) and overall survival (OS), were collected. RESULTS: A total of 253 cases of LPD and RPD were performed, and 101 cases with pancreatic cancer were included, of which 54 were LPD and 47 were RPD. The conversion rate (4.3% vs. 29.6%, p = 0.001) and blood loss (400 vs. 575 mL, p < 0.05) were lower in the RPD group. No significant difference was observed between the two groups in terms of operative time, vessel resection rates, and TNM-stage diagnosis; however, R0 resection rates (80.9% vs. 70.4%) and lymph node harvest (24.2 vs. 21.9) had a higher tendency in the RPD group, and postoperative length of stay was shorter in the RPD cohort (11 vs. 13 days). Moreover, improved 1- to 3-years DFS (75.7%, 61.7%, and 36.0% vs. 59.0%, 35.6%, and 21.9%) and OS (94.7%, 84.7%, and 50.8% vs. 84.1%, 63.6%, and 45.5%) was found in the RPD group in comparison with the LPD group. CONCLUSIONS: RPD had advantages in surgical safety and oncological outcomes compared with LPD, but was similar to the latter in perioperative outcomes. Long-term outcomes require further study.