Diagnostic evaluation of upper tract urothelial carcinoma: can we safely omit diagnostic ureteroscopy?

OBJECTIVE: To identify clinicopathological or radiological factors that may predict a diagnosis of upper urinary tract urothelial cell carcinoma (UTUC) to inform which patients can proceed directly to radical nephroureterectomy (RNU) without the delay for diagnostic ureteroscopy (URS). PATIENTS AND METHODS: All consecutive patients investigated for suspected UTUC in a high-volume UK centre between 2011 and 2017 were identified through retrospective analysis of surgical logbooks and a prospectively maintained pathology database. Details on clinical presentation, radiological findings, and URS/RNU histopathology results were evaluated. Multivariate regression analysis was performed to evaluate predictors of a final diagnosis of UTUC. RESULTS: In all, 260 patients were investigated, of whom 230 (89.2%) underwent URS. RNU was performed in 131 patients (50.4%), of whom 25 (9.6%) proceeded directly without URS - all of whom had a final histopathological diagnosis of UTUC - and 15 (11.5%) underwent RNU after URS despite no conclusive histopathological confirmation of UTUC. Major surgery was avoided in 77 patients (33.5%) where a benign or alternative diagnosis was made on URS, and 14 patients (6.1%) underwent nephron-sparing surgery. Overall, 178 patients (68.5%) had a final diagnosis of UTUC confirmed on URS/RNU histopathology. On multivariate logistic regression analysis, a presenting complaint of visible haematuria (hazard ratio [HR] 5.17, confidence interval [CI] 1.91-14.0; P = 0.001), a solid lesion reported on imaging (HR 37.8, CI = 11.7-122.1; P < 0.001) and a history of smoking (HR 3.07, CI 1.35-6.97; P = 0.007), were predictive of a final diagnosis of UTUC. From this cohort, 51 (96.2%) of 53 smokers who presented with visible haematuria and who had a solid lesion on computed tomography urogram had UTUC on final histopathology. CONCLUSION: We identified specific factors which may assist clinicians in selecting which patients may reliably proceed to RNU without the delay of diagnostic URS. These findings may inform a prospective multicentre analysis including additional variables such as urinary cytology.

Assessment of association between lower ureteric excision technique and oncological outcomes for upper urinary tract urothelial carcinoma: retrospective analysis from the Scottish Renal Cancer Consortium.

PURPOSE: Nephroureterectomy(NU) remains the gold-standard surgical option for the management of upper urinary tract urothelial carcinoma(UTUC). Controversy exists regarding the optimal excision technique of the lower ureter. We sought to compare post-UTUC bladder tumour recurrence across the Scottish Renal Cancer Consortium(SRCC). METHODS: Patients who underwent NU for UTUC across the SRCC 2012-2019 were identified. The impact of lower-end surgical technique along with T-stage, N-stage, tumour location and focality, positive surgical margin, pre-NU ureteroscopy, upper-end technique and adjuvant mitomycin C administration were assessed by Kaplan-Meier and Cox-regression. The primary outcome was intra-vesical recurrence-free survival (B-RFS). RESULTS: In 402 patients, the median follow-up was 29 months. The lower ureter was managed by open transvesical excision in 90 individuals, transurethral and laparoscopic dissection in 76, laparoscopic or open extra-vesical excision in 31 and 42 respectively, and transurethral dissection and pluck in 163. 114(28.4%) patients had a bladder recurrence during follow-up. There was no difference in B-RFS between lower-end techniques by Kaplan-Meier (p = 0.94). When all factors were taken into account by adjusted Cox-regression, preceding ureteroscopy (HR 2.65, p = 0.001), lower ureteric tumour location (HR 2.16, p = 0.02), previous bladder cancer (HR 1.75, p = 0.01) and male gender (HR 1.61, p = 0.03) were associated with B-RFS. CONCLUSION: These data suggest in appropriately selected patients, lower ureteric management technique does not affect B-RFS. Along with lower ureteric tumour location, male gender and previous bladder cancer, preceding ureteroscopy was associated with a higher recurrence rate following NU, and the indication for this should be carefully considered.

Adipocyte-Derived Serum Amyloid A Promotes Angiotensin II-Induced Abdominal Aortic Aneurysms in Obese C57BL/6J Mice.

BACKGROUND: Obesity increases the risk for human abdominal aortic aneurysms (AAAs) and enhances Ang II (angiotensin II)-induced AAA formation in C57BL/6J mice. Obesity is also associated with increases in perivascular fat that expresses proinflammatory markers including SAA (serum amyloid A). We previously reported that deficiency of SAA significantly reduces Ang II-induced inflammation and AAA in hyperlipidemic apoE-deficient mice. In this study. we investigated whether adipose tissue-derived SAA plays a role in Ang II-induced AAA in obese C57BL/6J mice. METHODS: The development of AAA was compared between male C57BL/6J mice (wild type), C57BL/6J mice lacking SAA1.1, SAA2.1, and SAA3 (TKO); and TKO mice harboring a doxycycline-inducible, adipocyte-specific SAA1.1 transgene (TKO-Tgfat; SAA expressed only in fat). All mice were fed an obesogenic diet and doxycycline to induce SAA transgene expression and infused with Ang II to induce AAA. RESULTS: In response to Ang II infusion, SAA expression was significantly increased in perivascular fat of obese C57BL/6J mice. Maximal luminal diameters of the abdominal aorta were determined by ultrasound before and after Ang II infusion, which indicated a significant increase in aortic luminal diameters in wild type and TKO-TGfat mice but not in TKO mice. Adipocyte-specific SAA expression was associated with MMP (matrix metalloproteinase) activity and macrophage infiltration in abdominal aortas of Ang II-infused obese mice. CONCLUSIONS: We demonstrate for the first time that SAA deficiency protects obese C57BL/6J mice from Ang II-induced AAA. SAA expression only in adipocytes is sufficient to cause AAA in obese mice infused with Ang II.

A stepwise external cardioversion protocol for atrial fibrillation to maximize acute success rate.

AIMS: Cardioversion is a very commonly performed procedure for persistent atrial fibrillation (AF). However, there is no well-defined protocol to address failed external electrical direct current cardioversion. The aim of the study is to test the efficacy of a pre-defined stepwise cardioversion protocol for patients with persistent AF of ≤12 months. Success was the achievement of sinus rhythm. METHODS AND RESULTS: The study population included patients with persistent AF of ≤12 months duration requiring rhythm management. Patients were offered cardioversion using a pre-defined stepwise protocol using different electrode placement locations, applying compression at end of expiration, and higher energy delivered simultaneously through two defibrillators. : A total of 414 patients were included in the study, of which 362 (87.4%) required a single successful cardioversion. The remaining 52 (12.5%) patients required additional cardioversion attempts using the stepwise cardioversion protocol with an overall success rate of 99.3%. Two simultaneous defibrillators were required in 14 patients (3.4%). Patients with multiple cardioversions (13.5%) experienced more local skin irritation and pain compared with patients with single cardioversion (13.5% vs. 3.5%, P = 0.004). The predictor for the need for multiple cardioversion attempts is high body mass index, while high transthoracic impedance is associated with failed cardioversion. No major complications were observed during the study. CONCLUSION: The stepwise cardioversion protocol has a high success rate of >99% and can be safely performed in outpatient or inpatient settings.

A Phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA).

BACKGROUND: Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor. METHODS: NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity. RESULTS: In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype. CONCLUSIONS: NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery. CLINICAL TRIAL REGISTRATION: NCT03494816.

Highlights of the Virtual Society for Cardiovascular Magnetic Resonance 2022 Scientific Conference: CMR: improving cardiovascular care around the world.

The 25th Society for Cardiovascular Magnetic Resonance (SCMR) Annual Scientific Sessions saw 1524 registered participants from more than 50 countries attending the meeting virtually. Supporting the theme "CMR: Improving Cardiovascular Care Around the World", the meeting included 179 invited talks, 52 sessions including 3 plenary sessions, 2 keynote talks, and a total of 93 cases and 416 posters. The sessions were designed so as to showcase the multifaceted role of cardiovascular magnetic resonance (CMR) in identifying and prognosticating various myocardial pathologies. Additionally, various social networking sessions as well as fun activities were organized. The major areas of focus for the future are likely to be rapid efficient and high value CMR exams, automated and quantitative acquisition and post-processing using artificial intelligence and machine learning, multi-contrast imaging and advanced vascular imaging including 4D flow.

Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial.

BACKGROUND: Atrial fibrillation and delirium are common consequences of cardiac surgery. Dexmedetomidine has unique properties as sedative agent and might reduce the risk of each complication. This study coprimarily aimed to establish whether dexmedetomidine reduces the incidence of new-onset atrial fibrillation and the incidence of delirium. METHODS: A randomised, placebo-controlled trial was done at six academic hospitals in the USA. Patients who had had cardiac surgery with cardiopulmonary bypass were enrolled. Patients were randomly assigned 1:1, stratified by site, to dexmedetomidine or normal saline placebo. Randomisation was computer generated with random permuted block size 2 and 4, and allocation was concealed by a web-based system. Patients, caregivers, and evaluators were all masked to treatment. The study drug was prepared by the pharmacy or an otherwise uninvolved research associate so that investigators and clinicians were fully masked to allocation. Participants were given either dexmedetomidine infusion or saline placebo started before the surgical incision at a rate of 0·1 µg/kg per h then increased to 0·2 µg/kg per h at the end of bypass, and postoperatively increased to 0·4 µg/kg per h, which was maintained until 24 h. The coprimary outcomes were atrial fibrillation and delirium occurring between intensive care unit admission and the earlier of postoperative day 5 or hospital discharge. All analyses were intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT02004613 and is closed. FINDINGS: 798 patients of 3357 screened were enrolled from April 17, 2013, to Dec 6, 2018. The trial was stopped per protocol after the last designated interim analysis. Among 798 patients randomly assigned, 794 were analysed, with 400 assigned to dexmedetomidine and 398 assigned to placebo. The incidence of atrial fibrillation was 121 (30%) in 397 patients given dexmedetomidine and 134 (34%) in 395 patients given placebo, a difference that was not significant: relative risk 0·90 (97·8% CI 0·72, 1·15; p=0·34). The incidence of delirium was non-significantly increased from 12% in patients given placebo to 17% in those given dexmedetomidine: 1·48 (97·8% CI 0·99-2·23). Safety outcomes were clinically important bradycardia (requiring treatment) and hypotension, myocardial infarction, stroke, surgical site infection, pulmonary embolism, deep venous thrombosis, and death. 21 (5%) of 394 patients given dexmedetomidine and 8 (2%) of 396 patients given placebo, had a serious adverse event as determined by clinicians. 1 (<1%) of 391 patients given dexmedetomidine and 1 (<1%) of 387 patients given placebo died. INTERPRETATION: Dexmedetomidine infusion, initiated at anaesthetic induction and continued for 24 h, did not decrease postoperative atrial arrhythmias or delirium in patients recovering from cardiac surgery. Dexmedetomidine should not be infused to reduce atrial fibrillation or delirium in patients having cardiac surgery. FUNDING: Hospira Pharmaceuticals.

Effect of 6% Hydroxyethyl Starch 130/0.4 on Inflammatory Response and Pulmonary Function in Patients Having Cardiac Surgery: A Randomized Clinical Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass induces a profound inflammatory response that, when severe, can lead to multiorgan system dysfunction. Preliminary data suggest that administration of hydroxyethyl starch (HES) solutions may mitigate an inflammatory response and improve pulmonary function. Our goal was to examine the effect of 6% HES 130/0.4 versus 5% human albumin given for intravascular plasma volume replacement on the perioperative inflammatory response and pulmonary function in patients undergoing cardiac surgery. METHODS: This was a subinvestigation of a blinded, parallel-group, randomized clinical trial of patients undergoing elective aortic valve replacement surgery at the Cleveland Clinic main campus, titled "Effect of 6% Hydroxyethyl Starch 130/0.4 on Kidney and Haemostatic Function in Cardiac Surgical Patients." Of 141 patients who were randomized to receive either 6% HES 130/0.4 or 5% human albumin for intraoperative plasma volume replacement, 135 patients were included in the data analysis (HES n = 66, albumin n = 69). We assessed the cardiopulmonary bypass-induced inflammatory response end points by comparing the 2 groups' serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF), measured at baseline and at 1 and 24 hours after surgery. We also compared the 2 groups' postoperative pulmonary function end points, including the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2:Fio2 ratio), dynamic lung compliance, oxygenation index (OI), and ventilation index (VI) at baseline, within 1 hour of arrival to the intensive care unit, and before tracheal extubation. The differences in the postoperative levels of inflammatory response and pulmonary function between the HES and albumin groups were assessed individually in linear mixed models. RESULTS: Serum concentrations of the inflammatory markers (TNF-α, IL-6, MIF) were not significantly different (P ≥ .05) between patients who received 6% HES 130/0.4 or 5% albumin, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). The results of pulmonary function parameters (Pao2:Fio2 ratio, dynamic compliance, OI, VI) were not significantly different (P ≥ .05) between groups, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). CONCLUSIONS: Our investigation found no significant difference in the concentrations of inflammatory markers and measures of pulmonary function between cardiac surgical patients who received 6% HES 130/0.4 versus 5% albumin.

Prognostic Utility of KDIGO Urine Output Criteria After Cardiac Surgery.

OBJECTIVES: Kidney Disease: Improving Global Outcomes (KDIGO) guidelines include assessment of creatinine and urine output to identify acute kidney injury (AKI). Whether urine output is an accurate indicator of AKI after cardiac surgery, however, is unclear. The authors' goal was to examine whether cardiac surgery patients who fulfilled criteria for AKI by KDIGO urine output criteria also demonstrated kidney injury by elevated creatinine, other kidney biomarkers, or had worse clinical outcomes. DESIGN: Secondary analysis of prospectively collected data from a clinical trial, "6% Hydroxyethyl starch 130/0.4 in Cardiac Surgery (NCT02192502)." SETTING: Academic, quaternary care hospital. PARTICIPANTS: Patients undergoing elective aortic valve replacement INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: One hundred forty-one patients were classified into AKI stage by KDIGO urine output criteria within 24 hours after surgery. Kidney biomarkers (serum creatinine, urinary neutrophil gelatinase-associated lipocalin [NGAL], urinary interleukin-18 [IL-18]) and hospital and intensive care unit length of stay were analyzed across AKI stages. Urine output criteria classified four times as many patients with AKI than creatinine criteria (95 [67%] v 21 [15%]). Most patients meeting KDIGO urine output criteria for AKI postoperatively did not satisfy KDIGO creatinine criteria for AKI within one week (77 of 95 [81%]) or six-to-12 months (27 of 29 [93%]). Higher AKI stage assessed by urine output was not associated with higher NGAL, IL-18, or longer hospital or intensive care unit stays. CONCLUSIONS: Acute kidney injury classified by KDIGO urine output criteria was not associated with other biomarkers of kidney injury or worse patient outcomes. These data suggested that KDIGO urine output criteria after cardiac surgery may overclassify AKI stage; further research is needed.

Point-of-Care Ultrasound to Identify Landmarks of the Proximal Humerus: Potential Use for Intraosseous Vascular Access.

OBJECTIVES: The inability to identify landmarks is an absolute contraindication for intraosseous access. The feasibility of landmark identification using ultrasound (US) has been demonstrated on human cadavers. We aimed to study the feasibility of point-of-care US in identifying proximal humerus landmarks in living human patients. METHODS: This was a prospective cohort study conducted from May 3 to June 7, 2017, after approval from the Institutional Review Board at the Cleveland Clinic. Sixty upper extremities of 30 consenting participants across 3 distinct body mass index (BMI) groups (normal, obese, and morbidly obese) were alternately examined with a 12 L-RS linear US transducer (GE Healthcare, Chicago, IL) by 2 investigators. Six anatomic landmarks were identified: the humeral shaft, the surgical neck of the humerus, the lesser tubercle, the greater tubercle, the inter tubercular sulcus, and the target site for needle insertion on the greater tubercle. Rates of successful identification of all 6 landmarks as defined by independent agreement between the investigators were reported as estimated incidence rates with 95% bootstrap confidence interval (CI) sampling at the participant level. RESULTS: Ultrasound had an overall success rate of 0.87 (95% CI, 0.78-0.95) in identifying all 6 landmarks with slight variability among various BMI groups. After excluding the surgical neck, the overall success rate improved to 0.93 (95% CI, 0.87-0.98), with minimum variability across BMI groups and no change in the ability to identify the target site. CONCLUSIONS: Ultrasound is reliable in identifying proximal humerus intraosseous landmarks, with reasonable accuracy across various BMI groups.

A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation.

BACKGROUND: Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed. METHODS: To develop a tool for stratifying patients' risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012-2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR <45 ml/min per 1.73 m2 at 12 months postnephrectomy. We used prespecified predictors-age ≥65 years old, diabetes mellitus, preoperative eGFR, and nephrectomy type (partial/radical)-to fit logistic regression models and grouped patients according to degree of risk of clinically significant CKD (negligible, low, moderate, or high risk). RESULTS: Absolute risks of stage 3b or higher CKD were <2%, 3% to 14%, 21% to 26%, and 46% to 69% across the four strata of negligible, low, moderate, and high risk, respectively. The negative predictive value of the negligible risk category was 98.9% for clinically significant CKD. The c statistic for this score ranged from 0.84 to 0.88 across derivation and validation cohorts. CONCLUSIONS: Our simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool's quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.

T1 mapping performance and measurement repeatability: results from the multi-national T1 mapping standardization phantom program (T1MES).

BACKGROUND: The T1 Mapping and Extracellular volume (ECV) Standardization (T1MES) program explored T1 mapping quality assurance using a purpose-developed phantom with Food and Drug Administration (FDA) and Conformité Européenne (CE) regulatory clearance. We report T1 measurement repeatability across centers describing sequence, magnet, and vendor performance. METHODS: Phantoms batch-manufactured in August 2015 underwent 2 years of structural imaging, B0 and B1, and "reference" slow T1 testing. Temperature dependency was evaluated by the United States National Institute of Standards and Technology and by the German Physikalisch-Technische Bundesanstalt. Center-specific T1 mapping repeatability (maximum one scan per week to minimum one per quarter year) was assessed over mean 358 (maximum 1161) days on 34 1.5 T and 22 3 T magnets using multiple T1 mapping sequences. Image and temperature data were analyzed semi-automatically. Repeatability of serial T1 was evaluated in terms of coefficient of variation (CoV), and linear mixed models were constructed to study the interplay of some of the known sources of T1 variation. RESULTS: Over 2 years, phantom gel integrity remained intact (no rips/tears), B0 and B1 homogenous, and "reference" T1 stable compared to baseline (% change at 1.5 T, 1.95 ± 1.39%; 3 T, 2.22 ± 1.44%). Per degrees Celsius, 1.5 T, T1 (MOLLI 5s(3s)3s) increased by 11.4 ms in long native blood tubes and decreased by 1.2 ms in short post-contrast myocardium tubes. Agreement of estimated T1 times with "reference" T1 was similar across Siemens and Philips CMR systems at both field strengths (adjusted R2 ranges for both field strengths, 0.99-1.00). Over 1 year, many 1.5 T and 3 T sequences/magnets were repeatable with mean CoVs < 1 and 2% respectively. Repeatability was narrower for 1.5 T over 3 T. Within T1MES repeatability for native T1 was narrow for several sequences, for example, at 1.5 T, Siemens MOLLI 5s(3s)3s prototype number 448B (mean CoV = 0.27%) and Philips modified Look-Locker inversion recovery (MOLLI) 3s(3s)5s (CoV 0.54%), and at 3 T, Philips MOLLI 3b(3s)5b (CoV 0.33%) and Siemens shortened MOLLI (ShMOLLI) prototype 780C (CoV 0.69%). After adjusting for temperature and field strength, it was found that the T1 mapping sequence and scanner software version (both P < 0.001 at 1.5 T and 3 T), and to a lesser extent the scanner model (P = 0.011, 1.5 T only), had the greatest influence on T1 across multiple centers. CONCLUSION: The T1MES CE/FDA approved phantom is a robust quality assurance device. In a multi-center setting, T1 mapping had performance differences between field strengths, sequences, scanner software versions, and manufacturers. However, several specific combinations of field strength, sequence, and scanner are highly repeatable, and thus, have potential to provide standardized assessment of T1 times for clinical use, although temperature correction is required for native T1 tubes at least.

Incidental Coronary Artery Calcification and Stroke Risk in Patients With Atrial Fibrillation.

OBJECTIVE. Atrial fibrillation (AF) is a major risk factor for stroke. The CHA2DS2-VASc score is used to risk stratify patients, and the score includes known coronary artery disease (CAD) as a variable. The aim of this study was to assess if the presence of incidental coronary artery calcification (CAC), without known CAD, is associated with stroke independent of CHA2DS2-VASc variables. MATERIALS AND METHODS. A retrospective review of health records was performed for patients who had AF, a chest CT scan performed within 1 year, and a subsequent visit for stroke. Patients with CAD and other vascular disease, a mechanical valve, or who were older than 74 years old were excluded. Included patients were one-to-one matched by age and CHA2DS2-VASc risk factors to patients who had had similar follow-up but who did not have a stroke. Nongated CT images were reviewed for CAC. Univariate and Cox regression analyses were performed. RESULTS. A total of 203 patients met the study criteria, and 203 matched patients without stroke were identified. Median age was 61 years old with stroke and 62 years old without stroke (p = 0.99). In both groups, 82 (39.0%) were women and the median CHA2DS2-VASc was 2 (interquartile range, 1-2). Anticoagulation medication was prescribed to 46 (22.7%) patients in the group who had had a stroke and 52 (25.6%) in the group without stroke (p = 0.49). On Cox regression analysis, CAC was associated with stroke (hazard ratio [HR], 1.47; 95% CI, 1.10-1.97; p < 0.01) and mortality (adjusted HR, 1.41; 95% CI, 1.02-1.95; p = 0.04). CONCLUSION. Patients with AF and incidental CAC depicted on chest CT have an increased risk of stroke and mortality beyond established risk factors.

Low Tidal Volumes Are Associated With Slightly Improved Oxygenation in Patients Having Cardiac Surgery: A Cohort Analysis.

BACKGROUND: Mechanical ventilation with low tidal volumes appears to provide benefit in patients having noncardiac surgery; however, whether it is beneficial in patients having cardiac surgery is unclear. METHODS: We retrospectively examined patients having elective cardiac surgery requiring cardiopulmonary bypass through a median sternotomy approach who received mechanical ventilation with a single lumen endotracheal tube from January 2010 to mid-August 2016. Time-weighted average tidal volume (milliliter per kilogram predicted body weight [PBW]) during the duration of surgery excluding cardiopulmonary bypass was analyzed. The association between tidal volumes and postoperative oxygenation (measured by arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen ratio [PaO2/FIO2]), impaired oxygenation (PaO2/FIO2 <300), and clinical outcomes were examined. RESULTS: Of 9359 cardiac surgical patients, larger tidal volumes were associated with slightly worse postoperative oxygenation. Postoperative PaO2/FIO2 decreased an estimated 1.05% per 1 mL/kg PBW increase in tidal volume (97.5% confidence interval [CI], -1.74 to -0.37; PBon = .0005). An increase in intraoperative tidal volumes was also associated with increased odds of impaired oxygenation (odds ratio [OR; 97.5% CI]: 1.08 [1.02-1.14] per 1 mL/kg PBW increase in tidal volume; PBon = .0029), slightly longer intubation time (5% per 1 mL/kg increase in tidal volume (hazard ratio [98.33% CI], 0.95 [0.93-0.98] per 1 mL/kg PBW; PBon < .0001), and increased mortality (OR [98.33% CI], 1.34 [1.06-1.70] per 1 mL/kg PBW increase in tidal volume; PHolm = .0144). An increase in intraoperative tidal volumes was also associated with acute postoperative respiratory failure (OR [98.33% CI], 1.16 [1.03-1.32] per 1 mL/kg PBW increase in tidal volume; PHolm = .0146), but not other pulmonary complications. CONCLUSIONS: Lower time-weighted average intraoperative tidal volumes were associated with a very modest improvement in postoperative oxygenation in patients having cardiac surgery.

Supplemental Intraoperative Oxygen Does Not Promote Acute Kidney Injury or Cardiovascular Complications After Noncardiac Surgery: Subanalysis of an Alternating Intervention Trial.

BACKGROUND: Perioperative hyperoxia has been recommended by the World Health Organization and the Centers for Disease Control and Prevention for the prevention of surgical site infections. Based on animal studies and physiological concerns, the kidneys and heart may be at risk from hyperoxia. We therefore conducted 2 unplanned subanalyses of a previous alternating cohort trial in which patients having colorectal surgery were assigned to either 30% or 80% inspired intraoperative oxygen. Specifically, we tested 2 coprimary hypotheses: (1) hyperoxia increases the incidence of acute kidney injury (AKI) within 7 postoperative days (PODs); and (2) hyperoxia worsens a composite of myocardial injury, in-hospital cardiac arrest, and 30-day mortality. METHODS: The underlying controlled trial included 5749 colorectal surgeries in 4481 patients, with the exposure alternating between 30% and 80% fraction of inspired oxygen (FIO2) during general anesthesia at 2-week intervals over a period of 39 months. AKI was defined as a 1.5-fold increase in creatinine from the preoperative level to the highest value measured during the initial 7 PODs. Myocardial injury was defined by fourth-generation troponin-T level >0.03 ng/mL. We assessed the effect of 80% vs 30% oxygen on the outcomes using generalized estimating equation (GEE) logistic models that adjusted for the possible within-patient correlation across multiple potential operations for a patient on different visits. RESULTS: For the AKI outcome, 2522 surgeries were allocated to 80% oxygen and 2552 to 30% oxygen. Hyperoxia had no effect on the primary outcome of postoperative AKI, with an incidence of 7.7% in the 80% oxygen group and 7.7% in the 30% oxygen group (relative risk = 0.99; 95% confidence interval [CI], 0.82-1.2; P = .95). One thousand six hundred forty-seven surgeries (all with scheduled troponin monitoring) were analyzed for the composite cardiovascular outcome. Hyperoxia had no effect on the collapsed composite of myocardial injury, cardiac arrest, and 30-day mortality, nor on any of its components (estimated relative risk = 0.71; 95% CI, 0.44-1.16; P = .17). CONCLUSIONS: We found no evidence that intraoperative hyperoxia causes AKI or cardiovascular complications in adults undergoing colorectal surgery. Consequently, we suggest that clinicians select intraoperative inspired oxygen fraction based on other considerations.

Acute Postoperative Pain Is Associated With Myocardial Injury After Noncardiac Surgery.

BACKGROUND: Uncontrolled pain after noncardiac surgery activates the sympathetic nervous system, which causes tachycardia, hypertension, and increased cardiac contractility-all of which may increase myocardial oxygen demand. We therefore determined whether time-weighted average pain scores over the initial 72 postoperative hours are associated with myocardial injury after noncardiac surgery (MINS). METHODS: We conducted a retrospective cohort analysis of adults with routine postoperative troponin monitoring after noncardiac surgery under general, regional, or combined anesthesia at tertiary level centers in Cleveland from January 2012 to December 2015. Time-weighted average pain scores were calculated from all the available pain scores, typically at 4-hour intervals, until a troponin elevation was detected. MINS was defined as peak troponin T concentrations exceeding 0.03 ng/mL within 72 hours after surgery. We used a generalized linear mixed model to assess the association between pain and MINS with 3 hospitals as clusters, adjusting for potential confounders. RESULTS: Among 2892 eligible patients, 4.5% had myocardial injury within 72 hours after surgery. Higher time-weighted average pain scores were associated with increased hazard of myocardial injury. The estimated hazard ratio for a 1-unit increase in pain score was 1.12 (95% confidence interval [CI], 1.02-1.22; P = .013), adjusting for confounding variables. CONCLUSIONS: Among patients undergoing noncardiac surgery, time-weighted average pain scores within 72 hours after surgery were significantly associated with myocardial injury.

CEST MRI reveals a correlation between visceral fat mass and reduced myocardial creatine in obese individuals despite preserved ventricular structure and function.

Systolic cardiac function is typically preserved in obese adults, potentially masking underlying declines in cardiomyocyte metabolism that may contribute to heart failure. We used chemical exchange saturation transfer (CEST) MRI, a sensitive method for measurement of myocardial creatine, to examine whether myocardial creatine levels correlate with cardiac structure, contractile function, or visceral fat mass in obese adults. In this study, obese (body mass index, BMI > 30, n = 20) and healthy (BMI < 25, n = 11) adults were examined with dual-energy x-ray absorptiometry to quantify fat masses. Cine MRI and myocardial tagging were performed at 1.5 T to measure ventricular structure and global function. CEST imaging with offsets in the range of ±10 parts per million (ppm) were performed in one mid-ventricular slice, where creatine CEST contrast was calculated at 1.8 ppm following field homogeneity correction. Ventricular structure, global function (ejection fraction 69.4 ± 4.3% healthy versus 69.6 ± 9.3% obese, NS), and circumferential strain (-17.0 ± 2.3% healthy versus -16.5 ± 1.5% obese, NS) and strain rate were preserved in obese adults. However, creatine CEST contrast was significantly reduced in obese adults (6.8 ± 1.3% healthy versus 4.1 ± 2.7% obese, p = 0.001). Creatine CEST contrast was inversely correlated with total body fat% (ρ = -0.45, p = 0.011), visceral fat mass (ρ = -0.58, p = 0.001), and septal wall thickness (ρ = -0.44, p = 0.013), but uncorrelated to ventricular function or contractile function. In conclusion, creatine CEST-MRI reveals a strong correlation between heightened body and visceral fat masses and reduced myocardial metabolic function that is independent of ventricular structure and global function in obese adults.

Association of Neuraxial Anesthesia With Postoperative Venous Thromboembolism After Noncardiac Surgery: A Propensity-Matched Analysis of ACS-NSQIP Database.

BACKGROUND: Neuraxial anesthesia improves components of the Virchow's triad (hypercoagulability, venous stasis, and endothelial injury) which are key pathogenic contributors to venous thrombosis in surgical patients. However, whether neuraxial anesthesia reduces the incidence of venous thromboembolism (VTE) remain unclear. We therefore tested the primary hypothesis that neuraxial anesthesia reduces the incidence of 30-day VTE in adults recovering from orthopedic surgery. Secondarily, we tested the hypotheses that neuraxial anesthesia reduces 30-day readmission, 30-day mortality, and the duration of postoperative hospitalization. METHODS: Inpatient orthopedic surgeries from American College of Surgeons National Surgical Quality Improvement Program database (2011-2015) in adults lasting more than 1 hour with either neuraxial or general anesthesia were included. Groups were matched 1:1 by propensity score matching for appropriate confounders. Logistic regression model was used to assess the effect of neuraxial anesthesia on 30-day VTE, 30-day mortality, and readmission, while Cox proportional hazard regression model was used to assess its effect on length of stay. RESULTS: Neuraxial anesthesia decreased odds of 30-day VTE (odds ratio 0.85, 95% confidence interval, 0.78-0.95; P = .002) corresponding to number-needed-to-treat of 500. Although there was no difference in 30-day mortality, neuraxial anesthesia reduced 30-day readmission (odds ratio 0.90, 98.3% confidence interval, 0.85-0.95; P < .001) corresponding to number-needed-to-treat of 250 and had a shortened hospitalization (2.87 vs 3.11; P < .001). CONCLUSIONS: Neuraxial anesthesia appears to provide only weak VTE prophylaxis, but can be offered as an adjuvant to current thromboprophylaxis in high-risk patients.

Intra-operative high inspired oxygen fraction does not increase the risk of postoperative respiratory complications: Alternating intervention clinical trial.

BACKGROUND: The WHO recommends routine intra-operative and early postoperative use of high inspired oxygen concentrations (hyperoxia). However, a high intra-operative inspired oxygen fraction (FiO2) might result in an increased risk of postoperative respiratory complications. AIM: To test the hypothesis that intra-operative FiO2 of 80% compared with 30% inspired oxygen decreases the postoperative ratio of arterial saturation to fraction of inspired oxygen (SpO2/FiO2). Secondarily, to evaluate whether an intra-operative inspired FiO2 of 80% increases the incidence of pulmonary complications. DESIGN: Posthoc subanalysis of a large alternating cohort trial. SETTING: Cleveland Clinic, Cleveland, United States, from 2013 to 2016. PATIENTS: Adults having colorectal surgery. Cases lasting less than 2 h, re-operations on the same hospitalisation, and cases with missing intra-operative or postoperative data were excluded. INTERVENTION: Maintaining intra-operative FiO2 at 30 or 80% and alternating this management every 2 weeks for a study period of 39 months. MAIN OUTCOME: Minimal SpO2/FiO2 ratio value in the postanaesthesia care unit. Secondary outcome was a composite of postoperative pulmonary complications throughout hospitalisation. RESULTS: A total of 5056 patients were included. Groups were well balanced on all demographic, baseline and procedural variables. Median time-weighted averages of intra-operative FiO2 in the 30 and 80% groups were 43% (IQR 38 to 54%, N=2486) and 81% (IQR 78 to 82%, N=2570), respectively. No difference was found in the lowest SpO2/FiO2 ratio (estimated median difference 0 [95% confidence interval: 0, 0], P = 0.91). The incidence of postoperative pulmonary complications was 16.3 and 17.6% in the 30 and 80% FiO2 groups, respectively (relative risk 1.07 [95% confidence interval: 0.95, 1.21], P = 0.25). CONCLUSION: Intra-operative hyperoxia did not change the postoperative SpO2/FiO2 ratio or the risk for pulmonary complications. Clinicians should not refrain from using hyperoxia for fear of provoking respiratory complications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01777568.

Postoperative Hypotension and Surgical Site Infections After Colorectal Surgery: A Retrospective Cohort Study.

BACKGROUND: Hypotension compromises local tissue perfusion, thereby reducing tissue oxygenation. Hypotension might thus be expected to promote infection. Hypotension on surgical wards, while usually less severe than intraoperative hypotension, is common and often prolonged. In this retrospective cohort study, we tested the hypotheses that there is an association between surgical site infections and low postoperative time-weighted average mean arterial pressure and/or postoperative minimum mean arterial pressure. METHODS: We considered patients who had colorectal surgery lasting ≥1 hour at the Cleveland Clinic between 2009 and 2013. We defined blood pressure exposures as time-weighted average (primary) and minimum mean arterial pressure (secondary) within 72 hours after surgery. We assessed associations between continuous blood pressure exposures with a composite of deep and superficial surgical site infection using separate severity-weighted average relative effect generalized estimating equations models, each using an unstructured correlation structure and adjusting for potentially confounding variables. RESULTS: A total of 5896 patients were eligible for analysis. Time-weighted mean arterial pressure and surgical site infection were not significantly associated, with an estimated odds ratio (95% CI) of 1.03 (0.99-1.08) for a 5-mm Hg decrease (P = .16). However, there was a significant inverse association between minimum postoperative mean arterial pressure and infection, with an estimated odds ratio of 1.08 (1.03-1.12) per 5-mm Hg decrease (P = .001). CONCLUSIONS: Postoperative time-weighted mean arterial pressure was not associated with surgical site infection, but lowest postoperative mean arterial pressure was. Whether the relationship is causal remains to be determined.