Cytomegalovirus infection among people living with HIV in Sweden: Case profiles, treatment strategies and patient outcomes at Karolinska University Hospital 2010-2020.

OBJECTIVES: In countries with access to early antiretroviral treatment (ART), opportunistic infections caused by cytomegalovirus (CMV) in people living with HIV (PLWH) are becoming increasingly rare. As potential complications are severe, it is critical to remain aware of this important diagnosis. However, clinical characteristics and prognosis of CMV infection in PLWH in the era of modern ART have not been well described. METHODS: Here, we compiled the clinical presentation, management and outcome of CMV infection in PLWH treated at the infectious diseases clinic of Karolinska University Hospital during 2010-2020. RESULTS: We identified 51 cases of active CMV infection, based on detection of CMV-DNA, mainly diagnosed in patients with CD4 T-cell count <200 cells/µL (86%). Median time from HIV diagnosis to detection of CMV infection was 16 days. In 20 cases (39%), CMV infection was symptomatic with retinitis identified as a manifestation in 70% of cases. Symptomatic CMV infection was treated for 73 (20-313) days upon diagnosis, mostly using valganciclovir. One-year mortality was 22% and was associated with longer time to ART initiation from HIV diagnosis and with comorbidities, but not with CMV-DNA levels or CD4 count. Immune reconstitution was not significantly compromised in patients with symptomatic CMV, although CD4/8 ratio tended to be lower in patients with systemic CMV infection. CONCLUSIONS: Retinitis remains the most common manifestation of symptomatic CMV infection in PLWH. Recognizing CMV infection is important, especially in the management of 'late presenters'. Adequate duration of antiviral therapy and appropriate follow-up must be ensured to avoid complications.

Preoperative Heart Failure Treatment Prevents Postoperative Cardiac Complications in Patients With Lower Risk: A Retrospective Cohort Study.

OBJECTIVE: The objective of this study was to identify undertreated subgroups of patients with heart failure who would benefit from better perioperative optimization. SUMMARY OF BACKGROUND DATA: Patients with heart failure have increased risks of postoperative cardiac complications after noncardiac surgery. METHODS: In this analysis of hospital registry data of 130,677 patients undergoing noncardiac surgery, the exposure was preoperative history of heart failure. The outcome, cardiac complications, was defined as a composite of myocardial infarction, cardiac arrest, acute heart failure, and mortality within 30 postoperative days. RESULTS: History of heart failure (n = 10,256; 7.9%) was associated with increased risk of cardiac complications [8.1% vs 1.1%; adjusted odds ratio, 2.28 (95% CI, 2.02-2.56); P < 0.001). Patients with heart failure and who carried a lower risk profile had increased risks of postoperative cardiac complications secondary to heart failure [adjusted absolute risk difference, 1.7% (95% CI, 1.4%-2.0%, lower risk); P < 0.001 vs 0.5% (95% CI, -0.6% to 1.6%, higher risk); P = 0.38]. Patients with heart failure and lower risk received a lower level of health care utilization preoperatively, and less frequently received anti-heart failure medications (59% vs 72% and 61% vs 82%; both P < 0.001). These preventive therapies significantly decreased the risk of cardiac complications in patients with heart failure. CONCLUSIONS: In patients with heart failure who have a lower preoperative risk profile, clinicians often make insufficient attempts to optimize their clinical condition preoperatively. Preoperative preventive treatment reduces the risk of postoperative cardiac complications in these lower-risk patients with heart failure.

Asymmetric Assembly and Self-Adjuvanted Antigen Delivery Platform for Improved Antigen Uptake and Antitumor Effect.

The development of effective tumor vaccines is an important direction in the field of cancer prevention/immunotherapy. Efficient antigen delivery is essential for inducing effective antitumor responses for tumor vaccines. Lumazine synthase (BLS) from Brucella spp. is a decameric protein with delivery and adjuvant properties, but its application in tumor vaccines is limited. Here, we developed an antigen delivery platform by combining a BLS asymmetric assembly and the Plug-and-Display system of SpyCatcher/SpyTag. An asymmetric assembly system consisting of BLSke and BLSdr was developed to equally assemble two molecules. Then, the MHC-I-restricted ovalbumin peptide (OVA(257-264) SIINFEKL) was conjugated with BLSke, and a cell-penetrating peptide (CPP) KALA was conjugated with BLSdr using the SpyCatcher/SpyTag system. KALA modification enhanced internalization of OVA peptides by DCs as well as promoted the maturation of DCs and the cross-presentation of SIINFEKL. Moreover, the immunotherapy of a KALA-modified vaccine suppressed tumor growth and enhanced CD8+ T cell responses in E.G7-OVA tumor-bearing mice. In the prophylactic model, KALA-modified vaccination showed the most significant protective effect and significantly prolonged the survival period of tumor challenged mice. In conclusion, the asymmetric assembly platform equally assembles two proteins or peptides, avoiding their spatial or functional interference. This asymmetric assembly and Plug-and-Display technology provide a universal platform for rapid development of personalized tumor vaccines.

Intraoperative Hypotension and Acute Kidney Injury, Stroke, and Mortality during and outside Cardiopulmonary Bypass: A Retrospective Observational Cohort Study.

BACKGROUND: In cardiac surgery, the association between hypotension during specific intraoperative phases or vasopressor-inotropes with adverse outcomes remains unclear. This study's hypothesis was that intraoperative hypotension duration throughout the surgery or when separated into hypotension during and outside cardiopulmonary bypass may be associated with postoperative major adverse events. METHODS: This retrospective observational cohort study included data for adults who had cardiac surgery between 2008 and 2016 in a tertiary hospital. Intraoperative hypotension was defined as mean arterial pressure of less than 65 mmHg. The total duration of hypotension was divided into three categories based on the fraction of overall hypotension duration that occurred during cardiopulmonary bypass (more than 80%, 80 to 60%, and less than 60%). The primary outcome was a composite of stroke, acute kidney injury, or mortality during the index hospitalization. The association with the composite outcome was evaluated for duration of hypotension during the entire surgery, outside cardiopulmonary bypass, and during cardiopulmonary bypass and the fraction of hypotension during cardiopulmonary bypass adjusting for vasopressor-inotrope dose, milrinone dose, patient, and surgical factors. RESULTS: The composite outcome occurred in 256 (5.1%) of 4,984 included patient records; 66 (1.3%) patients suffered stroke, 125 (2.5%) had acute kidney injury, and 109 (2.2%) died. The primary outcome was associated with total duration of hypotension (adjusted odds ratio, 1.05; 95% CI, 1.02 to 1.08; P = 0.032), hypotension outside cardiopulmonary bypass (adjusted odds ratio, 1.06; 95% CI, 1.03 to 1.10; P = 0.001) per 10-min exposure to mean arterial pressure of less than 65 mmHg, and fraction of hypotension duration during cardiopulmonary bypass of less than 60% (reference greater than 80%; adjusted odds ratio, 1.67; 95% CI, 1.10 to 2.60; P = 0.019) but not with each 10-min period hypotension during cardiopulmonary bypass (adjusted odds ratio, 1.04; 95% CI, 0.99 to 1.09; P = 0.118), fraction of hypotension during cardiopulmonary bypass of 60 to 80% (adjusted odds ratio, 1.45; 95% CI, 0.97 to 2.23; P = 0.082), or total vasopressor-inotrope dose (adjusted odds ratio, 1.00; 95% CI, 1.00 to 1.00; P = 0.247). CONCLUSIONS: This study confirms previous single-center findings that intraoperative hypotension throughout cardiac surgery is associated with an increased risk of acute kidney injury, mortality, or stroke.

Multimodal prediction of pain and functional outcomes 6 months following total knee replacement: a prospective cohort study.

BACKGROUND: Knee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence and impact around the globe. In the U.S., the rising prevalence of knee OA has been paralleled by an increase in annual rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, post-operative trajectories of pain and functional status vary substantially; a significant minority of patients report ongoing pain and impaired function following TKA. A number of studies have identified sets of biopsychosocial risk factors for poor post-TKA outcomes (e.g., comorbidities, negative affect, sensory sensitivity), but few prospective studies have systematically evaluated the unique and combined influence of a broad array of factors. METHODS: This multi-site longitudinal cohort study investigated predictors of 6-month pain and functional outcomes following TKA. A wide spectrum of relevant biopsychosocial predictors was assessed preoperatively by medical history, patient-reported questionnaire, functional testing, and quantitative sensory testing in 248 patients undergoing TKA, and subsequently examined for their predictive capacity. RESULTS: The majority of patients had mild or no pain at 6 months, and minimal pain-related impairment, but approximately 30% reported pain intensity ratings of 3/10 or higher. Reporting greater pain severity and dysfunction at 6 months post-TKA was predicted by higher preoperative levels of negative affect, prior pain history, opioid use, and disrupted sleep. Interestingly, lower levels of resilience-related "positive" psychosocial characteristics (i.e., lower agreeableness, lower social support) were among the strongest, most consistent predictors of poor outcomes in multivariable linear regression models. Maladaptive profiles of pain modulation (e.g., elevated temporal summation of pain), while not robust unique predictors, interacted with psychosocial risk factors such that the TKA patients with the most pain and dysfunction exhibited lower resilience and enhanced temporal summation of pain. CONCLUSIONS: This study underscores the importance of considering psychosocial (particularly positively-oriented resilience variables) and sensory profiles, as well as their interaction, in understanding post-surgical pain trajectories.

Impact of Left Atrial Appendage Exclusion on Short-Term Outcomes in Isolated Coronary Artery Bypass Graft Surgery.

BACKGROUND: The objective of this study was to evaluate the impact of left atrial appendage (LAA) exclusion on short-term outcomes in patients with atrial fibrillation undergoing isolated coronary artery bypass graft surgery. METHODS: We queried the 2010 to 2014 National Readmissions Database for patients who underwent coronary artery bypass graft repair with and without LAA ligation by using International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes (International Classification of Diseases, Ninth Revision, Clinical Modification: 36.1xx). Only patients with a history of atrial fibrillation were included in our analysis. The primary outcome of our study was 30-day readmissions following discharge. Secondary outcomes were in-hospital mortality and stroke. To assess the postoperative outcomes, we used multivariate logistic regression models to adjust for clinical and demographic covariates. RESULTS: In total, we analyzed 253 287 patients undergoing coronary artery bypass graft surgery, 7.0% of whom received LAA closure. LAA exclusion was associated with a greater risk of postoperative respiratory failure (8.2% versus 6.2%, P<0.0001) and acute kidney injury (21.8% versus 18.5%, P<0.0001), but it did not significantly change the rate of blood transfusions or occurrence of cardiac tamponade. LAA exclusion was associated with a nonsignificant reduction in stroke (7.9% versus 8.6%, P=0.12), no difference in in-hospital mortality (2.2% versus 2.2% P=0.99), and a greater risk of 30-day readmission (16.0% versus 9.6%, P<0.0001). After covariate adjustment, LAA ligation remained a significant predictor of 30-day readmission (odds ratio, 1.640 [95% CI, 1.603-1.677], P<0.0001). CONCLUSIONS: LAA exclusion during isolated coronary artery bypass graft surgery in patients with atrial fibrillation is associated with a higher rate of 30-day readmission. Postoperative measures to mitigate the loss of the hormonal and hemodynamic effects of the LAA may increase the therapeutic benefit of this procedure.

Effects of the Level and Duration of Mobilization Therapy in the Surgical ICU on the Loss of the Ability to Live Independently: An International Prospective Cohort Study.

OBJECTIVES: It is unclear whether early mobilization in the surgical ICU helps improve patients' functional recovery to a level that enables independent living. We assessed dose of mobilization (level + duration). We tested the research hypotheses that dose of mobilization predicts adverse discharge and that both duration of mobilization and maximum mobilization level predict adverse discharge. DESIGN: International, prospective cohort study. SETTING: Study conducted in five surgical ICUs at four different institutions. PATIENTS: One hundred fifty patients who were functionally independent before admission (Barthel Index ≥ 70) and who were expected to stay in the ICU for greater than or equal to 72 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mobilization was quantified daily, and treatments from all healthcare providers were included. We developed and used the Mobilization Quantification Score that quantifies both level and duration of mobilization. We assessed the association between the dose of mobilization (level + duration; exposure) and adverse discharge disposition (loss of the ability to live independently; primary outcome). There was wide variability in the dose of mobilization across centers and patients, which could not be explained by patients' comorbidity or disease severity. Dose of mobilization was associated with reduced risk of adverse discharge (adjusted odds ratio, 0.21; 95%CI, 0.09-0.50; p < 0.001). Both level and duration explained variance of adverse discharge (adjusted odds ratio, 0.28; 95% CI, 0.12-0.65; p = 0.003; adjusted odds ratio, 0.14; 95% CI, 0.06-0.36; p < 0.001, respectively). Duration compared with the level of mobilization tended to explain more variance in adverse discharge (area under the curve duration 0.73; 95% CI, 0.64-0.82; area under the curve mobilization level 0.68; 95% CI, 0.58-0.77; p = 0.10). CONCLUSIONS: We observed wide variability in dose of mobilization treatment applied, which could not be explained by patients' comorbidity or disease severity. High dose of mobilization is an independent predictor of patients' ability to live independently after discharge. Duration of mobilization sessions should be taken into account in future quality improvement and research projects.

Optimal Sedation in Patients Who Receive Neuromuscular Blocking Agent Infusions for Treatment of Acute Respiratory Distress Syndrome-A Retrospective Cohort Study From a New England Health Care Network.

OBJECTIVES: Two previously published trials (ARDS et Curarisation Systematique [ACURASYS] and Reevaluation of Systemic Early Neuromuscular Blockade [ROSE]) presented equivocal evidence on the effect of neuromuscular blocking agent infusions in patients with acute respiratory distress syndrome (acute respiratory distress syndrome). The sedation regimen differed between these trials and also within the ROSE trial between treatment and control groups. We hypothesized that the proportion of deeper sedation is a mediator of the effect of neuromuscular blocking agent infusions on mortality. DESIGN: Retrospective cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: Intubated and mechanically ventilated ICU patients with acute respiratory distress syndrome (Berlin definition) admitted between January 2008 until June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The proportion of deeper sedation was defined as days with nonlight sedation as a fraction of mechanical ventilation days in the ICU after acute respiratory distress syndrome diagnosis. Using clinical data obtained from a hospital network registry, 3,419 patients with acute respiratory distress syndrome were included, of whom 577 (16.9%) were treated with neuromuscular blocking agent infusions, for a mean (sd) duration of 1.8 (±1.9) days. The duration of deeper sedation was prolonged in patients receiving neuromuscular blocking agent infusions (4.6 ± 2.2 d) compared with patients without neuromuscular blocking agent infusions (2.4 ± 2.2 d; p < 0.001). The proportion of deeper sedation completely mediated the negative effect of neuromuscular blocking agent infusions on in-hospital mortality (p < 0.001). Exploratory analysis in patients who received deeper sedation revealed a beneficial effect of neuromuscular blocking agent infusions on mortality (49% vs 51%; adjusted odds ratio, 0.80; 95% CI, 0.63-0.99, adjusted absolute risk difference, -0.05; p = 0.048). CONCLUSIONS: In acute respiratory distress syndrome patients who receive neuromuscular blocking agent infusions, a prolonged, high proportion of deeper sedation is associated with increased mortality. Our data support the view that clinicians should minimize the duration of deeper sedation after recovery from neuromuscular blocking agent infusion.

Supraglottic airway device versus tracheal intubation and the risk of emergent postoperative intubation after general anaesthesia in adults: a retrospective cohort study.

BACKGROUND: We examined the association between emergent postoperative tracheal intubation and the use of supraglottic airway devices (SGAs) vs tracheal tubes. METHODS: We included data from adult noncardiac surgical cases under general anaesthesia between 2008 and 2018. We only included cases (n=59 991) in which both airways were deemed to be feasible options. Multivariable logistic regression, instrumental variable analysis, propensity matching, and mediation analysis were used. RESULTS: Use of a tracheal tube was associated with a higher risk of emergent postoperative intubation (adjusted absolute risk difference [ARD]=0.80%; 95% confidence interval (CI), 0.64-0.97; P<0.001), and a higher risk of post-extubation hypoxaemia (ARD=3.9%; 95% CI, 3.4-4.4; P<0.001). The effect was modified by the use of non-depolarising neuromuscular blocking agents (NMBAs); mediation analyses revealed that 28.9% (95% CI, 14.4-43.4%; P<0.001) of the main effect was attributable to NMBA. Airway management modified the association of NMBA and risk of emergent postoperative intubation (Pinteraction=0.02). Patients managed with an SGA had higher odds of NMBA-associated reintubation compared to patients managed with a tracheal tube (adjusted odds ratio [aOR]=3.65, 95% CI, 1.99-6.67 vs aOR=1.68, 95% CI, 1.29-2.18 [P<0.001], respectively). CONCLUSIONS: In patients undergoing procedures under general anaesthesia that could be managed with either SGA or tracheal tube, use of an SGA was associated with lower risk of emergent postoperative intubation. The effect can partly be explained by use of NMBAs. Use of NMBAs in patients with an SGA appears to increase the risk of emergent postoperative intubation.

Development and external validation of a prognostic model for ischaemic stroke after surgery.

BACKGROUND: There is an under-recognised patient cohort at elevated risk of postoperative ischaemic stroke. We aimed to develop and validate a prognostic model for the identification of such patients at high risk of ischaemic stroke within 1 yr after noncardiac surgery. METHODS: This was a hospital registry study of adult patients undergoing noncardiac surgery between 2005 and 2017 at two independent healthcare networks in Massachusetts, USA without a preoperative indication for therapeutic anticoagulation. Logistic regression was used to fit a model from a priori defined candidate predictors for the outcome 1 yr postoperative ischaemic stroke. To enhance clinical applicability, the model was simplified to a scoring system and externally validated. RESULTS: In the development (n=107 756) and validation (n=141 724) cohorts, 1.4% and 0.5% of patients had an ischaemic stroke up to 1 yr postoperatively. The final model included 13 variables (patient characteristics, comorbidities, procedural factors), considering sub-models conditional on a previous history of ischaemic stroke. Areas under the curve were 0.89 (95% confidence interval 0.89-0.90) and 0.88 (95% confidence interval 0.86-0.89) in the development and validation cohorts. Decision curve analysis indicated positive net benefits superior to other prediction instruments. CONCLUSIONS: Stroke after surgery (STRAS) screening can reliably identify patients with a high risk for ischaemic stroke during the first year after surgery. A STRAS-guided risk stratification may inform the recruitment to future randomised trials testing the efficacy of treatments for the prevention of postoperative ischaemic stroke.

Outcomes after endoscopic retrograde cholangiopancreatography with general anaesthesia versus sedation.

BACKGROUND: We tested the primary hypothesis that use of general anaesthesia vs sedation increases vulnerability to adverse discharge (in-hospital mortality or new discharge to a nursing facility) after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: In this retrospective cohort study, adult patients undergoing ERCP with general anaesthesia or sedation at a tertiary care hospital were included. We calculated adjusted absolute risk differences between patients receiving general anaesthesia vs sedation using provider preference-based instrumental variable analysis. We also used mediation analysis to determine whether intraoperative hypotension during general anaesthesia mediated its effect on adverse discharge. RESULTS: Among 17 538 patients undergoing ERCP from 2007 through 2018, 16 238 received sedation and 1300 received GA. Rates of adverse discharge were 5.8% (n=938) after sedation and 16.2% (n=210) after general anaesthesia. Providers' adjusted mean predicted probabilities of using general anaesthesia for ERCP ranged from 0.2% to 63.2% of individual caseloads. Utilising provider-related variability in the use of general anaesthesia for instrumental variable analysis resulted in an 8.6% risk increase (95% confidence interval, 4.5-12.6%; P<0.001) in adverse discharge among patients receiving general anaesthesia vs sedation. Intraoperative hypotensive events occurred more often during general anaesthesia and mediated 23.8% (95% confidence interval, 3.9-43.7%: P=0.019) of the primary association. CONCLUSIONS: These results suggest that use of sedation during ERCP facilitates reduced adverse discharge for patients for whom general anaesthesia is not clearly indicated. Intraoperative hypotension during general anaesthesia for ERCP partly mediates the increased vulnerability to adverse discharge.

A Tool to Predict Readmission to the Intensive Care Unit in Surgical Critical Care Patients-The RISC Score.

BACKGROUND: Readmission to the Intensive Care Unit (ICU) is associated with a high risk of in-hospital mortality and higher health care costs. Previously published tools to predict ICU readmission in surgical ICU patients have important limitations that restrict their clinical implementation. We sought to develop a clinically intuitive score that can be implemented to predict readmission to the ICU after surgery or trauma. We designed the score to emphasize modifiable predictors. METHODS: In this retrospective cohort study, we included surgical patients requiring critical care between June 2015 and January 2019 at Beth Israel Deaconess Medical Center, Harvard Medical School, MA, USA. We used logistic regression to fit a prognostic model for ICU readmission from a priori defined, widely available candidate predictors. The score performance was compared with existing prediction instruments. RESULTS: Of 7,126 patients, 168 (2.4%) were readmitted to the ICU during the same hospitalization. The final score included 8 variables addressing demographical factors, surgical factors, physiological parameters, ICU treatment and the acuity of illness. The maximum score achievable was 13 points. Potentially modifiable predictors included the inability to ambulate at ICU discharge, substantial positive fluid balance (>5 liters), severe anemia (hemoglobin <7 mg/dl), hyperglycemia (>180 mg/dl), and long ICU length of stay (>5 days). The score yielded an area under the receiver operating characteristic curve of 0.78 (95% CI 0.74-0.82) and significantly outperformed previously published scores. The performance of the underlying model was confirmed by leave-one-out cross-validation. CONCLUSION: The RISC-score is a clinically intuitive prediction instrument that helps identify surgical ICU patients at high risk for ICU readmission. The simplicity of the score facilitates its clinical implementation across surgical divisions.

REsidual Neuromuscular Block Prediction Score Versus Train-of-Four Ratio and Respiratory Outcomes: A Retrospective Cohort Study.

BACKGROUND: Residual neuromuscular blockade is associated with an increased incidence of postoperative respiratory complications. The REsidual neuromuscular block Prediction Score (REPS) identifies patients at high risk for residual neuromuscular blockade after surgery. METHODS: A total of 101,510 adults undergoing noncardiac surgery under general anesthesia from October 2005 to December 2018 at a tertiary care center in Massachusetts were analyzed for the primary outcome of postoperative respiratory complications (invasive mechanical ventilation requirement within 7 postoperative days or immediate postextubation desaturation [oxygen saturation {Spo2} <90%] within 10 minutes). The primary objective was to assess the association between the REPS and respiratory complications. The secondary objective was to compare REPS and train-of-four (TOF) ratio <0.90 on the strength of their association with respiratory complications. RESULTS: A high REPS (≥4) was associated with an increase in odds of respiratory complications (adjusted odds ratio [OR], 1.13 [95% confidence interval {CI}, 1.06-1.21]; P < .001). In 6224 cases with available TOF ratio measurements, a low TOF ratio (<0.9) was associated with respiratory complications (adjusted OR, 1.43 [95% CI, 1.11-1.85]; P = .006), whereas a high REPS was not (adjusted OR, 0.96 [95% CI, 0.74-1.23]; P = .73) (P = .018 for comparison between ORs). CONCLUSIONS: The REPS may be implemented as a screening tool to encourage clinicians to use quantitative neuromuscular monitoring in patients at risk of residual neuromuscular blockade. A positive REPS should be followed by a quantitative assessment of the TOF ratio.

Discharge Prediction for Patients Undergoing Inpatient Surgery: Development and validation of the DEPENDENSE score.

BACKGROUND: A substantial proportion of patients undergoing inpatient surgery each year is at risk for postoperative institutionalization and loss of independence. Reliable individualized preoperative prediction of adverse discharge can facilitate advanced care planning and shared decision making. METHODS: Using hospital registry data from previously home-dwelling adults undergoing inpatient surgery, we retrospectively developed and externally validated a score predicting adverse discharge. Multivariable logistic regression analysis and bootstrapping were used to develop the score. Adverse discharge was defined as in-hospital mortality or discharge to a skilled nursing facility. The model was subsequently externally validated in a cohort of patients from an independent hospital. RESULTS: In total, 106 164 patients in the development cohort and 92 962 patients in the validation cohort were included, of which 16 624 (15.7%) and 7717 (8.3%) patients experienced adverse discharge, respectively. The model was predictive of adverse discharge with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI 0.87-0.88) in the development cohort and an AUC of 0.86 (95% CI 0.86-0.87) in the validation cohort. CONCLUSION: Using preoperatively available data, we developed and validated a prediction instrument for adverse discharge following inpatient surgery. Reliable prediction of this patient centered outcome can facilitate individualized operative planning to maximize value of care.

Association Between Intraoperative Hypotension and Postoperative Adverse Outcomes in Patients Undergoing Vascular Surgery - A Retrospective Observational Study.

OBJECTIVE: Intraoperative hypotension (IOH) is associated with adverse outcomes. It could be challenging to define IOH in vascular surgical patients with increased baseline blood pressure (BP). The authors studied the relationship between (1) absolute and relative BP thresholds of IOH, (2) preoperative pulse pressure (PP) and isolated systolic hypertension, and (3) endovascular versus open surgical approach with adverse outcomes in vascular surgical patients. DESIGN: Retrospective observational study. SETTING: Teaching hospital. PATIENTS: A total of 566 vascular surgical patients from 2011 to 2018. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: BP thresholds were as follows: IOH - absolute mean arterial pressure (MAP) <65 mmHg, relative MAP >20% decrease from baseline, preoperative PP hypertension - PP >40 mmHg, isolated systolic hypertension - baseline systolic BP ≥140 mmHg with diastolic BP <90 mmHg. Thresholds were characterized by (1) total duration and (2) area under the curve. Primary outcome was a composite of postoperative in-hospital complications (acute kidney injury, stroke, myocardial infarction, congestive heart failure, and mortality). Forty-six (8.1%) patients had in-hospital complications. Only IOH duration-MAP <65 mmHg (odds ratio 1.01; 95% confidence interval 1.00-1.02; p = 0.004) was significantly associated with outcome. No associations were found with MAP >20% decrease from baseline and preoperative BP. Significant interaction was observed with the surgical approach and outcome (p = 0.031), which was stronger after 60 minutes of IOH in endovascular approach. CONCLUSION: Longer periods of IOH (MAP <65 mmHg for >60 minutes) during endovascular surgery were associated with adverse outcomes. Relative fall in BP from baseline, preoperative isolated systolic, and PP hypertension were not associated with postoperative complications.

Association between propofol dose and 1-year mortality in patients with or without a diagnosis of solid cancer.

BACKGROUND: Preclinical data suggest suppression of cancer proliferation by propofol, and retrospective studies suggest improved survival after cancer surgery with propofol-based anaesthesia. METHODS: To determine whether propofol dose administered for anaesthesia is associated with 1-yr mortality in patients with and without a diagnosis of solid cancer, we analysed adult patients undergoing monitored anaesthesia care or general anaesthesia at two academic medical centres in Boston, MA, USA. Logistic regression with interaction term analysis was applied with propofol dose (mg kg-1) as primary and diagnosis of solid cancer as co-primary exposure, and 1-yr mortality as the primary outcome. RESULTS: Of 280 081 patient cases, 10 744 (3.8%) died within 1 yr. Increasing propofol dose was associated with reduced odds of 1-yr mortality (adjusted odds ratio [aOR] 0.93 per 10 mg kg-1; 95% confidence interval [CI]: 0.89-0.98; absolute risk reduction fifth vs first quintile 0.5%; 95% CI: 0.2-0.7). This association was modified by a diagnosis of solid cancer (P<0.001 for interaction). Increasing propofol dose was associated with reduced odds of 1-yr mortality in patients without solid cancer (aOR: 0.78; 95% CI: 0.71-0.85), but not in patients with solid cancer (0.99; 0.94-1.04), a finding that was replicated when examining 5-yr mortality. CONCLUSIONS: Increasing propofol dose is associated with lower 1-yr mortality in patients without, but not in patients with, a diagnosis of solid cancer. We found evidence for competing effects, modifying the association between propofol dose and mortality.

Trends in Postpartum Hemorrhage in the United States From 2010 to 2014.

Postpartum hemorrhage (PPH) is a leading cause of morbidity and mortality in the United States; its prevalence increased during the 1990s-2000s. The purpose of this study was to reevaluate trends in PPH using the National Inpatient Sample. From 2010 to 2014, the prevalence of PPH increased from 2.9% (95% confidence interval [CI], 2.7%-3.1%) to 3.2% (95% CI, 3.1%-3.3%) of deliveries. Adjusting for PPH risk factors did not substantially attenuate this trend. Among patients with PPH, there was a decline in associated coagulopathy, acute respiratory failure, and maternal death, but an increase in sepsis and acute renal failure. Continued focus on PPH management is warranted.

BOSTN Bundle Intervention for Perioperative Screening and Management of Patients With Suspected Obstructive Sleep Apnea: A Hospital Registry Study.

BACKGROUND: We developed and implemented a perioperative guideline for obstructive sleep apnea (OSA), comprising a preoperative screening tool (BOSTN) and clinical management pathways. OSA was suspected with 2 or more of the following: body mass index ≥30 kg/m, observed apnea, loud snoring, daytime tiredness, and neck circumference ≥16.5 inches in women or ≥ 17.5 inches in men. The primary objective of this study was to assess the association between high BOSTN scores and the requirement of invasive mechanical ventilation after surgery. METHODS: In this hospital registry study, 169,662 noncardiac surgical cases performed at Beth Israel Deaconess Medical Center (BIDMC), Boston, MA, between May 2008 and September 2017 were analyzed. We assessed the association between a high BOSTN Score (score ≥2) and the primary outcome of requirement of invasive mechanical ventilation within 7 days after surgery using multivariable logistic regression adjusted for patient-specific factors and case-specific surgical and anesthesiological confounders. Patients with a BOSTN Score ≥2 were assumed to have a high likelihood of suffering from OSA. Key secondary outcome was postoperative desaturation, defined as a peripheral oxygen saturation measurement <90% within 10 minutes of extubation. RESULTS: Invasive mechanical ventilation within 7 days of surgery was necessary in 3170 (2.3%) low-risk cases (BOSTN Score <2) and 664 (2.1%) high-risk cases (BOSTN Score ≥2). A score ≥2 was associated with significantly lower odds of requiring postoperative invasive ventilation (adjusted odds ratio [aOR], 0.89; 95% confidence interval [CI], 0.80-0.98; P = .017), but with an increased risk of postextubation desaturation (aOR, 1.34; 99.3% CI, 1.21-1.48; P < .001). Patients with a score ≥2 were hospitalized for an average of 3.71 days after surgery, compared to 4.27 days with a score <2 (adjusted incidence rate ratio [aIRR], 0.87; 99.3% CI, 0.84-0.91; P < .001). CONCLUSIONS: Patients at high risk of OSA required postoperative mechanical ventilation less frequently, had higher odds of postoperative desaturation, and were hospitalized for shorter periods of time.

Effects of Anticholinesterase Reversal Under General Anesthesia on Postoperative Cardiovascular Complications: A Retrospective Cohort Study.

BACKGROUND: The anticholinesterase neostigmine and the muscarinic inhibitor glycopyrrolate are frequently coadministered for the reversal of neuromuscular blockade. This practice can precipitate severe bradycardia or tachycardia, but whether it affects the incidence of cardiovascular complications remains unclear. We hypothesized that anticholinesterase reversal with neostigmine and glycopyrrolate versus no anticholinesterase reversal increases the risk of postoperative cardiovascular complications among adult patients undergoing noncardiac surgery with general anesthesia. METHODS: We conducted a prespecified retrospective analysis of hospital registry data from a major health care network for patients undergoing surgery with general anesthesia from January 2007 to December 2015. The primary outcome was a composite of cardiac dysrhythmia, acute heart failure, transient ischemic attack, ischemic stroke, and acute myocardial infarction within 30 days after surgery. We performed sensitivity analyses in subgroups and propensity score adjustment and explored the association between exposure and outcome in subgroups of patients with high risk of cardiovascular complications. RESULTS: Of the 98,147 cases receiving neuromuscular blockade, 73,181 (74.6%) received neostigmine and glycopyrrolate, while 24,966 (25.4%) did not. A total of 5612 patients (7.7%) in the anticholinesterase reversal group and 1651 (6.6%) in the control group (P < .001) experienced the primary outcome. After adjustment for clinical covariates, neostigmine and glycopyrrolate exposure was significantly associated in a dose-dependent fashion (P for trend <.001, respectively) with tachycardia (adjusted odds ratio = 2.1 [95% CI, 1.97-2.23]; P < .001) and bradycardia (adjusted odds ratio = 2.84 [95% CI, 2.49-3.24]; P < .001) but not with postoperative cardiovascular complications (adjusted odds ratio = 1.03 [95% CI, 0.97-1.1]; P = .33). We identified a significant effect modification of anticholinesterase reversal by high age, high-risk surgery, and history of atrial fibrillation (P for interaction = .002, .001, and .02, respectively). By using linear combinations of main effect and exposure-risk interaction terms, we detected significant associations between anticholinesterase reversal and cardiovascular complications toward a higher vulnerability in these patient subgroups. CONCLUSIONS: Neuromuscular blockade reversal with neostigmine and glycopyrrolate was associated with an increased incidence of intraoperative tachycardia and bradycardia but not with 30-day postoperative cardiovascular complications. Exploratory analyses suggest that a high postoperative cardiovascular complication risk profile may modify the effects of anticholinesterase reversal toward clinical relevance.

Effects of high neuromuscular blocking agent dose on post-operative respiratory complications in infants and children.

BACKGROUND: This study evaluated the association between neuromuscular blocking agent dose and post-operative respiratory complications in infants and children. METHODS: Data from 6507 general anaesthetics provided to children aged 0-10 years undergoing surgery were analysed to examine the effects of neuromuscular blocking agent dose on post-operative respiratory complications (primary endpoint) and secondary endpoints. Confounder-adjusted analyses addressed age, surgical duration, and comorbidity burden. RESULTS: In confounder-adjusted analyses, high doses of neuromuscular blocking agents were associated with higher risk of post-operative respiratory complications (OR 2.27; 95% CI 1.12-4.59; P = .022). The effect was modified by age (P-for-interaction = .016) towards a more substantial risk in infants ≤1 year (OR 3.84; 95% CI 1.35-10.94; P = .012), by duration of surgery (P-for-interaction = .006) towards a higher difference in odds for surgeries <90 minutes (OR 4.25; 95% CI 1.19-15.18; P = .026), and by ASA physical status (P-for-interaction = .015) with a greater effect among patients with higher operative risk (ASA >1: OR 3.17; 95% CI 1.43-7.04; P = .005). Neostigmine reversal did not modify the association between neuromuscular blocking agents and post-operative respiratory complications (P-for-interaction = .38). Instrumental variable analysis confirmed that high doses of neuromuscular blocking agents were associated with post-operative respiratory complications (probit coefficient 0.25; 95% CI 0.04-0.46; P = .022), demonstrating robust results regarding concerns of unobserved confounding. CONCLUSIONS: High dose of neuromuscular blocking agents is associated with post-operative respiratory complications. We have identified subcohorts of paediatric patients who are particularly vulnerable to the respiratory side-effects of neuromuscular blocking agents: infants, paediatric patients undergoing surgeries of short duration, and those with a high ASA risk score.