Background Colorectal surgery is associated with considerable morbidity and prolonged length of stay (LOS). Recognizing the need for improvement, we implemented an enhanced recovery (ER) protocol for ...all patients undergoing elective colorectal surgery at an academic institution. Study Design A multidisciplinary team implemented an ER protocol based on: preoperative counseling with active patient participation, carbohydrate loading, multimodal analgesia with avoidance of intravenous opioids, intraoperative goal-directed fluid resuscitation, immediate postoperative feeding, and ambulation. Discharge requirements remained identical throughout. A before and after study design was undertaken comparing patients before (August 2012 to February 2013) and after implementation of an ER protocol (August 2013 to February 2014). Risk stratification was performed using the NSQIP risk calculator to calculate the predicted LOS for each patient based on 23 variables. Results One hundred and nine consecutive patients underwent surgery within the ER protocol compared with 98 consecutive historical controls (conventional). The risk-adjusted predicted LOS was similar for each group at 5.1 and 5.2 days. Substantial reductions were seen in LOS, morphine equivalents, intravenous fluids, return of bowel function, and overall complications with the ER group. There was a $7,129/patient reduction in direct cost, corresponding to a cost savings of $777,061 in the ER group. Patient satisfaction as measured by Press Ganey improved considerably during the study period. Conclusions Implementation of an ER protocol led to improved patient satisfaction and substantial reduction in LOS, complication rates, and costs for patients undergoing both open and laparoscopic colorectal surgery. These data demonstrate that small investments in the perioperative environment can lead to large returns.
Background New-onset postoperative atrial fibrillation (POAF) is the most common complication following cardiac surgery. However, the magnitude of POAF on length of stay, resource utilization, and ...readmission rates remains an area of clinical interest. The purpose of this study was to examine the risk-adjusted impact of POAF on measures of mortality, hospital resources, and costs among multiple centers. Methods A total of 49,264 patient records from a multi-institutional Society of Thoracic Surgeons (STS) certified database for cardiac operations (2001 to 2012) were extracted and stratified by the presence of POAF (19%) versus non-POAF (81%). The influence of POAF on outcomes was assessed by hierarchic regression modeling, adjusted for calculated STS predictive risk indices. Results Mean age was 64 ± 11 years, and median STS predicted risk of mortality for patients who developed POAF were incrementally higher (2% vs 1%, p < 0.001) compared with non-POAF patients. The rate of POAF was highest among those undergoing aortic valve replacement + coronary artery bypass grafting, aortic valve, and mitral valve replacement operations. The POAF patients had a higher unadjusted incidence of mortality, morbidity, hospital readmission, longer intensive care unit (ICU) and postoperative length of stay, and higher hospital costs. After risk adjustment, POAF was associated with a twofold increase in the odds of mortality (adjusted odds ratio = 2.04, p < 0.001), greater hospital resource utilization, and increased costs; POAF was associated with 48 additional ICU hours ( p < 0.001), 3 additional hospital days ( p < 0.001), and $3,000 ( p < 0.001) and $9,000 ( p < 0.001) of increased ICU and total hospital-related costs, respectively. Conclusions New onset POAF is associated with increased risk-adjusted mortality, hospital costs, and readmission rates. Protocols to reduce the incidence of POAF have the potential to significantly impact patient outcomes and the delivery of high-quality, cost-effective patient care.
Abstract Objectives The Cardiothoracic Surgical Trials Network recently reported no difference in the primary end point of left ventricular end-systolic volume index at 1 year postsurgery in patients ...randomized to repair (n = 126) or replacement (n = 125) for severe ischemic mitral regurgitation. However, patients undergoing repair experienced significantly more recurrent mitral regurgitation than patients undergoing replacement (32.6% vs 2.3%). We examined whether baseline echocardiographic and clinical characteristics could identify those who will develop moderate/severe recurrent mitral regurgitation or die. Methods Our analysis includes 116 patients who were randomized to and received mitral valve repair. Logistic regression was used to estimate a model-based probability of recurrence or death from baseline factors. Receiver operating characteristic curves were constructed from these estimated probabilities to determine classification cut-points maximizing accuracy of prediction based on sensitivity and specificity. Results Of the 116 patients, 6 received a replacement before leaving the operating room; all other patients had mild or less mitral regurgitation on intraoperative echocardiogram after repair. During the 2-year follow-up period, 76 patients developed moderate/severe mitral regurgitation or died (53 mitral regurgitation recurrences, 13 mitral regurgitation recurrences and death, and 10 deaths). The mechanism for recurrent mitral regurgitation was largely mitral valve leaflet tethering. Our model (including age, body mass index, sex, race, effective regurgitant orifice area, basal aneurysm/dyskinesis, New York Heart Association class, history of coronary artery bypass grafting, percutaneous coronary intervention, or ventricular arrhythmias) yielded an area under the receiver operating characteristic curve of 0.82. Conclusions The model demonstrated good discrimination in identifying patients who will survive 2 years without recurrent mitral regurgitation after mitral valve repair. Although our results require validation, they offer a clinically relevant risk score for selection of surgical candidates for this procedure.
Cardiac surgery is the largest consumer of blood products in medicine; although believed life saving, transfusion carries substantial adverse risks. This study characterizes the relationship between ...transfusion and risk of major infection after cardiac surgery. In all, 5,158 adults were prospectively enrolled to assess infections after cardiac surgery. The most common procedures were isolated coronary artery bypass graft surgery (31%) and isolated valve surgery (30%); 19% were reoperations. Infections were adjudicated by independent infectious disease experts. Multivariable Cox modeling was used to assess the independent effect of blood and platelet transfusions on major infections within 60 ± 5 days of surgery. Red blood cells (RBC) and platelets were transfused in 48% and 31% of patients, respectively. Each RBC unit transfused was associated with a 29% increase in crude risk of major infection ( p < 0.001). Among RBC recipients, the most common infections were pneumonia (3.6%) and bloodstream infections (2%). Risk factors for infection included postoperative RBC units transfused, longer duration of surgery, and transplant or ventricular assist device implantation, in addition to chronic obstructive pulmonary disease, heart failure, and elevated preoperative creatinine. Platelet transfusion decreased the risk of infection ( p = 0.02). Greater attention to management practices that limit RBC use, including cell salvage, small priming volumes, vacuum-assisted venous return with rapid autologous priming, and ultrafiltration, and preoperative and intraoperative measures to elevate hematocrit could potentially reduce occurrence of major postoperative infections.
Lung ischemia-reperfusion (IR) injury after transplantation as well as acute shortage of suitable donor lungs are two critical issues impacting lung transplant patients. This study investigates the ...anti-inflammatory and immunomodulatory role of human mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) to attenuate lung IR injury and improve of ex-vivo lung perfusion (EVLP)-mediated rehabilitation in donation after circulatory death (DCD) lungs.
C57BL/6 wild-type (WT) mice underwent sham surgery or lung IR using an in vivo hilar-ligation model with or without MSCs or EVs. In vitro studies used primary iNKT cells and macrophages (MH-S cells) were exposed to hypoxia/reoxygenation with/without co-cultures with MSCs or EVs. Also, separate groups of WT mice underwent euthanasia and 1 h of warm ischemia and stored at 4 °C for 1 h followed by 1 h of normothermic EVLP using Steen solution or Steen solution containing MSCs or EVs.
Lungs from MSCs or EV-treated mice had significant attenuation of lung dysfunction and injury (decreased edema, neutrophil infiltration and myeloperoxidase levels) compared to IR alone. A significant decrease in proinflammatory cytokines (IL-17, TNF-α, CXCL1 and HMGB1) and upregulation of keratinocyte growth factor, prostaglandin E2 and IL-10 occurred in the BAL fluid from MSC or EV-treated mice after IR compared to IR alone. Furthermore, MSCs or EVs significantly downregulated iNKT cell-produced IL-17 and macrophage-produced HMGB1 and TNF-α after hypoxia/reoxygenation. Finally, EVLP of DCD lungs with Steen solution including MSCs or EVs provided significantly enhanced protection versus Steen solution alone. Co-cultures of MSCs or EVs with lung endothelial cells prevents neutrophil transendothelial migration after exposure to hypoxia/reoxygenation and TNF-α/HMGB1 cytomix.
These results suggest that MSC-derived EVs can attenuate lung inflammation and injury after IR as well as enhance EVLP-mediated reconditioning of donor lungs. The therapeutic benefits of EVs are in part mediated through anti-inflammatory promoting mechanisms via attenuation of immune cell activation as well as prevention of endothelial barrier integrity to prevent lung edema. Therefore, MSC-derived EVs offer a potential therapeutic strategy to treat post-transplant IR injury as well as rehabilitation of DCD lungs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives Vascular smooth muscle cells can undergo profound changes in phenotype, defined by coordinated repression of smooth muscle cell marker genes and production of matrix metalloproteinases in ...response to injury. However, little is known of the role of smooth muscle cells in aortic aneurysms. We hypothesized that smooth muscle cells undergo phenotypic modulation early in the development of aortic aneurysms. Methods Abdominal aortas from C57B6 mice (n = 79) were perfused with elastase or saline (control) and harvested at 1, 3, 7, or 14 days. Aortas were analyzed by means of quantitative polymerase chain reaction and immunohistochemistry for smooth muscle cell marker genes, including SM22A, smooth muscle α-actin, and matrix metalloproteinases 2 and 9. In complimentary experiments human aneurysms (n = 10) and control aorta (n = 10) were harvested at the time of surgical intervention and analyzed. Results By 14 days, aortic diameter was larger after elastase perfusion compared with control diameter (100% ± 9.6% vs 59.5% ± 18.9%, P = .0002). At 7 days, elastase-perfused mice had a 78% and 85% reduction in SM22α and smooth muscle α-actin expression, respectively, compared with that seen in control animals well before aneurysms were present, and these values remained repressed at 14 days. Immunohistochemistry confirmed less SM22α and smooth muscle α-actin in experimental aneurysms at 14 days in concert with increased matrix metalloproteinase 2 and 9 expression at 7 and 14 days. Similarly, human aneurysms had less SM22α and smooth muscle α-actin and increased matrix metalloproteinase 2 and 9 staining, compared with control values, as determined by means of quantitative polymerase chain reaction. Conclusions Aneurysms demonstrate smooth muscle cell phenotypic modulation characterized by downregulation of smooth muscle cell marker genes and upregulation of matrix metalloproteinases. These events in experimental models occur before aneurysm formation. Targeting smooth muscle cells to a reparative phenotype might provide a novel therapy in the treatment of aortic aneurysms.
BACKGROUND:Secondary mitral regurgitation (SMR) occurs in the absence of organic mitral valve disease and may develop as the left ventricle dilates or remodels or as a result of leaflet tethering ...with impaired coaptation, most commonly from apical and lateral distraction of the subvalvular apparatus, with late annular dilatation. The optimal therapy for SMR is unclear. This study sought to evaluate the 1-year adjudicated outcomes of all patients with SMR undergoing the MitraClip procedure in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Investigational Device Exemption program, which is comprised of the randomized clinical trial, the prospective High-Risk Registry, and the REALISM Continued Access Registry (Multicenter Study of the MitraClip System).
METHODS:Patients with 3+/4+ SMR enrolled in EVEREST II were stratified by non-high surgical risk (non-HR) and high surgical risk (HR) status (defined as Society of Thoracic Surgeons risk of mortality ≥12% or predefined risk factors). Clinical, echocardiographic, and functional outcomes at 1 year were evaluated.
RESULTS:A total of 616 patients (482 HR, 134 non-HR; mean age, 73.3±10.5 years; Society of Thoracic Surgeons risk, 10.2±6.9%) with SMR underwent the MitraClip procedure. At baseline, 80.5% of patients were in New York Heart Association class III/IV. Major adverse events at 30 days included death (3.6%), stroke (2.3%), and renal failure (1.5%). At discharge, 88.8% had MR ≤2+. At 1 year, there were 139 deaths, and the Kaplan-Meier estimate of freedom from mortality was 76.8%. The majority of surviving patients (84.7%) remained with MR ≤2+ and New York Heart Association class I/II (83.0%). Kaplan-Meier survival at 1 year was 74.1% in HR patients and 86.4% in non-HR patients (P=0.0175). At 1 year, both groups achieved comparable MR reduction (MR ≤2+, 84.0% versus 87.0%) and improvement in left ventricular end-diastolic volume (−8.0 mL versus −12.7 mL), whereas New York Heart Association class I/II was found in 80.1% versus 91.8% (P=0.008) of HR and non-HR patients, respectively. In HR patients, the annualized rate of heart failure hospitalizations decreased from 0.68 to 0.46 in the 12 months before to 12 months after the procedure (P<0.0001).
CONCLUSIONS:Transcatheter mitral valve repair with the MitraClip in patients with secondary MR is associated with acceptable safety, reduction of MR severity, symptom improvement, and positive ventricular remodeling.
CLINICAL TRIAL REGISTRATION:https://www.clinicaltrials.gov. Unique identifiersNCT00209274, NCT01940120, and NCT01931956.
Background: In addition to the airway-relaxing effects, β2 adrenergic receptor (β2AR) agonists are also found to have broad anti-inflammatory effects. The current study was conducted to define the ...role of β2AR agonists in limiting myocardial ischemia/reperfusion injury (IRI). Methods and Results: Adult male wild-type (WT) and interleukin (IL)-10 knockout (KO) mice underwent a 40-min left coronary artery ligation and 60-min reperfusion. A selective β2AR agonist, Clenbuterol, at doses of 0.1 μg or 1 μg/g weight i.v. 5 min before reperfusion, significantly reduced myocardial infarct size (IS) by 28% and 39% (vs. control, P<0.05) in WT mice respectively, but had no protective effect in IL-10 KO mice. Inhalational therapy with nebulized Clenbuterol, Albuterol, Salmeterol or Arformoterol immediately before ischemia significantly reduced IS (P<0.05) in WT mice. Splenectomy similarly reduced IS as Clenbuterol-treated mice, but intravenous Clenbuterol did not further reduce IS in splenectomized mice. In splenectomized WT mice, acute transfer of isolated splenocytes, not the Clenbuterol-pretreated splenocytes, restored the myocardial IS to the level of intact mice. Intravenous Clenbuterol significantly increased splenic protein levels of β2AR, phosphorylated Akt and IL-10 and plasma IL-10, and inhibited the expression of pro-inflammatory mRNAs. Conclusions: Both intravenous and inhalational β2AR agonists exert a cardioprotective effect against IRI by activating the anti-inflammatory β2AR-IL-10 pathway.
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