Risk factors for postoperative delirium in orthopaedic hip surgery patients: a database review.

BACKGROUND: Postoperative delirium is a common problem affecting admitted patients that decreases patient satisfaction and increases the cost and complexity of care. The purpose of this study was to use the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to compare rates and risk factors of postoperative delirium for total hip arthroplasty (THA) and hemiarthroplasty patients indicated for osteoarthritis or proximal femur fracture. METHODS: The 2021 NSQIP database was queried for patients using Current Procedural Terminology (CPT) codes for THA and hemiarthroplasty and ICD-10 codes for osteoarthritis or proximal femur fracture. Demographic, past medical history, preoperative labs, and functional status data were recorded. Procedural data were also collected. Finally, postoperative outcomes and complications were reviewed. RESULTS: Overall, 16% of patients had postoperative delirium. Delirium patients were older on average (82.4 years vs. 80.7 years, p < 0.001), had a lower BMI (19.5 vs. 24.8, p < 0.001), were more likely to have a history of dementia (54.6% vs. 13.6%, p < 0.001), were less likely to have an independent functional status (p < 0.001) or live alone (p < 0.001), and were more likely to have sustained a recent fall (p < 0.001). Delirium patients were more likely to be hyponatremic or hypernatremic (p = 0.002), anemic (p < 0.001), and severely dehydrated (p < 0.001), among other lab abnormalities. Delirium patients were also more likely to experience additional postoperative complications, including pneumonia, pulmonary embolism, urinary tract infection, stroke, cardiac arrest, sepsis, and unplanned reoperation and readmission after discharge (all p < 0.05). CONCLUSIONS: In this study, factors associated with postoperative delirium in patients undergoing hemiarthroplasty and THA were identified, including older age, lower BMI, certain medical conditions, decreased functional status, certain lab abnormalities, and postoperative complications. These findings can be used by clinicians to better inform care and to determine when orthopaedic joint replacement patients may be at an increased risk for postoperative delirium.

Repeat High-Dose Dexamethasone May Improve Recovery 48 Hours after Total Hip Arthroplasty.

Objectives: Perioperative dexamethasone is an effective anti-emetic and systemic analgesic in total hip arthroplasty (THA) that may reduce opioid consumption and enhance rapid recovery. However, there is no consensus on the optimal perioperative dosing that is safe and effective for faster rehabilitation and improved pain control while maintaining safe blood glucose levels. Methods: A retrospective review of 101 primary THA patients at a single institution who received perioperative dexamethasone was conducted. Patients were stratified by dexamethasone induction dosage (10 mg as high, <6mg as low) and whether a repeat dose was given 16-24 hours postoperatively. Age, gender, BMI, diabetes status, and ASA were controlled between groups. The pain was evaluated with inpatient morphine milligram equivalents (MME) requirements and visual analog scale (VAS) at 8, 16, and 24 hours postoperatively. Mobility was assessed by inpatient ambulation distance, Boston AM-PAC mobility score, and percentage of gait assistance as determined by a physical therapist. Secondary outcomes included postoperative nausea and vomiting (PONV) limiting therapy sessions, PONV requiring breakthrough anti-emetics, glucose levels, surgical site infection, wound healing complications, and discharge destination. Results: Compared to patients receiving one dose of high or low dexamethasone, patients receiving two dosages of high-dose dexamethasone had significantly further ambulation distance and lower percentage of gait assistance on postoperative day 2. A generalized linear model also predicted that any repeat dexamethasone, regardless of dosage, significantly improved ambulation distance and gait assistance compared to the one-dose cohort. There was no statistically significant difference between VAS scores, MME requirements, PONV, postoperative glucose levels >200, discharge destination, or risk of infection between groups. Conclusion: A repeat high-dose dexamethasone, the morning after surgery, may improve percentage of gait assistance and ambulation endurance on postoperative day two. There was no risk of uncontrolled glucose levels or infections compared to receiving one dose of dexamethasone at induction.

Alkaline Phosphatase is an Independent Risk Factor for Periprosthetic Fractures in Total Joint Arthroplasty.

BACKGROUND: Serum alkaline phosphatase (ALP) is a biomarker for chronic low-grade inflammation along with hepatobiliary and bone disorders. High abnormal ALP levels in blood have been associated with metabolic bone disease and high bone turnover. METHODS: All primary total hip and knee arthroplasties from 2005 to 2019 were queried from the National Surgical Quality Improvement Program database. Patients with available serum ALP levels were included and stratified to low (<44 IU/L), normal (44 to 147 IU/L), and high (>147 IU/L). A risk-adjusted multivariate logistic regression was used to analyze ALP as an independent risk factor of complications. RESULTS: The analysis included 324,592 patients, consisting of 11,427 low ALP, 305,977 normal ALP, and 7,188 high preoperative ALP level patients undergoing total joint arthroplasty. Adjusted multivariate logistic regression analysis showed high ALP level patients had an overall increased risk of readmission within 30 days of surgery compared with the control group (odds ratio [OR], 1.69; P < 0.01). High ALP patients also had an increased risk of postoperative periprosthetic fracture (OR, 1.6), postoperative wound infection (OR, 1.81), pneumonia (OR, 2.24), renal insufficiency (OR, 2.39), cerebrovascular disease (OR, 2.2), postoperative bleeding requiring transfusion (OR, 1.83), sepsis (OR, 2.35), length of stay > 2 days (OR, 1.47), Clostridium difficile infection (OR, 2.07), and discharge to a rehab facility (OR, 1.41) (all P < 0.05). A low ALP level was also associated with increased postoperative bleeding transfusion risk (OR, 1.12; P < 0.01) and developing a deep vein thrombosis (OR, 1.25; P = 0.03). CONCLUSION: Abnormal serum ALP levels in patients undergoing primary total joint arthroplasty are associated with increased postoperative periprosthetic fracture risk and medical complications requiring increased length of stay and discharge to a rehabilitation facility.

The impact of dehydration on short-term postoperative complications in total knee arthroplasty.

BACKGROUND: As healthcare economics shifts towards outcomes-based bundled payment models, providers must understand the evolving dynamics of medical optimization and fluid resuscitation prior to elective surgery. Dehydration is an overlooked modifiable risk factor that should be optimized prior to elective total knee arthroplasty (TKA) to reduce postoperative complications and inpatient costs. METHODS: All primary TKA from 2005 to 2019 were queried from the National Surgical Quality Improvement Program (NSQIP) database, and patients were compared based on dehydration status: Blood Urea Nitrogen Creatinine ratio (BUN/Cr) < 20 (non-dehydrated), 20 ≤ BUN/Cr ≤ 25 (moderately-dehydrated), 25 < BUN/Cr (severely-dehydrated). A sub-group analysis involving only elderly patients > 65 years and normalized gender-adjusted Cr values was also performed. RESULTS: The analysis included 344,744 patients who underwent TKA. Adjusted multivariate logistic regression analysis showed that the severely dehydrated cohort had a greater risk of non-home discharge, postoperative transfusion, postoperative deep vein thrombosis (DVT), and increased length of stay (LOS) (all p < 0.01). Among the elderly, dehydrated patients had a greater risk of non-home discharge, progressive renal insufficiency, urinary tract infection (UTI), postoperative transfusion, and extended LOS (all p < 0.01). CONCLUSION: BUN/Cr > 20 is an important preoperative diagnostic tool to identify at-risk dehydrated patients. Providers should optimize dehydration to prevent complications, decrease costs, and improve discharge planning. LEVEL OF EVIDENCE: Level III; Retrospective Case-Control Design; Prognosis Study.

Preoperative Malnutrition and Metabolic Markers May Predict Periprosthetic Fractures in Total Hip Arthroplasty.

Background: Periprosthetic fractures are a devastating complication of total hip arthroplasty (THA) and are associated with significantly higher mortality rates in the postoperative period. Given the strain that periprosthetic fractures place on the patient as well as the healthcare system, identifying and optimizing medical comorbidities is essential in reducing complications and improving outcomes. Methods: All THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program database. Demographic data, preoperative laboratory values, medical comorbidities, hospital course, and acute complications were collected and compared between patients with and without readmission for a periprosthetic fracture. A multivariate logistic regression analysis was performed to determine associated independent risk factors for periprosthetic fractures after index THA. Results: The analysis included 275,107 patients, of which 2539 patients were readmitted for periprosthetic fractures. Patients with postoperative fractures were more likely to be older (>65 years), females, BMI >40, and increased medical comorbidities. Preoperative hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rates were independent risk factors for sustaining a periprosthetic fracture and readmission within 30 days. Modifiable patient-related factors of concurrent smoking and chronic steroid use at the time of index THA were also independent risk factors for periprosthetic fractures. Inpatient metrics of longer length of stay, operative time, and discharge to rehab predicted postarthroplasty fracture risk. Readmitted fracture patients subsequently had increased risks of developing a surgical site infection, urinary tract infection, and requiring blood transfusions. Conclusions: Patients with hypoalbuminemia, hyponatremia, and abnormal estimated glomerular filtration rate are at increased risk for sustaining periprosthetic fractures after THA. Preoperative optimization with close monitoring of metabolic markers and modifiable risk factors may help not only prevent acute periprosthetic fractures but also associated infection and bleeding risk with fracture readmission.

Kinematic Alignment May Reduce Opioid Consumption and Length of Stay Compared to Mechanically Aligned Total Knee Arthroplasty.

OBJECTIVE: Previous studies have sought to determine the effects of total knee arthroplasty (TKA) using kinematic alignment (KA) versus mechanical alignment (MA) to reproduce the native knee alignment and soft tissue envelope for improved patient satisfaction. There are limited studies that compare acute perioperative outcomes between KA and MA patients as it pertains to pain-related opioid consumption and hospital length of stay (LOS). This study aims to compare early KA and MA in restoring function and rehabilitation after surgery to reduce hospitalization and opioid consumption. METHODS: A retrospective review of 42 KA and 58 MA primary TKA patients performed by a single surgeon between 2020-2021 was conducted. Demographics were controlled between groups and radiographic measurements and functional outcomes were compared. Pain was evaluated with inpatient/outpatient morphine milligram equivalents (MME) and visual analogue scale (VAS) scores. Mobility was assessed using multiple measures by a physical therapist. Mean preoperative and 3-month postoperative flexion range of motion (ROM) were analyzed, and overall complications, LOS, and non-home discharge between groups compared. Continuous variables were compared using the Wilcoxon rank-sum test, and categorical variables were compared using the chi-square or Fisher exact test. Statistical significance was set at P < 0.05. RESULTS: KA patients had shorter LOS (1.8 vs 3.1 days) and less cumulative opioid requirements compared to MA patients (578 vs 1253 MME). On postoperative day 0, KA patients ambulated on average twice the distance of MA patients (20 vs 6.5 feet). KA patients had residual tibia component in varus (1.4° vs -0.3°), femoral component in valgus (-1.9° vs 0.2°), and valgus joint line obliquity compared with MA (-1.5° vs 0.2°). There were no significant differences between 3-month postoperative flexion arc motion, discharge destination, KOOS or SF-12 outcomes, and surgical complication rates between groups. CONCLUSIONS: By restoring the native joint line obliquity and minimizing the frequency of ligament releases, KA for TKA may improve pain relief, early mobility, and decreased length of stay compared with traditional methods of establishing neutral limb axis by MA.

Prior Diagnosis of COVID Has No Increased Complications in Total Joint Arthroplasty.

Introduction Although a substantial portion of the United States population has been infected with and recovered from Coronavirus Disease-19 (COVID-19), many patients may have persistent symptoms and complications from disease-driven respiratory disease, arrhythmias, and venous thromboembolism (VTE). With institutions resuming elective total joint arthroplasties (TJA), it is unclear whether a prior resolved diagnosis of COVID has any implications on postoperative outcomes. Methods All elective TJA performed in 2021 at our institution were retrospectively reviewed and a history of prior COVID+ result recorded. Baseline demographics, days from prior COVID+ result to surgery date, preoperative methicillin-resistant Staphylococcus aureus (MRSA) nares colonization, and laboratory markers were obtained to determine baseline characteristics. Postoperative estimated blood loss (EBL), length of stay (LOS), rate of revision surgery, and discharge destination were compared between groups. Perioperative and postoperative rates of VTE, urinary tract infection (UTI), pneumonia, postoperative oxygen supplementation, cardiac arrhythmia, renal disease, sepsis, and periprosthetic joint infections within six months of surgery were recorded. Results Of the 155 elective TJA performed in 2021, 24 patients had a prior COVID+ diagnosis with a mean of 253 days from positive result to surgery date. There were no significant differences in baseline demographics, comorbidities, and preoperative lab markers between groups. Surgeries on patients with a prior COVID+ had a significantly higher EBL (260 vs 175cc), but postoperative outcomes of VTE, UTI, pneumonia, oxygen supplementation requirement, nares MRSA+, cardiac disease, and infection rates between groups were similar. Bivariate logistic regression revealed increased days from COVID+ diagnosis (>6 months) to surgery date were associated with a shorter LOS. Conclusion Although a prior COVID+ diagnosis had increased intraoperative blood loss, there were no significant differences in respiratory, infectious, cardiac, and thromboembolic complications up to six months after elective TJA. This study suggests that asymptomatic C+ patients receiving elective TJA do not require more aggressive prophylactic anticoagulation or antibiotic regimens to prevent VTE or perioperative infections. As institutions around the nation resume pre-COVID rates of arthroplasty surgeries, a prior diagnosis of COVID appears to have no effects on postoperative complications.

Cryoneurolysis Is a Safe, Effective Modality to Improve Rehabilitation after Total Knee Arthroplasty.

Although long term pain and mobility outcomes in total knee arthroplasties (TKA) are successful, many patients experience significant amount of debilitating pain during the immediate post-operative period that necessitates narcotic use. Percutaneous cryoneurolysis to the infrapatellar saphenous and anterior femoral cutaneous nerves may help to better restore function and rehabilitation after surgery while limiting narcotic consumption. A retrospective chart review of primary TKA patients receiving pre-operative cryoneurolysis from 2019 to 2020 was performed to assess total opioid morphine milligram equivalents (MME) consumed inpatient and at interval follow-up. Demographics and medical comorbidities were compared between cryoneurolysis and age-matched control patients to assess baseline characteristics. Functional rehabilitation outcomes, including knee range of motion (ROM), ambulation distance, and Boston AM-PAC scores, as well as patient reported outcomes using the KOOS JR and SF-12 scores were analyzed using STATA 17 Software. The analysis included 29 cryoneurolysis and 28 age-matched control TKA patients. Baseline demographics and operative technique were not significant between groups. Although not statistically significant, cryoneurolysis patients had a shorter length of stay (2.5 vs. 3.5 days) and overall less inpatient and outpatient MME requirements. Cryoneurolysis patients had statistically significant improved 6-week ROM and 1-year follow-up KOOS JR and SF-12 mental scores compared to the control. There were no differences in complication rates. Cryoneurolysis is a safe, effective treatment modality to improve active functional recovery and patient satisfaction after TKA by reducing MME requirements. Patients who underwent cryoneurolysis had on average fewer MME prescribed during the perioperative period, improved active ROM, and improved patient-reported outcomes with no associated increased risk of infections, deep vein thrombosis, or neurologic complications.

Chlorhexidine gluconate lavage during total joint arthroplasty may improve wound healing compared to dilute betadine.

PURPOSE: Intraoperative wound irrigation prior to closure during total joint arthroplasty (TJA) is an essential component of preventing infections and limiting health care system costs. While studies have shown the efficacy of dilute betadine in reducing infection risk, there remains concerns over its safety profile and theoretical inactivation by blood and serum. This study aims to compare infection and wound complications between chlorhexidine gluconate (CHG) and betadine lavage during TJA. METHODS: All primary TJA between 2019-2021 were analyzed at a single institution, and periprosthetic joint infection (PJI), wound drainage, 30 and 90-day emergency room (ER) readmission due to wound complications, aseptic loosening, and revision surgery rate were compared between patients undergoing intraoperative CHG versus betadine lavage prior to closure. Baseline demographics were controlled, and multivariate logistic regression was performed to compare complication rates. RESULTS: A total of 410 TJA, including 160 hip and 250 knee arthroplasties were included. Compared to the dilute betadine cohort, all TJA patients undergoing CHG lavage had a statistically significant lower 30 and 90-day emergency room readmission rate due to wound complications. Both hip and knee arthroplasty patients with CHG had a statistically significant lower rate of postoperative superficial drainage and dressing saturation at clinic follow-up, but only knee arthroplasty patients had significant decreased readmission rate for incisional wound vacuum placement and close inpatient monitoring of wound healing. Among all TJA, there was no significant association in the rate of PJI requiring return to the OR between groups. CONCLUSIONS: Although betadine is cost-effective and has been shown to reduce PJI rates, there remains concerns in the literature over soft tissue toxicity and wound healing. This study suggests CHG may be as efficacious as dilute betadine in preventing PJI while also decreasing the risk of superficial drainage and wound complications needing unplanned ER visits during the acute postoperative period.

Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study.

Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from eight organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal presepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; one patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list.

Early US experience with cardiac donation after circulatory death (DCD) using normothermic regional perfusion.

BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation and the growing interest in donation after circulatory death (DCD), our institution recently began procuring cardiac allografts from DCD donors. METHODS: Between October 2020 and March 2021, 15 patients with heart failure underwent cardiac transplantation using DCD allografts. Allografts were procured using a modified extracorporeal membrane oxygenation circuit for thoracic normothermic regional perfusion (TA-NRP) and were subsequently transported using cold static storage. Data collection and analysis were performed with institutional review board approval. RESULTS: The mean age of the DCD donors was 23 ± 7 years and average time on TA-NRP was 56 ± 8 minutes. Total ischemic time was 183 ± 31 minutes and distance from transplant center was 373 ± 203 nautical miles. Recipient age was 55 ± 14 years, with 8 (55.3%) recipients on durable left ventricular assist device support. Post-transplant, 6 (40%) recipients experienced mild left ventricle primary graft dysfunction (PGD-LV), 3 (20%) recipients experienced moderate PGD-LV, and no recipients experienced severe PGD-LV. Postoperative transthoracic echocardiogram demonstrated left ventricular ejection fraction >55% in all recipients. One recipient (6.6%) developed International Society for Heart and Lung Transplantation 2R acute cellular rejection on first biopsy. At last follow-up, all 15 recipients were alive past 30-days. CONCLUSIONS: Cardiac DCD provides an opportunity to increase the availability of donor hearts for transplantation. Utilizing TA-NRP with cold static storage, we have extended the cold ischemic time of DCD allografts to almost 3 hours, allowing for inter-hospital organ transport.

Impact of increased donor distances following adult heart allocation system changes: A single center review of 1-year outcomes.

BACKGROUND: On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes. METHODS: In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006). CONCLUSIONS: Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed.

Prioritizing heart transplantation during the COVID-19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has significantly impacted the healthcare landscape in the United States in a variety of ways including a nation-wide reduction in operative volume. The impact of COVID-19 on the availability of donor organs and the impact on solid organ transplant remains unclear. We examine the impact of COVID-19 on a single, large-volume heart transplant program. METHODS: A retrospective chart review was performed examining all adult heart transplants performed at a single institution between March 2020 and June 2020. This was compared to the same time frame in 2019. We examined incidence of primary graft dysfunction, continuous renal replacement therapy (CRRT) and 30-day survival. RESULTS: From March to June 2020, 43 orthotopic heart transplants were performed compared to 31 performed during 2019. Donor and recipient demographics demonstrated no differences. There was no difference in 30-day survival. There was a statistically significant difference in incidence of postoperative CRRT (9/31 vs. 3/43; p = .01). There was a statistically significant difference in race (23 W/8B/1AA vs. 30 W/13B; p = .029). CONCLUSION: We demonstrate that a single, large-volume transplant program was able to grow volume with little difference in donor variables and clinical outcomes following transplant. While multiple reasons are possible, most likely the reduction of volume at other programs allowed us to utilize organs to which we would not have previously had access. More significantly, our growth in volume was coupled with no instances of COVID-19 infection or transmission amongst patients or staff due to an aggressive testing and surveillance program.

Early Outcomes of Multivisceral Transplant Using Hepatitis C-Positive Donors.

BACKGROUND: In the era of direct-acting antiviral therapies, hepatitis C-positive organs offer a strategy to expand the donor pool. Heart failure patients with concomitant renal insufficiency benefit from combined heart/kidney transplant. In 2017, we began utilizing organs from hepatitis C donors for heart/kidney transplants. METHODS: Characteristics and outcomes of heart/kidney transplants were collected at our institution from 2012 through 2019. We determined patient cohorts by donor hepatitis C antibody status, antibody positive (HCV+) vs antibody negative (HCV-). Outcomes of interest include survival, postoperative allograft function, and waitlist time. Summary and descriptive statistics, as well as survival analyses, were performed. RESULTS: Thirty-nine patients underwent heart/kidney transplantation from 2012-2019. Twelve patients received HCV+ organs, and 27 patients received HCV- organs with minimal differences in donor and recipient cohort characteristics. Recipients who consented to receive HCV+ organs had a shorter median waitlist time. HCV+ and HCV- groups had similar perioperative and early postoperative cardiac function and similar rates of delayed renal graft function. HCV+ recipients demonstrated higher creatinine levels at 3 months posttransplant compared with HCV- recipients, but by 1-year post-transplant, creatinine levels in both groups were similar. The groups had similar 30-day and 1-year survival. CONCLUSIONS: This study is a single-center series of heart/kidney transplant using HCV+ donors. When the potential increased risk of early postoperative renal dysfunction is balanced against similar survival and decreased waitlist time, the results suggest that HCV+ donors are an important source of transplantable organs for heart/kidney transplantation.

A Dual-Lumen Bicaval Cannula for Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Single-site, dual-lumen venovenous extracorporeal membrane oxygenation ECMO) facilitates mobilization, reduces recirculation, and mitigates insertion and infectious risks of an additional access site. This study reports the experience with a bicaval dual-lumen cannula that comprises a robust physical design allowing for easy and safe cannulation, precise positioning and monitoring, and appropriate physiologic support for patients with acute respiratory failure. METHODS: Statistical analysis was performed from data gathered retrospectively from the electronic medical records of 20 adult patients who were cannulated for ECMO with this bicaval dual-lumen cannula from August 2018 through May 2019. RESULTS: Gas exchange and blood flow were optimized in all patients after cannulation (median pH, 7.42 [interquartile range {IQR}, 7.39, 7.44], ratio of arterial partial pressure of oxygen to fraction of inspired oxygen, 186.5 [Pao2:Fio2, 116.5, 247.0]; pump flow, 3.9 L/min [IQR, 3.1, 4.3]). Eleven patients (55%) were able to be freed from mechanical ventilation after cannulation, 9 (45%) patients underwent a tracheostomy procedure while undergoing ECMO, and no patients required reintubation. No morbidity or mortality was related to the cannulation strategy or the catheter. Two patients required cannula repositioning. Survival to decannulation was 90%, and survival to hospital discharge was 80%. CONCLUSIONS: The bicaval dual-lumen cannula maintains the advantages of upper body single-site configuration to provide the adjunctive respiratory support necessary to facilitate awakening and rehabilitation while minimizing the use of invasive mechanical ventilation. This cannula introduces design qualities that may offer advantages for acute respiratory failure requiring venovenous ECMO.

LNK deficiency promotes acute aortic dissection and rupture.

Aortic dissection (AD) is a life-threatening vascular disease with limited treatment strategies. Here, we show that loss of the GWAS-identified SH2B3 gene, encoding lymphocyte adaptor protein LNK, markedly increases susceptibility to acute AD and rupture in response to angiotensin (Ang) II infusion. As early as day 3 following Ang II infusion, prior to the development of AD, Lnk-/- aortas display altered mechanical properties, increased elastin breaks, collagen thinning, enhanced neutrophil accumulation, and increased MMP-9 activity compared with WT mice. Adoptive transfer of Lnk-/- leukocytes into Rag1-/- mice induces AD and rupture in response to Ang II, demonstrating that LNK deficiency in hematopoietic cells plays a key role in this disease. Interestingly, treatment with doxycycline prevents the early accumulation of aortic neutrophils and significantly reduces the incidence of AD and rupture. PrediXcan analysis in a biobank of more than 23,000 individuals reveals that decreased expression of SH2B3 is significantly associated with increased frequency of AD-related phenotypes (odds ratio 0.81). Thus, we identified a role for LNK in the pathology of AD in experimental animals and humans and describe a new model that can be used to inform both inherited and acquired forms of this disease.

Mitochondrial Cyclophilin D in Vascular Oxidative Stress and Hypertension.

Vascular superoxide (O˙2 (-)) and inflammation contribute to hypertension. The mitochondria are an important source of O˙2 (-); however, the regulation of mitochondrial O˙2 (-) and the antihypertensive potential of targeting the mitochondria remain poorly defined. Angiotensin II and inflammatory cytokines, such as interleukin 17A and tumor necrosis factor-α (TNFα) significantly contribute to hypertension. We hypothesized that angiotensin II and cytokines co-operatively induce cyclophilin D (CypD)-dependent mitochondrial O˙2 (-) production in hypertension. We tested whether CypD inhibition attenuates endothelial oxidative stress and reduces hypertension. CypD depletion in CypD(-/-) mice prevents overproduction of mitochondrial O˙2 (-) in angiotensin II-infused mice, attenuates hypertension by 20 mm Hg, and improves vascular relaxation compared with wild-type C57Bl/6J mice. Treatment of hypertensive mice with the specific CypD inhibitor Sanglifehrin A reduces blood pressure by 28 mm Hg, inhibits production of mitochondrial O˙2 (-) by 40%, and improves vascular relaxation. Angiotensin II-induced hypertension was associated with CypD redox activation by S-glutathionylation, and expression of the mitochondria-targeted H2O2 scavenger, catalase, abolished CypD S-glutathionylation, prevented stimulation mitochondrial O˙2 (-), and attenuated hypertension. The functional role of cytokine-angiotensin II interplay was confirmed by co-operative stimulation of mitochondrial O˙2 (-) by 3-fold in cultured endothelial cells and impairment of aortic relaxation incubated with combination of angiotensin II, interleukin 17A, and tumor necrosis factor-α which was prevented by CypD depletion or expression of mitochondria-targeted SOD2 and catalase. These data support a novel role of CypD in hypertension and demonstrate that targeting CypD decreases mitochondrial O˙2 (-), improves vascular relaxation, and reduces hypertension.

Preoperative Predictors of 30-Day Mortality and Prolonged Length of Stay after Above-Knee Amputation.

BACKGROUND: The above-knee amputation (AKA) is an operation of last resort with high postoperative morbidity and mortality. This study identifies preoperative risk factors predictive of both 30-day mortality and extended length of stay (LOS) in AKA patients. METHODS: Two hundred ninety-five AKA patients from 2004 to 2013 from a single institution were retrospectively reviewed using a deidentified electronic medical record. Rationally selected factors potentially influencing 30-day mortality and LOS were chosen, including demographics, etiologies, vascular surgical history, lifestyle factors, comorbidities, and laboratory values. Variables trending with one of the end points on bivariate analysis (P ≤ 0.10) were entered into multivariate forward stepwise regression models to determine independence as a risk factor (P ≤ 0.05). Subgroup analysis of AKA patients without a traumatic, burn, or malignant etiology was similarly conducted. RESULTS: Within the 295 patient cohort, 60% of the patients were male, 18% were African American, mean age was 58 years and mean body mass index was 28 kg/m(2). The 30-day mortality rate was 9%, and mean postoperative LOS of discharged patients was 9.3 days. Upon logistic regression, thrombocytopenia (platelet count < 250 × 10(6)/mL, P < 0.001, odds ratio 6.1) and preoperative septic shock (P = 0.02, odds ratio 5.1) were identified as independent risk factors for 30-day mortality. Upon linear regression, burn etiology (P < 0.001, B = 15.8 days), leukocytosis (white blood cell count > 12 × 10(6)/mL, P < 0.001, B = 6.2 days), and guillotine amputation (P < 0.001, B = 7.6 days) were independently associated with prolonged LOS. Excluding patients with AKAs due to trauma, burn, or malignancy, only thrombocytopenia (platelet count < 250 × 10(6)/mL, P < 0.001, odds ratio 10.2) and leukocytosis (white blood cell count > 12 × 10(6)/mL, P = 0.01, B = 5.2 days) were independent risk factors for in-hospital mortality and prolonged LOS, respectively. CONCLUSIONS: Preoperative septic shock and thrombocytopenia are independent risk factors for 30-day mortality after AKA, while burn etiology, leukocytosis, and guillotine amputation contribute to prolonged LOS. Awareness of these risk factors may help enhance both preoperative decision making and expectations of the hospital admission.