Escalating Surgical Treatment for Left Ventricular Assist Device Infection and Expected Mortality: Clinical Risk Prediction Score.

BACKGROUND: Left ventricular assist devices (LVAD) improve survival for patients with cardiac failure, but LVAD specific infections (VSI) remain a challenge with poorly understood predictive risk factors. Furthermore, the indications and utility of escalating medical treatment to surgical debridement and potential flap reconstruction are not well-characterized. STUDY DESIGN: A retrospective review of consecutive patients undergoing primary LVAD implantation at a tertiary academic center was performed. The primary outcomes measures were 90-day and overall mortality after VSI. Cox proportional hazards regression was used to generate a risk-prediction score for mortality. RESULTS: Of the 760 patients undergoing primary LVAD implantation, 255 (34%) developed VSI; of these 91 (36%) were managed medically, 134 (52%) with surgical debridement, and 30 (12%) with surgical debridement and flap reconstruction. One-year survival after infection was 85% with median survival of 2.40 years. Factors independently associated with increased mortality were diabetes (hazard ratio (HR) 1.44, p=0.04), methicillin-resistant Staphylococcus aureus infection (HR 1.64, p=0.03), deep space (pump pocket/outflow cannula) involvement (HR 2.26, p<0.001) and extra-corporeal membrane oxygenation after LVAD (HR 2.52, p<0.01. Factors independently associated with decreased mortality were flap reconstruction (HR 0.49, p=0.02) and methicillin-sensitive Staphylococcus aureus infection (HR 0.63, p=0.03). A clinical risk prediction score was developed using these factors and showed significant differences in median survival, which was 5.67 years for low-risk (score 0-1), 3.62 years for intermediate-risk (score 2), and 1.48 years for high-risk (score >3) (p<0.001) patients. CONCLUSIONS: We developed a clinical risk prediction score to stratify VSI patients. In selected cases, escalating surgical treatment was associated with increased survival. Future work is needed to determine if early surgical debridement and flap reconstruction can alter outcomes in select cases of VSI.

Compound Effect of Hypoalbuminemia and Obesity on Complications after Autologous Breast Reconstruction.

BACKGROUND: Obesity is among the risk factors identified that impair postoperative wound healing. Recently, malnutrition and sarcopenia have also been found to correlate with poor surgical outcomes; however, the effect of malnutrition in the setting of obesity is understudied, particularly in reconstructive surgery. The authors examine the American College of Surgeons National Surgery Quality Improvement Program database to determine the impact of obesity plus hypoalbuminemia on complications after autologous breast reconstruction. METHODS: Autologous breast reconstruction procedures (pedicled and free flaps) were collected from the 2009 to 2019 National Surgery Quality Improvement Program databases by CPT codes ( n = 23,690). Patients without height, weight, or preoperative serum albumin data ( n = 12,825) were excluded. Demographics and postoperative outcomes were compared in patients with obesity (body mass index >30 kg/m 2 ) and malnutrition (albumin <3.5 g/dL). Propensity score-matched cohorts with and without malnutrition were also compared. RESULTS: A total of 10,865 procedures were included in analysis; 4565 involved patients with obesity (42%). Obesity was associated with increased length of stay, reoperations, wound complications, and medical complications (all P < 0.001). Among patients with obesity, 198 had malnutrition (4.3%). The combination of obesity and malnutrition was associated with a higher rate of wound complications (16%) over obesity alone (9.2%) or malnutrition alone (9.2%, both P < 0.05). This difference is recapitulated in propensity score-matched analysis. CONCLUSION: Hypoalbuminemia, a marker of malnutrition, is underappreciated in obese patients and is associated with worse surgical outcomes after autologous breast reconstruction compared with obesity alone. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Loss of Gata1 decreased eosinophils, macrophages, and type 2 cytokines in regenerating nerve and delayed axon regeneration after a segmental nerve injury.

The immune system has garnered attention for its role in peripheral nerve regeneration, particularly as it pertains to regeneration across segmental injuries. Previous work demonstrated that eosinophils are recruited to regenerating nerve and express interleukin-4, amongst potential cytokines. These results suggest a direct role for eosinophils in promoting nerve regeneration. Therefore, we further considered eosinophils roles in nerve regeneration using a segmental nerve injury and Gata1 knockout (KO) mice, which are severely eosinophil deficient, compared to wild-type BALB/c mice (WT). Mice receiving a sciatic nerve gap injury demonstrated distinct cytokine expression and leukocytes within regenerating nerve. Compared to controls, Gata1 KO regenerated nerves contained decreased expression of type 2 cytokines, including Il-5 and Il-13, and decreased recruitment of eosinophils and macrophages. At this early time point during ongoing regeneration, the macrophages within Gata1 KO nerves also demonstrated significantly less M2 polarization compared to controls. Subsequently, motor and sensory axon regeneration across the gap injury was decreased in Gata1 KO compared to WT during ongoing nerve regeneration. Over longer observation to allow for more complete nerve regeneration, behavioral recovery measured by grid-walk assessment was not different comparing groups but modestly delayed in Gata1 KO compared to WT. The extent of final axon regeneration was not different amongst groups. Our data provide additional evidence suggesting eosinophils contribute to nerve regeneration across a nerve gap injury, but are not essential to regeneration in this context. Our evidence also suggests eosinophils may regulate cytokines that promote distinct macrophage phenotypes and axon regeneration.

The Association between Breast Cancer Related Lymphedema and Area Deprivation Index.

BACKGROUND: Lymphedema affects up to 34% of patients after breast cancer treatment but remains underdiagnosed and undertreated. Here, we use area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, to determine how socioeconomic status may affect risk for and diagnosis of breast cancer-related lymphedema. METHODS: Records of patients who underwent surgical treatment of breast cancer between 2017-2020 were examined. Patients' nine-digit ZIP codes were utilized to determine their deprivation level as a national ADI percentile, and those fitting into the most and least deprived quartiles were compared with evaluate lymphedema risk factors and incidence. RESULTS: A total of 1,333 breast cancer patients were included, 812 (61%) of whom resided within the most disadvantaged ADI quartile nationally, and 521 within the least disadvantaged quartile. The most deprived group had higher rates of diabetes, obesity, and regional breast cancer, and received more extensive surgeries (7.5% modified radical mastectomy vs 1.9%, p < 0.001) and chemotherapy compared with the least disadvantaged quartile. The most disadvantaged cohort were more often at extreme risk of lymphedema utilizing the Risk Assessment Tool Evaluating Lymphedema Risk (9.1% versus 2.5%, p < 0.001); however, the incidence of lymphedema diagnoses was not significantly higher (13% vs 12%, p > 0.9). Logistic regression showed that the most deprived ADI quartile had 44% lower odds of a lymphedema diagnosis in comparison to the least deprived quartile. CONCLUSION: Residing in more socioeconomically disadvantaged neighborhoods is associated with lower odds of a lymphedema diagnosis, despite higher rates of risk factors for lymphedema, suggesting significant underdiagnosis in this population.

The impact of the COVID-19 pandemic on alloplastic breast reconstruction: An analysis of national outcomes.

BACKGROUND: Immediate alloplastic breast reconstruction shifted to the outpatient setting during the COVID-19 pandemic to conserve inpatient hospital beds while providing timely oncologic care. We examine the National Surgical Quality Improvement Program (NSQIP) database for trends in and safety of outpatient breast reconstruction during the pandemic. METHODS: NSQIP data were filtered for immediate alloplastic breast reconstructions between April and December of 2019 (before-COVID) and 2020 (during-COVID); the proportion of outpatient procedures was compared. Thirty-day complications were compared for noninferiority between propensity-matched outpatients and inpatients utilizing a 1% risk difference margin. RESULTS: During COVID, immediate alloplastic breast reconstruction cases decreased (4083 vs. 4677) and were more frequently outpatient (31% vs. 10%, p < 0.001). Outpatients had lower rates of smoking (6.8% vs. 8.4%, p = 0.03) and obesity (26% vs. 33%, p < 0.001). Surgical complication rates of outpatient procedures were noninferior to propensity-matched inpatients (5.0% vs. 5.5%, p = 0.03 noninferiority). Reoperation rates were lower in propensity-matched outpatients (5.2% vs. 8.0%, p = 0.003). CONCLUSION: Immediate alloplastic breast reconstruction shifted towards outpatient procedures during the COVID-19 pandemic with noninferior complication rates. Therefore, a paradigm shift towards outpatient reconstruction for certain patients may be safe. However, decreased reoperations in outpatients may represent undiagnosed complications and warrant further investigation.

Competing Risks to Transplant in Bridging With Continuous-flow Left Ventricular Assist Devices.

BACKGROUND: Continuous-flow left ventricular assist device (CF-LVAD) support is a mainstay in the hemodynamic management of patients with end-stage heart failure refractory to optimal medical therapy. In this report we evaluated waitlist complications and competing outcomes for CF-LVAD patients compared with primary transplant candidates listed for orthotopic heart transplantation at a single center. METHODS: All patients listed for orthotopic heart transplantation between 2006 and 2020 at our institution were retrospectively reviewed (CF-LVAD, 300; primary transplant, 244). Kaplan-Meier methodology with log-rank testing was used to evaluate survival outcomes. Terminal outcomes of death, delisting, and transplant were assessed as competing risks and compared between groups using Gray's test. Multivariable Fine-Gray regression was used to identify predictors of transplantation. RESULTS: One-year rates of transplant, delisting, and death were 48%, 8%, and 2%, respectively, for CF-LVAD patients and 45%, 15%, and 9%, respectively, for primary transplant (all P < .001). Waitlist mortality at 5 years was 4% among CF-LVAD patients and 13% for primary transplants. All-cause mortality after listing was lower for CF-LVAD patients (P = .017). There was no difference in posttransplant survival between groups (P = .250). On multivariable Fine-Gray regression stroke (P = .017), respiratory failure (P = .032), right ventricular failure (P = .019), and driveline infection (P = .050) were associated with decreased probability of transplantation. Posttransplant survival was not significantly worse for CF-LVAD patients who experienced device-related complications (P = .901). CONCLUSIONS: Although device-related complications were significantly associated with decreased rates of transplant, CF-LVAD patients had excellent waitlist outcomes overall. In light of the 2018 allocation score change the risk of complications should be taken into account when deciding whether to offer CF-LVAD as a bridge to transplant.

Cardiac allograft rejection in the current era of continuous flow left ventricular assist devices.

OBJECTIVE: Left ventricular assist device (LVAD) implantation has been shown to increase allosensitization before orthotopic heart transplantation, but the influence of LVAD support on posttransplant rejection is controversial. This study examines the postoperative incidence of acute cellular rejection (ACR) in patients bridged with continuous flow LVAD (CF-LVAD) relative to primary transplant (Primary Tx). METHODS: All patients who underwent orthotopic heart transplantation at our institution between July 2006 and March 2019 were retrospectively reviewed (n = 395). Patients were classified into Primary Tx (n = 145) and CF-LVAD (n = 207) groups. Propensity score matching on 13 covariates implemented a 0.1 caliper logistic model with nearest neighbor 1:1 matching. Development of moderate to severe (ie, 2R/3R) rejection was evaluated using a competing risks model. Potential predictors of 2R/3R ACR were evaluated using Fine-Gray regression on the marginal subdistribution hazard. RESULTS: Propensity score matching yielded 122 patients in each group (n = 244). At 12 and 24 months, the cumulative incidence of 2R/3R ACR was 17% and 23% for the CF-LVAD group and 26% and 31%, respectively, for the Primary Tx group (P = .170). CF-LVAD was not predictive of 2R/3R rejection on multivariable Fine-Gray regression (subdistribution hazard ratio, 0.73; 95% confidence interval, 0.40-1.33; P = .301). There was no difference in the 5-year incidence of antibody mediated rejection (10% [n = 12] vs 9% [n = 11]; P = .827). CONCLUSIONS: After adjusting for covariates, CF-LVAD was not associated with an increased risk of moderate to severe ACR during the 24 months after cardiac transplantation. Further investigation is warranted with larger cohorts, but CF-LVAD may have minimal influence on posttransplant ACR.

30 Years of Heart Transplant: Outcomes After Mechanical Circulatory Support From a Single Center.

BACKGROUND: Survival after bridge to transplantation with mechanical circulatory support (MCS) has yielded varying outcomes on the basis of device type and baseline characteristics. Continuous-flow left ventricular assist devices (CF-LVADs) have significantly improved waitlist mortality, but recent changes to the transplantation listing criteria have dramatically altered the use of MCS for bridge to transplantation. METHODS: Orthotopic heart transplantations from 1988 to 2019 at our institution (Washington University School of Medicine, Barnes-Jewish Hospital, St Louis, MO) were retrospectively reviewed and stratified by pretransplantation MCS status into CF-LVAD (n = 224), pulsatile LVAD (n = 49), temporary MCS (n = 71), and primary transplantation (n = 463) groups. Patients who underwent heart transplantation after the approval of CF-LVAD for bridge to transplantation and before the 2018 allocation policy changes underwent subgroup analysis to evaluate predictors of survival and complications in a contemporary cohort. RESULTS: Rates of primary transplantation declined from 88% to 14% over the course of the study. No significant difference in survival was detected in the cohort stratified by MCS status (P = .18). In the modern era, survival of patients treated with CF-LVADs and temporary MCS was noninferior to that seen with primary transplantation (P = .22). Notable predictors of long-term mortality included lower body mass index, peripheral vascular disease, previous coronary artery bypass graft, ABO nonidentical transplant, and increased donor age (all P ≤ .02). There were no differences in major postoperative complications. CONCLUSIONS: CF-LVAD has grown to account for the majority of transplantations at our center in the last decade, with no adverse effect on survival or postoperative complications. Temporary MCS increased after the 2018 listing criteria change, with acceptable early outcomes.