Anesthetic Considerations for Minimally Invasive, Off-Pump, HeartMate III Implantation.

OBJECTIVE: The authors developed and utilized an anesthetic protocol for the management of an off-pump approach for minimally invasive Heartmate III (HM3) implantation. Their goal was to determine if this method was safe and feasible for patients with in-situ mechanical support. DESIGN: The authors performed a retrospective study of consecutive patients undergoing off-pump HM3 implantation via bilateral minithoracotomies. SETTING: This was a single-institution study at the University of Rochester Medical Center, using the same cardiac anesthesiologist and cardiac surgeon pair. PARTICIPANTS: The authors studied 8 consecutive patients undergoing off-pump HM3 implantation from June 2019 to July 2020. INTERVENTIONS: The authors developed an anesthetic management protocol for off-pump HM3 implantation via bilateral minithoracotomies. MEASUREMENTS AND MAIN RESULTS: As a result, the authors evaluated 88% of men with a mean age of 55.0 ±13.0 years. The median time to extubation was 19.7 hours, with a median intensive care unit length of stay of 6.5 days. Fifty percent of patients required blood transfusions during the first 24 hours after surgery (postoperative), and 63% of patients were free from all postoperative complications. No patients required a right ventricular assist device. The mean hospital stay was 26.3 ± 11.3 days, with an 88% survival to discharge. CONCLUSION: In this single-center study, the authors have described the anesthetic consideration for the implantation of the HM3 left ventricular assist device using a complete sternal-sparing technique without the use of cardiopulmonary bypass. Their results have shown, in a case series of 8 patients, that this is a safe and feasible alternative to traditional techniques in patients with existing mechanical support.

HeartMate 3 pump exchange via sternal-sparing bilateral minithoracotomies.

As median survival for left ventricular assist device (LVAD) patients increases, the incidence of adverse events requiring device exchange is likely to increase as well. Less invasive surgical approaches for device exchange of older generation pumps have demonstrated multiple potential benefits compared with median sternotomy. However, there remains a paucity of data in regard to less invasive surgical techniques for the exchange of the newest generation intrapericardial devices. In this report we describe a complete sternal-sparing technique for the LVAD exchange of a HeartMate 3 via bilateral minithoracotomies.

Regional nerve block decreases opioid use after complete sternal-sparing left ventricular assist device implantation.

BACKGROUND: Less-invasive techniques for left ventricular assist device (LVAD) implantation have shown promising outcomes but are associated with significant postoperative pain. We aim to investigate the use of ultrasound-guided regional nerve blocks to improve pain management during these procedures. METHODS: We retrospectively reviewed patients implanted with a HeartMate 3 LVAD via complete sternal-sparing (CSS) approach at our institution from February 2018 to July 2018. Patients were grouped based on their postoperative pain management plan-those who received a regional nerve block plus multimodal analgesia and a control group who received standard multimodal analgesia alone. Pain scores and analgesic use were recorded for all patients during the initial 72 hours postoperatively. RESULTS: Preoperative characteristics were similar between cohorts. Of the 28 patients included in the study, 15 (54%) received a postoperative regional nerve block. Patients who received a nerve block had significantly lower pain scores and required a lower dose of opioid analgesics (70.7 ± 13.9 vs 124.6 ± 19.3 morphine equivalents, P = 0.029) during the first 72 hours postoperatively. There was no difference in time to extubation, intensive care unit length of stay, or hospital length of stay. CONCLUSIONS: Optimizing postoperative analgesia using a regional nerve block is associated with decreased opioid use and decreased postoperative pain after CSS LVAD implantation. Regional nerve blocks should be included as part of a protocol-based postoperative pain management program.

A Phase Ib Study of Sorafenib (BAY 43-9006) in Patients with Kaposi Sarcoma.

LESSONS LEARNED: Oral targeted agents are desirable for treatment of Kaposi sarcoma (KS); however, in patients with HIV, drug-drug interactions must be considered. In this study to treat KS, sorafenib was poorly tolerated at doses less than those approved by the U.S. Food and Drug Administration for hepatocellular carcinoma and other cancers, and showed only modest activity.Sorafenib's metabolism occurs via the CYP3A4 pathway, which is inhibited by ritonavir, a commonly used antiretroviral agent used by most patients in this study. Strong CYP3A4 inhibition by ritonavir may contribute to the observed sorafenib toxicity.Alternate antiretroviral agents without predicted interactions are preferred for co-administration in patients with HIV and cancers for which sorafenib is indicated. BACKGROUND: We conducted a phase Ib study of sorafenib, a vascular epithelial growth factor receptor (VEGFR), c-kit, and platelet derived growth factor receptor (PDGFR)-targeted treatment in Kaposi sarcoma (KS). We evaluated drug-drug interactions between sorafenib and ritonavir, an HIV medication with strong CYP3A4 inhibitory activity. METHODS: Two cohorts were enrolled: HIV-related KS on ritonavir (Cohort R) and HIV-related or classical KS not receiving ritonavir (Cohort NR). Sorafenib dose level 1 in cohort R (R1) was 200 mg daily and 200 mg every 12 hours in cohort NR (NR1). Steady-state pharmacokinetics were evaluated at cycle 1, day 8. KS responses and correlative factors were assessed. RESULTS: Ten patients (nine HIV+) were enrolled: R1 (eight), NR1 (two). Median CD4+ count (HIV+) was 500 cells/µL. Dose-limiting toxicities (DLTs) were grade 3 elevated lipase (R1), grade 4 thrombocytopenia (R1), and grade 3 hand-foot syndrome (NR1). Two of seven evaluable patients had a partial response (PR; 29%; 95% CI 4%-71%). Steady-state area under the curve of the dosing interval (AUCTAU) of sorafenib was not significantly affected by ritonavir; however, a trend for decreased AUCTAU of the CYP3A4 metabolite sorafenib-N-oxide (3.8-fold decrease; p = .08) suggests other metabolites may be increased. CONCLUSION: Sorafenib was poorly tolerated, and anti-KS activity was modest. Strong CYP3A4 inhibitors may contribute to sorafenib toxicity, and ritonavir has previously been shown to be a CYP3A4 inhibitor. Alternate antiretroviral agents without predicted interactions should be used when possible for concurrent administration with sorafenib. The Oncologist 2017;22:505-e49.

Intra-abdominal Hypertension and Postoperative Kidney Dysfunction in Cardiac Surgery Patients.

OBJECTIVE: To determine the incidence of intra-abdominal hypertension (IAH) in adult cardiac surgery patients and its association with postoperative kidney dysfunction. DESIGN: Prospective cohort study. SETTING: Single tertiary-care university hospital. PARTICIPANTS: Forty-two adult patients having cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Intra-abdominal pressure (IAP) was measured preoperatively, immediately after surgery, and at the following time points after surgery: 3 hours, 6 hours, 12 hours, and 24 hours. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels were measured as a marker of kidney dysfunction at the following time points: prior to surgery, immediately after surgery, 4 to 6 hours after surgery, and 16-to-18 hours after surgery. MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-two IAPs were measured, and 90 (35.7%) showed IAH. Thirty-five of 42 patients (83.3%) had IAH at 1 time point or more. Peak urine NGAL levels were lower in patients with normal IAP (mean difference = -130.6 ng/mL [95% CI = -211.2 to -50.1], p = 0.002). There was no difference in postoperative kidney dysfunction by risk, injury, failure, loss of kidney function, and end-stage kidney disease (RIFLE) criteria in patients with normal IAP (mean difference = -31.4% [95% CI = -48.0 to 6.3], p = 0.09). IAH was 100% sensitive for predicting postoperative kidney dysfunction by RIFLE criteria, but had poor specificity (54.8%). CONCLUSIONS: IAH occurs frequently during the perioperative period in cardiac surgery patients and may be associated with postoperative kidney dysfunction.

Review of Venoarterial Extracorporeal Membrane Oxygenation and Development of Intracardiac Thrombosis in Adult Cardiothoracic Patients.

Venoarterial extracorporeal membrane oxygenation (VA ECMO) has become an indispensable treatment option for adult cardiothoracic patients experiencing acute refractory cardiogenic shock. VA ECMO is not without inherent complications as in-hospital mortality has ranged from 45% to 65% (1-3). Intracardiac thrombosis (ICT) is a rare but life-threatening complication associated with VA ECMO. VA ECMO cases complicated by ICT were searched for using the MEDLINE (PubMed and OVID), Society of Cardiovascular Anesthesiology Headquarters, and Google Scholar databases. Twelve cases of VA ECMO-associated ICT were discovered for review. Indications for VA ECMO were postcardiotomy cardiogenic shock and heart failure. The primary location of thrombus was the left ventricle and aortic root. Majority of the cases did not report subtherapeutic systemic anticoagulation. Two patients survived after the development of ICT. VA ECMO-associated ICT is a devastating consequence with high mortality. The majority of ICT occurred in cases with perceived adequate anticoagulation, but this may not result in complete suppression of the coagulation response. Continued exposure to procoagulant stimuli and worsening ventricular function and intracardiac stasis can shift the balance toward a hypercoagulable state and development of thrombosis.

Less Invasive Left Ventricular Assist Device Implantation Is Safe and Feasible in Patients With Smaller Body Surface Area.

OBJECTIVE: Smaller body surface area (BSA) frequently precludes patients from left ventricular assist device (LVAD) therapy. We sought to investigate the clinical outcomes in patients with small BSA undergoing less invasive LVAD implantation. METHODS: We conducted a retrospective review of 216 patients implanted with HeartMate 3 LVAD (Abbott, Chicago, IL) via less invasive surgery at our institution. Patients were dichotomized based on their preimplant BSA for comparison between small BSA (≤1.8 m2) and normal/large BSA (>1.8 m2). We analyzed patient perioperative characteristics and outcomes. RESULTS: In our study, small BSA was found in 32 patients (14.8%), while 184 patients (85.2%) had normal/large BSA. Women were more prevalent in the small BSA group (50.0% vs 13.0%, P < 0.001). Preoperative and intraoperative data showed comparable results. Major complications and hospital length of stay did not differ by BSA group. Patients with smaller BSA had significantly decreased pump parameters at discharge, including LVAD flow (4.11 ± 0.49 vs 4.60 ± 0.54 L/min, P < 0.001) and pump speed (5,200 vs 5,400 rpm, P < 0.001). Survival to discharge and within 6 months after implantation were similar between the groups. CONCLUSIONS: Our study results suggest that less invasive HeartMate 3 implantation can be safely performed and demonstrates equivalent outcomes in patients with smaller body habitus. Randomized trials are required to confirm our data.

Cancer Treatment Patterns and Factors Affecting Receipt of Treatment in Older Adults: Results from the ASPREE Cancer Treatment Substudy (ACTS).

INTRODUCTION: Cancer treatment planning in older adults is complex and requires careful balancing of survival, quality of life benefits, and risk of treatment-related morbidity and toxicity. As a result, treatment selection in this cohort tends to differ from that for younger patients. However, there are very few studies describing cancer treatment patterns in older cohorts. METHODS: We used data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and the ASPREE Cancer Treatment Substudy (ACTS) to describe cancer treatment patterns in older adults. We used a multivariate logistic regression model to identify factors affecting receipt of treatment. RESULTS: Of 1893 eligible Australian and United States (US) participants with incident cancer, 1569 (81%) received some form of cancer treatment. Non-metastatic breast cancers most frequently received treatment (98%), while haematological malignancy received the lowest rates of treatment (60%). Factors associated with not receiving treatment were older age (OR 0.94, 95% CI 0.91-0.96), residence in the US (OR 0.34, 95% CI 0.22-0.54), smoking (OR 0.57, 95% CI 0.40-0.81), and diabetes (OR 0.56, 95% CI 0.39-0.80). After adjustment for treatment patterns in sex-specific cancers, sex did not impact receipt of treatment. CONCLUSIONS: This study is one of the first describing cancer treatment patterns and factors affecting receipt of treatment across common cancer types in older adults. We found that most older adults with cancer received some form of cancer treatment, typically surgery or systemic therapy, although this varied by factors such as cancer type, age, sex, and country of residence.

Application of ultrasensitive digital ELISA for p24 enables improved evaluation of HIV-1 reservoir diversity and growth kinetics in viral outgrowth assays.

The advent of combined antiretroviral therapy (cART) has been instrumental in controlling HIV-1 replication and transmission and decreasing associated morbidity and mortality. However, cART alone is not able to cure HIV-1 due to the presence of long-lived, latently infected immune cells, which re-seed plasma viremia when cART is interrupted. Assessment of HIV-cure strategies using ex vivo culture methods for further understanding of the diversity of reactivated HIV, viral outgrowth, and replication dynamics are enhanced using ultrasensitive digital ELISA based on single-molecule array (Simoa) technology to increase the sensitivity of endpoint detection. In viral outgrowth assays (VOA), exponential HIV-1 outgrowth has been shown to be dependent upon initial virus burst size surpassing a critical growth threshold of 5100 HIV-1 RNA copies. Here, we show an association between ultrasensitive HIV-1 Gag p24 concentrations and HIV-1 RNA copy number that characterize viral dynamics below the exponential replication threshold. Single-genome sequencing (SGS) revealed the presence of multiple identical HIV-1 sequences, indicative of low-level replication occurring below the threshold of exponential outgrowth early during a VOA. However, SGS further revealed diverse related HIV variants detectable by ultrasensitive methods that failed to establish exponential outgrowth. Overall, our data suggest that viral outgrowth occurring below the threshold necessary for establishing exponential growth in culture does not preclude replication competence of reactivated HIV, and ultrasensitive detection of HIV-1 p24 may provide a method to detect previously unquantifiable variants. These data strongly support the use of the Simoa platform in a multi-prong approach to measuring latent viral burden and efficacy of therapeutic interventions aimed at an HIV-1 cure.

Treatment of hemophagocytic lymphohistiocytosis with alemtuzumab in systemic lupus erythematosus.

Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder characterized by cytokine dysregulation and uncontrolled activation of T lymphocytes and macrophages. It is categorized as primary when associated with specific genetic mutations or secondary when associated with infections, malignancies, or autoimmune disorders. Clinical features of HLH include unexplained fever, hepatosplenomegaly, pancytopenia, and severe hyperferritinemia. Treatment of primary HLH has become standardized based on the HLH-2004 protocol using cyclosporine, etoposide, and dexamethasone with or without intrathecal methotrexate followed by hematopoietic stem cell transplantation. Treatment of secondary HLH is directed at control of the underlying condition. If unsuccessful, cytotoxic agents such as those in HLH-2004, steroids, intravenous γ-globulin, or targeted immune therapy have been used. Immunotherapy targeting CD52 expressed on immune effector cells of HLH is a rational therapeutic approach in patients too ill for traditional cytotoxic chemotherapy. We describe the successful use of alemtuzumab to treat HLH due to systemic lupus erythematosus.

Pulmonary function testing.

PURPOSE OF REVIEW: To review the recent literature related to pulmonary function testing and how it relates to the preoperative evaluation. RECENT FINDINGS: There is increased interest in the field of pulmonary arterial hypertension. It is important to determine the clinical implications of this disease and determine whether preoperative therapy is indeed effective. Also, there is a need for the development of new noninvasive diagnostic techniques to identify patients at risk of pulmonary arterial hypertension. SUMMARY: Pulmonary function testing can be used to quantify lung function, confirm an individual's functional status, evaluate regimen effectiveness, and determine disability. They may be essential in all candidates for lung resection. However, there are limits in the current testing of pulmonary function. There is new evidence that exercise testing may provide better diagnostic and prognostic information about patients with cardiovascular and pulmonary disease.

Adoptive transfer of costimulated CD4+ T cells induces expansion of peripheral T cells and decreased CCR5 expression in HIV infection.

To study the safety and feasibility of T-cell reconstitution in HIV-infected individuals, we adoptively transferred activated autologous CD4+ T cells. Polyclonal peripheral blood CD4+ cells were costimulated ex vivo and subjects were given infusions of up to 3 x 1010 activated CD4+ cells. Dose-dependent increases in CD4+ cell counts and in the CD4:CD8 ratio were observed. Sustained increases in the fraction of cytokine-secreting T cells and decreases in the percentage of CD4+CCR5+ cells were noted in vivo, suggesting enhanced function and resistance to HIV infection. The frequency of CD4+Ki-67+ cells increased whereas CD4+ T cells containing T cell-receptor rearrangement excision circles (TRECs) decreased. These findings indicate that expansion of the peripheral T-cell pool mediated the increase in CD4 counts and suggest that approaches to reconstitute CD4 helper cell activity and decrease CCR5 expression may augment natural immunity to HIV infection.

Study results suggest less invasive HeartMate 3 implantation is a safe and effective approach for obese patients.

BACKGROUND: Historically, obesity was considered a relative contraindication to left ventricular assist device (LVAD) implantation with less invasive surgery (LIS). The present study aimed to compare the outcomes of obese patients who underwent LVAD implantation through LIS with those who received full sternotomy (FS) implantation. METHODS: We retrospectively reviewed all patients implanted with HeartMate 3 LVAD in our institution between September 2015 and June 2020. Obese patients (BMI ≥ 30 kg/m2) were included and dichotomized based on surgical approach into the FS or LIS cohort. RESULTS: Of 231 implanted patients, 107 (46%) were obese and included in the study. FS was performed in 26 (24%) patients and LIS approach in 81 (76%) patients. Preoperative patient characteristics were similar between the cohorts. Postoperatively, patients in LIS cohort had less bleeding (p = 0.029), fewer transfusions (p = 0.042), shorter duration of inotropic support (p = 0.049), and decreased incidence of severe RV failure (11.1% vs 30.8%, p = 0.028). Survival to discharge for the obese population was 87.5% overall and did not differ based on an approach (91.4% LIS vs 76.9% FS, p = 0.079). More LIS patients were discharged home (60.0% vs 82.4%, p = 0.041) rather than to rehabilitation center. CONCLUSION: Our results showed that the LIS approach in obese patients is associated with fewer postoperative complications and a trend towards better short-term survival. These results suggest that less invasive LVAD implantation is a safe and effective approach for obese patients. Future prospective randomized trials are required to substantiate these results.

Effect of Aspirin on Cancer Incidence and Mortality in Older Adults.

BACKGROUND: ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality. METHODS: 19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records. RESULTS: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64). CONCLUSIONS: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group.

Dissection of the left main coronary artery during percutaneous intervention: successful surgical management.

Coronary dissection during diagnostic catheterization presents a therapeutic challenge. Medical management or percutaneous intervention may be an option in a stable patient. Unstable patients should promptly undergo surgical revascularization. We report on a patient in whom dissection of the left main coronary artery, the left anterior descending artery, and a diagonal branch occurred during catheterization. Clear signs of myocardial ischemia indicated immediate surgery. Coronary artery bypass grafting was carried out within a very short time frame and the patient survived. This case demonstrates the value of an expeditious surgical treatment strategy.