Prehabilitation Maximizing Functional Mobility in Patients With Cardiogenic Shock Supported on Axillary Impella.

Physical therapy (PT) benefits for critically ill patients are well recognized; however, little data exist on PT in patients receiving temporary mechanical circulatory support. In this single-center retrospective study (February 2017-January 2022), we analyzed 37 patients who received an axillary Impella device (Abiomed, Danvers, MA) and PT to "prehabilitate" them before durable left ventricular assist device (dLVAD) implantation. The Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility tool assessed the functional status at different points during admission. Immediately after Impella placement, the median AM-PAC score was 12.7 (interquartile range [IQR], 9-15), and the scores continued to significantly increase to 18.4 (IQR, 16-23) before dLVAD and up to 20.7 (IQR, 19-24) at discharge, indicating improved independence. No PT-related complications were reported. Thus, we hypothesize that critically ill patients initially deemed equivocal candidates may safely participate in PT while maximizing functional activities before dLVAD placement.

Healthcare resource utilisation and economic burden of patients with adequate and inadequate responses to biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis in Japan.

OBJECTIVE: To compare healthcare resource utilisation (HCRU) and direct costs between responders vs non-responders to advanced therapies for rheumatoid arthritis (RA). METHODS: Patients initiating ≥1 advanced therapy (Oct 2018-Sept 2019) with ≥1 RA claim (6-month pre-index period), ≥2 RA claims (any period), and ≥12 months follow-up were identified from the Medical Data Vision claims database. HCRU and all-cause and RA-related costs (direct medical, emergency department [ED], laboratory, and pharmacy) were compared between responders vs non-responders. Adjusted incidence rate ratios (IRRs) for HCRU or cost were calculated via multivariable analyses. RESULTS: Among 2,446 patients (non-responders [n=1,817]; responders [n=629]), non-responders had significantly longer hospitalisation days (IRR: 1.8 [95% CI: 1.2-2.6]), and significantly more ED visits (2.5 [1.5-4.2]) and prescriptions (1.1 [1.1-1.2]). Mean all-cause hospital/outpatient medical costs were significantly higher for non-responders (1.4 [1.3-1.6], ¥530,895 vs ¥357,009 [$;3,992 vs $;2,684] for responders; ¥173,886 [$;1,307] difference); RA-related medical costs showed a similar trend (¥351,306 vs ¥253,030 [$;2,641 vs $1,902]; ¥98,276 [$;739] difference). No differences between responders and non-responders were observed in mean all-cause and RA-related pharmacy costs. CONCLUSIONS: Non-responders to advanced therapies had greater HCRU and all-cause/RA-related direct costs as compared with responders, suggesting a need for more effective RA therapies to reduce the economic burden associated with non-response.

Surgical Explantation of Impella 5.5 With Inflow Thrombus in Patients Undergoing Durable Left Ventricular Assist Device Implantation.

The Impella 5.5® (Abiomed, Danvers, MA, USA) is a microaxial flow pump that promotes left ventricular unloading and improves end-organ perfusion before durable left ventricular assist device (LVAD) implantation. Thrombus formation after Impella 5.5 insertion can occur and represents a significant challenge to device explantation. Durable LVAD implantation is typically performed without aortic cross-clamping, so a dislodged thrombus can potentially embolize and lead to catastrophic events. We describe our technique to safely explant an Impella 5.5 in patients who develop a thrombus on the inflow portion of the device before surgical LVAD implantation.

Use of Percutaneous Left Ventricular Assist Device Before Durable Device Implantation in Patients With Cardiac Cachexia: Case Series.

Frailty and malnutrition in patients with heart failure are barriers to durable left ventricular assist device (D-LVAD) support and heart transplantation. Moreover, cachexia in patients with advanced heart failure carries a high mortality risk. There are no guidelines for these patients other than increased caloric intake and rehabilitation. Patients suffering from cardiac cachexia and heart failure may benefit from temporary, percutaneous assist device support to improve the underlying heart disease and reverse the catabolic state. We retrospectively reviewed patients from January 2017 to January 2022. All patients who received Impella support (5.0 or 5.5, Abiomed) before D-LVAD implantation were screened. Those who met the criteria for cardiac cachexia were included. Patient demographics, nutritional and biochemical markers, and survival data were collected. A total of 14 patients were included. The majority of patients were male (85.7%) with ischemic cardiomyopathy (64.3%). Caloric intake, physical strength, and ambulation improved. Prealbumin levels improved from a median of 13.7-18.0 mg/dl ( p < 0.006) while on Impella 5.0 or 5.5 support. All patients survived to discharge and the 6 month follow-up. In conclusion, use of the Impella device improves cardiogenic shock symptoms and, consequently, may improve cachexia status prior to D-LVAD implantation.

Perioperative Impella 5.5 Support for Surgical Aortic Valve Replacement: Pull Back/Push Through Technique, Safeguards, and Pitfalls.

In patients undergoing aortic valve surgery, preoperative reduced left ventricular ejection fraction is not uncommon and is associated with poor outcomes. Mechanical circulatory support (MCS) may be preemptively used in patients presenting with high periprocedural risk. The Impella 5.5 is a percutaneous left ventricular assist device that has been increasingly used in various cardiac surgeries. In this article, we present a step-by-step guide, safeguards, and pitfalls on how to replace the aortic valve and preserve this transaortic MCS device for postoperative support in patients with concomitant aortic valve pathology and left ventricular dysfunction.

Clinical and Economic Benefit of Achieving Disease Control in Psoriatic Arthritis and Ankylosing Spondylitis: A Retrospective Analysis from the OM1 Registry.

BACKGROUND: There is limited evidence on the clinical and economic benefit of achieving disease control in psoriatic arthritis (PsA) and ankylosing spondylitis (AS), thus we aimed to assess the impact of disease control on healthcare resource use (HCRU) and direct medical costs among US patients with PsA or AS over 1 year. METHODS: Data were derived from the US OM1 PsA/AS registries (PsA: 1/2013-12/2020; AS: 01/2013-4/2021) and the Optum Insight Clinformatics® Data Mart to identify adult patients with PsA or AS. Two cohorts were created: with disease control and without disease control. Disease control was defined as modified Disease Activity Index for Psoriatic Arthritis (DAPSA28) ≤ 4 for PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4 for AS. Outcomes were all-cause inpatient, outpatient, and emergency department (ED) visits and associated costs over a 1-year follow-up period. Mean costs per person per year (PPPY) were assessed descriptively and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were estimated for the likelihood of HCRU by logistic regression. RESULTS: The study included 1235 PsA (with disease control: N = 217; without: N = 1018) and 581 AS patients (with disease control: N = 342; without: N = 239). Patients without disease control were more likely to have an inpatient (aOR [95% CI]; PsA: 3.0 [0.9, 10.1]; AS: 7.7 [2.3, 25.1]) or ED (PsA: 1.6 [0.6, 4.2]; AS: 3.5 [1.5, 8.3]) visit than those with disease control. Those without disease control, vs. those with disease control, had greater PPPY costs associated with inpatient (PsA: $1550 vs. $443), outpatient (PsA: $1789 vs. $1327; AS: $2498 vs. $2023), and ED (PsA: $114 vs. $57; AS: $316 vs. $50) visits. CONCLUSIONS: Findings from this study demonstrate lower disease activity among patients with PsA and AS is associated with less HCRU and lower costs over the following year.

The use of veno-arterial extracorporeal membrane oxygenation in the octogenarian population: A single-center experience.

INTRODUCTION: Advanced age is a known risk factor for poor outcomes after veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for cardiac support. The use of ECMO support in patients over the age of 80 is controversial, and sometimes its use is contraindicated. We aimed to assess the use of ECMO in octogenarian patients to determine survival and complication rates. METHODS: A single-center, retrospective analysis was completed at a large, urban academic medical center. Patients requiring V-A ECMO support between December of 2012 and November of 2019 were included as long as the patient was at least 80 years of age at the time of cannulation. Post cardiotomy shock patients were excluded. RESULTS: A total of 46 patients met eligibility criteria; all received V-A ECMO support. Overall, the majority of patients (71.7%; 33/46) survived to decannulation, and 43.5% (20/46) survived to discharge. Patients who were previously rescued from percutaneous interventions tend to have a better survival than other patients (p = .06). The most common complications were renal and hemorrhagic. CONCLUSIONS: We demonstrated that advanced age alone should not disqualify patients from cannulating and supporting with V-A ECMO.

Aortic Root Dissection Due to an Automated Fastener Device.

Minimally invasive aortic valve replacement through a right thoracotomy is frequently performed in patients with aortic valve disease. The Cor-Knot Device (LSI Solutions) is an automated fastener that secures valve sutures. This case report is for a patient who developed postcardiotomy shock during a minimally invasive aortic valve surgery. The patient was found to have an aortic root dissection involving 90% of the aortic root circumference, including bilateral coronary ostia. The autopsy revealed that the aortic damage could be explained by a direct aortic intimal tear from the distal tip of the device shaft. The device was most likely not in perfect apposition to the sewing ring because of the restricted angle and space between the ribs.

Transaortic Placement of Percutaneous Mechanical Support Device via Partial Sternotomy: Feasible Option for Unsuitable Axillary Artery Access.

Acute decompensated refractory cardiogenic shock is an emergency in which the prompt instauration of mechanical circulatory support improves outcomes. The typical, initial approach for device delivery is via femoral vessels due to easy access and safety. If longer support is needed, the femoral access will severely impair the patient's mobility and can also limit the amount of support given as the new-generation devices are too large for direct arterial insertion. Upper-body arterial conduits (UBACs) are used for the delivery of larger, percutaneous ventricular assist devices (pVADs). The Impella 5.5 (Abiomed, Danvers, MA, USA) is a pVAD that can be deployed through a UBAC by either axillary/subclavian access or a transaortic approach. The latter approach is typically used in cases of postcardiotomy shock, in which the ascending aorta is already exposed through a full sternotomy. However, in some cases, the axillary artery is not suitable due to size (<6 mm in diameter), and a smaller pVAD is delivered into the heart. To avoid providing suboptimal support, we present an alternative, minimally invasive approach in which the larger device is delivered through the ascending aorta. This article summarizes the details of this approach through a mini upper partial sternotomy and reviews the relevant technical considerations.

Inter-Institutional Collaboration Between Quaternary and Tertiary Hospitals: Cardiac Surgery Impact.

BACKGROUND: An inter-institutional collaboration between a quaternary hospital (QH) with a high volume of cardiac surgery and a community-based, tertiary hospital (TH) with a newly established cardiac surgery program was established. METHODS: We retrospectively reviewed data of patients admitted to the TH between September 2015 and June 2017 for cardiac surgery. The decision to transfer a patient to the QH was based on a Society of Thoracic Surgeon-Predicted Risk of Mortality (STS-PROM) score of ≥ 3%, the potential need for hemodialysis, and other risk factors. The same team of surgeons performed operations at both hospitals. We analyzed the perioperative outcomes of the patients and the referral pattern. RESULTS: A total of 116 patients met eligibility criteria; 105 underwent surgery at the TH, while 11 were transferred to the QH. Among the 11 patients transferred to the QH, eight had a score of  3% (median = 8.2 [IQR 5.7-25.0]). The patients transferred to the QH prior to surgery had a significantly higher STS-PROM score (P = ≤ .001). Overall, the mortality of patients who underwent surgery at the TH was 0.9% (1/105); while surgeries at the QH had a mortality rate of 0% (0/11). CONCLUSION: The collaborative effort between high-volume cardiac surgery programs and emerging community-based hospitals showed acceptable outcomes in perioperative cardiac surgical mortality. Elevated STS-PROM scores (>3%), previous sternotomy and anticipation of coagulopathy, and low left ventricular ejection fraction or dilated ventricles are factors that influenced the need to transfer from a TH to QH.

Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial.

BACKGROUND: In previous clinical trials, patients with active rheumatoid arthritis (RA) treated with upadacitinib (UPA) have improved patient-reported outcomes (PROs). This post hoc analysis of SELECT-CHOICE, a phase 3 clinical trial, evaluated the impact of UPA vs abatacept (ABA) with background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on PROs in patients with RA with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR). METHODS: Patients in SELECT-CHOICE received UPA (oral 15 mg/day) or ABA (intravenous). PROs evaluated included Patient Global Assessment of Disease Activity (PtGA) by visual analog scale (VAS), patient's assessment of pain by VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), morning stiffness duration and severity, 36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Impairment (WPAI), and EQ-5D 5-Level (EQ-5D-5L) index score. Least squares mean (LSM) changes from baseline to weeks 12 and 24 were based on an analysis of covariance model. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) were compared using chi-square tests. RESULTS: Data from 612 patients were analyzed (UPA, n=303; ABA, n=309). Mean age was 56 years and mean disease duration was 12 years. One-third received ≥2 prior bDMARDs and 72% received concomitant methotrexate at baseline. At week 12, UPA- vs ABA-treated patients had significantly greater improvements in PtGA, pain, HAQ-DI, morning stiffness severity, EQ-5D-5L, 2/4 WPAI domains, and 3/8 SF-36 domains and Physical Component Summary (PCS) scores (P<0.05); significant differences persisted at week 24 for HAQ-DI, morning stiffness severity, SF-36 PCS and bodily pain domain, and WPAI activity impairment domain. At week 12, significantly more UPA- vs ABA-treated patients reported improvements ≥MCID in HAQ-DI (74% vs 64%) and SF-36 PCS (79% vs 66%) and 4/8 domain scores (P<0.05). CONCLUSIONS: At week 12, UPA vs ABA treatment elicited greater improvements in key domains of physical functioning, pain, and general health and earlier improvements in HAQ-DI. Overall, more UPA- vs ABA-treated patients achieved ≥MCID in most PROs at all timepoints; however, not all differences were statistically significant. These data, however, highlight the faster response to UPA treatment. TRIAL REGISTRATION: NCT03086343 , March 22, 2017.

Surgically Implanted Impella Device for Patients on Impella CP Support Experiencing Refractory Hemolysis.

The Impella CP (Abiomed Inc., Danvers, MA) is widely used in cardiac catheterization laboratories for patients presenting with cardiogenic shock, but it is also known to cause significant hemolysis. The risk of hemolysis can be reduced by properly positioning the device, ensuring an adequate volume status, and using full anticoagulation strategies; however, in some cases hemolysis persists. We present a case series of eight patients that were diagnosed with cardiogenic shock, underwent Impella CP placement, and then suffered from refractory hemolysis which was treated by upgrading the Impella device to the 5.0 or 5.5 version. Fifty percent (4/8) of the patients in this series were already receiving continuous renal replacement therapy, and the levels of plasma free hemoglobin (pFHb) and lactate dehydrogenase continued to increase after the implantation of the Impella CP. The median time between Impella CP placement and the diagnosis of refractory hemolysis was 16.5 hours (interquartile range [IQR], 8.0-26.0). The median time between the diagnosis of hemolysis to Impella upgrade was 6.0 hours (IQR, 4.0-7.0). A total of 87.5% (7/8) of patients experienced a drop in pFHb to below 40 mg/dl at 72 hours post-Impella upgrade, and they were discharged without any further need of dialysis. One patient expired due to irreversible multiple organ failure. We propose that early identification of hemolysis by close monitoring of pFHb and upgrading to the Impella 5.5 reduces hemolysis, prevents further kidney damage, and significantly improves clinical outcomes.

Impella CP to Impella 5.5 Uninterrupted Upgrade Using a Double Device Technique.

For the first time, we present a novel technique that enables the exchange of the Impella CP (Abiomed Inc., Danvers, Massachusetts, USA) to the Impella 5.5 (Abiomed Inc.) with no interruption of mechanical support in patients with minimal left ventricular reserve. Specifically, the aortic valve is crossed with the Impella 5.5 whereas the Impella CP is still functioning within the left ventricle. The Impella 5.5 is then initiated, and the Impella CP is weaned. Finally, the Impella CP is pulled out into the descending aorta. This exchange provides continuous support with no hemodynamic disarrangement.

Traumatic respiratory failure and veno-venous extracorporeal membrane oxygenation support.

BACKGROUND: Respiratory failure (RF) is a common cause of death and morbid complication in trauma patients. Extracorporeal membrane oxygenation (ECMO) is increasingly used in adults with RF refractory to invasive mechanical ventilation. However, use of ECMO remains limited for this patient population as they often have contraindications for anticoagulation. STUDY DESIGN: Medical records were retroactively searched for all adult patients who were admitted to the trauma service and received veno-venous ECMO (VV ECMO) support between June 2015 and August 2018. Survival to discharge and ECMO-related complications were collected and analyzed. RESULTS: Fifteen patients from a large Level I trauma center met the criteria. The median PaO2/FiO2 ratio was 53.0 (IQR, 27.0-76.0), median injury severity score was 34.0 (IQR, 27.0-43.0), and the median duration of ECMO support was 11 days (IQR, 7.5-20.0). For this cohort, the survival-to-discharge rate was 87% (13/15). The incidence of neurologic complications was 13%, and deep vein thrombosis was reported in two cases (13%). CONCLUSIONS: Survival rates of trauma patients in this study are equivalent to, or may exceed, those of non-trauma patients who receive ECMO support for other types of RF. With the employment of a multidisciplinary team assessment and proper patient selection, early cannulation, traumatic RF may be safely supported with VV ECMO in experienced centers.

Benefit-Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit-risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the number needed to harm (NNH). This analysis evaluated the comparative risk-benefit of UPA versus adalimumab (ADA). METHODS: Post-hoc analyses were performed using data from the SELECT-COMPARE trial of UPA versus placebo (PBO) and UPA versus ADA among patients with active RA who remained on stable methotrexate (MTX) treatment and had an inadequate response; patients who failed to achieve response were rescued by predefined criteria-PBO or ADA switch to UPA, and UPA switch to ADA (all patients on PBO were switched to UPA at week 26). This analysis assessed efficacy and adverse events of special interest (AESIs) at week 26, 48, and 156 (3 years). NNT and NNH (95% confidence intervals) values were calculated between UPA versus ADA for all time points, and between UPA versus PBO for week 26. NNT and NNH values were applied to a hypothetical cohort of 100 patients to estimate the comparative efficacy and safety profiles. RESULTS: UPA consistently showed greater efficacy than ADA, as evidenced by NNT values < 10 for achievement of Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) of < 2.6 and ≤ 3.2, respectively, and functional improvement. Based on indices for disease assessment other than the DAS28-CRP, remission outcomes were higher with UPA versus ADA over 26 weeks (NNTs: 7-12), 48 weeks (NNTs: 9-16), and 156 weeks (NNTs: 9-15). With the exception of herpes zoster, other AESIs demonstrated a similar risk with UPA versus ADA. CONCLUSION: In patients with active RA despite MTX use, UPA demonstrated an incremental achievement of clinical outcomes compared to ADA together with a similar profile of AESIs with ADA (with the exception of herpes zoster).

Oncogenic HSP90 Facilitates Metabolic Alterations in Aggressive B-cell Lymphomas.

HSP90 is critical for maintenance of the cellular proteostasis. In cancer cells, HSP90 also becomes a nucleating site for the stabilization of multiprotein complexes including signaling pathways and transcription complexes. Here we described the role of this HSP90 form, referred to as oncogenic HSP90, in the regulation of cytosolic metabolic pathways in proliferating B-cell lymphoma cells. Oncogenic HSP90 assisted in the organization of metabolic enzymes into non-membrane-bound functional compartments. Under experimental conditions that conserved cellular proteostasis, oncogenic HSP90 coordinated and sustained multiple metabolic pathways required for energy production and maintenance of cellular biomass as well as for secretion of extracellular metabolites. Conversely, inhibition of oncogenic HSP90, in absence of apparent client protein degradation, decreased the efficiency of MYC-driven metabolic reprogramming. This study reveals that oncogenic HSP90 supports metabolism in B-cell lymphoma cells and patients with diffuse large B-cell lymphoma, providing a novel mechanism of activity for HSP90 inhibitors. SIGNIFICANCE: The oncogenic form of HSP90 organizes and maintains functional multienzymatic metabolic hubs in cancer cells, suggesting the potential of repurposing oncogenic HSP90 selective inhibitors to disrupt metabolism in lymphoma cells.