Packing the donor heart: Is SherpaPak cold preservation technique safer compared to ice cold storage.

INTRODUCTION: The present study aimed to compare the clinical outcomes of heart transplant patients whose donor hearts were preserved with the SherpaPak controlled cold organ system versus the conventional ice storage technique. METHODS: All patients undergoing heart transplantation at our center between January 2019 and April 2021 were divided into two groups according to the technique used during donor heart preservation and transport. The first group consisted of 34 SherpaPak controlled temperature preservation patients, and the second group consisted of 47 patients where the conventional three bags and ice technique was utilized during organ transportation. The two groups were compared based on demographics, operative details, and postoperative outcomes. RESULTS: There were no significant differences between the groups regarding Vasoactive Inotropic Score (VIS), Primary Graft Dysfunction (PGD), and the need for a transient pacer. However, the VIS, PGD, and pacing trends were lower in the SherpaPak patients even though the total ischemic and cardiopulmonary bypass times were significantly longer. Furthermore, SherpaPak patients exhibited a shorter stay in the ICU with no severe PGD and mortality. CONCLUSION: The SherpaPak donor heart preservation provides safe outcomes in heart transplant patients. Further research is needed to utilize this method for longer durations of ischemic time and expand travel distances for organ transportation.

Controlled temperatures in cold preservation provides safe heart transplantation results.

BACKGROUND: We aimed to investigate the short-term outcomes of heart transplant patients who underwent SherpaPak™ donor organ preservation. METHOD: We prospectively collected the data of patients who underwent heart transplantation using SherpaPak™ system for donor organ transportation from February 2020 to March 2021. Donor and recipient demographic data, preoperative and postoperative echocardiographic and hemodynamic parameters, total ischemic time and SherpaPak temperatures, vasoactive inotropic scores (VIS), primary graft dysfunction (PGD) status, intensive care unit stay, complications, and mortality during follow-up were assessed. RESULTS: A total of 39 consecutive heart transplant patients with SherpaPak system were included in the study. The mean donor age was 32.2 ± 6.7 (range: 16-46). The mean recipient age was 57.5 ± 12 (range: 19-73). The mean preoperative ejection fraction (EF) was 23.7 ± 15.4 (range: 5-75). All recipients underwent a standard bicaval technique for orthotopic heart implantation. The mean total ischemic time was 230.1 ± 41 (range: 149-342) min. The mean Sherpa temperature was 5.6 ± 0.8°C (range: 3.7-7.5). The mean VIS was 10.2 ± 6.5 (range: 2-32). The number of mild PGD was 5 (14.7%), and moderate PGD was 4 (11.8%). There was no severe PGD. The postoperative EF was 64.3 ± 5.5 (range: 50-78). Mean intubation time was 47.4 ± 64 (range: 8-312, median: 22) h. The mean time of intensive care unit stay was 6.3 ± 5 (range: 2-31, median: 5) days. Two patients required chest revision (5.8%), two patients had lung infection (5.8%). Two patients had a stroke (5.8%). There was no mortality. CONCLUSION: Using the SherpaPak system during heart transplantation is safe and not associated with significant recipient morbidity. None of the recipients experienced significant PGD and mortality.

Can you hear me now? The effect of signal degradation on perceived predator threat in black-capped chickadees (Poecile atricapillus).

Avian predators vary in their degree-of-threat to chickadees; for example, smaller owls and hawks are of higher threat to chickadees as they can easily maneuver through the trees, while larger predators cannot. We conducted an operant go/no-go discrimination task to investigate the effect of signal degradation on perceived threat. Chickadees were trained to respond to high-threat northern saw-whet owl (NSWO) or low-threat great horned owl (GHOW) calls that were recorded at short distances, and then tested with high- and low-threat owl calls that were rebroadcast and re-recorded across six distances (25 m, 50 m, 75 m, 100 m, 150 m, and 200 m). Subjects were further tested with high-threat and low-threat synthetic tones produced to mimic the natural calls across the six distances. We predicted that birds would perceive and respond to: (1) high-threat predator calls at longer distances compared to low-threat predator calls, and (2) synthetic tones similarly compared to the stimuli that they were designed to mimic. We believed chickadees would continue to perceive and respond to predators that pose a high threat at further distances; however, only responding to low-threat stimuli was consistent across distance recordings. Synthetic tones were treated similarly to natural stimuli but at lower response levels. Thus, the results of this study provide insights into how chickadees perceive threat.

Acoustic discrimination of predators by black-capped chickadees (Poecile atricapillus).

Smaller owls and hawks are high-threat predators to small songbirds, like chickadees, in comparison to larger avian predators due to smaller raptors' agility (Templeton et al. in Proc Natl Acad Sci 104:5479-5482, 2005). The current literature focuses only on high- and low-threat predators. We propose that there may be a continuum in threat perception. In the current study, we conducted an operant go/no-go experiment investigating black-capped chickadees' acoustic discrimination of predator threat. After obtaining eight hawk and eight owl species' calls, we assigned each species as: (1) large, low-threat, (2) mid-sized, unknown-threat and (3) small-, high-threat predators, according to wingspan and body size. Black-capped chickadees were either trained to respond ('go') to high-threat predator calls or respond to low-threat predator calls. When either low-threat predator calls were not reinforced or high-threat predator calls were not reinforced the birds were to withhold responding ('no-go') to those stimuli. We then tested transfer of training with additional small and large predator calls, as well as with the calls of several mid-sized predators. We confirmed that chickadees can discriminate between high- and low-threat predator calls. We further investigated how chickadees categorize mid-sized species' calls by assessing transfer of training to previously non-differentially reinforced (i.e., pretraining) calls. Specifically, transfer test results suggest that mid-sized broad-winged hawks were perceived to be of high threat whereas mid-sized short-eared owls were perceived to be of low threat. However, mid-sized Cooper's hawks and northern hawk owls were not significantly differentially responded to, suggesting that they are of medium threat which supports the notion that perception of threat is along a continuum rather than distinct categories of high or low threat.

Kidney transplantation on extracorporeal life support for primary cardiac allograft dysfunction.

Patients undergoing heart-kidney transplants who have primary graft dysfunction (PGD) of the heart are at risk of losing both organs, which may cause reluctance on the part of the transplant team to proceed with transplanting the kidney while the transplanted heart is being supported by mechanical device. We describe a case series in which 2 patients received kidney transplants while on veno-arterial ECMO support for PGD after heart transplant. Both patients are alive more than 1 year following transplant, with good cardiac and renal function and no signs of cardiac rejection. Kidney transplant surgery is safe for patients on veno-arterial ECMO support for cardiac PGD. It allows the heart recipient to receive a kidney from the same donor with both immunologic and survival advantages.

Methanogenic Archaea dominate mature heartwood habitats of Eastern Cottonwood (Populus deltoides).

While recent reports demonstrate that the direct emission of methane from living tree trunks may be a significant terrestrial emission source, there has been debate whether tree emissions are due to transport from soils or produced in the wood environment itself. Reports of methanogens from wood of trees were prominent in the literature 40 years ago but have not been revisited with molecular ecology approaches. We examined communities associated with Populus deltoides using rRNA gene sequence analyses and how these vary with tree and wood properties. Our data indicate that wood environments are dominated by anaerobic microbiomes. Methanogens are prominent in heartwood (mean 34% relative abundance) compared to sapwood environments (13%), and dominant operational taxonomic units (OTUs) were classified as the Methanobacterium sp. Members of the Firmicutes phylum comprised 39% of total sequences and were in 42% greater abundance in sapwood over heartwood niches. Tree diameter was the strongest predictor of methanogen abundance, but wood moisture content and pH were also significant predictors of taxon abundance and overall community composition. Unlike microbiomes of the soil, rhizosphere and phyllosphere, wood associated communities are shaped by unique environmental conditions and may be prominent and overlooked sources of methane emissions in temperate forest systems.

Extracorporeal membrane oxygenation as a salvage therapy for patients with severe primary graft dysfunction after heart transplant.

BACKGROUND: Severe primary graft dysfunction (PGD) is the leading cause of early death after heart transplant. AIM: To examine the outcomes of heart transplant recipients who received venoarterial extracorporeal membrane oxygenation (VA-ECMO) for severe PGD. METHODS: We reviewed electronic health records of adult patients who underwent heart transplant from November 2005 through June 2015. We defined severe PGD according to International Society for Heart and Lung Transplantation consensus statements. RESULTS: Of 1030 heart transplant patients, 31 (3%) had severe PGD and required VA-ECMO. The mean (range) age was 59 (43-69) years. Fifteen patients (48%) underwent prior sternotomy and 10 (32%) received a left ventricular assist device as a bridge to transplant. Severe PGD manifested as failure to wean from cardiopulmonary bypass in 20 patients (65%) and as severe hemodynamic instability in the immediate postoperative period in 10 (32%), including cardiac arrest in 3 (10%). Twenty-five patients (81%) were successfully weaned from VA-ECMO, and 19 (61%) were discharged; the other 12 (39%) died. CONCLUSIONS: Although VA-ECMO is a common method for providing mechanical circulatory support to patients with PGD, multicenter studies are needed to assess factors associated with successful outcomes and improved survival of these patients.

Association of Anemia with Outcomes of Acute Heart Failure.

OBJECTIVES: Anemia is common in patients presenting with acute congestive heart failure (CHF); when hemoglobin (HGB) declines to low levels, it can result in worse outcomes. The aim of this study was to determine a level of HGB on admission or discharge that affects outcomes in patients with CHF and then to evaluate the effect of the low HGB levels on these outcomes. METHODS: We conducted a retrospective cohort study of 756 patients admitted with acute CHF during the period January 1, 2011-December 31, 2014. We used multivariable regression analysis to evaluate the relation among HGB levels and three major outcomes: 3-year mortality, 30-day readmission rate, and length of stay (LOS). RESULTS: Compared with patients with HGB ≥10 g/dL, patients with HGB <10 g/dL on discharge from the hospital had higher mortality (3-year survival 46% vs 33%, P = 0.023) and 30-day readmission rates (23% vs 14%; P = 0.008) and increased LOS (4.8 vs 3.2 days, P < 0.001). Patients with admission HGB <10 g/dL had higher mortality rates (3-year survival 45% vs 32%, P = 0.019) and increased LOS (4.5 vs 3.4 days, P = 0.014). A lower admission HGB value was associated with higher 30-day readmission rates, but it was not statistically significant (P = 0.06). CONCLUSIONS: An HGB level <10 g/dL on admission or discharge in patients hospitalized with acute CHF is associated with a significantly worse outcome.

Feasibility of Canine Therapy Among Hospitalized Pre-Heart Transplant Patients.

OBJECTIVES: Canine-assisted therapy (CAT) has been used in many settings with much success, yet no study has assessed its feasibility and receptiveness in hospitalized patients awaiting heart transplantation. METHODS: Patients admitted to our institution with a status I for heart transplantation during a 12-month period (April 2014-April 2015) were prospectively included in a feasibility pilot study. Patients were included if there was no history of transmittable disease or active infectious process and consented for study participation. Each patient was visited daily by a canine and quantitative and qualitative data regarding the visit were obtained. RESULTS: A total of 11 patients were included in the study. Most patients were men (n = 8, 72.7%) and the average age was 51.1 years. A total of 146 individual therapies took place, totaling 2718 minutes of CAT during the study period. Each patient had an average of 13.3 visits and each visit had an average duration of 14.7 minutes. Patient receptiveness, as measured by the CAT volunteer, averaged 9.9 (scale 0-10). No reports of infection transmission occurred. CONCLUSIONS: Our study found that CAT among hospitalized pre-heart transplant patients is feasible and is a welcomed adjunct to usual medical care.

Stiff right atrial syndrome? A complex clinical case report utilizing multimodality imaging and invasive hemodynamics.

Background: Stiff left atrial syndrome is a well-established cause of heart failure symptoms. A parallel entity involving the right atrium (RA) has not previously been described. We present a case of refractory right heart failure (RHF) 12 years following orthotopic heart transplantation. Case summary: Patient underwent annuloplasty ring placement for severe tricuspid regurgitation in 2018 and kidney transplantation in 2020. The use of multimodality imaging and a multidisciplinary approach suggested a stiff RA as a potential etiology to refractory symptoms. Redo-heart and kidney transplantation in March 2021 led to the resolution of symptoms without recurrence. Discussion: We propose stiff right atrial syndrome that may need to be considered in the setting of refractory RHF primarily suggested by significant right atrial enlargement and restrictive physiology.

Communication Training Helps to Reduce Burnout During COVID-19 Pandemic.

Objective: To determine the effectiveness of communication training and its impact on burnout among healthcare providers (physicians, physician assistants, nurse practitioners), in the setting of the COVID-19 pandemic. Methods: To evaluate the effectiveness of communication training on burnout during the COVID-19 pandemic, healthcare providers participating in a Communication in Healthcare (CIH) module between October 31, 2019, through February 20, 2020, were identified using a scanned sign-in sheet. A 3-question online survey regarding the utilization of communication skills during the COVID-19 pandemic was sent via email. An ordinal scale was used to rate the effectiveness of the training on subsequent burnout and work satisfaction during the pandemic. Results: Of the 98 surveys distributed via email, a total of 33 participants completed the survey. Seventy-three percent of respondents agreed that communication training helped prevent burnout, and 39% strongly agreed that the modules improved work satisfaction. Conclusion: Our study found communication training was effective in reducing burnout in healthcare providers, in the setting of the COVID-19 pandemic. The participants felt the communication tools learned from the training modules were useful in improving work satisfaction and communication with patients during the pandemic.

Donation after circulatory death: A transplant cardiologist's take on neuroprognostication.

Donation after circulatory death (DCD) is becoming increasingly utilized in heart transplantation and has the potential to further expand the donor pool. As transplant cardiologists gain more familiarity with DCD donor selection, there are many issues that lack consensus including how we incorporate the neurologic examination, how we measure functional warm ischemic time (fWIT), and what fWIT thresholds are acceptable. DCD donor selection calls for prognostication tools to help determine how quickly a donor may expire, and in current practice there is no standardization in how we make these predictions. Current scoring systems help to determine which donor may expire within a specified time window either require the temporary disconnection of ventilatory support or do not incorporate any neurologic examination or imaging. Moreover, the specified time windows differ from other DCD solid organ transplantation without standardization or strong scientific justification for these thresholds. In this perspective, we highlight the challenges faced by transplant cardiologists as they navigate the muddy waters of neuroprognostication in DCD cardiac donation. Given these difficulties, this is also a call to action for the creation of a more standardized approach to improve the DCD donor selection process for appropriate resource allocation and organ utilization.

One-year survival in recipients older than 50 bridged to heart transplant with Impella 5.5 via axillary approach.

BACKGROUND: Optimizing patients with advanced heart failure before orthotopic heart transplantation (OHT), especially in patients greater than 50 years old, is imperative to achieving successful post-transplant outcomes. Complications are well-described for patients bridged to transplant (BTT) with durable left ventricular assist device (LVAD) support. Given the lack of data available in older recipients after the recent increase in mechanical support use, we felt it crucial to report our center's one-year outcomes in older recipients after heart transplantation with percutaneously placed Impella 5.5 as a BTT. METHODS: Forty-nine OHT patients were supported with the Impella 5.5 intended as a bridge between December 2019 and October 2022 at Mayo Clinic in Florida. Data were extracted from the electronic health record at baseline and during their transplant episode of care after Institutional Review Boards approval as exempt for retrospective data collection. RESULTS: Thirty-eight patients aged 50 or older were supported with Impella 5.5 as BTT. Ten patients underwent heart and kidney transplantation within this cohort. The median age at OHT was 63 (58-68) years, with 32 male (84%) and six female patients (16%). Etiology was divided into ischemic (63%) and non-ischemic cardiomyopathy (37%). The baseline median ejection fraction was 19% (15-24). Most patients were in blood group O (60%), and 50% were diabetic. The average duration of support was 27 days (range 6-94). The median duration of follow-up is 488 days (185-693). For patients that have reached the 1-year follow-up timeframe (22 of 38, 58%), the 1-year post-transplant survival is 95%. CONCLUSION: Our single-center data provides awareness for using the Impella 5.5 percutaneously placed axillary support device in older heart failure patients in cardiogenic shock as a bridge to transplantation. One-year survival outcomes after heart transplantation are excellent despite the older recipient's age and prolonged pre-transplant support.

Axillary mechanical circulatory support improves renal function prior to heart transplantation in patients with chronic kidney disease.

Impaired kidney function is often associated with acute decompensation of chronic heart failure and portends a poor prognosis. Unfortunately, current data have demonstrated worse survival in patients with acute kidney injury than in patients with chronic kidney disease during durable LVAD placement as bridge therapy. Furthermore, end-stage heart failure patients undergoing combined heart-kidney transplantation have poorer short- and long-term survival than heart transplants alone. We evaluated the kidney function recovery in our heart failure population awaiting heart transplantation at our institution, supported by temporary Mechanical Circulatory Support (tMCS) with Impella 5.5. The protocol (#22004000) was approved by the Mayo Clinic institutional review board, after which we performed a retrospective review of all patients with acute on chronic heart failure and kidney disease in patients considered for only heart and kidney combined organ transplant and supported by tMCS between January 2020 and February 2021. Hemodynamic and kidney function trends were recorded and analyzed before and after tMCS placement and transplantation. After placement of tMCS, we observed a trend towards improvement in creatinine, Fick cardiac index, mixed venous saturation, and glomerular filtration rate (GFR), which persisted through transplantation and discharge. The average duration of support with tMCS was 16.5 days before organ transplantation. The median pre-tMCS creatinine was 2.1 mg/dL (IQR 1.75-2.3). Median hematocrit at the time of tMCS placement was 32% (IQR 32-34), and the median estimated glomerular filtration rate was 34 mL/min/BSA (34-40). The median GFR improved to 44 mL/min/BSA (IQR 45-51), and serum creatinine improved to 1.5 mg/dL (1.5-1.8) after tMCS. Median discharge creatinine was 1.1 mg/dL (1.19-1.25) with a GFR of 72 (65-74). None of these six patients supported with tMCS required renal replacement therapy after heart transplantation. Early adoption of Impella 5.5 in this patient population resulted in renal recovery without needing renal replacement therapies or dual organ transplantation and should be further evaluated.

Two mouse models of Alzheimer's disease accumulate amyloid at different rates and have distinct Aß oligomer profiles unaltered by ablation of cellular prion protein.

Oligomers formed from monomers of the amyloid ß-protein (Aß) are thought to be central to the pathogenesis of Alzheimer's disease (AD). Unsurprisingly for a complex disease, current mouse models of AD fail to fully mimic the clinical disease in humans. Moreover, results obtained in a given mouse model are not always reproduced in a different model. Cellular prion protein (PrPC) is now an established receptor for Aß oligomers. However, studies of the Aß-PrPC interaction in different mouse models have yielded contradictory results. Here we performed a longitudinal study assessing a range of biochemical and histological features in the commonly used J20 and APP-PS1 mouse models. Our analysis demonstrated that PrPC ablation had no effect on amyloid accumulation or oligomer production. However, we found that APP-PS1 mice had higher levels of oligomers, that these could bind to recombinant PrPC, and were recognised by the OC antibody which distinguishes parallel, in register fibrils. On the other hand, J20 mice had a lower level of Aß oligomers, which did not interact with PrPC when tested in vitro and were OC-negative. These results suggest the two mouse models produce diverse Aß assemblies that could interact with different targets, highlighting the necessity to characterise the conformation of the Aß oligomers concomitantly with the toxic cascade elicited by them. Our results provide an explanation for the apparent contradictory results found in APP-PS1 mice and the J20 mouse line in regards to Aß toxicity mediated by PrPC.

Short-term outcomes of heart transplant patients bridged with Impella 5.5 ventricular assist device.

AIMS: We sought to investigate the outcomes of heart transplant patients supported with Impella 5.5 temporary mechanical circulatory support. METHODS AND RESULTS: Patient demographics, perioperative data, hospital timeline, and haemodynamic parameters were followed during initial admission, Impella support, and post-transplant period. Vasoactive-inotropic score, primary graft failure, and complications were recorded. Between March 2020 and March 2021, 16 advanced heart failure patients underwent Impella 5.5 temporary left ventricular assist device support through axillary approach. Subsequently, all these patients had heart transplantation. All patients were either ambulatory or chair bound during their temporary mechanical circulatory support until heart transplantation. Patients were kept on Impella support median of 19 days (3-31) with the median lactate dehydrogenase level of 220 (149-430). All Impella devices were removed during heart transplantation. During Impella support, patients had improved renal function with median creatinine serum level of 1.55 mg/dL decreased to 1.25 (P = 0.007), pulmonary artery pulsatility index scores increased from 2.56 (0.86-10) to 4.2 (1.3-10) (P = 0.048), and right ventricular function improved (P = 0.003). Patients maintained improved renal function and favourable haemodynamics after their heart transplantation as well. All patients survived without any significant morbidity after their heart transplantation. CONCLUSIONS: Impella 5.5 temporary left ventricular assist device optimizes care of heart transplant recipients providing superior haemodynamic support, mobility, improved renal function, pulmonary haemodynamics, and right ventricular function. Utilizing Impella 5.5 as a direct bridging strategy to heart transplantation resulted in excellent outcomes.

Patellar Microfracture: Internal Stabilization House-on-Stilts Technique to Achieve Better Results.

Microfractures are the common first choice for the treatment of osteochondral lesions, because of their high efficacy and low cost and operating time compared with other surgical techniques. Results of microfractures for retropatellar chondral defects are subpar compared with other compartments of the knee, despite the patellofemoral compartment being the second most common compartment for such lesions. One major reason for the inferiority is the mobility of the patella, which is most prominent when the patient's knee is extended, as is the case in this type of surgery. Traditionally, this obstacle was dealt with by applying manual pressure, which is unreliable and prone to technical difficulties, such as skiving of the awl and a narrowed operating view, as well as complications such as fractures. This Technical Note introduces a new technique, which we have named "house-on-stilts," that uses multiple Kirschner wire fixations through the patella and femur to immobilize the patella and is essentially an internal stabilization. This technique aids not only the microfracturing process but also the preceding debridement stage, at no increased cost or operating time.

A high-content neuron imaging assay demonstrates inhibition of prion disease-associated neurotoxicity by an anti-prion protein antibody.

There is an urgent need to develop disease-modifying therapies to treat neurodegenerative diseases which pose increasing challenges to global healthcare systems. Prion diseases, although rare, provide a paradigm to study neurodegenerative dementias as similar disease mechanisms involving propagation and spread of multichain assemblies of misfolded protein ("prion-like" mechanisms) are increasingly recognised in the commoner conditions such as Alzheimer's disease. However, studies of prion disease pathogenesis in mouse models showed that prion propagation and neurotoxicity can be mechanistically uncoupled and in vitro assays confirmed that highly purified prions are indeed not directly neurotoxic. To aid development of prion disease therapeutics we have therefore developed a cell-based assay for the specific neurotoxicity seen in prion diseases rather than to simply assess inhibition of prion propagation. We applied this assay to examine an anti-prion protein mouse monoclonal antibody (ICSM18) known to potently cure prion-infected cells and to delay onset of prion disease in prion-infected mice. We demonstrate that whilst ICSM18 itself lacks inherent neurotoxicity in this assay, it potently blocks prion disease-associated neurotoxicity.

Parkin enhances the expression of cyclin-dependent kinase 6 and negatively regulates the proliferation of breast cancer cells.

Although mutations in the parkin gene are frequently associated with familial Parkinsonism, emerging evidence suggests that parkin also plays a role in cancers as a putative tumor suppressor. Supporting this, we show here that parkin expression is dramatically reduced in several breast cancer-derived cell lines as well as in primary breast cancer tissues. Importantly, we found that ectopic parkin expression in parkin-deficient breast cancer cells mitigates their proliferation rate both in vitro and in vivo, as well as reduces the capacity of these cells to migrate. Cell cycle analysis revealed the arrestment of a significant percentage of parkin-expressing breast cancer cells at the G1-phase. However, we did not observe significant changes in the levels of the G1-associated cyclin D1 and E. On the other hand, the level of cyclin-dependent kinase 6 (CDK6) is dramatically and selectively elevated in parkin-expressing breast cancer cells, the extent of which correlates well with the expression of parkin. Interestingly, a recent study demonstrated that CDK6 restrains the proliferation of breast cancer cells. Taken together, our results support a negative role for parkin in tumorigenesis and provide a potential mechanism by which parkin exerts its suppressing effects on breast cancer cell proliferation.