Psychosocial outcomes of children born via embryo donation.

STUDY QUESTION: What are parents' perceptions of their relationships with and the psychosocial adjustments of their children who are born via embryo donation? SUMMARY ANSWER: Families created through embryo donation have well-adjusted parent-child relationships and reassuring child psychosocial outcomes. WHAT IS KNOWN ALREADY: Embryo donation is an effective and growing form of third-party reproduction, but there is limited research in this field. Prior studies suggest that families created through gamete donation function well regarding parent-child relationship quality and child behavioral and socioemotional adjustment. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional survey study with 187 total participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: Parents of children born via embryo donation were recruited nationally by contacting all embryo donation programs registered with the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) as well as medically directed embryo donation or 'embryo adoption' centers. Participants completed three online Qualtrics questionnaires. The first was a survey including 33 questions on demographics, the procurement process, and self-reported obstetric outcomes. Participants also completed two standardized measures assessing children's behavior and parents' adjustment to parenthood: the Strengths and Difficulties Questionnaire (SDQ) and the Parental Acceptance-Rejection Questionnaire (PARQ). Scoring of the SDQ and PARQ was totaled and compared to standardized values (SDQ) or previously published results on other forms of gamete donation (PARQ), such as oocyte donation and sperm donation. MAIN RESULTS AND THE ROLE OF CHANCE: On the SDQ (n = 46), the average total difficulties scores by age were: 8.2 ± 0.98 for ages 2-4, 7.6 ± 0.93 for ages 5-10, and 3.5 ± 0.77 for ages 11-17; this is compared to the normal reported range of 0-13, which indicates that clinically significant psychosocial problems are unlikely. Across all ages and individual categories (emotional symptoms, conduct problem, hyperactivity, peer problem, prosocial), scores on the SDQ were within the normal ranges. The average PARQ score (n = 70) for all respondents was 27.5 ± 1.18 (range: 24-96), suggesting perceived parental acceptance. LIMITATIONS, REASONS FOR CAUTION: Because this study was cross-sectional, it could not capture familial relationships over time. This survey-based study design allows for potential selection bias (parents of well-adjusted children may be more likely to participate). Additionally, the overall sample size is relatively small; however, it remains one of the largest published to date. Another significant limitation to this study is the lack of generalizability: most participants were recruited from private, faith-based, embryo donation programs who are demographically similar. WIDER IMPLICATIONS OF THE FINDINGS: Though embryo donation is an established form of third-party reproduction, it is significantly less robustly studied compared to other forms of gamete donation (oocyte or sperm donation). This study provides a larger data set with a more expanded age range of children compared to the limited number of previously published studies. Furthermore, these findings indicate a high parental disclosure rate with respect to the use of embryo donation which contrasts previous findings. STUDY FUNDING/COMPETING INTEREST(S): No external funding source was utilized for the completion of this study. No conflicts are disclosed. TRIAL REGISTRATION NUMBER: N/A.

Donor Heart Recovery and Preservation Modalities in 2024.

Historically, heart transplantation (HT) has relied on the use of traditional cold storage for donor heart preservation. This organ preservation modality has several limitations, including the risk for ischemic and cold-induced graft injuries that may contribute to primary graft dysfunction and poor post-HT outcomes. In recent years, several novel donor heart preservation modalities have entered clinical practice, including the SherpaPak Cardiac Transport System of controlled hypothermic preservation, and the Transmedics Organ Care System of ex vivo perfusion. Such technologies are altering the landscape of HT by expanding the geographic reach of procurement teams and enabling both donation after cardiac death and the use of expanded criteria donor hearts. This paper will review the emerging evidence on the association of these modalities with improved post-HT outcomes, and will also suggest best practices for selecting between donor heart preservation techniques.

Cardiac Interventions in the Absence of Assent: An Ethical Dilemma.

A 63-year-old woman with schizophrenia presented with prosthetic mitral valve endocarditis complicated by complete heart block and declined surgical intervention. The patient was deemed to not have decisional capacity after a formal evaluation by the psychiatry service, and a surrogate decision-maker used the ethical principles of substituted judgment and best interest standards for surgical consent on behalf of the patient. The patient provided passive assent (did not resist transport to the operating room). The patient underwent successful redo mitral and aortic valve replacements and recovered well postoperatively. In conclusion, it is important for cardiovascular clinicians to be familiar with the ethical elements of surrogate decision-making, including patient autonomy and its limits, determination of decision-making capacity, and the standard of surrogate decision-making.

Diagnosis and treatment of right ventricular dysfunction in patients with COVID-19 on veno-venous extra-corporeal membrane oxygenation.

BACKGROUND: Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is an effective, but highly resource intensive salvage treatment option in COVID patients with acute respiratory distress syndrome (ARDS). Right ventricular (RV) dysfunction is a known sequelae of COVID-19 induced ARDS, yet there is a paucity of data on the incidence and determinants of RV dysfunction on VV ECMO. We retrospectively examined the determining factors leading to RV failure and means of early identification of this phenomenon in patients on VV ECMO. METHODS: The data was extracted from March 2020 to March 2021 from the regional University of Washington Extracorporeal Life Support database. The inclusion criteria included patients > 18 years of age with diagnosis of COVID-19. All had already been intubated and mechanically ventilated prior to VV ECMO deployment. Univariate analysis was performed to identify risk factors and surrogate markers for RV dysfunction. In addition, we compared outcomes between those with and without RV dysfunction. RESULTS: Of the 33 patients that met inclusion criteria, 14 (42%) had echocardiographic evidence of RV dysfunction, 3 of whom were placed on right ventricular assist device support. Chronic lung disease was an independent risk factor for RV dysfunction (p = 0.0002). RV dysfunction was associated with a six-fold increase in troponin I (0.07 ng/ml vs. 0.44 ng/ml, p = 0.039) and four-fold increase in brain natriuretic peptide (BNP) (158 pg/ml vs. 662 pg/ml, p = 0.037). Deep vein thrombosis (DVT, 21% vs. 43%, p = 0.005) and pulmonary embolism (PE, 11% vs. 21%, p = 0.045) were found to be nearly twice as common in the RV dysfunction group. Total survival rate to hospital discharge was 39%. Data trended towards shorter duration of hospital stay (47 vs. 65.6 days, p = 0.15), shorter duration of ECMO support (21 days vs. 36 days, p = 0.06) and improved survival rate to hospital discharge (42.1% vs. 35.7%, p = 0.47) for those with intact RV function compared to the RV dysfunction group. CONCLUSIONS: RV dysfunction in critically ill patients with COVID-19 pneumonia in common. Trends of troponin I and BNP may be important surrogates for monitoring RV function in patients on VV ECMO. We recommend echocardiographic assessment of the RV on such patients.

Right heart failure after left ventricular assist device: From mechanisms to treatments.

Left ventricular assist device (LVAD) therapy is a lifesaving option for patients with medical therapy-refractory advanced heart failure. Depending on the definition, 5-44% of people supported with an LVAD develop right heart failure (RHF), which is associated with worse outcomes. The mechanisms related to RHF include patient, surgical, and hemodynamic factors. Despite significant progress in understanding the roles of these factors and improvements in surgical techniques and LVAD technology, this complication is still a substantial cause of morbidity and mortality among LVAD patients. Additionally, specific medical therapies for this complication still are lacking, leaving cardiac transplantation or supportive management as the only options for LVAD patients who develop RHF. While significant effort has been made to create algorithms aimed at stratifying risk for RHF in patients undergoing LVAD implantation, the predictive value of these algorithms has been limited, especially when attempts at external validation have been undertaken. Perhaps one of the reasons for poor performance in external validation is related to differing definitions of RHF in external cohorts. Additionally, most research in this field has focused on RHF occurring in the early phase (i.e., ≤1 month) post LVAD implantation. However, there is emerging recognition of late-onset RHF (i.e., > 1 month post-surgery) as a significant cause of morbidity and mortality. Late-onset RHF, which likely has a unique physiology and pathogenic mechanisms, remains poorly characterized. In this review of the literature, we will describe the unique right ventricular physiology and changes elicited by LVADs that might cause both early- and late-onset RHF. Finally, we will analyze the currently available treatments for RHF, including mechanical circulatory support options and medical therapies.

Pathophysiology and management of valvular disease in patients with destination left ventricular assist devices.

Over the last two decades, implantable continuous flow left ventricular assist devices (LVAD) have proven to be invaluable tools for the management of selected advanced heart failure patients, improving patient longevity and quality of life. The presence of concomitant valvular pathology, including that involving the tricuspid, mitral, and aortic valve, has important implications relating to the decision to move forward with LVAD implantation. Furthermore, the presence of concomitant valvular pathology often influences the surgical strategy for LVAD implantation. Concomitant valve repair or replacement is not uncommonly required in such circumstances, which increases surgical complexity and has demonstrated prognostic implications both short and longer term following LVAD implantation. Beyond the index operation, it is also well established that certain valvular pathologies may develop or worsen over time following LVAD support. The presence of pre-existing valvular pathology or that which develops following LVAD implant is of particular importance to the destination therapy LVAD patient population. As these patients are not expected to have the opportunity for heart transplantation in the future, optimization of LVAD support including ameliorating valvular disease is critical for the maximization of patient longevity and quality of life. As collective experience has grown over time, the ability of clinicians to effectively address concomitant valvular pathology in LVAD patients has improved in the pre-implant, implant, and post-implant phase, through both medical management and procedural optimization. Nevertheless, there remains uncertainty over many facets of concomitant valvular pathology in advanced heart failure patients, and the understanding of how to best approach these conditions in the LVAD patient population continues to evolve. Herein, we present a comprehensive review of the current state of the field relating to the pathophysiology and management of valvular disease in destination LVAD patients.

The History of Durable Left Ventricular Assist Devices and Comparison of Outcomes: HeartWare, HeartMate II, HeartMate 3, and the Future of Mechanical Circulatory Support.

The utilization of left ventricular assist devices (LVADs) in end-stage heart failure has doubled in the past ten years and is bound to continue to increase. Since the first of these devices was approved in 1994, the technology has changed tremendously, and so has the medical and surgical management of these patients. In this review, we discuss the history of LVADs, evaluating survival and complications over time. We also aim to discuss practical aspects of the medical and surgical management of LVAD patients and future directions for outcome improvement in this population.

Does deeper hypothermia reduce the risk of acute kidney injury after circulatory arrest for aortic arch surgery?

OBJECTIVES: The impact of hypothermic circulatory arrest (HCA) temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between circulatory arrest temperatures and AKI in patients undergoing proximal aortic surgery with HCA. METHODS: A total of 759 consecutive patients who underwent proximal aortic surgery (ascending ± valve ± root) including arch replacement requiring HCA between July 2005 and December 2016 were identified from a prospectively maintained institutional aortic surgery database. The primary outcome was AKI as defined by Risk, Injury, Failure, Loss, End Stage Renal Disease (ESRD) criteria. The association between minimum nasopharyngeal (NP) and bladder temperatures during HCA and postoperative AKI was assessed, adjusting for patient-level factors using multivariable logistic regression. RESULTS: A total of 85% (n = 645) of patients underwent deep hypothermia (14.1-20.0°C), 11% (n = 83) low-moderate hypothermia (20.1-24.0°C) and 4% (n = 31) high-moderate hypothermia (24.1-28.0°C) as classified by NP temperature. When analysed by bladder temperature, 59% (n = 447) underwent deep hypothermia, 22% (n = 170) low-moderate, 16% (n = 118) high-moderate and 3% mild (n = 24) (28.1-34.0°C) hypothermia. The median systemic circulatory arrest time was 17 min. The incidence of AKI did not differ between hypothermia groups, whether analysed using minimum NP or bladder temperature. In the multivariable analysis, the association between degree of hypothermia and AKI remained non-significant whether analysed as a categorical variable (hypothermia group) or as a continuous variable (minimum NP or bladder temperature) (all P > 0.05). CONCLUSIONS: In patients undergoing proximal aortic surgery including arch replacement requiring HCA, degree of systemic hypothermia was not associated with the risk of AKI. These data suggest that moderate hypothermia does not confer increased risk of AKI for patients requiring circulatory arrest, although additional prospective data are needed.

Adjuvant Chemotherapy Improves Survival Following Resection of Locally Advanced Rectal Cancer with Pathologic Complete Response.

BACKGROUND: Controversy exists over the use of adjuvant chemotherapy for locally advanced (stages II-III) rectal cancer (LARC) patients who demonstrate pathologic complete response (pCR) following neoadjuvant chemoradiation. We conducted a retrospective analysis to determine whether adjuvant chemotherapy imparts survival benefit among this population. METHODS: The National Cancer Database (NCDB) was queried to identify LARC patients with pCR following neoadjuvant chemoradiation. The cohort was stratified by receipt of adjuvant chemotherapy. Multiple imputation and a Cox proportional hazards model were employed to estimate the effect of adjuvant chemotherapy on overall survival. RESULTS: There were 24,418 patients identified in the NCDB with clinically staged II or III rectal cancer who received neoadjuvant chemoradiation. Of these, 5606 (23.0%) had pCR. Among patients with pCR, 1401 (25%) received adjuvant chemotherapy and 4205 (75%) did not. Patients who received adjuvant chemotherapy were slightly younger, more likely to have private insurance, and more likely to have clinically staged III disease, but did not differ significantly in comparison to patients who did not receive adjuvant chemotherapy with respect to race, sex, facility type, Charlson comorbidity score, histologic tumor grade, procedure type, length of stay, or rate of 30-day readmission following surgery. On adjusted analysis, receipt of adjuvant chemotherapy was associated with a lower risk of death at a given time compared to patients who did not receive adjuvant chemotherapy (HR 0.808; 95% CI 0.679-0.961; p = 0.016). CONCLUSION: Supporting existing NCCN guidelines, the findings from this study suggest that adjuvant chemotherapy improves survival for LARC with pCR following neoadjuvant chemoradiation.

Risk Prediction Model for Major Adverse Outcome in Proximal Thoracic Aortic Surgery.

BACKGROUND: Proximal thoracic aortic surgery utilizing hypothermic circulatory arrest carries risks of mortality and major morbidity; however, these risks are not the same for every patient. The goal of the current study was to establish a risk prediction model for risk-stratifying patients undergoing proximal thoracic aortic surgery with hypothermic circulatory arrest for degenerative pathology, to facilitate preoperative physician-patient counseling. METHODS: A retrospective analysis was conducted on 489 patients who underwent proximal thoracic aortic surgery with hypothermic circulatory arrest for degenerative pathology between July 2005 and August 2014 at a single referral institution; patients with acute dissection (n = 139) were excluded. Multivariable logistic regression was used to build a risk prediction model and identify preoperative predictors of major adverse outcome-the composite endpoint of 30-day/inhospital mortality, stroke, acute renal failure, prolonged ventilation, or discharge to a location other than home. The results were validated using an independent cohort of 120 patients operated on from September 2014 to September 2016. RESULTS: Multivariable analysis identified age (p = 0.0002, odds ratio [OR] 2.01), total arch replacement (p ≤ 0.0001, OR 6.75), and procedure status (p = 0.0028; OR 2.73 for urgent, OR 43.58 for emergent) as independent predictors associated with major adverse outcome. The calibration curve for probability of major adverse outcome showed excellent agreement between the model and observations. The concordance index was 0.93 in external validation. CONCLUSIONS: The current study identified risk factors for major adverse outcome after proximal thoracic aortic surgery with hypothermic circulatory arrest for degenerative pathology. The proposed simple, accurate model can quantify risk and facilitate physician-patient counseling before possible surgical intervention.

Successful aneurysm resection and coronary artery revascularization following saphenous vein graft aneurysm rupture.

Saphenous vein graft aneurysms after coronary artery bypass grafting (CABG) have been rarely reported. Their incidence and natural history are poorly defined. Herein, we present a patient who presented acutely with contained rupture of a large saphenous vein graft aneurysm 12 years after CABG, which was successfully managed with open aneurysm resection and regrafting.

Vascular Complications and Use of a Distal Perfusion Cannula in Femorally Cannulated Patients on Extracorporeal Membrane Oxygenation.

Femoral arterial cannulation in adult venoarterial (VA) extracorporeal membrane oxygenation (ECMO) predisposes patients to ipsilateral limb ischemia. Placement of a distal perfusion catheter (DPC) is one of few techniques available to prevent or manage this complication. Although frequently used, the indications for and timing of DPC placement are poorly characterized, and no guidelines are available to guide its use. The purpose of this study was to compare the incidences of vascular complications and limb ischemia between patients who did and did not receive a DPC at the time of primary ECMO cannulation. Between June 2009 and April 2015, 132 adults underwent VA ECMO cannulation at our institution. Of the 80 femoral cannulations comprising this retrospective single-center study cohort, 14 (17.5%) received a DPC at the time of primary cannulation. Demographics, indications for ECMO, and cardiovascular history and risk factors were not significantly different between comparison groups. Median arterial cannula size was 17 French in both groups. Vascular complications occurred in 2 of the 14 patients with initial DPC (14.3%) compared with 21 of 66 without initial DPC (31.8%; p = 0.188). Limb ischemia occurred in 2 of 14 patients in the DPC group (14.3%) and 15 of 66 in the non-DPC group (22.7%; p = 0.483). In-hospital mortality was comparable between groups. DPC placement at the time of primary cannulation may lower the incidence of limb ischemia. The benefit of DPC placement once evidence of limb ischemia is apparent remains unclear.

Outcomes of Reoperation After Acute Type A Aortic Dissection: Implications for Index Repair Strategy.

BACKGROUND: The optimal surgical approach for management of acute type A aortic dissection remains controversial. This study aimed to assess outcomes of reoperation after acute type A dissection repair to help guide decision making around index operative strategy. METHODS AND RESULTS: All aortic reoperations (n=129) at a single referral institution from August 2005 to April 2016 after prior acute type A dissection repair were reviewed. The primary outcome was 30-day or in-hospital mortality. Secondary outcomes included organ-specific morbidity and 1- and 5-year outcomes as estimated using the Kaplan-Meier method. The majority of initial reoperations were proximal aortic (aortic valve, aortic root, or ascending) or aortic arch procedures (62.5%, n=55); most initial reoperations were performed in the elective setting (83.1%, n=74). Additional nonstaged second or more reoperations were required in 21 patients (23.6%) after the initial reoperation, during a median follow-up of 2.5 years after the initial reoperation. Thirty-day or in-hospital mortality for all reoperations was 7.0% (elective: 6.3%; nonelective: 11.1%) with acceptable rates of organ-specific morbidity, given the procedural complexity. One- and 5-year overall survival after initial reoperation was 85.9% and 64.9%, respectively, with aorta-specific survival of 88% at 5 years. CONCLUSIONS: Reoperation after acute type A aortic dissection repair is associated with low rates of mortality and morbidity. These data support more limited index repair for acute type A dissection, especially for patients undergoing index repair in lower volume centers without expertise in extensive repair, because reoperations, if needed, can be performed safely in referral aortic centers.

Central Cannulation as a Viable Alternative to Peripheral Cannulation in Extracorporeal Membrane Oxygenation.

Arterial cannulation for veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) is most commonly established via the aorta, axillary, or femoral vessels, yet their inherent complications are not well characterized. The purpose of this study was to compare the outcomes and complication rates of central vs peripheral cannulation. Adult patients undergoing VA ECMO between June 2009 and April 2015 were reviewed in this retrospective single-center study. Patient characteristics, clinical outcomes, and details related to deployment were extracted from the medical record. Complications and survival rates were compared between patients by cannulation strategy. Of 131 VA ECMO patients, there were 36 aortic (27.5%), 16 axillary (12.2%), and 79 femoral (60.3%) cannulations. Other than a lower mean age with femoral cannulations (53.9 ± 13.9 years) vs aortic (60.3 ± 12.2 years) and axillary (59.8 ± 12.4 years) (P = 0.032), the baseline patient characteristics were not statistically different. Central cannulation was more common in patients transferred from outside facilities (74.3% central vs 51.6% peripheral) (P = 0.053). Seven of 36 aortic cannulations were via anterior thoracotomy (19.4%). Forty of 131 patients underwent extracorporeal cardiopulmonary resuscitation (30.5%), 33 of whom were femorally cannulated. Peripheral cannulation carried a 29.5% rate of vascular complications compared with an 11.1% rate of mediastinal bleeding with central cannulation. Incidence of stroke and overall survival between groups were not statistically different. Central cannulation is a viable alternative to peripheral cannulation. Central cannulation avoids high rates of extremity morbidity without causing significant risks of alternative morbidity or death.

Mitochondrial quality-control dysregulation in conditional HO-1-/- mice.

The heme oxygenase-1 (Hmox1; HO-1) pathway was tested for defense of mitochondrial quality control in cardiomyocyte-specific Hmox1 KO mice (HO-1[CM]-/-) exposed to oxidative stress (100% O2). After 48 hours of exposure, these mice showed persistent cardiac inflammation and oxidative tissue damage that caused sarcomeric disruption, cardiomyocyte death, left ventricular dysfunction, and cardiomyopathy, while control hearts showed minimal damage. After hyperoxia, HO-1(CM)-/- hearts showed suppression of the Pgc-1α/nuclear respiratory factor-1 (NRF-1) axis, swelling, low electron density mitochondria by electron microscopy (EM), increased cell death, and extensive collagen deposition. The damage mechanism involves structurally deficient autophagy/mitophagy, impaired LC3II processing, and failure to upregulate Pink1- and Park2-mediated mitophagy. The mitophagy pathway was suppressed through loss of NRF-1 binding to proximal promoter sites on both genes. These results indicate that cardiac Hmox1 induction not only prevents heme toxicity, but also regulates the timing and registration of genetic programs for mitochondrial quality control that limit cell death, pathological remodeling, and cardiac fibrosis.