Altered conformational dynamics contribute to species-specific effects of cytochrome c mutations on caspase activation.

Variants in the gene encoding human cytochrome c (CYCS) cause mild autosomal dominant thrombocytopenia. Despite high sequence conservation between mouse and human cytochrome c, this phenotype is not recapitulated in mice for the sole mutant (G41S) that has been investigated. The effect of the G41S mutation on the in vitro activities of cytochrome c is also not conserved between human and mouse. Peroxidase activity is increased in both mouse and human G41S variants, whereas apoptosome activation is increased for human G41S cytochrome c but decreased for mouse G41S cytochrome c. These apoptotic activities of cytochrome c are regulated at least in part by conformational dynamics of the main chain. Here we use computational and in vitro approaches to understand why the impact of the G41S mutation differs between mouse and human cytochromes c. The G41S mutation increases the inherent entropy and main chain mobility of human but not mouse cytochrome c. Exclusively in human G41S cytochrome c this is accompanied by a decrease in occupancy of H-bonds between protein and heme during simulations. These data demonstrate that binding of cytochrome c to Apaf-1 to trigger apoptosome formation, but not the peroxidase activity of cytochrome c, is enhanced by increased mobility of the native protein conformation.

Frequency and Distribution of Chest Radiographic Findings in Patients Positive for COVID-19.

Background Current coronavirus disease 2019 (COVID-19) radiologic literature is dominated by CT, and a detailed description of chest radiography appearances in relation to the disease time course is lacking. Purpose To describe the time course and severity of findings of COVID-19 at chest radiography and correlate these with real-time reverse transcription polymerase chain reaction (RT-PCR) testing for severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, nucleic acid. Materials and Methods This is a retrospective study of patients with COVID-19 confirmed by using RT-PCR and chest radiographic examinations who were admitted across four hospitals and evaluated between January and March 2020. Baseline and serial chest radiographs (n = 255) were reviewed with RT-PCR. Correlation with concurrent CT examinations (n = 28) was performed when available. Two radiologists scored each chest radiograph in consensus for consolidation, ground-glass opacity, location, and pleural fluid. A severity index was determined for each lung. The lung scores were summed to produce the final severity score. Results The study was composed of 64 patients (26 men; mean age, 56 years ± 19 [standard deviation]). Of these, 58 patients had initial positive findings with RT-PCR (91%; 95% confidence interval: 81%, 96%), 44 patients had abnormal findings at baseline chest radiography (69%; 95% confidence interval: 56%, 80%), and 38 patients had initial positive findings with RT-PCR testing and abnormal findings at baseline chest radiography (59%; 95% confidence interval: 46%, 71%). Six patients (9%) showed abnormalities at chest radiography before eventually testing positive for COVID-19 with RT-PCR. Sensitivity of initial RT-PCR (91%; 95% confidence interval: 83%, 97%) was higher than that of baseline chest radiography (69%; 95% confidence interval: 56%, 80%) (P = .009). Radiographic recovery (mean, 6 days ± 5) and virologic recovery (mean, 8 days ± 6) were not significantly different (P = .33). Consolidation was the most common finding (30 of 64; 47%) followed by ground-glass opacities (21 of 64; 33%). Abnormalities at chest radiography had a peripheral distribution (26 of 64; 41%) and lower zone distribution (32 of 64; 50%) with bilateral involvement (32 of 64; 50%). Pleural effusion was uncommon (two of 64; 3%). The severity of findings at chest radiography peaked at 10-12 days from the date of symptom onset. Conclusion Findings at chest radiography in patients with coronavirus disease 2019 frequently showed bilateral lower zone consolidation, which peaked at 10-12 days from symptom onset. © RSNA, 2020.

A novel approach to extraction of a large thrombus on the intraventricular guide-wire during transcatheter aortic valve replacement.

For appropriate patients with severe symptomatic aortic stenosis with a prohibitively high surgical risk, trans-catheter aortic valve replacement (TAVR) is now established as a viable option. Thrombosis on the intra-ventricular guide-wire during TAVR is a recognized complication (Wiper et al., Cardiovasc Revasc Med 2014). There is an obvious potential for embolization with particular concern for stroke in this situation. We describe a case in which a >1cm thrombus was noted on the intra-ventricular guide-wire by trans-esophageal echocardiogram (TEE) during a TAVR procedure. Balloon aortic valvuloplasty was still performed and an Edwards Sapien valve was deployed. After valve deployment a multi-purpose guiding catheter was advanced with continuous suction. The guide-wire and thrombus were withdrawn inside the guiding catheter. The guide-wire and catheter were removed as a single unit, allowing the thrombus to be safely retrieved. We believe that this is a novel technique of aspiration thrombectomy in this potentially hazardous clinical circumstance. As our experience with TAVR increases, so does our experience with the complications. In the PARTNER trial there was a higher rate of neurological events in TAVR patients than those who had open aortic valve replacement (Smith et al. N Engl J Med 2011;364:2187-2198.). This may be related to peri-procedural formation of thrombus and subsequent embolization. We report a case where a large guide-wire thrombus identified during TAVR was successfully removed using a novel approach, preventing a potentially major stroke in this high-risk patient. © 2015 Wiley Periodicals, Inc.

Evaluating living donor kidney transplant rates: Are you reaching your potential?

BACKGROUND: Traditionally, living donor kidney transplant (LDKT) rate has been calculated as a percentage of total kidney transplant volume. We believe this calculation to be inherently flawed because the number of deceased donor kidney transplants has no bearing on the number of LDKT performed. We propose an alternative calculation of LDKT rate as a percentage of the number of new waitlist registrants. METHODS: We evaluated 192 adult transplant centers in the United States with respect to their LDKT rate according to both the traditional and proposed calculations, using data from the scientific registry of transplant recipients between July 2014 and June 2015. RESULTS: The median LDKT rate for every 100 new waitlist registrants was 12.3, compared to 27.9 for every 100 total kidney transplants. Based on our proposed calculation of LDKT rate, 16.7% of transplant centers were misevaluated when compared to the national mean using the traditional method. CONCLUSIONS: A new calculation of LDKT rate based on new waitlist registrants, and not total kidney transplants, is necessary to eliminate the bias associated with the traditional method, allowing for the identification of centers for improvement as well as each individual center's true potential based on their patient demographics.

Postnatal Outcome of Fetal Left Ventricular Hypertrabeculation/Noncompaction.

Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology. Prenatal diagnosis of LVHT can be established by fetal echocardiography. A review of 106 published cases showed that 46 cases with prenatally diagnosed LVHT were alive 0.5-120 months after birth. Since the course of cases with prenatally LVHT after publication is unknown, we aimed to collect follow-up-information. Information regarding vital status, cardiac and extracardiac morbidity was gathered by contacting the authors of the 46 cases. Fourteen of the 28 authors answered and gave information about 18 cases (six females, seven males, five gender-unknown, age 18 months to 10 years, mean follow-up 60 months). No differences were found between the 18 cases with follow-up and the 28 cases without follow-up regarding age, gender, cardiac or extracardiac comorbidities, and interventions. Three of the 18 cases had died subsequently from heart failure, osteosarcoma, and enterocolitis, respectively. Mutations or chromosomal abnormalities were found in six of the seven examined patients, extracardiac abnormalities in nine patients. Three patients received a pacemaker because of complete AV block, and two patients underwent heart transplantation. Cardiac surgical or interventional procedures were carried out in four patients. None suffered from malignant arrhythmias or had a cardioverter-defibrillator implanted. Based on the limited information, there are indications that cases with fetal diagnosis of LVHT have a continuing morbidity and mortality, even if they receive appropriate care. Since fetal LVHT is frequently associated with genetic abnormalities, further research about survival and underlying genetic causes is needed.

Modeling the behavior of monoclonal antibodies on hydrophobic interaction chromatography resins.

Monoclonal antibodies (mAbs) require a high level of purity for regulatory approval and safe administration. High-molecular weight (HMW) species are a common impurity associated with mAb therapies. Hydrophobic interaction chromatography (HIC) resins are often used to remove these HMW impurities. Determination of a suitable HIC resin can be a time and resource-intensive process. In this study, we modeled the chromatographic behavior of seven mAbs across 13 HIC resins using measurements of surface hydrophobicity, surface charge, and thermal stability for mAbs, and hydrophobicity and zeta-potential for HIC resins with high fit quality (adjusted R2 > 0.80). We identified zeta-potential as a novel key modeling parameter. When using these models to select a HIC resin for HMW clearance of a test mAb, we were able to achieve 60% HMW clearance and 89% recovery. These models can be used to expedite the downstream process development for mAbs in an industry setting.

Professional footballers have a limited understanding of the precompetition medical assessment and the possible outcomes including disqualification: a cross-sectional survey.

OBJECTIVES: To determine professional footballers' level of understanding of the purpose of the precompetition medical assessment (PCMA) and to evaluate their knowledge of potential outcomes following a PCMA, including disqualification. METHODS: Professional footballers from the Australasian A-League and Westfield W-League were asked to complete a 25-question survey. The relationship between dichotomised outcomes and explanatory variables was analysed with multivariate logistic regression; p<0.05 was considered statistically significant. RESULTS: A total of 212 players participated (response rate=48.8%). Most respondents selected 'To detect medical conditions that may affect performance' and 'To detect current injuries' (n=137, 64.6%; n=130, 61.3%) as the purpose of a PCMA. Approximately one-third (n=74, 38.1%) were neutral or believed that a normal PCMA prevented cardiac arrest. Receiving more PCMAs (p<0.0003) and receiving an explanation during their PCMA (p=0.0175) led to greater awareness of the assessment's limitations. Most participants did not know the definitions of syncope (n=181, 93.3%) or Marfan syndrome (n=183, 94.3%). Fifty players (28.1%) did not know that disqualification was a possible outcome of a PCMA, and younger players were less aware of this possible outcome (p=0.0216). CONCLUSION: Professional footballers appear to have a limited understanding of the purpose of a PCMA, emphasising the musculoskeletal system and performance. They also appear unfamiliar with the components of the PCMA and medical terms. Finally, many are unaware that disqualification can result from an abnormal PCMA. Player health knowledge must be improved; the informed consent process appears an ideal time to provide this education.

Surgical management of intrapericardial teratoma in the fetus.

Intrapericardial teratomas often present as life-threatening problems when diagnosed during fetal life. They are large lesions that compress the heart and lungs and can result in tamponade if not treated expeditiously. We present a case of a large teratoma that was managed by prenatal pericardiocentesis followed by surgical resection.

Detection of COVID-19 Using Deep Learning Algorithms on Chest Radiographs.

PURPOSE: To evaluate the performance of a deep learning (DL) algorithm for the detection of COVID-19 on chest radiographs (CXR). MATERIALS AND METHODS: In this retrospective study, a DL model was trained on 112,120 CXR images with 14 labeled classifiers (ChestX-ray14) and fine-tuned using initial CXR on hospital admission of 509 patients, who had undergone COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR). The test set consisted of a CXR on presentation of 248 individuals suspected of COVID-19 pneumonia between February 16 and March 3, 2020 from 4 centers (72 RT-PCR positives and 176 RT-PCR negatives). The CXR were independently reviewed by 3 radiologists and using the DL algorithm. Diagnostic performance was compared with radiologists' performance and was assessed by area under the receiver operating characteristics (AUC). RESULTS: The median age of the subjects in the test set was 61 (interquartile range: 39 to 79) years (51% male). The DL algorithm achieved an AUC of 0.81, sensitivity of 0.85, and specificity of 0.72 in detecting COVID-19 using RT-PCR as the reference standard. On subgroup analyses, the model achieved an AUC of 0.79, sensitivity of 0.80, and specificity of 0.74 in detecting COVID-19 in patients presented with fever or respiratory systems and an AUC of 0.87, sensitivity of 0.85, and specificity of 0.81 in distinguishing COVID-19 from other forms of pneumonia. The algorithm significantly outperforms human readers (P<0.001 using DeLong test) with higher sensitivity (P=0.01 using McNemar test). CONCLUSIONS: A DL algorithm (COV19NET) for the detection of COVID-19 on chest radiographs can potentially be an effective tool in triaging patients, particularly in resource-stretched health-care systems.

Development and validation of risk prediction models for COVID-19 positivity in a hospital setting.

OBJECTIVES: To develop: (1) two validated risk prediction models for coronavirus disease-2019 (COVID-19) positivity using readily available parameters in a general hospital setting; (2) nomograms and probabilities to allow clinical utilisation. METHODS: Patients with and without COVID-19 were included from 4 Hong Kong hospitals. The database was randomly split into 2:1: for model development database (n = 895) and validation database (n = 435). Multivariable logistic regression was utilised for model creation and validated with the Hosmer-Lemeshow (H-L) test and calibration plot. Nomograms and probabilities set at 0.1, 0.2, 0.4 and 0.6 were calculated to determine sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: A total of 1330 patients (mean age 58.2 ± 24.5 years; 50.7% males; 296 COVID-19 positive) were recruited. The first prediction model developed had age, total white blood cell count, chest x-ray appearances and contact history as significant predictors (AUC = 0.911 [CI = 0.880-0.941]). The second model developed has the same variables except contact history (AUC = 0.880 [CI = 0.844-0.916]). Both were externally validated on the H-L test (p = 0.781 and 0.155, respectively) and calibration plot. Models were converted to nomograms. Lower probabilities give higher sensitivity and NPV; higher probabilities give higher specificity and PPV. CONCLUSION: Two simple-to-use validated nomograms were developed with excellent AUCs based on readily available parameters and can be considered for clinical utilisation.

Randomized controlled study of ECP with methoxsalen as first-line treatment of patients with moderate to severe cGVHD.

The investigation of extracorporeal photopheresis (ECP) plus standard of care (SoC) (SoC+ECP) in chronic graft-versus-host disease (cGVHD) within prospective, randomized clinical studies is limited, despite its frequent clinical use. This phase 1/pilot study was the first randomized, prospective study to investigate ECP use as first-line therapy in cGVHD, based on the 2015 National Institutes of Health (NIH) consensus criteria for diagnosis and response assessment. Adult patients with new-onset (≤3 years of hematopoietic stem cell transplantation) moderate or severe cGVHD were randomized 1:1 to 26 weeks of SoC+ECP vs SoC (corticosteroids and cyclosporine A/tacrolimus) between 2011 and 2015. The primary endpoint was overall response rate (ORR), defined as complete or partial response, at week 28 in the intention-to-treat population (ITT). Other outcomes included quality of life (QoL) measures and safety. Sixty patients were randomized; ITT included 53 patients (SoC+ECP: 29; SoC: 24). Week 28 ORR was 74.1% (SoC+ECP) and 60.9% (SoC). Investigator-assessed ORR was 56.0% (SoC+ECP) and 66.7% (SoC). Patients treated with SoC experienced a decline in QoL over the 28-week study period; QoL remained unchanged in SoC+ECP patients. Most frequent treatment-emergent adverse events (TEAEs) in SoC+ECP patients were hypertension (31.0%), cough (20.7%), dyspnea (17.2%), and fatigue (17.2%). Seventeen patients (SoC+ECP: 8; SoC: 9) experienced 35 serious adverse events (SAEs). No TEAEs or SAEs were considered related to the ECP instrument or methoxsalen. The encouraging short-term results of this study could inform the design of subsequent studies. This trial was registered at www.clinicaltrials.gov as #NCT01380535.

Trisomy 18 and Congenital Heart Disease: Single-Center Review of Outcomes and Parental Perspectives.

BACKGROUND: In patients with trisomy 18, congenital heart surgery is controversial due to anticipated poor patient outcome. Data are lacking regarding clinical outcomes and family opinions about care received. METHODS: A retrospective chart review of patients with trisomy 18 and congenital heart disease from 2005 to 2017 was performed. Patients were grouped into those receiving cardiac intervention (surgery or cardiac catheterization) versus medical management. A telephone survey was used to assess completeness of family counseling provided prior to treatment selection and parental opinions on the care received. RESULTS: Seventeen infants were assessed. In the medical management group (n = 7), there were five deaths at a median age of 1.5 months (range: 1.2-4.1 months) and two survivors aged 29 and 44 months at latest follow-up. In the intervention group (n = 10), cardiac surgery was performed in nine patients at a median age of 4.3 months (0.2-23.4 months) and weight of 3.2 kg (1.5-12.2 kg); catheter intervention was performed in one patient at one week of age. At latest follow-up, seven intervention patients are alive at a median age of 50 months (5-91 months). Survey respondents (n = 12) unanimously stated that their child's quality of life was improved by their specific treatment strategy, that the experience of the parents was enhanced, and that they would choose the same treatment course again. CONCLUSIONS: Surgical repair may be associated with favorable early outcomes and may be judiciously offered in selected circumstances. In this limited experience, parental perceptions were positive regarding the quality of care and overall experience independent of the chosen treatment strategy or eventual outcome.

Postoperative atrial fibrillation in patients undergoing non-cardiac non-thoracic surgery: A practical approach for the hospitalist.

New postoperative atrial fibrillation (POAF) is the most common perioperative arrhythmia and its reported incidence ranges from 0.4 to 26% in patients undergoing non-cardiac non-thoracic surgery. The incidence varies according to patient characteristics such as age, presence of structural heart disease and other co-morbidities, as well as the type of surgery performed. POAF occurs as a consequence of adrenergic stimulation, systemic inflammation, or autonomic activation in the intra or postoperative period (e.g. due to pain, hypotension, infection) in the setting of a susceptible myocardium and other predisposing factors (e.g. electrolyte abnormalities). POAF develops between day 1 and day 4 post-surgery and it is often considered a self-limited entity. Its acute management involves many of the same strategies used in non-surgical patients but the optimal long-term management is challenging because of the limited available evidence. Several studies have shown an association between occurrence of POAF and in-hospital morbidity, mortality, and length of stay. Although, traditionally, POAF was considered to have a generally favorable long-term prognosis, recent data have shown an association with an increased risk of stroke at 1 year after hospitalization. It is unknown, however, whether strategies to prevent POAF or for rate/rhythm control when it does occur, lead to a reduction in morbidity or mortality. This suggests the need for future studies to better understand the risks associated with POAF and to determine optimal strategies to minimize long-term thromboembolic risks. In this article, we summarize the current knowledge on epidemiology, pathophysiology, and short- and long-term management of POAF after non-cardiac non-thoracic surgery with the goal of providing a practical approach to managing these patients for the non-cardiologist clinician.

Severe acute respiratory syndrome (SARS): the pharmacist's role.

OBJECTIVES: After two outbreaks of severe acute respiratory syndrome (SARS) occurred in Toronto, Ontario, Canada, from March-June 2003, we reviewed the unexpected role and responsibilities of pharmacists during these two crises, and present strategies for better crisis preparedness. METHODS AND RESULTS: Pharmacists were actively involved in battling the SARS crises. After conducting extensive literature searches and evaluations, pharmacists prepared administration and dosing guidelines for the two investigational drugs, ribavirin and interferon alfacon-1, that were being used to treat the syndrome. They provided direct patient care under modified conditions. They revised drug distribution procedures and developed new ones to meet more stringent infection-control standards. Collaborative teamwork with key stakeholders was important in accomplishing tasks in an efficient and timely manner. Regular communication with health care staff took place internally and externally. Education and updated information for pharmacists was crucial. CONCLUSION: Pharmacists can play a vital role during crises in the areas of drug distribution, drug information, and direct patient care. Collaborative teamwork and close communication are keys to success. Pharmacists must be proactive and take a leadership role in assuming pharmacy-related responsibilities. By evaluating what worked and what didn't, pharmacists can develop procedures for future crises requiring pharmacy support.

Posterior urethral valves presenting as abdominal distension and undifferentiated shock in a neonate: the role of screening emergency physician-directed bedside ultrasound.

We present a case of shock in a 7-week-old neonate with obstructive uropathy secondary to posterior urethral valves (PUV). The antenatal ultrasound and the 2-week maintenance visit were unremarkable. A screening emergency physician directed bedside ultrasound (SEPUS) served to rapidly establish the diagnosis, initiate appropriate management, and facilitate early relief of urinary obstruction. We discuss the potential role of SEPUS in a critically ill neonate and briefly review the management of PUV.

Early detection of cardiac disease masquerading as acute bronchospasm: The role of bedside limited echocardiography by the emergency physician.

We report two cases in which the patients experienced dyspnea, cough, and acute bronchospasm. Pulmonary pathology was initially suspected. Failure to respond to an initial trial of inhaled bronchodilator prompted the use of bedside limited echocardiography by the emergency physician. The potential role of limited echocardiography by the emergency physician as a triage tool in facilitating early diagnosis and emergent therapy, reducing time to final discharge, and enhancing interaction between the pediatric emergency physician and cardiology consultants is highlighted.

Phase I trial, pharmacokinetics, and pharmacodynamics of vandetanib and dasatinib in children with newly diagnosed diffuse intrinsic pontine glioma.

PURPOSE: Testing of promising drug combinations is crucial in the treatment of diffuse intrinsic pontine glioma (DIPG). As the VEGF and platelet-derived growth factor (PDGF) pathways are critical in gliomas, we evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of vandetanib, a VEGFR-2 inhibitor, combined with dasatinib, a potent PDGFR inhibitor, during and after radiotherapy in children with newly diagnosed DIPG. EXPERIMENTAL DESIGN: Dasatinib was started concurrently with radiotherapy. Vandetanib was started 8 days later. We tested increasing doses of vandetanib (65 and 85 mg/m(2) once daily) and dasatinib (65 and 85 mg/m(2) twice daily). Dose-limiting toxicities were evaluated during the first 6 weeks of therapy. Plasma pharmacokinetics was obtained on days 8 and 42 ± 3 in all patients and concomitantly with cerebrospinal fluid (CSF) when possible. Inhibition of targets of dasatinib in peripheral blood mononuclear cells (PBMC) was evaluated. RESULTS: Twenty-five patients were treated. Treatment was well tolerated. The median duration of treatment was 184 days. Diarrhea was the most significant toxicity. Three patients experienced substantial myelosuppression. The steady-state plasma pharmacokinetics of vandetanib was comparable with previous studies. Although the plasma exposure to dasatinib decreased from days 8 to 42, it remained similar to adult studies. CSF to plasma exposure of vandetanib and dasatinib were approximately 2% in 2 patients. Phosphorylated 70S6K decreased during therapy in PBMCs. CONCLUSIONS: The MTD of vandetanib and dasatinib in combination was 65 mg/m(2) for each drug. Other studies are underway to test dasatinib and other PDGFR inhibitors alone or in combination for this deadly cancer.

Direct thermal to electrical energy conversion using 9.5/65/35 PLZT ceramics in the ergodic relaxor phase.

This paper reports on direct thermal to electrical energy conversion by performing the Olsen cycle on 9.5/65/35 lead lanthanum zirconate titanate (PLZT). The Olsen cycle consists of two isothermal and two isoelectric field processes in the electric displacement versus electric field diagram. It was performed by alternatively dipping the material in hot and cold dielectric fluid baths under specified electric fields. The effects of applied electric field, sample thickness, electrode material, operating temperature, and cycle frequency on the energy and power densities were investigated. A maximum energy density of 637 ± 20 J/L/cycle was achieved at 0.054 Hz with a 250-µm-thick sample featuring Pt electrodes and coated with a silicone conformal coating. The operating temperatures varied between 3°C and 140°C and the electric field was cycled between 0.2 and 6.0 MV/m. A maximum power density of 55 ± 8 W/L was obtained at 0.125 Hz under the same operating temperatures and electric fields. The dielectric strength of the material, and therefore the energy and power densities generated, increased when the sample thickness decreased from 500 to 250 µm. Furthermore, the electrode material was found to have no significant effect on the energy and power densities for samples subject to the same operating temperatures and electric fields. However, samples with electrode material possessing thermal expansion coefficients similar to that of PLZT were capable of withstanding larger temperature swings. Finally, a fatigue test showed that the power generation gradually degraded when the sample was subject to repeated thermoelectrical loading.

Apical Left Ventriculotomy is Safe in Infants and Young Children Requiring Cardiac Surgery.

OBJECTIVES: Incisions in the left ventricle have previously been associated with increased mortality and morbidity, particularly in infants. In order to determine whether this assumption is still true in the current era, we reviewed our recent experience with apical left ventriculotomy in neonates and infants. METHODS: The records of five consecutive patients requiring a left ventriculotomy between 2007 and 2010 were reviewed. Weight and age ranged from 2.6 to 16 kilograms and 5 days to 2 years. The diagnoses were three multiple ventricular septal defects, one rhabdomyoma, and one apical aneurysm. The primary end point was left ventricular ejection fraction, with other end points being intensive care unit length of stay, time to extubation, inotrope requirement, arrhythmias, and mitral valve function. RESULTS: There were no early or late deaths. Although lower than their preoperative values, early postoperative ejection fractions were greater than 50% in all patients. Two patients required no inotropes, and 3 required only minimal support. Hospital length of stay was 9 ± 7 days for multiple ventricular septal defect patients, with intensive care unit stays of 2 to 5 days. There were no postoperative arrhythmias requiring pharmacological therapy, and one patient had a significant reduction in mitral insufficiency postoperatively. CONCLUSIONS: Based on our experience, we believe that an apical left ventriculotomy does not significantly impair left ventricular function even in small infants, and is not associated with significant morbidity, based on short-term follow-up. Although the long-term effects are still unknown, early results suggest that a left ventriculotomy may safely be used when alternative approaches are inadequate for complex cardiac defects.