Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors.

BACKGROUND: Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636). PATIENTS AND METHODS: In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability. RESULTS: Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths. CONCLUSIONS: Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.

Multi-institutional and multi-disciplinary care: A successfully managed aortic dissection in the third trimester of pregnancy.

Multi-disciplinary collaborative care for pregnant women with complex and emergent conditions is essential. Logistical planning, clear communication and human factor awareness are all non-clinical skills which need to be utilised in order to maximise outcomes. We describe the case of a proximal aortic dissection in the late third trimester of pregnancy diagnosed in a peripheral hospital that was transferred to a cardiothoracic centre for successful operative management 160 km away. This required the time-sensitive mobilisation and liaison of a receiving cardiothoracic, anaesthesiology and perfusionist team in conjunction with obstetric and midwifery support from an affiliated maternity hospital, as well as the national neonatal transport team. We emphasise the importance of multidisciplinary team management in complex cases and how imperative good inter-disciplinary communication is to ensure safe inter-hospital transfer.

[Immunotherapy in head and neck squamous cell carcinoma : Abscopal effects in combination with radiotherapy, extraordinary responses in combination with chemotherapy, and pseudoprogression]. / Immuntherapie bei Kopf-Hals-Plattenepithelkarzinomen : Abskopale Effekte in Kombination mit Radiotherapie, außergewöhnliche Reaktionen in Kombination mit Chemotherapie und Pseudoprogression.

BACKGROUND: The clinical implementation of immunotherapy has broadened the therapeutic options for recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). Until 2016, the only molecularly targeted therapy was epidermal growth factor receptor (EGFR) blockade. However, immune checkpoint inhibition has recently become part of first-line treatment in recurrent and/or metastatic HNSCC. OBJECTIVES: The occurrence of abscopal effects of radiotherapy and synergisms between immunotherapy and chemotherapy as well as the phenomenon of pseudoprogression in HNSCC were investigated. MATERIALS AND METHODS: Key publications of recent clinical trials and preclinical studies on the underlying biological mechanisms were analyzed. RESULTS: As already observed in other tumor entities, synergistic effects upon combination of immunotherapy with radio- and/or chemotherapy are observed in the clinical management of recurrent and/or metastatic HNSCC, and this is mediated by (re)activation of host antitumor immune mechanisms. In selected patients, this may be radiologically detected as pseudoprogression. Reliable biomarkers for these phenomena have not yet been clinically established. CONCLUSIONS: For recurrent and/or metastatic HNSCC, the occurrence of systemic effects upon radiochemoimmunotherapy in the clinic is on the rise. Hence, the identification of biomarkers for abscopal effects of radiotherapy and unexpected synergisms between chemotherapy and immunotherapy as well as for pseudoprogression is gaining in importance.

Essential Oil Emulsions as Postharvest Sanitizers To Mitigate Salmonella Cross-Contamination on Peppers.

Alternative postharvest sanitizers to chlorine are of increasing interest for many organic growers and consumers. An emulsion of clove bud oil (CBO; 0.2 and 0.5%) or thyme oil (0.2 and 0.5%) was evaluated as a sanitizer for produce washing against a five-serovar cocktail of Salmonella on snacking peppers and compared for antimicrobial efficacy with sodium hypochlorite (200 ppm). To further evaluate these compounds, the sanitation efficacy of an emulsion was examined after the addition of 1% organic load (OL). Emulsion treatments at 0.2 and 0.5% thyme oil and 0.5% CBO were the least effected by OL and effectively reduced cross-contamination of Salmonella on clean peppers, in many cases to below the limit of detection (1 CFU/10 g; P < 0.05). Chlorine and 0.2% CBO were rendered ineffective by the addition of OL in preventing cross-contamination and performed similarly to the water control. For surface-inoculated peppers, none of the evaluated treatments performed better than a water-only wash. The antimicrobial efficacy of the essential oil emulsions in the presence of OL indicates these emulsions may be suitable replacements for chlorine in postharvest produce wash systems.

Atypical meningioma. A study on recurrence and disease-specific survival.

BACKGROUND: To analyse the outcome of patients with WHO grade II meningioma and identify factors that may influence recurrence and survival. MATERIAL AND METHODS: Between January 2000 and October 2016, a retrospective search identified 215 WHO grade II meningiomas operated on at our institution. A survival analysis was conducted on clinical and histological criteria. RESULTS: Eighteen patients (8.4%) had a previous history of grade I meningioma. The cohort underwent a total of 302 surgical resections and 29.7% received radiotherapy. Forty-one patients (19.1%) had been re-operated on for a WHO grade II meningioma relapse. Median follow-up was 4.5 years. At the end of the study, 105 patients (53.6%) had no residual tumour on the last scan. Surgical recurrence-free survival at 5 years was 82%, 95% CI [75.9-88.5]. Secondary grade II meningioma (HR=4.27, P=0.001), Simpson resection grade 1 and 2 vs. 3, 4 and 5 (HR=0.25, P=0.001) and, Ki-67 index (HR=0.22, P<0.001) were independently associated with the surgical recurrence-free survival. Forty-four patients died from their tumours (20.5%). Cause-specific survival probability at 5 years was 83.2%, 95% CI [77.6-89.1]. Age at diagnosis (HR=0.31, P<0.001), Simpson resection grade 1 and 2 vs. 3, 4 and 5 (HR=0.32, P<0.001) and, redo surgery for recurrence (HR=2.39, P=0.010) were independently associated with the cause-specific survival. Patients who received radiotherapy did not demonstrate either a reduced risk of recurrence or a longer survival (P=0.280). CONCLUSION: In this large series, atypical meningioma recurrence correlated with progression from grade I to II, incomplete resection and high Ki-67 index; shorter survival with an older age, incomplete resection, and redo surgery for recurrence. We did not observe a significant improvement in any of the clinical outcomes after radiotherapy.

A phase II study of temsirolimus added to low-dose weekly carboplatin and paclitaxel for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Background: Activating events along the PI3K/mTOR pathway are common in head and neck squamous cell carcinomas (HNSCC), and preclinical studies suggest additive or synergistic effects when combining mTORC1 inhibitors with carboplatin and paclitaxel chemotherapy. Patients and methods: In this single-institution phase II study, the combination of temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m2 administered on days 1 and 8 of a 21-day cycle was evaluated in 36 patients with recurrent and/or metastatic (R/M) HNSCC. The primary end point was objective response rate after two cycles of treatment. Secondary end points include the safety and tolerability profile and overall survival. Correlative studies with exome mutational analysis were performed in pre-treatment biopsy samples from 21 patients. Results: Fifteen (41.7%) patients had an objective response, which were all partial responses, and 19 (52.3%) patients had stable disease as best response. The two patients who were designated as 'non-responders' were removed from study prior to two cycles of treatment, but are included in the efficacy and safety analyses. The median duration on study was 5.3 months and the median progression-free survival and overall survival were 5.9 months (95% confidence interval, 4.8-7.1) and 12.8 months (95% confidence interval, 9.8-15.8), respectively. The most common grade 3 and 4 adverse events were hematologic toxicities. Three (3.8%) patients developed neutropenic fever on study. Three of four patients with PIK3CA mutations experienced tumor regressions, and responses were also seen in patients with other genetic alterations in the PI3K/mTOR pathway. Conclusion: The combination of temsirolimus with low-dose weekly carboplatin and paclitaxel appears to have meaningful clinical efficacy in the treatment of R/M HNSCC. This regimen has a relatively high response rate compared to other treatments evaluated in R/M HNSCC, and potential associations with genetic alterations in the PI3K/mTOR pathway should be further explored.

The symptom phenotype of oncology outpatients remains relatively stable from prior to through 1 week following chemotherapy.

Some oncology outpatients experience a higher number of and more severe symptoms during chemotherapy (CTX). However, little is known about whether this high risk phenotype persists over time. Latent transition analysis (LTA) was used to examine the probability that patients remained in the same symptom class when assessed prior to the administration of and following their next dose of CTX. For the patients whose class membership remained consistent, differences in demographic and clinical characteristics, and quality of life (QOL) were evaluated. The Memorial Symptom Assessment Scale (MSAS) was used to evaluate symptom burden. LTA was used to identify subgroups of patients with distinct symptom experiences based on the occurrence of the MSAS symptoms. Of the 906 patients evaluated, 83.9% were classified in the same symptom occurrence class at both assessments. Of these 760 patients, 25.0% were classified as Low-Low, 44.1% as Moderate-Moderate and 30.9% as High-High. Compared to the Low-Low class, the other two classes were younger, more likely to be women and to report child care responsibilities, and had a lower functional status and a higher comorbidity scores. The two higher classes reported lower QOL scores. The use of LTA could assist clinicians to identify higher risk patients and initiate more aggressive interventions.

Impact of Home- and Hospital-Based Exercise in Cardiac Rehabilitation on Hopelessness in Patients With Coronary Heart Disease.

PURPOSE: Hopelessness is associated with increased adverse events and decreased survival in patients with coronary heart disease (CHD). The purpose of this research was to examine the effect of regular home- and hospital-based cardiac rehabilitation (CR) exercise on hopelessness levels in patients with CHD, hypothesizing that increased exercise in either setting would lead to decreased state hopelessness. METHODS: A descriptive longitudinal design was used at a large teaching hospital in Michigan. A total of 324 patients provided data during hospitalization and at least 1 followup time point (3, 8, and 12 months). RESULTS: The patients had persistent, modest levels of state and trait hopelessness across all time points. Among home exercisers with moderate to severe state hopelessness at baseline, both mean state (P = .002) and trait (P = .02) hopelessness were reduced at later time points compared with those who quit or did not start exercise. Multivariable models showed that when individuals had moderate to severe baseline state hopelessness, home exercise remained associated with decreases in state hopelessness compared with no exercise, even after adjusting for hospital exercise, depression, and demographic variables. CONCLUSIONS: Exercise may be effective in reducing moderate to severe hopelessness in patients with CHD. Moderate to severe baseline state hopelessness was a predictor of attrition in this cohort, especially for home exercisers, but this was mediated in hospital-based programs. Further research is needed to determine how hopeless individuals can be encouraged to exercise and whether home- or a hospital-based CR exercise is superior in impacting hopelessness.

Home- and Hospital-Based Cardiac Rehabilitation Exercise: The Important Role of Physician Recommendation.

Exercise reduces morbidity and mortality for patients with heart disease. Despite clear guidelines and known benefits, most cardiac patients do not meet current exercise recommendations. Physician endorsement positively affects patient participation in hospital-based Phase II cardiac rehabilitation programs, yet the importance of physician recommendation for home-based cardiac rehabilitation exercise is unknown. A prospective observational design was used to examine predictors of both home-based and Phase II rehabilitation exercise in a sample of 251 patients with coronary heart disease. Regression analyses were done to examine demographic and clinical characteristics, physical functioning, and patient's report of physician recommendation for exercise. Patients with a strong physician referral, who were married and older, were more likely to participate in Phase II exercise. Increased strength of physician recommendation was the unique predictor of home-based exercise. Further research is needed to examine how health professionals can motivate cardiac patients to exercise in home and outpatient settings.

A phase II study of axitinib (AG-013736) in patients with incurable adenoid cystic carcinoma.

BACKGROUND: Recurrent/metastatic adenoid cystic carcinoma (ACC) is an incurable disease with no standard treatments. The majority of ACCs express the oncogenic transcription factor MYB (also c-myb), often in the context of a MYB gene rearrangement. This phase II trial of the tyrosine kinase inhibitor (TKI) axitinib (Pfizer) tested the hypothesis that targeting pathways activated by MYB can be therapeutically effective for ACC. PATIENTS AND METHODS: This is a minimax two-stage, phase II trial that enrolled patients with incurable ACC of any primary site. Progressive or symptomatic disease was required. Patients were treated with axitinib 5 mg oral twice daily; dose escalation was allowed. The primary end point was best overall response (BOR). An exploratory analysis correlating biomarkers to drug benefit was conducted, including next-generation sequencing (NGS) in 11 patients. RESULTS: Thirty-three patients were registered and evaluable for response. Fifteen patients had the axitinib dose increased. Tumor shrinkage was achieved in 22 (66.7%); 3 (9.1%) had confirmed partial responses. Twenty-five (75.8%) patients had stable disease, 10 of whom had disease stability for >6 months. The median progression-free survival (PFS) was 5.7 months (range 0.92-21.8 months). Grade 3 axitinib-related toxicities included hypertension, oral pain and fatigue. A trend toward superior PFS was noted with the MYB/NFIB rearrangement, although this was not statistically significant. NGS revealed three tumors with 4q12 amplification, producing increased copies of axitinib-targeted genes PDGFR/KDR/KIT. Two 4q12 amplified patients achieved stable disease for >6 months, including one with significant tumor reduction and the longest PFS on study (21.8 months). CONCLUSIONS: Although the primary end point was not met, axitinib exhibited clinical activity with tumor shrinkage achieved in the majority of patients with progressive disease before trial enrollment. Analysis of MYB biomarkers and genomic profiling suggests the hypothesis that 4q12 amplified ACCs are a disease subset that benefit from TKI therapy.

DOSE AND GAMMA-RAY SPECTRA FROM NEUTRON-INDUCED RADIOACTIVITY IN MEDICAL LINEAR ACCELERATORS FOLLOWING HIGH-ENERGY TOTAL BODY IRRADIATION.

Production of radioisotopes in medical linear accelerators (linacs) is of concern when the beam energy exceeds the threshold for the photonuclear interaction. Staff and patients may receive a radiation dose as a result of the induced radioactivity in the linac. Gamma-ray spectroscopy was used to identify the isotopes produced following the delivery of 18 MV photon beams from a Varian 21EX and an Elekta Synergy. The prominent radioisotopes produced include 187W, 63Zn, 56Mn, 24Na and 28Al in both linac models. The dose rate was measured at the beam exit window (12.6 µSv in the first 10 min) following 18 MV total body irradiation (TBI) beams. For a throughput of 24 TBI patients per year, staff members are estimated to receive an annual dose of up to 750 µSv at the patient location. This can be further reduced to 65 µSv by closing the jaws before re-entering the treatment bunker.

Development and evaluation of an intervention to support family caregivers of people with cancer to provide home-based care at the end of life: a feasibility study.

PURPOSE: To design and evaluate an intervention to address carers' needs for practical information and support skills when caring for a person with cancer at end of life. METHOD: Phase I 29 carers were interviewed about need for practical information, support skills and their preferences for information delivery. The preferred format was a booklet. Phase 2 evaluated the booklet. 31 carers and 14 district nurses participated. Validated questionnaires: on perceptions of caregiving and carer health before and after the booklet was used and interviews with both carers and nurses were untertaken.24 carers completed both interviews. Quantitative data were coded using scale manuals and analysed using SPSSv20 and interview data was analysed thematically. RESULTS: Carers were aged 31-82 and cared for people aged 50-92; 8 carers were male and 23 female; 20 cared for a partner, 8 for a parent and 1 for a sibling (2 undisclosed). Carers were positive about the booklet, however many carers would have liked the booklet earlier. Carers reported feeling more positive about caregiving, and more reassured and competent in their role. District nurses found the booklet useful and reported receiving fewer phone calls from study carers than others in similar situations. CONCLUSIONS: The booklet intervention was a source of reassurance to carers and it has the potential to be incorporated into everyday practice. The challenge is in when and how to distribute the booklet and more work is required on the timing of delivery in order to maximise the usefulness of booklet to carers.

Columnar metaplasia in the esophageal remnant after esophagectomy: a systematic review.

Barrett's metaplasia is a well-recognized risk factor for esophageal adenocarcinoma. It is believed to develop in response to the injurious effects of gastroesophageal reflux. Following subtotal esophagectomy and reconstruction with a gastric conduit, many patients experience profound reflux into the remnant esophagus. Barrett's-like epithelium has been described in these patients, and they have been identified as a potential human model in which to study the early events in the development of metaplasia. This phenomenon also raises clinical concerns about the long-term fate of the esophageal remnant following surgery and the potential for further malignant change. This systematic review summarizes the literature on the prevalence and timing of Barrett's metaplasia occurring after esophagectomy, reviews the evidence regarding risk factors and malignant progression in such patients, and considers the implications for clinical practice.

A large-scale, rapid public health response to rabies in an organ recipient and the previously undiagnosed organ donor.

This article describes and contrasts the public health response to two human rabies cases: one organ recipient diagnosed within days of symptom onset and the transplant donor who was diagnosed 18 months post-symptom onset. In response to an organ-transplant-related rabies case diagnosed in 2013, organ donor and recipient investigations were conducted by multiple public health agencies. Persons with potential exposure to infectious patient materials were assessed for rabies virus exposure. An exposure investigation was conducted to determine the source of the organ donor's infection. Over 100 persons from more than 20 agencies spent over 2700 h conducting contact investigations in healthcare, military and community settings. The 564 persons assessed include 417 healthcare workers [5.8% recommended for post-exposure prophylaxis (PEP)], 96 community contacts (15.6% recommended for PEP), 30 autopsy personnel (50% recommended for PEP), and 21 other persons (4.8% recommended for PEP). Donor contacts represented 188 assessed with 20.2% recommended for PEP, compared with 5.6% of 306 recipient contacts recommended for PEP. Human rabies cases result in substantial use of public health and medical resources, especially when diagnosis is delayed. Although rare, clinicians should consider rabies in cases of encephalitis of unexplained aetiology, particularly for cases that may result in organ donation.

The demographics of the United States haemophilia treatment centre social workers: the results of a national survey.

Social Workers (SWs) are vital members of the multidisciplinary health care teams at Hemophilia Treatment Centers (HTCs) across the US. However, little research has been done to identify the demographics and qualifications of HTC SWs. In response to this lack of data, a subcommittee from the Social Work Working Group sponsored by the National Hemophilia Foundation conducted a national online survey in 2010. The authors attempted to ascertain the demographics and characteristics of SWs who work at HTCs across the country. The purpose of this article is to report the results of this online survey and evaluate the parameters of SW demographics in HTCs. Electronic surveys were sent to 143 HTC SWs. Ten were excluded and 100 were completed and returned, yielding a 75% response rate. The great majority of HTC SWs are women and almost half are middle-aged (aged 40-59). They represent a highly educated, very experienced group of professionals. When asked why respondents stayed in their positions at the HTCs, answers appeared to highly correlate to factors related to the HTC multidisciplinary team model. The high survey response rate of 75% reflects the interest of HTC SWs in obtaining data that describe and quantify their qualifications. This information may serve as validation of the haemophilia SW role in times of funding cuts. It may also give a basis for the recruitment and retention of SWs in the haemophilia field.

The effect of irregular breathing patterns on internal target volumes in four-dimensional CT and cone-beam CT images in the context of stereotactic lung radiotherapy.

PURPOSE: Stereotactic lung radiotherapy is complicated by tumor motion from patient respiration. Four-dimensional CT (4DCT) imaging is a motion compensation method used in treatment planning to generate a maximum intensity projection (MIP) internal target volume (ITV). Image guided radiotherapy during treatment may involve acquiring a volumetric cone-beam CT (CBCT) image and visually aligning the tumor to the planning 4DCT MIP ITV contour. Moving targets imaged with CBCT can appear blurred and currently there are no studies reporting on the effect that irregular breathing patterns have on CBCT volumes and their alignment to 4DCT MIP ITV contours. The objective of this work was therefore to image a phantom moving with irregular breathing patterns to determine whether any configurations resulted in errors in volume contouring or alignment. METHODS: A Perspex thorax phantom was used to simulate a patient. Three wooden "lung" inserts with embedded Perspex "lesions" were moved up to 4 cm with computer-generated motion patterns, and up to 1 cm with patient-specific breathing patterns. The phantom was imaged on 4DCT and CBCT with the same acquisition settings used for stereotactic lung patients in the clinic and the volumes on all phantom images were contoured. This project assessed the volumes for qualitative and quantitative changes including volume, length of the volume, and errors in alignment between CBCT volumes and 4DCT MIP ITV contours. RESULTS: When motion was introduced 4DCT and CBCT volumes were reduced by up to 20% and 30% and shortened by up to 7 and 11 mm, respectively, indicating that volume was being under-represented at the extremes of motion. Banding artifacts were present in 4DCT MIP images, while CBCT volumes were largely reduced in contrast. When variable amplitudes from patient traces were used and CBCT ITVs were compared to 4DCT MIP ITVs there was a distinct trend in reduced ITV with increasing amplitude that was not seen when compared to true ITVs. Breathing patterns with a rest period following expiration resulted in well-defined superior edges and were better aligned using an edge-to-edge alignment technique. In most cases, sinusoidal motion patterns resulted in the closest agreements to true values and the smallest misalignments. CONCLUSIONS: Strategies are needed to compensate for volume losses at the extremes of motion for both 4DCT MIP and CBCT images for larger and varied amplitudes, and for patterns with rest periods following expiration. Lesions moving greater than 2 cm would warrant larger treatment margins added to the 4DCT MIP ITV to account for the volume being under-represented at the extremes of motion. Lesions moving with a rest period following expiration would be better aligned using an edge-to-edge alignment technique. Sinusoidal patterns represented the ideal clinical scenario, reinforcing the importance of investigating clinically relevant motions and their effects on 4DCT MIP and CBCT volumes. Since most patients do not breathe sinusoidally this may lead to misinterpretation of previous studies using only sinusoidal motion.

Adverse cardiac remodeling due to maternal low protein diet is associated with alterations in expression of genes regulating glucose metabolism.

BACKGROUND AND AIMS: We have previously shown that a maternal low protein (LP) diet during pregnancy in the rat results in adverse ventricular remodeling and contractile deficiencies of the neonatal rat heart. Since pathological cardiac hypertrophy is associated with increased expression of genes involved in glucose handling, this study was undertaken to examine if maternal LP diet alters the expression of genes encoding for some key components of glucose metabolism and uptake, and of the insulin receptor (IR) signal transduction in the heart of male offspring. METHODS AND RESULTS: We determined the effect of maternal LP and normal diet (90 and 180 g/casein/kg respectively) on IR ß-subunit, insulin receptor substrate (IRS)-1, phosphotyrosyl protein phosphatase (PTP) 1B, GLUT4 and phosphatidylinositol (PI) 3-kinase in male rat offspring at 24 h and at 1, 4 and 8 wks post-partum. Quantitative real-time RT-PCR revealed significant age-dependent increases in the expression of IR ß-subunit, IRS-1, PTP1B, GLUT4 and PI3-kinase in the LP group with concomitant increases in corresponding protein abundance at 4 wks of age. These changes were associated with increases in left ventricular (LV) internal diameters as well as increases in LV wall thickness. CONCLUSION: A maternal LP diet can induce increases in the gene expression and protein levels of key components of glucose metabolism and the IR signal transduction pathway in the neonatal rat heart, which may be related to accelerated energy supply, demand and utilization for ventricular remodeling due to compromised contractile performance during early life.