Bicuspid valve CT registry of balloon-expandable TAVR: BETTER TAVR registry.

BACKGROUND: The anatomic substrate of bicuspid valves may lead to suboptimal TAVR stent expansion and geometry. AIM: We evaluated determinants of stent geometry in bicuspid valves treated with Sapien transcatheter aortic valve replacement (TAVR) valves. METHODS: A multicenter retrospective registry of patients (February 2019 to August 2022) who underwent post-TAVR computed tomography to determine stent area (vs. nominal valve area) and stent ellipticity (maximum diameter/minimum diameter). Predictors of relative stent expansion (minimum area/average of inflow + outflow area) and stent ellipticity were evaluated in a multivariable regression model, including valve calcium volume (indexed by annular area), presence of raphe calcium, sinus diameters indexed by area-derived annular diameter, and performance of pre-dilation and post-dilation. RESULTS: The registry enrolled 101 patients from four centers. The minimum stent area (vs. nominal area) was 88.1%, and the maximum ellipticity was 1.10, with both observed near the midframe of the valve in all cases. Relative stent expansion ≥90% was observed in 64/101 patients. The only significant predictor of relative stent expansion ≥90% was the performance of post-dilation (OR: 4.79, p = 0.018). Relative stent expansion ≥90% was seen in 86% of patients with post-dilation compared to 57% without (p < 0.001). The stent ellipticity ≥1.1 was observed in 47/101 patients. The significant predictors of stent ellipticity ≥1.1 were the indexed maximum sinus diameter (OR: 0.582, p = 0.021) and indexed intercommisural diameter at 4 mm (OR: 2.42, p = 0.001). Stent expansion has a weak negative correlation with post-TAVR mean gradient (r = -0.324, p < 0.001). CONCLUSION: Relative stent expansion ≥90% was associated with the performance of post-dilation, and stent ellipticity ≥1.1 was associated with indexed intercommisural diameter and indexed maximum sinus diameter. Further studies to determine optimal deployment strategies in bicuspid valves are needed.

Phaleria macrocarpa (Scheff.) Boerl.: An updated review of pharmacological effects, toxicity studies, and separation techniques.

Phaleria macrocarpa (Scheff.) Boerl. is geographically distributed around Papua Island, Indonesia. Traditionally, P. macrocarpa is exercised to reduce pain, stomachache, diarrhea, tumor problems, blood glucose, cholesterol, and blood pressure. A growing interest in the medicinal values of P. macrocarpa especially in Asia reflects the usage of diverse extraction techniques, particularly modern approaches. In this review article, the extraction methods and solvents relevant to P. macrocarpa were discussed, with the extent of its pharmacological activities. Recent bibliographic databases such as Google Scholar, PubMed, and Elsevier between 2010 and 2022 were assessed. Based on the findings, the pharmacological studies of P. macrocarpa are still pertinent to its traditional uses but primarily emphasise anti-proliferative activity especially colon and breast cancer cells with low toxicity and fruit as the most studied plant part. The utilization of modern separation techniques has predominantly been aimed at extracting mangiferin and phenolic-rich compounds and evaluating their antioxidant capacity. However, the isolation of bioactive compounds remains a challenge, leading to the extensive utilization of the extracts in in vivo studies. This review endeavors to highlight modern extraction methods that could potentially be used as a point of reference in the future for exploring novel bioactive compounds and drug discovery on a multi-scale extraction level.

Synthesis, characterization and biological investigation of zinc nanoparticles using Acacia modesta Wall. leaves.

The study aimed to synthesize zinc nanoparticles (Zn-NPs) using an aqueous extract derived from Acacia modesta Wall. leaves. Several characterization techniques were employed to confirm the successful formation of zinc nanoparticles. UV-visible spectrophotometry indicated a peak at 374 nm, validating the bioreduction process. Scanning electron microscopy (SEM) was utilized to analyze the morphology, transmission electron microscopy (TEM) to determine particle size and shape, X-ray diffraction (XRD) for crystalline structure analysis, energy-dispersive X-ray spectroscopy (EDX) for elemental composition and Fourier-transform infrared spectroscopy (FTIR) to identify functional groups. The synthesized Zn-NPs demonstrated remarkable antibacterial activity against Escherichia coli (95% inhibition) and moderate antifungal activity against Candida albicans (70% inhibition). In phytotoxicity tests, the Zn-NPs exhibited a 55% reduction in the growth of Lamina minor at the highest dilution (1000 µl). Based on these findings, the study concluded that the green-synthesized Zn-NPs hold great potential as effective antibiotics against pathogenic bacteria and could be utilized in various industrial and agricultural applications.

Clinical prediction of genotypes in hypertrophic cardiomyopathy: A systematic review.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition and the most common cause of sudden cardiac death (SCD) in patients below the age of 35. Genetic testing is a vital part of HCM diagnostics, yet correlation with clinical phenotypes remains complex. Identifying clinical predictors of informative genetic testing may prevent unnecessary investigations and improve cost-effectiveness of services. This article reviews the current literature pertinent to identifying such predictors. METHODS: Five literature databases were screened using a suitably designed search strategy. Studies investigating the correlation between having a positive genetic test for HCM and a range of clinical and radiological parameters were included in the systematic review. RESULTS: Twenty-nine observational studies of a total of 9,486 patients were included. The main predictors of informative genetic testing were younger age, higher septal thickness, reverse septal curvature, family history of HCM and SCD and the absence of hypertension. Two externally validated scoring systems have also been developed: the Mayo and Toronto scores. Novel imaging markers and complex algorithmic models are emerging predictors. CONCLUSION: Using clinical predictors to decide whom to test is a feasible alternative to investigating all comers. Nonetheless, currently there is not enough evidence to unequivocally recommend for or against this strategy. Further validation of current predictors and identification of new ones remain open research avenues.

Intravascular lithotripsy in calcified-coronary lesions: A real-world observational, European multicenter study.

BACKGROUND: The recently introduced intravascular lithotripsy (IVL) appears promising and relatively safer than conventional approaches when dealing with calcified lesions. Although there are published reports on this novel technology, data from the real world are limited. In this study, we aim to report on the experience of IVL from a real-world population derived from six European centers that undertake high-volume complex coronary interventions. METHODS AND RESULTS: We enrolled all patients treated with IVL between November 2018 and February 2020 at six centers. Procedural success and complications were assessed along with clinical outcomes, which included: cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularisation (TLR), and major adverse cardiac event (MACE) (composite of cardiac death, TVMI, and TLR). Hundred and ninety patients (200 lesions) with a mean age of 72 years were treated using IVL. Diabetes and chronic kidney disease were present in 50% (n = 95) and 16% (n = 30) of cases, respectively. Acute-coronary syndromes accounted for 91 (48%) of the cases. Most were de-novo lesions (77%; n = 154). Upfront use of IVL occurred in 26% of cases, while the rest were bail-out procedures due to inadequate predilatation with conventional balloons. Adjuvant rotational atherectomy was needed in 17% of cases. Procedural success was achieved in 99% of cases with a complication rate of 3%. During the median follow-up of 222 days, there was two cardiac deaths (1%), one case of TVMI (0.5%), 3 TLR (1.5%) taking the MACE rate to 2.6%. CONCLUSION: Use of IVL appears to be safe and effective in dealing with calcified-coronary lesions. A high success rate was observed with low procedural complications and event rates.

Blood loss after intraarticular and intravenous tranexamic acid in total knee arthroplasty.

OBJECTIVE: To compare postoperative blood loss after intravenous and intraarticular tranexamic acid injection in patients of bilateral total knee arthroplasty. METHODS: This comparative randomised study was conducted at Ghurki Trust Teaching Hospital, Lahore, between July 2015 and January 2016, and comprised all patients admitted for bilateral total knee replacement. Patients were randomly divided into two equal groups. Group-A received intraarticular while Group-B received intravenous injection of 1.5 gmtranexamic acid. All data was analysed using SPSS 17. RESULTS: The total 140 patients were divided into two equal groups of 70(50%) each. In Group-A there were 32(45.7%) males and 38(54.3%) females, while in Group-B, there were 28(40%) males and 42(60%) females. The mean ages were 64.39±9.07 years in Group-A and 63.30±9.51 years in Group B. Blood loss in Group-A was significantly lower than Group-B (p=0.01).. CONCLUSIONS: Intraarticular administration of tranexamic acid was more effective than intravenous administration in terms of reducing blood loss.

The use of Macitentan in Fontan circulation: a case report.

BACKGROUND: The Fontan circulation, a result of a palliative procedure in patients with single systemic ventricles, is defined by chronically elevated pulmonary vascular resistance. When traditional heart failure therapies fail, pharmacological agents that reduce pulmonary artery pressures may be used. These include endothelial-receptor antagonists, prostanoids and phosphodiesterase type 5 inhibitors. We report the first use of macitentan, an endothelin-receptor antagonist, in a patient with a Fontan circulation. CASE PRESENTATION: We describe the case of a 50 year old female with tricuspid atresia and transposition of the great arteries. Following complex surgery as a child, she subsequently underwent a fenestrated modified atrial pulmonary Fontan operation which was later converted to a total cavopulmonary anastomosis Fontan circulation. Due to failure of various medications to relieve her worsening symptoms, she was commenced on macitentan in April 2016. Few months later, she demonstrated a significant symptomatic improvement and associated increase in her incremental shuttle walking test distance. CONCLUSIONS: Macitentan has slower receptor dissociation kinetics compared to other endothelin-receptor antagonists, leading to enhanced pharmacological activity with promising effects in patients with pulmonary arterial hypertension. The patient we report has shown considerable improvement in exercise capacity following introduction of this medication and thus we suggest further randomised trials to establish the role of different endothelin-receptor antagonists in the management of the Fontan circulation.

Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype.

OBJECTIVES: Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. APPROACH AND RESULTS: We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R(+/-)). Endothelial regeneration after arterial injury was accelerated in IGF1R(+/-) mice. Although the yield of angiogenic progenitor cells was lower in IGF1R(+/-) mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R(+/-) bone marrow-derived CD117(+) cells into wild-type mice. IGF1R(+/-) cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. CONCLUSIONS: Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117(+) cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury.

Co-morbidities and mortality associated with intracranial bleeds and ischaemic stroke.

Stroke is a leading cause of mortality and acquired disability; however, there has been no comprehensive comparison of co-morbid risk factors between different stroke subtypes. The aim of this study was to compare risk factors and mortality for subdural haematoma (SDH), subarachnoid haemorrhage (SAH) and ischaemic and haemorrhagic stroke. We compiled a database of all patients admitted with these conditions to a large teaching hospital in Birmingham, United Kingdom during the period 2000-2007 using the International Classification of Disease (ICD) 10th revision codes. Generalised linear models were constructed to calculate relative risks (RRs) associated with co-morbidities. In total, 4804 patients were admitted with diagnoses of SDH (1004), SAH (807), ischaemic stroke (2579) and haemorrhagic stroke (414). Patients with SDH were less likely to have pneumonia (0.492, 95% CI, 0.330-0.734; p < 0.001), whereas alcohol abuse (4.21, 95% CI, 2.82-6.28; p < 0.001) was more common. In SAH, ischaemic heart disease (0.56, 95% CI, 0.40-0.79; p < 0.001) was less common. As expected, a range of cardiovascular risk factors were associated with ischaemic stroke. Epilepsy was positively associated with ischaemic stroke (1.94, 95% CI, 1.36-2.76; p < 0.001), indicating a role for targeted primary prevention in patients with epilepsy. Five-year survival was lower in ischaemic and haemorrhagic strokes (41% and 40% respectively, vs. 73% in SDH and 64% in SAH; p < 0.001). These findings may guide clinical risk stratification, and improve the prognostic information given to patients.

Introducing a novel and robust technique for determining lymph node status in colorectal cancer.

OBJECTIVE: This study aims to harness the potential of public gene expression repositories, to develop gene expression profiles that could accurately determine nodal status in colorectal cancer. BACKGROUND: Currently, techniques that determine lymph node positivity (before resection) have poor sensitivity and specificity. The ability to determine lymph node status, based on preoperative biopsies, would greatly assist in planning treatment in colorectal cancer. This is particularly relevant in polyp-detected cancers. METHODS: Public gene expression repositories were screened for experiments comparing metastatic and nonmetastatic colorectal cancer. A customized graphic user interface was developed to extract genes dysregulated across most identified studies (ie, consensus profiles). The utility of consensus profiles was tested by determining whether classifiers could be derived that determined nodal positivity or negativity. Consensus profiles-derived classifiers were tested on separate Affymetrix- and Illumina-based experiments, and collated outputs were compiled in summary receiver operator curve characteristic format, with area under the curve (AUC) reflecting accuracy. The association between classification and oncologic outcome was determined using an additional, independent data set. Final validation was conducted using the Ingenuity network-linkage environment. RESULTS: Four consensus profiles were generated from which classifiers were derived that accurately determined node positive and negative status (pooled AUC were 0.79 ± 0.04 and 0.8 ± 0.03 for nodal positivity and negativity, respectively). Overall AUC ranged from 0.73 to 0.86, demonstrating high accuracy across consensus profile type, classification technique, and array platform used. As consensus profile enabled classification of nodal status, survival outcomes could be compared for those predicted node negative or positive. Patterns of disease-free and overall survival were identical to those observed for standard histopathologic nodal status. Genes contained within consensus profiles were strongly linked to the metastatic process and included (among others) FYN, WNT5A, COL8A1, BMP, and SMAD family members. CONCLUSIONS: Microarray expression data available in public gene expression repositories can be harnessed to generate consensus profiles. The latter are a source of classifiers that have prognostic and predictive properties.

Multi-vessel spontaneous coronary artery dissection in a patient with aortic dissection: a case report.

Background: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome that is often misdiagnosed. Case summary: We describe a case of multi-vessel SCAD in a 73-year-old patient with no evidence of fibromuscular dysplasia that is presented with Type A aortic dissection after undergoing an ascending aorta and aortic arch replacement with stent placement in the abdominal aorta. The use of percutaneous coronary intervention with cutting balloons and drug-eluting stent implantation helped wean the patient off extracorporeal membrane oxygenation successfully. Discussion: To our knowledge, this is the first reported case of multi-vessel SCAD presenting concomitantly with aortic dissection. More research is needed to help understand the pathophysiology of the two conditions as well as possible links between them.

Sonothrombolysis Augments Reperfusion in ST-Elevation Myocardial Infarction With Primary Percutaneous Coronary Intervention: Insights From the SONOSTEMI Study.

Reperfusion injury is common following primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction. In a prospective Canadian single-arm study of 15patients, the use of myocardial contrast echocardiography with high mechanical index ultrasound impulses (sonothrombolysis) initiated prior to primary PCI resulted in 7 patients with pre-PCI thrombolysis in myocardial infarction-2/3 flow (46.7%). Following reperfusion, all 15 patients had thrombolysis in myocardial infarction-3 flow, and 14 patients achieved ST-segment resolution ≥ 50% at 30 minutes post-PCI (93.3%). At 90 days, 12 patients had normal left ventricular ejection fraction ≥ 50% (80.0%). Our results demonstrate the feasibility of a novel technique to enhance reperfusion in ST-elevation myocardial infarction and provide a rationale for a randomized Canadian study.

La lésion de reperfusion est fréquente après l'intervention coronarienne percutanée (ICP) primaire chez les patients atteints d'un infarctus du myocarde avec élévation du segment ST. Dans une étude prospective canadienne, à volet unique, auprès de 15 patients, l'utilisation de l'échocardiographie myocardique de contraste par des impulsions ultrasonores à indice mécanique élevé (sonothrombolyse) amorcée avant l'ICP primaire s'est traduite par sept patients qui ont eu une thrombolyse pré-ICP de l'infarctus du myocarde de flux de grade 2/3 (46,7 %). Après la reperfusion, les 15 patients ont subi une thrombolyse de l'infarctus du myocarde de flux de grade 3, et 14 patients ont eu une résolution du segment ST ≥ 50 % 30 minutes après l'ICP (93,3 %). Après 90 jours, 12 patients ont eu une fraction d'éjection ventriculaire gauche normale ≥ 50 % (80,0 %). Nos résultats démontrent la faisabilité d'une nouvelle technique pour améliorer la reperfusion des infarctus du myocarde avec élévation du segment ST et justifient la réalisation d'une étude canadienne à répartition aléatoire.

Clinical features and complications of Loeys-Dietz syndrome: A systematic review.

INTRODUCTION: Loeys-Dietz syndrome (LDS) is a connective tissue disorder that arises from mutations altering the transforming growth factor ß signalling pathway. Due to the recent discovery of the underlying genetic mutations leading to LDS, the spectrum of characteristics and complications is not fully understood. METHODS: Our search included five databases (Pubmed, SCOPUS, Web of Science, EMBASE and google scholar) and included variations of "Loeys-Dietz Syndrome" as search terms, using all available data until February 2021. All study types were included. Three reviewers screened 1394 abstracts, of which 418 underwent full-text review and 392 were included in the final analysis. RESULTS: We identified 3896 reported cases of LDS with the most commonly reported features and complications being: aortic aneurysms and dissections, arterial tortuosity, high arched palate, abnormal uvula and hypertelorism. LDS Types 1 and 2 share many clinical features, LDS Type 2 appears to have a more aggressive aortic disease. LDS Type 3 demonstrated an increased prevalence of mitral valve prolapse and arthritis. LDS Type 4 and 5 demonstrated a lower prevalence of musculoskeletal and cardiovascular involvement. Amongst 222 women who underwent 522 pregnancies, 4% experienced an aortic dissection and the peripartum mortality rate was 1%. CONCLUSION: We observed that LDS is a multisystem connective tissue disorder that is associated with a high burden of complications, requiring a multidisciplinary approach. Ongoing attempts to better characterise these features will allow clinicians to appropriately screen and manage these complications.

Rapid transformation of the medical on-call rotas to deal with the COVID-19 pandemic: a case study.

At Sandwell and West Birmingham Hospitals Trust, an emergency rota was put into place in anticipation of the COVID-19 pandemic. Key changes included re-deploying non-general medical (GIM) consultants on to the GIM on-call rota and re-deploying junior doctors on to medical rotas, and introducing a COVID-19 induction training programme to support these redeployments. Results from a survey showed 100% of consultants felt the rotas were resilient, with 96% of consultants stating they felt the rotas were well-staffed and 77% stating that they observed no drop in quality of care. Here we outline how these changes were made and present quantitative and qualitative feedback, with the aim of informing other trusts carrying out similar urgent reconfigurations in the future, or seeking to apply the lessons learnt to their non-emergency rotas.

General medicine consultant of the week model shortens hospital length of stay and improves the patient journey.

BACKGROUND AND AIMS: The consultant of the week (COW) model of inpatient care means the consultants' primary focus is to deliver ward-based care daily. At Sandwell and West Birmingham Hospitals NHS Trust, a COW model has been successfully used for cardiology and stroke services. This has improved continuity of care and developed a 7-day working week. Our aim was to extend this model to all general medical consultants who manage inpatients. METHODS: We introduced the COW model to the unselected general medical take. Restructuring of consultant job plans allowed daily ward presence, 5 days per week. Outcome measures included length of stay (LOS) and accuracy of expected date of discharge (EDD). RESULTS: LOS over a 12-month period improved from an average of 9.17 days to 6.61 days. The number of EDD changes reduced, from a previous average of 3.0 changes to 1.8 changes. Consultant feedback showed there was an improvement in collaboration between teams, improved training of junior doctors and higher job satisfaction. CONCLUSIONS: Improved 5-day consultant presence is associated with reduced LOS. Learning points included the delay in implementation due to the complexity of consultant job planning. We plan to extend COW to 7-days for all general medical wards.

Impact of COVID-19 on primary percutaneous coronary intervention centres in the UK: a survey.

During the coronavirus disease (COVID-19) pandemic, the British Cardiovascular Society/British Cardiovascular Intervention Society and the British Heart Rhythm Society recommended to postpone non-urgent elective work and that primary percutaneous coronary intervention (PCI) should remain the treatment of choice for patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the impact of COVID-19 on the primary PCI service within the United Kingdom (UK). A survey of 43 UK primary PCI centres was performed and a significant reduction in the number of cath labs open was found (pre-COVID 3.6±1.8 vs. post-COVID 2.1±0.8; p<0.001) with only 64% of cath labs remained open during the COVID-19 pandemic. Primary PCI remained first-line treatment for STEMI in all centres surveyed.

Clinical Outcome of Laminoplasty in Cervical Myelopathy.

OBJECTIVE: The objective of the study was to assess the effectiveness of laminoplasty in terms of improvement in the Japanese Orthopedics Association (JOA) score in cervical spondylotic myelopathy (CSM). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Neurosurgery, Lahore General Hospital, Lahore, from June 2014 to October 2016. METHODOLOGY: All patients having CSM were assessed preoperatively and postoperatively by JOA score and radiological findings. Preoperative X-rays of cervical spine were done to rule out kyphotic deformity. CT scan and MRI of cervical spine were obtained preoperatively to assess the pathology. Single-door laminoplasty with modified trauma plates were applied in each case by making the hinge over the right side. Digital cervical spine X-rays and CT scans with axial reconstruction were obtained postoperatively in all patients, ensuring spinal canal widening and stability. RESULTS: Among the 36 patients, 24 were males and 12 females, age ranging from 35 to 80 years. All the patients did extremely well with marked improvement in the symptomatology. The JOA scored improved in 32 patients, remained static in three patients and one patient had slight deterioration, which later on improved. Three patients developed postoperative kyphotic deformity, which settled in three months. Postoperative radiology showed significant increase in the axial diameter of spine. CONCLUSION: Cervical laminoplasty remains an effective method for posterior decompression of spine. The most promising approach to cervical myelopathy ought to take into account both the features of patients and disease, as well as the competency and skills of the surgeon.

Insulinlike Growth Factor-Binding Protein-1 Improves Vascular Endothelial Repair in Male Mice in the Setting of Insulin Resistance.

Insulin resistance is associated with impaired endothelial regeneration in response to mechanical injury. We recently demonstrated that insulinlike growth factor-binding protein-1 (IGFBP1) ameliorated insulin resistance and increased nitric oxide generation in the endothelium. In this study, we hypothesized that IGFBP1 would improve endothelial regeneration and restore endothelial reparative functions in the setting of insulin resistance. In male mice heterozygous for deletion of insulin receptors, endothelial regeneration after femoral artery wire injury was enhanced by transgenic expression of human IGFBP1 (hIGFBP1). This was not explained by altered abundance of circulating myeloid angiogenic cells. Incubation of human endothelial cells with hIGFBP1 increased integrin expression and enhanced their ability to adhere to and repopulate denuded human saphenous vein ex vivo. In vitro, induction of insulin resistance by tumor necrosis factor α (TNFα) significantly inhibited endothelial cell migration and proliferation. Coincubation with hIGFBP1 restored endothelial migratory and proliferative capacity. At the molecular level, hIGFBP1 induced phosphorylation of focal adhesion kinase, activated RhoA and modulated TNFα-induced actin fiber anisotropy. Collectively, the effects of hIGFBP1 on endothelial cell responses and acceleration of endothelial regeneration in mice indicate that manipulating IGFBP1 could be exploited as a putative strategy to improve endothelial repair in the setting of insulin resistance.

Endothelial Insulin Receptor Restoration Rescues Vascular Function in Male Insulin Receptor Haploinsufficient Mice.

Reduced systemic insulin signaling promotes endothelial dysfunction and diminished endogenous vascular repair. We investigated whether restoration of endothelial insulin receptor expression could rescue this phenotype. Insulin receptor knockout (IRKO) mice were crossed with mice expressing a human insulin receptor endothelial cell-specific overexpression (hIRECO) to produce IRKO-hIRECO progeny. No metabolic differences were noted between IRKO and IRKO-hIRECO mice in glucose and insulin tolerance tests. In contrast with control IRKO littermates, IRKO-hIRECO mice exhibited normal blood pressure and aortic vasodilatation in response to acetylcholine, comparable to parameters noted in wild type littermates. These phenotypic changes were associated with increased basal- and insulin-stimulated nitric oxide production. IRKO-hIRECO mice also demonstrated normalized endothelial repair after denuding arterial injury, which was associated with rescued endothelial cell migration in vitro but not with changes in circulating progenitor populations or culture-derived myeloid angiogenic cells. These data show that restoration of endothelial insulin receptor expression alone is sufficient to prevent the vascular dysfunction caused by systemically reduced insulin signaling.

Feasibility study of the retrospective use of the Adult Comorbidity Evaluation index (ACE-27) in patients with cancer of the head and neck who had radiotherapy.

The Adult Comorbidity Evaluation index (ACE-27) is a relatively new measure of comorbidity and the aim of this study was to assess the feasibility of retrospective examination of casenotes to estimate this index in patients who were given radiotherapy for head and neck cancer. We examined the casenotes of 157 of 168 consecutive patients diagnosed with an index primary tumour of the head and neck at the Clatterbridge Centre of Oncology in 1992 and 1993. Three comorbidity measures, the ACE-27, Charlson comorbidity index (CL) and Washington University Head Neck Cancer Index (WUHNCI) were calculated. In the grading of the ACE-27, 5 patients (3%) were grade 3, 21 (13%) were grade 2, 57 (36%) were grade 1 and 74 (47%) were grade zero. There was a trend in survival by ACE-27 grading with little difference between mild and moderate severity (p=0.08). There were no significant correlations between survival and either the Charlson index (p=0.80) or the WUHNCI (p=0.68). There were no significant correlations of any of the indices or of clinico-demographic factors with recurrence rates.