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BACKGROUND: Aortic root evaluation is conventionally based on two-dimensional measurements at a single phase of the cardiac cycle. This work presents an image analysis method for assessing dynamic three-dimensional changes in the aortic root of minimally calcified bicuspid aortic valves (BAVs) with and without moderate to severe aortic regurgitation. METHODS: The aortic root was segmented over the full cardiac cycle in three-dimensional transesophageal echocardiographic images acquired from 19 patients with minimally calcified BAVs and from 16 patients with physiologically normal tricuspid aortic valves (TAVs). The size and dynamics of the aortic root were assessed using the following image-derived measurements: absolute mean root volume and mean area at the level of the ventriculoaortic junction, sinuses of Valsalva, and sinotubular junction, as well as normalized root volume change and normalized area change of the ventriculoaortic junction, sinuses of Valsalva, and sinotubular junction over the cardiac cycle. RESULTS: Normalized volume change over the cardiac cycle was significantly greater in BAV roots with moderate to severe regurgitation than in normal TAV roots and in BAV roots with no or mild regurgitation. Aortic root dynamics were most significantly different at the mid-level of the sinuses of Valsalva in BAVs with moderate to severe regurgitation than in competent TAVs and BAVs. CONCLUSIONS: Echocardiographic reconstruction of the aortic root demonstrates significant differences in dynamics of BAV roots with moderate to severe regurgitation relative to physiologically normal TAVs and competent BAVs. This finding may have implications for risk of future dilatation, dissection, or rupture, which warrant further investigation.

Expression of ATP‐binding cassette B5 (ABCB5) has been demonstrated to confer chemoresistance, enhance cancer stem cell properties and associate with poor prognosis in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the genetic variations of ABCB5 in HCC patients with reference to healthy individuals and the clinicopathological significance. A pilot study has examined 20 out of 300 pairs HCC and paralleled blood samples using conventional sequencing method to cover all exons and exon/intron regions to investigate whether there will be novel variant sequence and mutation event. A total of 300 HCC and 300 healthy blood DNA samples were then examined by Sequenom MassARRAY genotyping and pyrosequencing for 38 SNP and 1 INDEL in ABCB5. Five novel SNPs were identified in ABCB5. Comparison of DNA from blood samples of HCC and healthy demonstrated that ABCB5 SNPs rs75494098, rs4721940 and rs10254317 were associated with HCC risk. Specific ABCB5 variants were associated with aggressive HCC features. SNP rs17143212 was significantly associated with ABCB5 expression level. Nonetheless, the paralleled blood and tumour DNA sequences from HCC patients indicated that ABCB5 mutation in tumours was not common and corroborated the TCGA data sets. In conclusion, ABCB5 genetic variants had significant association with HCC risk and aggressive tumour properties.

Mindfulness interventions have been shown to be effective in the treatment of anxiety for both adolescent and adult populations. However, little research has investigated and tested the use of mind...

BACKGROUND: The first UK guidelines for the management of hidradenitis suppurativa (HS) were published by the British Association of Dermatologists (BAD) in 2018. The guidelines contained a set of audit criteria. AIM: To evaluate current HS management against the audit standards in the BAD guidelines. METHODS: BAD members were invited to complete audit questionnaires between January and May 2020 for five consecutive patients with HS per department. RESULTS: In total, 88 centres participated, providing data for 406 patients. Disease staging using the Hurley system and disease severity using a validated tool during follow-ups was documented in 75% and 56% of cases, respectively, while quality of life and pain were documented in 49% and 50% of cases, respectively. Screening for cardiovascular disease risk factors was as follows: smoking 75%, body mass index 27% and others such as lipids and diabetes 57%. Screening for depression and anxiety was performed in 40% and 25% of cases, respectively. Support for smokers or obese patients was documented in 35% and 23% of cases. In total, 182 patients were on adalimumab, of whom 68% had documentation of baseline disease severity, and 76% were reported as having inadequate response or contraindications to systemic treatments; 44% of patients continued on adalimumab despite having < 25% improvement in lesion count. CONCLUSION: UK dermatologists performed well against several audit standards, including documenting disease staging at baseline and smoking status. However, improvements are needed, particularly with regard to screening and management of comorbidities that could reduce the long-term complications associated with HS. A re-audit is required to evaluate changes in practice in the future.

Tumor hypoxia induces the large-scale adaptive reprogramming of cancer cells, promoting their transformation into highly invasive and metastatic species that lead to highly negative prognoses for cancer patients. We describe the synthesis and application of a hypoxia-responsive trigger derived from previously inaccessible enamine N-oxide structures. Hypoxia-dependent reduction of this motif by hemeproteins results in the concomitant activation of a caged molecule and a latent electrophile. We exploit the former in a hypoxia-activated prodrug application using a caged staurosporine molecule as a proof-of-principle. We demonstrate the latter in in vivo tumor labeling applications with enamine-N-oxide-modified near-infrared probes. Hypoxia-activated prodrug development has long been complicated by the heterogeneity of tumor hypoxia in patients. The dual drug release and imaging modalities of the highly versatile enamine N-oxide motif present an attractive opportunity for theranostic development that can address the need not only for new therapeutics but paired methods for patient stratification.

Background There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. Objective To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. Methods We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. Results Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. Conclusions Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.

Background: Economic evidence for vitiligo treatments is absent. Objectives: To determine the cost-effectiveness of (i) handheld narrowband ultraviolet B (NB-UVB) and (ii) a combination of topical corticosteroid (TCS) and NB-UVB compared with TCS alone for localized vitiligo. Methods: Cost-effectiveness analysis alongside a pragmatic, three-arm, placebo-controlled randomized controlled trial with 9 months’ treatment. In total 517 adults and children (aged ≥ 5 years) with active vitiligo affecting < 10% of skin were recruited from secondary care and the community and were randomized 1: 1: 1 to receive TCS, NB-UVB or both. Cost per successful treatment (measured on the Vitiligo Noticeability Scale) was estimated. Secondary cost–utility analyses measured quality-adjusted life-years using the EuroQol 5 Dimensions 5 Levels for those aged ≥ 11 years and the Child Health Utility 9D for those aged 5 to < 18 years. The trial was registered with number ISRCTN17160087 on 8 January 2015. Results: The mean ± SD cost per participant was £775 ± 83·7 for NB-UVB, £813 ± 111.4 for combination treatment and £600 ± 96·2 for TCS. In analyses adjusted for age and target patch location, the incremental difference in cost for combination treatment compared with TCS was £211 (95% confidence interval 188–235), corresponding to a risk difference of 10·9% (number needed to treat = 9). The incremental cost was £1932 per successful treatment. The incremental difference in cost for NB-UVB compared with TCS was £173 (95% confidence interval 151–196), with a risk difference of 5·2% (number needed to treat = 19). The incremental cost was £3336 per successful treatment. Conclusions: Combination treatment, compared with TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost-effective if decision makers are willing to pay £1932 per additional treatment success.

The anesthetic and perioperative management of patients with acute aortic dissection is important for achieving successful outcomes. Because early mortality is contingent on the time to definitive treatment, open communication between the admitting, surgical, and anesthesia teams is necessary to safely expedite the management of patients with life-threatening complications such as aortic regurgitation, cardiac tamponade, or malperfusion who require emergency operation. The wide availability of intraoperative transesophageal echocardiography (TEE) has enabled aortic dissection to be diagnosed or confirmed in the operating room. TEE can also diagnose complications associated with acute aortic dissection, identify the location of the intimal tear, characterize the extent of the dissection or guide central cannulation for cardiopulmonary bypass. During operations on the thoracic aorta, the brain, spinal cord, and end-organs require protection during periods of ischemia. Postoperative intensive care is necessary for temporary mechanical ventilatory support and circulation management with vasoactive medications. In addition, lung injury, acute kidney injury, encephalopathy, bleeding, mesenteric ischemia, limb ischemia, and metabolic acidosis are common problems that require critical care after operations for acute aortic dissection.

Spinal cord ischemia, spinal cord infarction, and paraplegia remain an important complication of patients undergoing open surgical or endovascular repair of the thoracic and thoracoabdominal aorta. Improvements in surgical techniques such as endovascular repair, partial left heart bypass, reimplantation of segmental arteries, and staged repairs combined with anesthetic techniques that include arterial pressure augmentation, deliberate hypothermia, lumbar cerebrospinal fluid drainage, and intraoperative neurophysiologic monitoring has decreased the risk of intraoperative spinal cord ischemia. Despite improvements, patients remain at risk for delayed onset spinal cord ischemia. Serial neurologic assessment and precise circulatory management are necessary to prevent and detect delayed onset spinal cord ischemia. Immediate treatment of delayed onset spinal cord ischemia with arterial pressure augmentation and lumbar cerebrospinal fluid drainage is often effective for preventing paraplegia or decreasing the severity of the permanent neurologic injury in patients with reversible ischemic spinal cord syndrome.

Background: Evidence for the effectiveness of vitiligo treatments is limited. Objectives: To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. Methods: A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting

SummaryBackground Diagnosis and management of nonmelanoma skin cancer (NMSC) represents a large part of the dermatology workload, and complete excision is a required surgical standard for treatment. Aim To conduct an audit of the surgical practice for the treatment of NMSC by dermatologists in the UK. Methods Data on 10 consecutive nonmicrographic excisions of nonmelanoma skin cancer by UK dermatologists. Data collected included site, preoperative diagnosis, histological diagnosis, proximity to previous scars, and histological deep and peripheral margins. Results A total of 227 responses from 135 centres reported 2739 excisions. Excisions on the head and neck accounted for 58.3% of cases. Tumour diameter (mean ± SD) was 10.61 ± 6.9 mm (maximum 130 mm), and 96.7% of cases were primary excisions, with 3.3% being re-excisions. Basal cell carcinomas (BCCs) accounted for 79.1% (n = 2167) of the total cases and squamous cell carcinomas (SCCs) for 17.9% n = 491). Of the suspected BCCs and SCCS, 94.4% (n = 2045) and 66.8% (328), respectively, were confirmed histologically to be the respective carcinomas. Similar proportions of BCC and SCC cases were within 10 mm of a previous excision. Lateral and deep margins were clear in 98.3% and 99.2% of BCC cases, respectively, and in 98.4% and 97.1% of SCC cases, respectively. Reported surgical complication rate in the audit was 3.4%. Conclusions The majority of excisions for NMSC are for BCC and SCC. Our figures for diagnostic accuracy are at the upper range of previously published figures. Most patients were not followed up in secondary care, hence complication rates may be under-reported.

Objective We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. Design We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models. Results We identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of TSC1 and TSC2 genes in the HCC samples. The spectrum of TSC1/2 mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of TSC1 and TSC2 was also observed in HCC cell lines and our PDTX models. TSC -mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant TSC2 -mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment. Conclusions Taken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent TSC1/2 mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy.

Article, see p 1770 Brain injury remains an important and potentially preventable complication of cardiac surgery. Although clinically overt strokes occur in a minority of patients, studies using frequent neurological assessments after surgery have found a much higher rate than had been previously appreciated.1 Even more commonly, patients manifest nonfocal or nonspecific neurological signs and symptoms of brain dysfunction such as encephalopathy, seizure, delirium, or postoperative cognitive impairment, at least some of which are also attributable to acute infarct. Recent investigations using perioperative magnetic resonance diffusion-weighted imaging (DWI) have demonstrated that cerebral infarction is frequently present after cardiac operations and interventions even in the absence of overt stroke.1,2 These findings have led a research consortium guideline to recommend combining neurological examinations, neurocognitive testing, and brain imaging in clinical trials designed to assess neurological outcomes after cardiac procedures to fully characterize the incidence, severity, and clinical sequelae of perioperative brain injury.3 Perioperative cerebral infarction associated with cardiac operations can be attributed to preexisting vascular disease, transient hypercoagulability, procedure-related thromboembolism, hypoperfusion, or a combination of these factors. Among these mechanisms, hypoperfusion stands out as an obvious modifiable risk factor. Early observational studies found an association between the incidence and severity of postoperative brain damage and low mean arterial pressure (MAP) during cardiopulmonary bypass (CPB).4,5 Subsequent brain imaging studies suggested that up to 48% of cardiac surgical patients with postoperative stroke had infarction in the watershed regions of the brain and that hypotension was a risk factor for stroke.6 Furthermore, although thromboembolism is an important mechanism for stroke, hypotension may exacerbate these injuries by impairing “washout” or clearance of microemboli.7 However, randomized controlled studies8–10 and observational studies11,12 have yielded inconclusive or conflicting results on the effect of …

Objectives Mortality in acute aortic dissection varies depending on anatomic location, extent, and associated complications. The Stanford classification guides surgical versus medical management. The Penn classification stratifies mortality risk in patients with Stanford type A aortic dissections undergoing surgery. The objective of the present study was to determine whether the Penn classification can predict hospital mortality in patients with acute Stanford type A and type B aortic dissections undergoing surgical or medical management. Design Retrospective, observational study. Setting Tertiary care, university hospital. Participants Patients with acute aortic dissection between January 2008 and December 2017. Interventions Examination of hospital mortality after surgical or medical management. Measurements and Main Results Three hundred fifty-two patients had confirmed dissections (186 type A, 166 type B). The overall mortality was 18.8% for type A and 13.3% for type B. Penn class A patients with type A or type B dissections undergoing surgical repair had the lowest mortality (both 3.1%). Penn class B, C, or B+C patients with type A dissections and Penn class B+C patients with type B dissections undergoing medical management had the greatest incidence of mortality (50.0%-57.1%). All others had intermediate mortality (6.7%-39.3%). Logistic regression analysis demonstrated that Penn class B, C, and B+C patients had a greater odds of mortality and predicted mortality than did Penn class A patients. Conclusions The Penn classification predicts hospital mortality in patients with acute Stanford type A or type B aortic dissections undergoing surgical or medical management. Early endovascular repair may confer lower risk of mortality in patients with type B dissections presenting without ischemia.

Background Bullous pemphigoid (BP) is an autoimmune, subepidermal, blistering condition that typically affects elderly people. Aim To undertake a national clinical audit based on standards derived from the British Association of Dermatologists (BAD) clinical guidelines on the management of BP. Methods In 2018, BAD members were invited to submit data for five consecutive adults with BP per centre, who had been under hospital supervision for at least 12 months, in a national audit over an 11-week period. Results In total, 123 responders from 120 hospitals provided data for 524 cases. Diagnosis was made either clinically (10.7%; 56 of 524) or through histology with direct immunofluorescence (41.6%; 218 of 524), indirect immunofluorescence (10.3%; 54 of 524) or both (37.4%; 196 of 524). Most patients had very mild baseline disease (63.9%; 225 of 352) with 21.9% (77 of 352) considered mild, 9.8% (31 of 352) moderate and 5.4% (19 of 352) severe. Documentation of diabetes, glycated haemoglobin (HbA1c), blood pressure and hypertension was available for 54.1% (283 of 523), 51% (267 of 524), 44.2% (231 of 522) and 61.5% (321 of 522) of cases, respectively. Oral corticosteroids were commenced in 85.5% (448 of 524) of patients, with 38.4% (172 of 448) of these having documented risk of osteoporosis; data regarding prescription of bone-protection therapies were available for 99.7% (447 of 448) of cases, with 75.6% (338 of 447) of these having a bone-protection prescription. Patient satisfaction was documented in 59.3% (310 of 523) of cases. Systemic treatment was commenced in 95.9% (502 of 524) of cases during the 12-month assessment period, with baseline blood test and follow-up data available for 96.6% (485 of 502) and 95.6% (480 of 502), respectively. Documentation of baseline blood tests was available for 87.4% (424 of 485) of cases, with follow-up tests recorded in 69.8% (335 of 480). Conclusion Overall, compliance with elements of documentation was moderate or low, whereas standards pertaining to direct care were high.

In the absence of randomized controlled data and even propensity-matched data, indications for, and outcomes of, laparoscopic repeat liver resection for hepatocellular carcinoma (HCC) remain uncertain. This study aimed to clarify the current indications for laparoscopic repeat liver resection for HCC, and to evaluate outcomes.Forty-two liver surgery centres around the world registered patients who underwent repeat liver resection for HCC. Patient characteristics, preoperative liver function, tumour characteristics, surgical method, and short- and long-term outcomes were recorded.Analyses showed that the laparoscopic procedure was generally used in patients with relatively poor performance status and liver function, but favourable tumour characteristics. Intraoperative blood loss (mean(s.d.) 254(551) versus 748(1128) ml; P 0·001), duration of operation (248(156) versus 285(167) min; P 0·001), morbidity (12·7 versus 18·1 per cent; P = 0·006) and duration of postoperative hospital stay (10·1(14·3) versus 11·8(11·8) days; P = 0·013) were significantly reduced for laparoscopic compared with open procedures, whereas survival time was comparable (median 10·04 versus 8·94 years; P = 0·297). Propensity score matching showed that laparoscopic repeat liver resection for HCC resulted in less intraoperative blood loss (268(730) versus 497(784) ml; P = 0·001) and a longer operation time (272(187) versus 232(129); P = 0·007) than the open approach, and similar survival time (12·55 versus 8·94 years; P = 0·086).Laparoscopic repeat liver resection is feasible in selected patients with recurrent HCC.Dado que no existen ensayos clínicos controlados ni estudios de datos emparejados por puntaje de propensión, todavía hay dudas sobre las indicaciones y los resultados de la resección iterativa laparocópica de un carcinoma hepatocelular (hepatocellular carcinoma, HCC). Este estudio tuvo como objetivo esclarecer las indicaciones actuales y los resultados de la resección hepática laparoscópica iterativa del HCC. MÉTODOS: Se incluyeron los pacientes de 42 centros de cirugía hepática a nivel mundial en los que se había realizado una resección hepática iterativa por HCC. Se analizaron las características del paciente, la función hepática preoperatoria, las características del tumor, el abordaje quirúrgico y los resultados a corto y largo plazo.El análisis demostró que la vía laparoscópica generalmente se utilizaba en pacientes con carácteristicas tumorales favorables, pero con estado funcional y función hepatica relativamente peores. La pérdida de sangre intraoperatoria (254,3 ± 551,2 versus 748,0 ± 1127,7 mL, P 0,001), la duración de la intervención (247,6 ± 155,8 versus 285,1 ± 167,0 minutos, P 0,001), la morbilidad (12,7 versus 18,1%, P = 0,005) y la estancia hospitalaria postoperatoria (10,07 ± 14,29 versus 11,80 ± 11,79 días, P = 0,010) fueron significativamente menores para los pacientes tratados por via laparoscópica en comparacion con la vía abierta, mientra que el tiempo de supervivencia fue comparable (mediana 10,04 versus 8,94 años, P = 0,297). El estudio de emparejamiento por puntaje de propensión mostró que la resección hepática iterativa por vía laparoscópica de un HCC (frente a la vía abierta) conllevaba una menor pérdida sanguínea intraoperatoria (268,0 ± 730,2 versus 496,5 ± 784,2 mL, P = 0,01), una mayor duración de la intervención (272,1 ± 187,2 versus 231,8 ± 129,1 minutos , P = 0,07) y un tiempo de supervivencia similar (mediana 12,55 versus 8,94 años, P = 0,0855). CONCLUSIÓN: La resección hepática iterativa por vía laparoscópica es factible en pacientes seleccionados con HCC recidivado.

To provide a theoretically grounded understanding of engagement in interactive computer play-based motor therapies by children with cerebral palsy in home settings.A motivational framework for engagement and its relationship with three contemporary theories (self-determination theory, expectancy-value theory, social cognitive theory of self-regulation) was overviewed. A scoping review was conducted to understand how engagement is influenced by features of the technology and intervention design that impact intrinsic and extrinsic motivation, child and parent values and expectancies, and the processes of self-regulation. Multiple reviewers screened and extracted data from 26 articles describing home-based clinical trials of interactive computer play-based motor interventions for children with cerebral palsy. A narrative synthesis framework was used for analysis.Features of theOptimizing engagement in interactive computer play-based motor interventions requires closer alignment with client-led values/goals; design of technologies and interventions that sustain intrinsic motivation; and feedback that informs/builds self-efficacy. Implications for rehabilitation The decision to prescribe an interactive computer play-based motor intervention should be guided by client-led goals and an informed understanding of the capacity of the interactive computer play-based intervention to meet individual client values/expectancies. Sustaining intrinsic motivation in interactive computer play-based motor therapies is greatly influenced by features of the technology (e.g., calibration, feedback, personalization)

Objectives: Repair for ischemic mitral regurgitation with undersized annuloplasty is characterized by high recurrence rates. We sought to determine the value of pre-repair 3-dimensional echocardiography over 2-dimensional echocardiography in predicting recurrence at 6 months.Methods: Intraoperative transesophageal 2-dimensional echocardiography and 3-dimensional echocardiography were performed in 50 patients undergoing undersized annuloplasty for ischemic mitral regurgitation. Two-dimensional echocardiography annular diameter and tethering parameters were measured in the apical 2-and 4-chamber views. A customized protocol was used to assess 3-dimensional annular geometry and regional leaflet tethering. Recurrence (grade >= 2) was assessed with 2-dimensional transthoracic echocardiography at 6 months.Results: Preoperative 2- and 3-dimensional annular geometry were similar in all patients with ischemic mitral regurgitation. Preoperative 2- and 3-dimensional leaflet tethering were significantly higher in patients with recurrence (n = 13) when compared with patients without recurrence (n = 37). Multivariate logistic regression revealed preoperative 2-dimensional echocardiography posterior tethering angle as an independent predictor of recurrence with an optimal cutoff value of 32.0 degrees (area under the curve, 0.81; 95% confidence interval, 0.68-0.95; P = .002) and preoperative 3-dimensional echocardiography P3 tethering angle as an independent predictor of recurrence with an optimal cutoff value of 29.9 degrees (area under the curve, 0.92; 95% confidence interval, 0.84-1.00; P Conclusions: Preoperative 3-dimensional echocardiography P3 tethering angle is a stronger predictor of ischemic mitral regurgitation recurrence after annuloplasty than preoperative 2-dimensional echocardiography posterior tethering angle, which is highly influenced by viewing plane. In patients with a preoperative P3 tethering angle of 29.9 degrees or larger (especially when combined with basal aneurysm/dyskinesis), chordal-sparing valve replacement should be strongly considered.

Objective: Metabolic acidosis after deep hypothermic circulatory arrest (DHCA) for thoracic aortic operations is commonly managed with sodium bicarbonate (NaHCO 3 ). The purpose of this study was to determine the relationships between total NaHCO 3 dose and the severity of metabolic acidosis, duration of mechanical ventilation, duration of vasoactive infusions, and Intensive Care Unit (ICU) or hospital length of stay (LOS). Methods: In a single center, retrospective study, 87 consecutive elective thoracic aortic operations utilizing DHCA, were studied. Linear regression analysis was used to test for the relationships between the total NaHCO 3 dose administered through postoperative day 2, clinical variables, arterial blood gas values, and short-term clinical outcomes. Results: Seventy-five patients (86%) received NaHCO 3 . Total NaHCO 3 dose averaged 136 ± 112 mEq (range: 0.0-535 mEq) per patient. Total NaHCO 3 dose correlated with minimum pH (r = 0.41, P < 0.0001), minimum serum bicarbonate (r = −0.40, P < 0.001), maximum serum lactate (r = 0.46, P = 0.007), duration of metabolic acidosis (r = 0.33, P = 0.002), and maximum serum sodium concentrations (r = 0.29, P = 0.007). Postoperative hypernatremia was present in 67% of patients and peaked at 12 h following DHCA. Eight percent of patients had a serum sodium ≥ 150 mEq/L. Total NaHCO 3 dose did not correlate with anion gap, serum chloride, not the duration of mechanical ventilator support, vasoactive infusions, ICU or hospital LOS. Conclusion: Routine administration of NaHCO 3 was common for the management of metabolic acidosis after DHCA. Total dose of NaHCO 3 was a function of the severity and duration of metabolic acidosis. NaHCO 3 administration contributed to postoperative hypernatremia that was often severe. The total NaHCO 3 dose administered was unrelated to short-term clinical outcomes.

To determine the severity, duration, and contributing factors for metabolic acidosis after deep hypothermic circulatory arrest (DHCA).Retrospective observational study.University hospital.Eighty-seven consecutive patients undergoing elective thoracic aortic surgery with DHCA.Regression analysis was used to test for relationships between the severity of metabolic acidosis and clinical and laboratory variables.Minimum pH averaged 7.27±0.06, with 76 (87%) having a pH7.35; 55 (63%), a pH7.30; and 7 (8%), a pH7.20. The mean duration of metabolic acidosis was 7.9±5.0 hours (range: 0.0 - 26.8), and time to minimum pH after DHCA was 4.3±2.0 hours (1.0 - 10.0 hours). Hyperchloremia contributed to metabolic acidosis in 89% of patients. The severity of metabolic acidosis correlated with maximum lactate (p0.0001) and hospital length of stay (LOS) (r = 0.22, p0.05), but not with DHCA time, DHCA temperature, duration of vasoactive infusions, or ICU LOS. Patient BMI was the sole preoperative predictor of the severity of postoperative metabolic acidosis.This retrospective analysis involved short-term clinical outcomes related to pH severity and duration, which indirectly may have included the impact of sodium bicarbonate administration.Metabolic acidosis was common and severe after DHCA and was attributed to both lactic and hyperchloremic acidosis. DHCA duration and temperature had little impact on the severity of metabolic acidosis. The severity of metabolic acidosis was best predicted by the BMI and had minimal effects on short-term outcomes. Preventing hyperchloremic acidosis has the potential to decrease the severity of metabolic acidosis after DHCA.

Objectives: To study the effectiveness of noninvasive positive pressure ventilation (NIPPV) in the treatment of acute respiratory failure (ARF) in severe acute respiratory syndrome (SARS), and the associated infection risk. Methods: All patients with the diagnosis of probable SARS admitted to a regional hospital in Hong Kong from March 9 to April 28, 2003, and who had SARS-related respiratory distress complications were recruited for NIPPV usage. The health status of all health-care workers working in the NIPPV wards was closely monitored, and consent was obtained to check serum for coronavirus serology. Patient outcomes and the risk of SARS transmission to health-care workers were assessed. Results: NIPPV was applied to 20 patients (11 male patients) with ARF secondary to SARS. Mean age was 51.4 years, and mean acute physiology and chronic health evaluation II score was 5.35. Coronavirus serology was positive in 95% (19 of 20 patients). NIPPV was started 9.6 days (mean) from symptom onset, and mean duration of NIPPV usage was 84.3 h. Endotracheal intubation was avoided in 14 patients (70%), in whom the length of ICU stay was shorter (3.1 days vs 21.3 days, p < 0.001) and the chest radiography score within 24 h of NIPPV was lower (15.1 vs 22.5, p = 0.005) compared to intubated patients. Intubation avoidance was predicted by a marked reduction in respiratory rate (9.2 breaths/min) and supplemental oxygen requirement (3.1 L/min) within 24 h of NIPPV. Complications were few and reversible. There were no infections among the 105 health-care workers caring for the patients receiving NIPPV. Conclusions: NIPPV was effective in the treatment of ARF in the patients with SARS studied, and its use was safe for health-care workers.

Background: The effectiveness of the Patient Empowerment Program (PEP) has been demonstrated in people with diabetes mellitus (DM); however, the underlying reasons for its effectiveness remain unclear. To improve effectiveness, we need to study the psychological mechanism(s) of PEP to understand why it is effective. This study hypothesized that the Theory of Planned Behavior (TPB), modified specifically for people with DM, could describe the mechanism explaining PEP effects. Methods: A longitudinal design was used. Patients with type 2 DM ( n = 365; 151 males; mean age = 62.9 ± 9.6 years) received two education sessions (i.e. seminars delivered by registered nurses to provide disease-specific knowledge), and some ( n = 210) further enrolled afterwards in five empowerment sessions (i.e. small-group interactive workshops conducted by social workers to practice action planning, problem solving, and experience sharing). Validated questionnaires were used to measure risk perception, health literacy, attitude, subjective norm, perceived behavioral control and behavioral intention on diabetes self-care behaviors, and four diabetes self-care behaviors (diet control, exercise, blood glucose monitoring, and foot care) at baseline. Three months later (i.e. at the end of PEP), all participants completed the behavioral intention and diabetes self-care behaviors measures again. Attitude, subjective norm, perceived behavioral control, behavioral intention, and diabetes self-care behaviors were assessed to represent the TPB constructs. Risk perception and health literacy elements relevant to people with DM were assessed and added to modify the TPB. Results: The behavioral intention was associated with three diabetes self-care behaviors: exercise, blood glucose monitoring, and foot care. The behavioral intention was found to be a significant mediator in the following relationships: empowerment session participation and exercise (β = 0.045, p = 0.04), and empowerment session participation and foot care (β = 0.099, p Conclusions: The effects of enrollment of empowerment sessions in PEP on exercise and foot care were likely to be mediated through behavioral intention.

Background and aims While a “Treat-to-target” principle is widely advocated in management of systemic lupus erythematosus (SLE), there is currently no internationally agreed definition of low disease activity in lupus. In 2015, the Asia-Pacific Lupus Collaboration presented a novel consensus definition of a safe state in lupus, the “Lupus Low Disease Activity State” (LLDAS). (http://dx.doi.org/10.1136/annrheumdis-2015-207726) Methods This was a prospective study to determine whether LLDAS predicted lower flare-ups, damage and mortality. 339 SLE patients were recruited and followed for 30 months. Multivariable binomial regression was used to determine factors associated with LLDAS and Cox proportional hazard model to determine whether prior higher% of days in LLDAS would be associated with lower future flare-ups. Results Mean patient age was 48.1 years and mean disease duration 19.6 years. Female to male ratio=16 to 1. 79 flare-ups were documented. 92.6% of patients had ever achieved LLDAS during the study period and 62.1% of patient-days were in LLDAS. No major demographic or prior disease presentations were found to be associated with the attainment of LLDAS. Patients with prior higher percentage of days in LLDAS had lower hazard of lupus flare-ups (HR=0.420, p=0.015) after adjustment for gender and age. The numbers of patient damage and death were insufficient for analysis. Conclusions LLDAS is an independent construct achievable by most patients of different history or background. Our preliminary study shows LLDAS can predict the risk of future flare-ups though further studies are needed to determine whether it is associated less lupus-related damage and lower mortality.

Objective: Normative values of left ventricular (LV) end-diastolic area and diameter (EDA and EDD) for intraoperative transoesophageal echocardiography (TEE) have not been established. We aimed to define the ranges of LV EDA and EDD for intraoperative TEE examinations in patients undergoing coronary artery bypass graft (CABG) surgery. Methods: A MEDLINE search for studies reporting LV EDA and EDD in CABG patients was performed. Individual-level dataset from 333 anaesthetised and mechanically ventilated patients with preserved LV function (study population) were received from 8 studies. EDA and calculated EDD values in the study population were compared with summary mean EDD values obtained by transthoracic echocardiography (TTE) in 2 studies of 500 awake patients with coronary artery disease (CAD). Further, the influence of prespecified factors on EDD was evaluated through a multivariate regression model. Results: LV EDA and EDD values measured by TEE in anaesthetised CABG patients were 16.7±4.7 cm 2 and 4.6±0.6 cm, respectively. EDD values measured by TEE in anaesthetised patients were 10% to 13% less those measured by TTE in 2 studies of awake patients (p

The contemporary oncologic pathology report conveys diagnostic, prognostic, predictive, and hereditary predisposition information. Each component may be premised on a morphologic feature or a biomarker. Clinical validity and reproducibility are paramount as is standardization of reporting and clinical response to ensure individualization of patient care. Regarding hereditary predisposition, morphology-based genetic referral systems in some instances have eclipsed genealogy-based systems, for example, cell type in ovarian cancer and BRCA screening. In other instances such as Lynch syndrome, morphology-based schemas supplement clinical schemas and there is an emerging standard of care for reflex biomarker testing. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome predisposes patients to uterine and cutaneous leiomyomas (LMs) and renal cell carcinomas (RCCs). Several authors have emphasized the role pathologists may play in identifying this syndrome by recognizing the morphologic characteristics of syndromic uterine LMs and RCCs. Recently immunohistochemical overexpression of S-(2-succinyl) cysteine (2SC) has been demonstrated as a robust biomarker of mutation status in tumors from HLRCC patients. In this blinded control-cohort study we demonstrate that the proposed morphologic criteria used to identify uterine LMs in HLRCC syndrome are largely irreproducible among pathologists and lack sufficient robustness to serve as a trigger to triage cases for 2SC immunohistochemistry or patients for further family/personal history inquiry. Although refinement of morphologic criteria can be considered, in view of the availability of a clinically robust biomarker, consideration should be given to reflex testing of uterine LMs with an appropriate age cut off or in the setting of a suspicious family history.

Background— The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results— We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1–9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P =0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P =0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions— Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality.

Background: In previous studies, the Forkhead/winged-helix-box-class-O3 (FOXO3) transcription factor has displayed both tumour suppressive and metastasis-promoting properties. To clarify its role in human colorectal cancer (CRC) progression, we examined in vivo FOXO3 expression at key points of the metastatic cascade. Methods: Formalin-fixed paraffin-embedded resection specimens from normal colon, adenomas, primary CRC specimens of different pathological stage and CRC specimens with matched liver metastases were used to generate three separate custom-designed tissue microarray (TMA) representations of metastatic progression. Triplicate cores, immunostained for FOXO3 were scored semiquantitatively by two investigators. Results: The FOXO3 expression is significantly reduced in CRC specimens compared with normal tissue, and progressive FOXO3 downregulation is associated with advancing pathological stage. In addition, recurrent stage I/II primary tumours show a significantly lower FOXO3 expression compared with stage-matched non-recurrent tumours. When stratified according to high and low FOXO3 expression, mean disease-free survival in the low-expressing group was 28 months (95% CI 15.8–50.6) compared with 64 months (95% CI 52.9–75.4) in the high-expressing group. Conclusion: We have demonstrated an association between low FOXO3 expression and CRC progression in vivo using purpose-designed TMAs. Forkhead/winged-helix-box-class-O3 may represent a novel biomarker of nodal and distant disease spread with clinical utility in CRC.

Despite recent concerns over youthful problem gambling, few gambling studies have looked into Asian adolescent populations. This study of a stratified, random sample of high school students in Hong Kong is designed to estimate the prevalence of gambling pathology among Chinese adolescents and to examine the relationships between social strain, self-control and gambling pathology. Based on the DSM-IV-J gambling screen, the rates of probable pathological gambling and at-risk gambling in this sample are 1.1% and 2.4%, respectively. Social strain and low self-control are predictive of gambling pathology, and a higher level of self-control can dilute the adverse effect of social strain on gambling pathology. These findings suggest that besides the social control, support and learning mechanisms often emphasized in juvenile gambling research, a greater understanding of the role that social strain plays and how it interacts with personality traits such as self-control may be informative in the management of gambling-related addictions in adolescents.

Background The effect of aortic valve replacement on three-dimensional mitral annular geometry has not been well described. Emerging transcatheter approaches for aortic valve replacement employ fundamentally different mechanical techniques for achieving fixation and seal of the prosthetic valve than standard surgical aortic valve replacement. This study compares the immediate impact of transcatheter aortic valve replacement (TAVR) and standard surgical aortic valve replacement (AVR) on mitral annular anatomy. Methods Real-time three-dimensional echocardiography was performed in patients undergoing TAVR using the Edwards Sapien valve (n = 10 [Edwards Lifesciences, Irvine, CA]) or AVR (n = 10) for severe aortic stenosis. Mitral annular geometric indexes were measured using Tomtec EchoView (Tomtec Imaging Systems, Munich, Germany) to assess regional and global annular geometry. Results Mixed between-within analysis of variance showed no differences between TAVR and AVR groups in any of the mitral annular geometric indices preoperatively. However, postoperative analysis did demonstrate an effect of AVR on geometry. Patients undergoing open AVR had significant decrease in annular height, septolateral diameter, mitral valve transverse diameter, and mitral annular area after valve replacement (p ≤ 0.006). Similar changes were not noted in the TAVR group. Conclusions Mitral annular geometry is better preserved by TAVR than by AVR. Thus, TAVR may be a more physiologic approach to aortic replacement.

Objective: To examine the results of open or endovascular abdominal aortic aneurysm (AAA) repair following prior open or endovascular thoracic aortic surgery. Methods: A retrospective review of all patients who underwent AAA repair in a delayed fashion following prior thoracic aortic surgery at a single university hospital between 1999 and 2011 was performed. Results: Thirteen patients underwent AAA repair following prior thoracic aortic repair. Mean age was 68.9 ± 6.9 years and 77% (n = 10) were male. Three patients experienced transient delayed-onset spinal cord ischemia (SCI) following initial thoracic surgery. Mean time interval between initial thoracic aortic surgery and subsequent AAA repair was 2.0 ± 1.8 years. Overall rate of SCI and 30-day mortality after delayed AAA repair was 0%. Conclusions: This series does not demonstrate any evidence of increased risk of perioperative mortality or SCI in patients undergoing delayed AAA repair after prior thoracic aortic surgery.

Background Degenerative mitral valve disease is associated with variable and complex defects in valve morphology. Three-dimensional echocardiography (3DE) has shown promise in aiding preoperative planning for patients with this disease but to date has not been as transformative as initially predicted. The clinical usefulness of 3DE has been limited by the laborious methods currently required to extract quantitative data from the images. Methods To maximize the utility of 3DE for preoperative valve evaluation, this work describes an automated 3DE image analysis method for generating models of the mitral valve that are well suited for both qualitative and quantitative assessment. The method is unique in that it captures detailed alterations in mitral leaflet and annular morphology and produces image-derived models with locally varying leaflet thickness. The method is evaluated on midsystolic transesophageal 3DE images acquired from 22 subjects with myxomatous degeneration and from 22 subjects with normal mitral valve morphology. Results Relative to manual image analysis, the automated method accurately represents both normal and complex leaflet geometries with a mean boundary displacement error on the order of one image voxel. A detailed quantitative analysis of the valves is presented and reveals statistically significant differences between normal and myxomatous valves with respect to numerous aspects of annular and leaflet geometry. Conclusions This work demonstrates a successful methodology for the relatively rapid quantitative description of the complex mitral valve distortions associated with myxomatous degeneration. The methodology has the potential to significantly improve surgical planning for patients with complex mitral valve disease.

SummaryBackground In 2010, the British Association of Dermatologists (BAD) published clinical guidelines for the safe introduction and continued use of isotretinoin in patients with acne in the UK. The BAD provides UK dermatologists with a facility for national audit, and it undertook an audit on compliance with these guidelines in 2012. Aim To determine current clinical practices relating to use of isotretinoin among dermatologists in the UK (including geographical variations) as measured against BAD standards, and to ascertain any improvement since the 2012 audit. Methods The 2012 isotretinoin audit proforma was used, with additional questions on clinical setting, complaints and litigation. A web-based survey tool was used for data entry and submission, with email invitation to working, UK-based BAD members (n = 1226) in December 2013 and weekly reminders during the 8.5-week data collection period. Responders were requested to enter data for the three most recent consecutive patients (including one male and one female patient) who had completed treatment within the previous 6 months. Results In total, 338 (27.6%) respondents provided data on 1013 patients. Serum lipids were checked in 93.4% of patients and documentation of mental health and/or mood state was recorded in 82.1%. Regarding the Pregnancy Prevention Programme (PPP), 91.6% of female patients of childbearing potential had signed the PPP information form, while 93.3% who had followed the PPP had taken pregnancy tests both before and during treatment, and 54.7% had taken a pregnancy test 5 weeks post-treatment. Conclusion Overall, there is currently good compliance with standards. Certain aspects of care that are less frequently preformed, such as pregnancy testing post-treatment, are highlighted.

The study objective was to determine safety and efficacy of a treated bovine vascular xenograft, in two Good Laboratory Practice compliant studies in sheep following carotid graft implantation. In one study, a 3- to 5-mm diameter xenograft was implanted into the right carotid artery of male sheep and compared to autologous jugular vein and a polymeric grafts similarly implanted. In a second study, a 9.5- to 14-mm diameter xenograft similarly implanted into the right carotid artery was compared to an autologous saphenous vein. Monthly Doppler ultrasound evaluation of implant patency and flow in implants and contralateral control carotid arteries was performed. The small vessel cohort 6 month xenograft patency was equivalent (or better) than animals with polymeric vascular graft or autologous vein implants; the aneurysm incidence was less than that of autologous vein grafts. In the large vessel cohort, all 15 xenografts and 12/15 saphenous vein implants were patent at 6 month follow-up. Tissue histology showed mild inflammatory responses in the xenografts that was slightly greater than suture material. In summary, treated bovine xenograft performance in this small study suggests it may be superior to polymeric autologous vein grafts, and may have a similar failure rate as autologous vein grafts after implantation.

Descending aortic (DA) surgery poses a high risk for spinal and cerebral infarction and routine use of lumbar drains allows for measurement of CSF markers of neurologic injury. Erythropoiesis medications have extensive preclinical data demonstrating neuroprotection. We hypothesized that prophylactic darbepoetin alfa (DARB) given before surgery reduces neurologic injury in patients undergoing DA repair. We performed a prospective adaptive dose-finding trial of prophylactic DARB ( www.clinicaltrials.gov NCT00647998) that terminated prematurely following publication of an erythropoietin stroke study showing possible harm. Enrollment halted before dose adjustments; nine patients each received 1 mg/kg IV DARB immediately before surgery. A prospective cohort of nine untreated patients was subsequently obtained for comparison. The primary outcome of death or neurologic impairment at discharge occurred in 1/9 (11 %) DARB patients and 3/9 (33 %) controls (p = 0.58). There were no statistical differences in changes of CSF biomarkers from baseline to 48 h comparing DARB patients to controls: S100β, median 214 versus 260 ng/ml (p = 0.69); glial fibrillary acidic protein (GFAP), median 0.022 versus 0.58 ng/ml (p = 0.45). In patients with early perioperative neurologic ischemia, there were greater changes in CSF biomarkers, compared to those without ischemia: S100β, median 2301 versus 124 ng/ml (p = 0.04); GFAP, median 31.78 versus 0.31 ng/ml (p = 0.34). There were no significant effects of prophylactic DARB on clinical outcome or CSF markers of neurologic injury in this pilot study, although all point estimates favored treatment. DA repair is a promising model of prophylactic neuroprotection.

Recent advances in the management of acute Stanford type A dissection have highlighted the clinical importance of clinical presentation and extent of dissection. The Penn classification of type A clinical presentations is based on ischemic profiles that not only determine mortality but also influence management options. The extent of type A dissection as summarized by the DeBakey classification significantly determines the role of endovascular intervention in this important disease. We propose an integration of these three classifications of acute type A dissection as a framework for future advances in diagnosis, intervention and prognosis.

Germline mutations in the two breast cancer susceptibility genes, BRCA1 and BRCA2 account for a significant portion of hereditary breast/ovarian cancer. De novo mutations such as multiple exon deletion are rarely occurred in BRCA1 and BRCA2. During our mutation screening for BRCA1/2 genes to Chinese women with risk factors for hereditary breast/ovarian cancer, we identified a novel germline mutation, consisting of a deletion from exons 1 to 12 in BRCA1 gene, in a patient diagnosed with early onset triple negative breast cancer with no family history of cancer. None of her parents carried the mutation and molecular analysis showed that this novel de novo germline mutation resulted in down-regulation of BRCA1 gene expression. © 2011 The Author(s)., published_or_final_version

Background: Our recent work has shown the feasibility of using a refined immunomagnetic enrichment (IE) assay to detect cytokeratin 20-positive circulating tumour cells (CK20 pCTCs) in colorectal cancer (CRC) patients. We attempted to improve the sensitivity for CRC by detecting another intestinal-type differentiation marker, CDX2 pCTCs, using the same methodology. Methods: CDX2 pCTCs were detected in patients with CRC, colorectal adenoma (CAD), benign colorectal diseases (BCD), other common cancers (OCC) and normal subjects (NS). Statistical analysis was used to correlate CDX2 pCTCs to the clinicohistopathological factors, recurrence, metastasis and survival after follow-up for 42 months in CRC patients. Results: CDX2 pCTCs were detected in 81% CRC patients (73 out of 90, median number=21.5 CTCs), 7.5% CAD patients (3 out of 40), 0% patients with BCD (0 out of 90), 2.5% patients with OCC (2 out of 80) and 0% NS (0 out of 40). Furthermore, statistical analysis showed that CDX2 pCTC numbers were associated with tumour- node-metastasis stage and lymph node status. Using the median CDX2 pCTC numbers as the cutoff points, stratified groups of CRC patients had significant differences in their recurrence and survival. Conclusions: This study showed that the refined IE assay can detect CDX2 pCTCs with high sensitivity and that CDX2 pCTCs can generate clinically important information for CRC patients.

Background: Endometrial cancer is the most common gynaecological malignancy in the United Kingdom. Diagnosis currently involves subjective expert interpretation of highly processed tissue, primarily using microscopy. Previous work has shown that infrared (IR) spectroscopy can be used to distinguish between benign and malignant cells in a variety of tissue types. Methods: Tissue was obtained from 76 patients undergoing hysterectomy, 36 had endometrial cancer. Slivers of endometrial tissue (tumour and tumour-adjacent tissue if present) were dissected and placed in fixative solution. Before analysis, tissues were thinly sliced, washed, mounted on low-E slides and desiccated; 10 IR spectra were obtained per slice by attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. Derived data was subjected to principal component analysis followed by linear discriminant analysis. Post-spectroscopy analyses, tissue sections were haematoxylin and eosin-stained to provide histological verification. Results: Using this approach, it is possible to distinguish benign from malignant endometrial tissue, and various subtypes of both. Cluster vector plots of benign (verified post-spectroscopy to be free of identifiable pathology) vs malignant tissue indicate the importance of the lipid and secondary protein structure (Amide I and Amide II) regions of the spectrum. Conclusion: These findings point towards the possibility of a simple objective test for endometrial cancer using ATR-FTIR spectroscopy. This would facilitate earlier diagnosis and so reduce the morbidity and mortality associated with this disease.

AIMS: Ovarian cancer has the highest mortality of any gynaecological malignancy; this is due to rapid peritoneal spread of tumour cells and neovascularization. Understanding the mechanisms underlying this is critical to developing early diagnostic or treatment strategies. We devised a pilot study to examine the role of γ-SYNUCLEIN (γ-SYN), oestrogen receptor (ER)α, and the splice variant ERαΔ3. METHODOLOGY: With ethical approval, ovarian tissue was collected from patients (n=24) undergoing oopherectomy for non-ovarian pathology or primary surgery for suspected ovarian cancer. Quantitative gene expression analysis was employed for γ-SYN, ERα, and ERαΔ3. To identify the in situ localization, immunofluorescence for γ-syn was carried out. RESULTS: Ovarian tumour tissue exhibited an elevated expression of γ-SYN and high-grade tumours had an elevated ERαΔ3:ERα ratio compared with benign tissue. The majority of previous studies point to the γ-syn protein being present in epithelial cells of high-grade disease. Our study supports this, but additionally we conclusively identify its presence in the endothelial cells of vasculature surrounding low-grade disease; immunofluorescence was strongest in the apical cells surrounding the lumen. CONCLUSION: Our results demonstrate for the first time that there are readily-expressed levels of γ-SYN and ERαΔ3 in normal ovarian tissue and ovarian tumours. In high-grade disease, γ-syn and an elevated ERαΔ3:ERα ratio might confer metastatic potential to the tumourigenic cells and promote neoangiogenesis. Future in vitro studies might be necessary to delineate such a mechanism, which could potentially be the basis of early intervention.

Background A comprehensive three-dimensional echocardiography based approach is applied to preoperative mitral valve (MV) analysis in patients with ischemic mitral regurgitation (IMR). This method is used to characterize the heterogeneous nature of the pathologic anatomy associated with IMR. Methods Intraoperative real-time three-dimensional transesophageal echocardiograms of 18 patients with IMR (10 with anterior, 8 with inferior infarcts) and 17 patients with normal MV were analyzed. A customized image analysis protocol was used to assess global and regional determinants of annular size and shape, leaflet tethering and curvature, relative papillary muscle anatomy, and anatomic regurgitant orifice area. Results Both mitral annular area and MV tenting volume were increased in the IMR group as compared with patients with normal MV (mitral annular area=1,065 ± 59 mm 2 versus 779 ± 44 mm 2 , p = 0.001; and MV tenting volume=3,413 ± 403 mm 3 versus 1,696 ± 200 mm 3 , p = 0.001, respectively). Within the IMR group, patients with anterior infarct had larger annuli (1,168 ± 99 mm 2 ) and greater tenting volumes (4,260 ± 779 mm 3 versus 2,735 ± 245 mm 3 , p = 0.06) than the inferior infarct subgroup. Papillary-annular distance was increased in the IMR group relative to normal; these distances were largest in patients with anterior infarcts. Whereas patients with normal MV had very consistent anatomic determinants, annular shape and leaflet tenting distribution in the IMR group were exceedingly variable. Mean anatomic regurgitant orifice area was 25.8 ± 3.0 mm 2 , and the number of discrete regurgitant orifices varied from 1 to 4. Conclusions Application of custom analysis techniques to three-dimensional echocardiography images allows a quantitative and systematic analysis of the MV, and demonstrates the extreme variability in pathologic anatomy that occurs in patients with severe IMR.