Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study.

BACKGROUND: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. METHODS: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. FINDINGS: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. INTERPRETATION: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators. FUNDING: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.

Satisfaction of orthodontic Post-CCST training: A survey of trainee perceptions.

INTRODUCTION: This survey was undertaken as a second part to 'Barriers to Post-CCST training in orthodontics: A survey of trainee perceptions'. Recruitment of Post-CCST trainees in certain areas of the country has attracted concerns as it has become increasingly difficult. This survey was undertaken to assess trainee satisfaction with Post-CCST training and to look at possible ways to improve trainee satisfaction and make Post-CCST training more desirable. METHODS: The Training Grades Group (TGG) committee of the British Orthodontic Society (BOS) produced an online survey that was sent to all TGG members and newly qualified consultants in May 2021. All Post-CCSTs who entered training between February 2017 and October 2020, were asked to complete the survey. RESULTS: There were 37 respondents, which gave a response rate of 62%. While 61% of respondents were satisfied with their Post-CCST training, 17% were 'neither satisfied or dissatisfied' and 6% were either 'dissatisfied' or 'very dissatisfied'. Of the 37 respondents, 25 (67%) would apply for Post-CCST training again, 6 (16%) would not and 6 (16%) did not answer this question. When asked for possible suggestions for improvements to Post-CCST training to encourage greater satisfaction, the responses could be grouped into the following themes: Part-time training; Teaching; Time commitment; Salary; and Experience. CONCLUSION: In general, respondents were satisfied with Post-CCST training. There was a significant range of positive and negative responses to various aspects of training including multidisciplinary team clinic preparation, support, supervision and management experience. Suggestions for improvements echo the barriers to Post-CCST training survey.

Genetic Architecture of Acute Myocarditis and the Overlap With Inherited Cardiomyopathy.

BACKGROUND: Acute myocarditis is an inflammatory condition that may herald the onset of dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM). We investigated the frequency and clinical consequences of DCM and ACM genetic variants in a population-based cohort of patients with acute myocarditis. METHODS: This was a population-based cohort of 336 consecutive patients with acute myocarditis enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterized cardiomyopathy-associated genes with comparison to healthy controls (n=1053) sequenced on the same platform. Case ascertainment in England was assessed against national hospital admission data. The primary outcome was all-cause mortality. RESULTS: Variants that would be considered pathogenic if found in a patient with DCM or ACM were identified in 8% of myocarditis cases compared with <1% of healthy controls (P=0.0097). In the London cohort (n=230; median age, 33 years; 84% men), patients were representative of national myocarditis admissions (median age, 32 years; 71% men; 66% case ascertainment), and there was enrichment of rare truncating variants (tv) in ACM-associated genes (3.1% of cases versus 0.4% of controls; odds ratio, 8.2; P=0.001). This was driven predominantly by DSP-tv in patients with normal LV ejection fraction and ventricular arrhythmia. In Maastricht (n=106; median age, 54 years; 61% men), there was enrichment of rare truncating variants in DCM-associated genes, particularly TTN-tv, found in 7% (all with left ventricular ejection fraction <50%) compared with 1% in controls (odds ratio, 3.6; P=0.0116). Across both cohorts over a median of 5.0 years (interquartile range, 3.9-7.8 years), all-cause mortality was 5.4%. Two-thirds of deaths were cardiovascular, attributable to worsening heart failure (92%) or sudden cardiac death (8%). The 5-year mortality risk was 3.3% in genotype-negative patients versus 11.1% for genotype-positive patients (Padjusted=0.08). CONCLUSIONS: We identified DCM- or ACM-associated genetic variants in 8% of patients with acute myocarditis. This was dominated by the identification of DSP-tv in those with normal left ventricular ejection fraction and TTN-tv in those with reduced left ventricular ejection fraction. Despite differences between cohorts, these variants have clinical implications for treatment, risk stratification, and family screening. Genetic counseling and testing should be considered in patients with acute myocarditis to help reassure the majority while improving the management of those with an underlying genetic variant.

Safety and efficacy of laparoscopic sleeve gastrectomy in patients with portal hypertension with liver function of Childs A.

INTRODUCTION: Advanced liver disease and portal hypertension (PH) are seen as a relative contraindication for bariatric and metabolic surgery. Several studies have shown significant improvement in liver function and liver histology after bariatric surgery. There are very few studies describing bariatric surgery in patients with PH. The purpose of this retrospective study is to evaluate the feasibility and results of laparoscopic sleeve gastrectomy (SG) in patients with PH. MATERIAL AND METHODS: We present our experience of performing laparoscopic SG in 15 patients with evidence of PH. All the patients were Childs Pugh Criteria A. PH was confirmed by the presence of dilated esophageal varices on endoscopy. RESULTS: The mean operative time was 77.33 ± 15.22 min and mean blood loss was 80.67 ± 37.12 ml. The mean length of stay was 2.73 ± 0.59 days. There were no intraoperative or immediate postoperative complications. None of the patients required blood transfusion in the postoperative period. The weight, BMI, Excess body weight loss% (EBWL%), Total weight loss (TWL) and TWL% at 1 year were 86.05 ± 14.40 kg, 31.16 kg/m2 ± 3.82, 63.84% ± 15.24, 31.49 ± 9.54 kg and 26.50 ± 5.42%, respectively. Diabetes and hypertension resolution at 1 year was 80% and 72.72%, respectively. All the patients were followed up for mean 3 ± 1.5 years. There were no immediate or long-term morbidity and mortality noted. CONCLUSION: SG is a feasible and safe option for the treatment of obesity in carefully selected patients with PH with good weight loss and comorbidity resolution.

Proliferative fasciitis arising from the abdominal wall: A rare tumour excised by laparoscopy.

Proliferative fasciitis (PF) is a rare pseudosarcomatous lesion arising from the subcutaneous fascia and the fibrous septa. Only few hundred cases have been reported in the literature. In the largest series of 53 patients, only two patients had PF lesion arising from the flank. The most common site of origin is extremities followed by abdomen and head and neck. Its origin from the abdominal wall layer and presentation as the fever has been rarely reported in the literature. A PF lesion larger than 5 cm dimension has been sparsely noted. We report the presence of this rare entity in a 68-year-old gentleman who presented to us with low-grade fever and the presence of large lump arising from the abdominal wall. In our patient, the lesion was arising from transervsalis fascia and was excised in toto laparoscopically without damaging the abdominal muscles. It is imperative to differentiate both these lesions from sarcoma on histopathological examination as the follow-up treatment protocols for both vary.

Barriers to Post-CCST training in orthodontics: A survey of trainee perceptions.

INTRODUCTION: In order to be eligible for consultant appointments within the NHS, orthodontists can undertake higher specialty training after their Certificate of Completion of Specialist Training (CCST). These training posts are known as Post-CCST positions and orthodontists must be eligible for inclusion on the General Dental Council's (GDC) specialist list for orthodontics before applying. There has been a decline in the number of applicants and the number of filled Post-CCST positions in recent years, leading to concerns over a potential shortage of appropriately trained consultant orthodontists to provide a secondary care service in the near future. This survey was undertaken to identify barriers to applying for Post-CCST training and assess potential options for increasing trainee numbers. METHODS: An online survey was distributed, by email, to current orthodontic trainees and those that had recently completed training in the last six months via the British Orthodontic Society Training Grades Group. Reminder emails were sent at two and four weeks. A total of 201 trainees were invited to complete the survey. RESULTS: Eighty-nine trainees completed the survey (response rate of 44.3%). Regarding applying to Post-CCST training, 32.6% and 47.7% of respondents, respectively, either wanted to or were considering applying for Post-CCST training. The South East was the most preferred region for Post-CCST training (38.0%). Reasons for not wishing to complete Post-CCST training included salary (71.9%), lack of consultant posts in desired regions (64.1%) and inability/unwillingness to relocate (63.5%). Part-time training (91.0%) and a higher salary during training (86.0%) were most likely to incentivise application for Post-CCST training. CONCLUSION: Financial, family and geographical concerns appear to be the main reasons why trainees might not consider Post-CCST training. Part-time and run-through training options may encourage trainees to apply for Post-CCST training.

Rapid deployment aortic valve replacement through anterior right thoracotomy: Clinical outcomes and haemodynamic performance.

BACKGROUND: The ease of implantation of the rapid deployment (RD) and sutureless valves has contributed to the adoption of anterior right thoracotomy (ART) approach for aortic valve replacement (AVR). AIM OF THE STUDY: This study evaluates the safety and haemodynamic performance of minimally invasive AVR through ART using the RD valves. METHODS: This is a retrospective, single-center review of a total of 50 consecutive patients who received RD-AVR through ART. RESULTS: The median age of patients was 75 years (interquartile range [IQR]: 69-80), and median Euroscore II was 5.1 (IQR: 2.4-7.5). ART RD-AVR was successfully performed in all cases with no conversion to sternotomy, paravalvular leaks or need for valve explantation. The mean size of the implanted valve was 23.2 ± 2.3 mm. In-hospital mortality was 2%. The mean and maximum pressure gradients across the aortic prosthesis were 10 mm Hg (IQR: 9-12) and 19 mm Hg (IQR: 16-23). CONCLUSIONS: Rapid deployment aortic valve replacement can be safely performed through anterior right thoracotomy wit excellent haemodynamic performance and low postoperative complications rate.

Real-world comparison of the new 34 mm self-expandable transcatheter aortic prosthesis Evolut R to its 31 mm core valve predecessor.

OBJECTIVES: The aim of the present study was to compare the incidence of periprocedural complications and short-term outcomes between the second-generation recapturable 34 mm Evolut-R and its first-generation 31 mm predecessor. BACKGROUND: Although already in extensive clinical use in real world patients, the periprocedural complications and clinical outcomes of the new 34 mm device have not been investigated yet. METHODS: Consecutive patients who had undergone transcatheter aortic valve implantation in two centers with either a 31 mm CoreValve or a 34 mm Evolut-R device were retrospectively studied. Periprocedural complications of malpositioning, valve-in-valve implantation, conversion to full sternotomy or percutaneous coronary intervention and vascular complications were compared between the two groups. Short-term outcomes at discharge were compared using Valve Academic Research Consortium (VARC-2) criteria. RESULTS: The study group included 106 patients (35 Evolut-R 34 mm; 71 CoreValve 31 mm). Significantly lower rates of valve-in-valve implantation were demonstrated for the 34 mm group compared to the first-generation device (0% vs. 11.9%, respectively, P = 0.036). All other periprocedural complications were similar between groups. At discharge, the rates of new pacemaker implantation (5.7% vs. 26.8%, P = 0.037) and bleeding complications (2.9% vs. 19.6%, P = 0.025) were statistically significantly lower among the 34 mm group. With regards to VARC-2 defined combined endpoints, rates of early safety were significantly improved among the 34 mm group compared to 31 mm group (0% vs. 27.9%, respectively, P = 0.004). CONCLUSIONS: The recently introduced 34 mm Evolut-R seems to demonstrate an improved safety profile, as evidenced by the reduced bleeding rates, lower rates of valve-in-valve implantation and lower PPM rates compared to its 31 mm predecessor.

Outcome Measures in UCLP: The Modified 5-Year-Olds'-Index-Development and Reliability.

OBJECTIVE: Can we reliably discriminate severity within the existing categories of the 5-Year-Olds' Index? DESIGN: Retrospective method comparison and development study. SETTING: School of Oral and Dental Science, University of Bristol. METHODS: Dental study models of 5-year-olds with unilateral cleft lip and palate (UCLP) were collected from the archives of 2 national cleft surveys (n = 351). One hundred randomly selected models were ranked to construct the modified 5-Year-Olds' Index and also scored using a visual analogue scale (VAS). Reliability testing was performed on 51 study models. Visual analogue scale scores were used to aid statistical analysis and investigate the reliability of a VAS for outcome measurement. The modified 5-Year-Olds' Index was then applied to 198 study models of 5-year-olds with UCLP. RESULTS: The modified 5-Year-Olds' Index showed excellent intra and interexaminer agreement (intraclass correlation > 0.94) and good discrimination of severity. When applied to the Cleft Care UK participants (n = 198), the modified 5-Year-Olds' Index showed good discrimination of severity within the better categories (groups 1-3) of the 5-Year-Olds' Index. Visual analogue Scale scores resulted in unacceptable variation between measurements. CONCLUSIONS: The new modified 5-Year-Olds' Index is a reliable method of assessing outcomes at 5 years of age and showed improved discriminatory power between the "better" outcome categories than the original 5-Year-Olds' Index. A VAS was found to be unsuitable for assessing outcome at 5 years of age for children with UCLP.

Efficacy of ultrasound-guided transversus abdominis plane (TAP) block for postoperative analgesia in laparoscopic gastric sleeve resection: a randomized single blinded case control study.

BACKGROUND: Pain following bariatric surgery can be quite troublesome and prolongs recovery. Transversus abdominis plane (TAP) block is a new regional anesthetic technique to reduce postoperative pain and is an important part of current analgesic regimen for many abdominal surgeries. The primary objective of our study was to assess the efficacy of the TAP block in controlling postoperative pain in laparoscopic sleeve gastrectomy. Secondary outcomes assessed in this study were postoperative nausea and vomiting (PONV), time to ambulate, readiness for discharge, and whether it leads to improved patient satisfaction. METHODS: This is a prospective single blind randomized controlled study. A total of 60 patients were included in the study. Patients were allocated in two groups, using a computer generated randomization sequence using http://www.randomization.com . Test group included 30 patients who received Ultrasound-guided transversus abdominis plane (USG-TAP) block along with systemic analgesia and the Control group included 30 patients who received only systemic analgesia. Postoperatively patients were evaluated for pain and satisfaction using VAS scores and 'Capuzzo' satisfaction score, respectively. RESULTS: Sixty patients were enrolled in the study after fulfilling the eligibility criteria. No patient was lost to follow-up. The difference of VAS scores between test (TAP) and control (Non-TAP) was statistically significant both at rest and on movement. The patient satisfaction score in TAP group was higher than the control group (p value < 0.001). The patients who received TAP block showed earlier readiness for discharge, early ambulation, early resumption of bowel activity, and decreased incidence of PONV as compared to the non-TAP group. CONCLUSION: USG-guided TAP block is a feasible, minimally invasive technique and can be a part of an effective multimodal analgesia in morbidly obese patients undergoing bariatric surgery. Limitations of this study would be the small sample size and the study being Single-blinded.

Acute Kidney Injury Requiring Dialysis in Severe Sepsis.

RATIONALE: Understanding the changing incidence and impact of acute kidney injury requiring dialysis in patients with severe sepsis will allow better risk stratification, design of clinical trials, and guide resource allocation. OBJECTIVES: To assess the longitudinal incidence of acute kidney injury requiring dialysis and its impact on mortality in patients with severe sepsis. METHODS: Retrospective cohort study of adults (≥20 yr) hospitalized with severe sepsis from 2000 to 2009 in the United States using a nationally representative database. MEASUREMENTS AND MAIN RESULTS: We calculated the incidences of acute kidney injury requiring dialysis and mortality over time. We used linear regression to assess temporal trends. We used logistic regression to estimate the odds of acute kidney injury requiring dialysis and mortality. Of the estimated 5,257,907 hospitalizations with severe sepsis, 6.1% had acute kidney injury requiring dialysis. The odds of acquiring acute kidney injury requiring dialysis increased by 14% in 2009 compared with 2000. Mortality in patients with acute kidney injury requiring dialysis was higher (43.6% vs. 24.9%; P < 0.001). After multivariable adjustment, odds of mortality declined 61% by the year 2009. Acute kidney injury requiring dialysis remained an independent predictor of mortality in patients with severe sepsis, although its influence on mortality declined with time. CONCLUSIONS: Incidence of acute kidney injury requiring dialysis in patients with severe sepsis has increased over time; conversely, associated mortality has declined. The likelihood of demise from acute kidney injury requiring dialysis in patients with severe sepsis has also declined.

Congenital absence of the common bile duct: A rare anomaly of extrahepatic biliary tract.

Congenital absence of the common bile duct (CBD) is an extremely rare developmental anomaly with right and left hepatic ducts draining directly into the gallbladder (GB). Other synonyms for this clinical condition are "cholecystohepatic ducts", "transverse lie of the GB" or "interposition of the GB". The potential for iatrogenic injury is high, because of either inadvertent division or ligation of the ducts. Diagnosis is mostly made intraoperatively, and needs some form of biliary reconstruction. Herein, we are reporting a case of congenital absence of the CBD in a 36-year-old lady that was detected intraoperatively.

Aspirin Action in Endothelial Cells: Different Patterns of Response Between Chemokine CX3CL1/CX3CR1 and TNF-α/TNFR1 Signaling Pathways.

PURPOSE: TNF-α induces fractalkine (CX3CL1) and its receptor CX3CR1 in endothelial cells through NF-қB activation. NF-қB inhibitors may reduce the expression of CX3CL1, and modulation of the CX3CL1/CX3CR1 signaling was proposed as a new target for aspirin. We examined the effects of aspirin on CX3CL1 and TNF-α production, as well as CX3CR1 and TNFR1 expression. METHODS: HUVECs isolated after term pregnancies (N = 28) were cultured in vitro. Lipopolysaccharide (1 µg/ml) was used as CX3CL1 inducer. HUVECs were exposed to six different concentrations of aspirin (between 1.0 and 6.0 mM) during 7 days. The levels of CX3CL1 and TNF-α in the culture media were measured using ELISA. After termination of the cultures, mean expressions of CX3CR1 and TNFR1 were examined in the immunostained paraffin sections using quantitative immunohistochemistry. RESULTS: Aspirin significantly (p < .05) decreased CX3CL1 production, and the mean decrease in CX3CL1 production was inversely proportional to increased (p < 0.05) expression of CX3CR1. The combined mean CX3CL1 concentrations, including all time points, equaled 782.18 ± 74.4 pg/ml in aspirin treated HUVECs compared to a total concentration of 2467.53 ± 127.5 pg/ml combined from the respective time points in the controls. An inhibition of TNF-α production in HUVECs after pretreatment with aspirin was observed. Unlike in the case of CX3CR1 expression, there were no signs of TNFR1 upregulation. CONCLUSIONS: Autoregulation between CX3CL1 and CX3CR1 may explain overexpression of CX3CR1 as the compensatory effect in aspirin-treated HUVECs. Inhibition of CX3CR1 could prevent thrombotic complications in the early period after discontinuation of aspirin.

Myometrial contractility influences oxytocin receptor (OXTR) expression in term trophoblast cells obtained from the maternal surface of the human placenta.

BACKGROUND: Oxytocin (OXT) acts through its specific receptor (OXTR) and increased density of OXTR and/or augmented sensitivity to OXT were postulated as prerequisites of normal onset of labor. Expression of OXTR in the placental term trophoblast cells has not yet been analyzed in the context of contractile activity of the uterus. Here we examine comparatively OXT contents in the placental tissue adjacent to the uterine wall and expressions of OXTR in this tissue and corresponding isolated placental trophoblast cells. METHODS: Twenty eight placentae after normal labors at term (group I, N = 14) and after cesarean sections performed without uterine contractile activity (group II, N = 14) have been collected. Tissue excised from the maternal surface of examined placenta was used for OXT concentration measurement, cytotrophoblast cell cultures preparation and immunohistochemistry of OXTR. Concentration of OXT was estimated in the tissue homogenates by an enzyme immunoassay with colorimetric detection. Cytotrophoblast cells were isolated using Kliman's method based on trypsin, DNase, and a 5-70% Percoll gradient centrifugation. The cultures were incubated for 5 days in normoxia. Both placental specimens and terminated cytotrophoblast cultures were fixed and embedded in paraffin before being immunostained for OXTR. Using light microscopy with computed morphometry for quantitative analysis, OXTR expressions were estimated in calibrated areas of the paraffin sections. RESULTS: There were not significant differences between the groups in respect to the mean OXT concentration. However, in both groups the median value of OXT concentration was significantly (p < 0.05) higher in the tissue obtained from the peripheral regions of the maternal surface of the placenta, compared to the samples from the central region of this surface. In placental tissue the mean expression of OXTR in group I was significantly (p < 0.05) increased by approximately 3.2-fold and 3.45-fold (the samples collected from central and peripheral regions, respectively) compared to the values obtained in group II. In the isolated primary trophoblast cultures the differences were even more evident (p < 0.02) and the mean change in OXTR expression in group I comprised approximately 6.9-fold increase and 6.5-fold increase (the samples collected from central and peripheral regions, respectively) compared to the values obtained in group II. CONCLUSIONS: Upregulation of OXTR within placental trophoblast cells localized close or adherent to uterine wall may play a crucial role in labor with efficient contractile activity (vaginal delivery). Further studies may disclose if this local OXT/OXTR signaling is utilized in the third stage of labor to elicit placental detachment or contribute in a more versatile way throughout the labor period.

CX3CL1 (fractalkine) and TNFα production by perfused human placental lobules under normoxic and hypoxic conditions in vitro: the importance of CX3CR1 signaling.

OBJECTIVE: Inflammation and hypoxia activate the fractalkine (CX3CL1) receptor (CX3CR1)-related signaling pathway. Tumor necrosis factor alpha (TNFα) induces CX3CL1, influencing a mechanism of CX3CL1 autoregulation by CX3CR1 expression. We compared spontaneous and lipopolysaccharide (LPS)-induced CX3CL1 and TNFα production by human placenta under normoxic vs. hypoxic conditions, with respect to CX3CR1 expression and its functional status. METHODS: Placental lobules of term placentae (N = 24) were perfused extracorporeally. CX3CL1 and TNFα concentrations were measured in the perfusion fluid by ELISA. LPS, anti-CX3CR1 antibodies and pirfenidone were used in respective subgroups. After perfusion, CX3CR1 expression was estimated in placental tissue using quantitative immunohistochemistry, and the final results were adjusted for the mean microvascular density. RESULTS: The highest increase in CX3CL1 concentration in response to LPS was observed in hypoxia (p < 0.05). Unlike in normoxia, anti-CX3CR1 administration in hypoxia significantly reduced the LPS-evoked response. CX3CR1 expression was augmented by hypoxia and reached 260.9 ± 41 (% ±SEM) of the reference value in normoxia. Positive immunostaining for CX3CR1 corresponded to the vascular endothelium. Pirfenidone inhibited hypoxia + LPS-related increase in TNFα production and prevented the up-regulation of CX3CR1. CONCLUSION: The modulatory influence of TNFα on CX3CR1 expression in hypoxia and CX3CL1/CX3CR1 interaction may serve as a compensatory mechanism to preserve or augment the pro-inflammatory course of intercellular interactions in placental endothelium.

Four-dimensional analysis of aortic root motion in normal population using retrospective multiphase computed tomography.

Aims: Aortic root motion is suspected to contribute to proximal aortic dissection. While motion of the aorta in four dimensions can be traced with real-time imaging, displacement and rotation in quantitative terms remain unknown. The hypothesis was to show feasibility of quantification of three-dimensional aortic root motion from dynamic CT imaging. Methods and results: Dynamic CT images of 40 patients for coronary assessment were acquired using a dynamic protocol. Scans were ECG-triggered and segmented in 10 time-stepped phases (0-90%) per cardiac cycle. With identification of the sinotubular junction (STJ), a patient-specific co-ordinate system was created with the z-axis (out-of-plane) parallel to longitudinal direction. The left and right coronary ostia were traced at each time-step to quantify downward motion in reference to the STJ plane, motion within the STJ plane (in-plane), and the degree of rotation. Enrolled individuals had an age of 65 ± 12, and 14 were male (35%). The out-of-plane motion was recorded with the largest displacement of 10.26 ± 2.20 and 8.67 ± 1.69 mm referenced by left and right coronary ostia, respectively. The mean downward movement of aortic root was 9.13 ± 1.86 mm. The largest in-plane motion was recorded at 9.17 ± 2.33 mm and 6.51 ± 1.75 mm referenced by left and right coronary ostia, respectively. The largest STJ in-plane motion was 7.37 ± 1.96 mm, and rotation of the aortic root was 11.8 ± 4.60°. Conclusion: In vivo spatial and temporal displacement of the aortic root can be identified and quantified from multiphase ECG-gated contrast-enhanced CT images. Knowledge of normal 4D motion of the aortic root may help understand its biomechanical impact in patients with aortopathy and pre- and post-surgical or transcatheter aortic valve replacement.

Cardiac allograft vasculopathy after heart transplantation: electrocardiographically gated cardiac CT angiography for assessment.

PURPOSE: To evaluate the diagnostic accuracy of cardiac computed tomographic (CT) angiography without the use of ß-blockers compared with that of invasive angiography for the detection of cardiac allograft vasculopathy (CAV) in heart transplant recipients. MATERIALS AND METHODS: The study was approved by the research ethics committee and informed consent was obtained. Heart transplant recipients (n = 138) scheduled for routine invasive angiography were prospectively enrolled to undergo CT to evaluate coronary artery calcification and retrospectively gated cardiac CT angiography with a 64-section scanner. The cardiac CT angiographic images were systematically analyzed for image quality. Degree of CAV was assessed by using a 15-coronary segments model. The area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values of cardiac CT angiography for detection of CAV with any degree of stenosis and greater than or equal to 50% stenosis were calculated. RESULTS: Coronary artery calcification was absent in 82 patients, five (6%) of whom had CAV with 50% or more stenosis. Interpretable image quality was obtained in 130 (96%) of the 136 patients who completed the study and 1900 (98%) of 1948 segments. At the patient level, cardiac CT angiography had an area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of 0.880 (95% confidence interval: 0.819, 0.941), 98%, 78%, 77%, and 98%, respectively, for diagnosis of CAV with any degree of stenosis, but for CAV with 50% or more stenosis, the corresponding values were 0.942 (95% confidence interval: 0.885, 1.000), 96%, 93%, 72%, and 99%, respectively. None of the 61 patients with normal cardiac CT angiographic results had CAV on the basis of invasive angiographic images. CONCLUSION: The study results show that cardiac CT angiography compares favorably with invasive angiography in detecting CAV in heart transplant recipients and may be a preferable screening technique because of its noninvasive nature. The absence of coronary artery calcification alone is not reliable enough for excluding CAV.

Fractalkine (CX3CL1) and its receptor CX3CR1 may contribute to increased angiogenesis in diabetic placenta.

Chemokine CX3CL1 is unique, possessing the ability to act as a dual agent: chemoattractant and adhesive compound. Acting via its sole receptor CX3CR1, CX3CL1 participates in many processes in human placental tissue, including inflammation and angiogenesis. Strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokines secretion, CX3CL1 may act locally as a key angiogenic factor. Both clinical observations and histopathological studies of the diabetic placenta have confirmed an increased incidence of hypoxia and inflammatory reactions with defective angiogenesis. In this study we examined comparatively (diabetes class C complicated versus normal pregnancy) the correlation between CX3CL1 content in placental tissue, the mean CX3CR1 expression, and density of the network of placental microvessels. A sandwich enzyme immunoassay was applied for CX3CL1 measurement in placental tissue homogenates, whereas quantitative immunohistochemical techniques were used for the assessment of CX3CR1 expression and the microvascular density. Significant differences have been observed for all analyzed parameters between the groups. The mean concentration of CX3CL1 in diabetes was increased and accompanied by augmented placental microvessel density as well as a higher expression of CX3CR1. In conclusion, we suggest involvement of CX3CL1/CX3CR1 signaling pathway in the pathomechanism of placental microvasculature remodeling in diabetes class C.

Gastric Metastasis of Primary Neuroendocrine Tumor of Skin: Rare Tumor with Rare Presentation.

Merkel cell carcinoma (MCC) is a rare primary neuroendocrine tumor of the skin. It has an aggressive biological behavior and shows early local and distant metastasis. Diagnosis of MCC is a challenge and requires confirmation by immunohistochemistry (IHC). However, metastasis of MCC to the stomach is extremely uncommon and is rarely reported in the literature. We hereby describe a patient with gastric metastasis of MCC, who presented with black tarry stool and was finally diagnosed on the basis of clinical history, histology, and IHC.