Metabolic and hormonal blood flow modeling in patients with coronary heart disease: In vitro and clinical study

The blood flow pattern investigations are of great importance in coronary blood flow destabilization pathogenesis understanding, and consequently in acute coronary event (ACE) risk stratification in patients with coronary heart disease. The aim of the study was to research the principal hormonal and metabolic blood flow regulative aspects and its structure in patients with ischemic heart disease and the contribution to cumulative ACE risk.A total of 182 patients with stable angina pectoris were included in the prospective study (2000–2006). Complex clinical examination, biochemical tests and blood tests were performed. Whole-blood (WB) viscosity, erythrocyte aggregation and deformation ability, WB suspension stability, and initial erythrocytes disaggregation parameter were studied. Dynamic characteristics of blood flow were obtained in the experiment.Received results allow marking the principle components of blood flow pattern with proven high prognostic value of ACE in patients with ischemic heart disease. ACE risk stratification program was developed.     

小鼠肥大细胞瘤P815特异抗原P1A的克隆与表达

目的 克隆小鼠肥大细胞瘤Ｐ８１５细胞株的ＰＩＡ基因以制备肿瘤ＤＮＡ疫苗,方法 用ＲＴ－ＰＣＲ方法制备ＰＩＡ基因,以哺乳细胞高效表达质粒ｐＣＩ－ｎｅｏ为载体,构建重组ＤＮＡ疫苗。重组体用克隆位点上游和下游的Ｔ７和Ｔ１３启动了序列为测序引物,用自动测序仪测定鉴定克隆的正确性。再将鉴定过的重组质粒用磷酸钙法转化２９３细胞,用ＲＴ－ＰＣＲ法鉴定转化细胞中ＰＩＡ基因的表达。结果 正确构建了ＰＩＡ／ｐＣＩ－ｎ     

Oftalmoplejía completa izquierda por metástasis ósea de cáncer de próstata

Prognosis in prostate cancer is determined, in greater part, by the presence of metastases. Bone metastases can occur in any part of the skeleton even, for example, at the base of the skull. We present a case of a 78 year old male who, in December 2001, presented with paralysis of the third cranial nerve. The NMR and CAT scans were normal and circulating levels of PSA were elevated. He was referred to the Urology Service where the treatment guidelines included complete androgen block. Subsequently, he developed retro-orbital pain, divergent strabismus and palpebral ptosis. CAT and NMR indicated a soft tissue mass at the sphenoid level. Treatment was Gamma Knife Radio-surgery. Since August 2004, in conjunction with the latest rise in PSA, the patient's general status deteriorated considerably and he was referred to the Oncology Service. there was an increase in the paralysis of the third, fourth and sixth cranial nerve (complete left ophthalmoplegia) and left-central facial paralysis. Metastases from prostate cancer can be disseminated via the lymphatic or the blood system. Currently, there are more metastases from large-size tumours. Metastases are critical in prostate cancer because of their adverse effect on the patient's survival. Measurements of circulating levels of prostate specific antigen and prostate acid phosphatase are very useful in the clinical diagnosis of the primary tumour, or its metastases.     

La técnica de superposición de cúspides en TAVI con dispositivo autoexpandible optimiza la profundidad del implante y reduce la necesidad de marcapasos permanente

Introduction and objectivesThis study aimed to determine the safety and efficacy of modifying the classic implantation technique for aortic transcatheter heart valve (THV) implantation to a cusp-overlap-projection (COP) technique to achieve a higher implantation depth and to reduce the burden of new permanent pacemaker implantation (PPMI) at 30 days. Aortic self-expanding THV carries an elevated risk for PPMI. A higher implantation depth minimizes the damage in the conduction system and may reduce PPMI rates.MethodsFrom March 2017, 226 patients were consecutively included: 113 patients were treated using the COP implantation technique compared with the previous 113 consecutive patients treated using the classic technique. In all patients, implantation depth was assessed by 3 methods (noncoronary cusp to the THV, mean of the noncoronary cusp and the left coronary cusp to the THV, and the deepest edge from the left coronary cusp and the noncoronary cusp to the THV).ResultsThe COP group had a lower implantation depth than the group treated with the classic technique (4.8 mm ± 2.2 vs 5.7 mm ± 3.1; P = .011; 5.8 mm ± 3.1 vs 6.5 mm ± 2.4; P = .095; 7.1 mm ± 2.8 vs 7.4 mm ± 3.2; P = .392). Forty patients (17.7%) required a new PPMI after the 30-day follow-up but this requirement was significantly lower in the COP group (12.4% vs 23%, P = .036). The COP implantation technique consistently protected against the main event (OR, 0.45; 95%CI, 0.21-0.97; P = .043), with similar procedural success rates and complications.ConclusionsThe COP implantation technique is a simple modification of the implantation protocol and provides a higher implantation depth of self-expanding-THV with lower conduction disturbances and PPMI rates.     

Bone regeneration by means of a three‐dimensional printed scaffold in a rat cranial defect

Recently, computer‐designed three‐dimensional (3D) printing techniques have emerged as an active research area with almost unlimited possibilities. In this study, we used a computer‐designed 3D scaffold to drive new bone formation in a bone defect. Poly‐L‐lactide (PLLA) and bioactive β‐tricalcium phosphate (TCP) were simply mixed to prepare ink. PLLA + TCP showed good printability from the micronozzle and solidification within few seconds, indicating that it was indeed printable ink for layer‐by‐layer printing. In the images, TCP on the surface of (and/or inside) PLLA in the printed PLLA + TCP scaffold looked dispersed. MG‐63 cells (human osteoblastoma) adhered to and proliferated well on the printed PLLA + TCP scaffold. To assess new bone formation in vivo, the printed PLLA + TCP scaffold was implanted into a full‐thickness cranial bone defect in rats. The new bone formation was monitored by microcomputed tomography and histological analysis of the in vivo PLLA + TCP scaffold with or without MG‐63 cells. The bone defect was gradually spontaneously replaced with new bone tissues when we used both bioactive TCP and MG‐63 cells in the PLLA scaffold. Bone formation driven by the PLLA + TCP30 scaffold with MG‐63 cells was significantly greater than that in other experimental groups. Furthermore, the PLLA + TCP scaffold gradually degraded and matched well the extent of the gradual new bone formation on microcomputed tomography. In conclusion, the printed PLLA + TCP scaffold effectively supports new bone formation in a cranial bone defect.     

Evaluación multimodal de la degeneración estructural de válvulas percutáneas en el seguimiento a largo plazo

Introduction and objectivesWe assessed the long-term hemodynamic performance of transcatheter heart valve (THV) by paired transthoracic echocardiography (TTE), and the incidence, characteristics and factors associated with THV structural valve degeneration (SVD).MethodsA total of 212 patients who underwent transcatheter aortic valve replacement and had a potential follow-up > 5 years with at least 1 TTE ≥ 1-year postprocedure were included. All patients had a TTE at 1 to 5 years and 36 had another one at 6 to 10 years. SVD was defined as subclinical (increase > 10 mmHg in mean transvalvular gradient +  decrease > 0.3 cm² in valve area and/or new-onset mild or moderate aortic regurgitation) and clinically relevant (increase > 20 mmHg in mean transvalvular gradient + decrease > 0.6 cm² in valve area and/or new-onset moderate-to-severe aortic regurgitation). Fifteen patients had a transesophageal echocardiography at the time of SVD diagnosis, and 85 an opportunistic computed tomography examination at 1 (0.5-2) years.ResultsTransvalvular mean gradient increased and valve area decreased over time (P < .01). At 8 years of follow-up, SVD occurred in 30.2% of patients (clinically relevant: 9.3%). Transesophageal echocardiography revealed thickened and reduced-mobility leaflets in 80% and 73% of SVD cases, respectively. No baseline or procedural factors were associated with SVD. THV underexpansion (3.5%) or eccentricity (8.2%) had no impact on valve hemodynamics/SVD at follow-up.ConclusionsA gradual THV hemodynamic deterioration occurred throughout a 10-year period, leading to SVD in ～30% of patients (clinically relevant in < 10%). Leaflet morphology/mobility were frequently impaired in SVD cases, but THV geometry did not influence valve hemodynamics or SVD.     

Renal insufficiency and vascular complications after primary angioplasty via femoral route. Impact of vascular closure devices use

Introduction and objectives

We sought to determine the incidence of vascular complications in patients with chronic kidney disease undergoing primary angioplasty via the femoral route; we also evaluated the safety and efficacy of the use of vascular closure devices in this setting.

Methods

Registry of 527 patients undergoing primary angioplasty via the femoral route from January 2003 to December 2008. Chronic kidney disease was defined as creatinine clearance less than 60 mL/min. The primary endpoint was the presence of major vascular complications.

Results

Baseline chronic kidney disease was observed in 166 (31.5%) patients. Patients with chronic kidney disease experienced higher rates of major vascular complications compared to those without worsening of renal function (8.4% vs 4.2%; P=.045), especially those requiring transfusion (6.6% vs 1.9%; P=.006). Among patients with chronic kidney disease, 129 (77.7%) received a vascular closure device and manual compression was used in 37 patients (22.3%). The risk of major vascular complications was significantly lower with vascular closure device use compared to manual compression (4.7% vs 21.6%; P=.003). Multivariable logistic regression analysis showed that the use of a vascular closure device was independently associated with a decreased risk of major vascular complications in patients with chronic kidney disease undergoing primary angioplasty (odds ratio=0.11; 95% confidence interval, 0.03-0.41; P=.001).

Conclusions

Patients with chronic kidney disease undergoing primary angioplasty via the femoral route experience higher rates of major vascular complications. The use of vascular closure devices in this group of patients is safe and is associated with lower rates of major vascular complications compared to manual compression.Full English text available from:www.revespcardiol.org     

Patterns of Care in the Administration of Neo‐adjuvant Chemotherapy for Breast Cancer. A Population‐Based Study

Neo‐adjuvant chemotherapy (NAC) is used to facilitate radical surgery for initially irresectable or locally advanced breast cancer. The indication for NAC has been extended to clinically node negative (cN0) patients in whom adjuvant systemic therapy is foreseen. A population‐based study was conducted to evaluate the increasing use of NAC, breast conserving surgery (BCS) after NAC and timing of the sentinel node biopsy (SNB). All female breast cancer patients, treated in 10 hospitals in the Eindhoven Cancer Registry area in the Netherlands between January 2003 and June 2012 were included (N = 18,427). In total, 1,402 patients (7.6%) received NAC. The administration increased from 2.5% in 2003 to 13.0% in 2011 (p < 0.001). Use of NAC increased from 0.5% to 2.3% for cT1 tumors, from 2.8% to 27.0% for cT2, from 30.6% to 70.9% for cT3, and from 40.5% to 58.1% for cT4 tumors (p < 0.001). In cN0 patients, use of NAC increased from 1.0% to 4.4% and in clinically node positive patients from 12.0% to 57.5% (p < 0.001). Downsizing of the tumor and BCS are achieved increasingly. In 2011, in three hospitals NAC was administered in <10% of patients, in five hospitals in 10–15% and in two hospitals the proportion of patients receiving NAC was >20% (p < 0.001). Of the 1,402 patients with NAC, 495 patients underwent SNB, 91.5% of whom prior to NAC. In the Netherlands up to one in eight patients receive NAC. The administration of NAC and the percentage of BCS increased over the past decade, especially in cT2 tumors. Considerable hospital variation in the administration of NAC exists.     

Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

Background

In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity varies widely and depends on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model.

Methods

Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5.

Results

When the dams in Mthfr^+/− × Mthfr^+/− matings were treated with 7.2 mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr^+/+ × Mthfr^+/−, Mthfr^+/− × Mthfr^+/− and Mthfr^−/− × ^Mthfr+/−) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote × wild-type versus wild-type × nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights.

Conclusions

Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure.