Contemporary Transcatheter Mitral Valve Replacement for Mitral Annular Calcification or Ring

ObjectivesThe aim of this study was to evaluate outcomes of commercial transcatheter mitral valve replacement (TMVR) for annular rings and calcification using contemporary techniques.BackgroundTMVR is evolving in the absence of other viable treatment options for severe mitral annular calcification and failing ring repairs. The concomitant use of laceration of the anterior mitral valve leaflet to prevent left ventricular outflow tract obstruction and pre-emptive alcohol septal ablation is not well studied in clinical practice.MethodsA single-center study was conducted of valve–in–mitral annular calcification (ViMAC) and valve-in-ring (ViRing) TMVR from September 2015 to April 2020. In-hospital and 30-day outcomes were assessed.ResultsForty patients underwent TMVR (28 ViMAC and 12 ViRing). Sixteen ViMAC (57%) and 5 ViRing (42%) patients underwent attempted laceration of the anterior mitral valve leaflet to prevent left ventricular outflow tract obstruction. Three patients underwent pre-emptive alcohol septal ablation. The median index hospitalization was 7 days. Six patients died within 30 days of the procedure, 6 (21%) in the ViMAC group and none in the ViRing group. Five patients (13%) had left ventricular outflow tract obstruction: 4 (14%) in the ViMAC cohort and 1 (8%) in the ViRing cohort. Five patients (13%) had either intraprocedural valve embolization or late migration (4 ViMAC and 1 ViRing). Technical success defined according to Mitral Valve Academic Research Consortium criteria was present in 25 patients (63%): 9 (75%) in the ViRing cohort and 16 (57%) in the ViMAC cohort. At 30 days, the mitral valve gradient was significantly reduced (5.5 ± 2.1 vs. 10.6 ± 4.8; p < 0.01). Three patients (8%) had at least moderate residual mitral regurgitation.ConclusionsTranscatheter ViMAC and ViRing can be successfully performed but frequently require the use of contemporary adjunctive techniques.     

Morphine and Cardiovascular Outcomes Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing Coronary Angiography

BackgroundMechanistic studies have shown that morphine blunts the antiplatelet effects of oral adenosine diphosphate receptor blockers. However, the clinical relevance of this interaction is controversial.ObjectivesThis study sought to explore the association between morphine and ischemic events in 5,438 patients treated with concomitant clopidogrel presenting with non-ST-segment elevation acute coronary syndromes (NSTEACS) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome) trial. Patients not treated with clopidogrel (n = 3,462) were used as negative controls.MethodsEndpoints were the composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout at 96 h (4-way endpoint) and the composite of death or MI at 30 days.ResultsIn patients treated with clopidogrel, morphine use was associated with higher rates of the 4-way endpoint at 96 h (adjusted odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.04 to 1.87; p = 0.026). There was a trend for higher rates of death or MI at 30 days (adjusted OR: 1.29; 95% CI: 0.98 to 1.70; p = 0.072), driven by events in the first 48 h (adjusted hazard ratio: 1.54; 95% CI: 1.07 to 2.23; p = 0.021). In patients not treated with clopidogrel, morphine was not associated with either the 4-way endpoint at 96 h (adjusted OR: 1.05; 95% CI: 0.74 to 1.49; p = 0.79; p_interaction = 0.36 ) or death or MI at 30 days (adjusted OR: 1.07; 95% CI: 0.77 to 1.48; p = 0.70; p_interaction = 0.46).ConclusionsWhen used concomitantly with clopidogrel pre-treatment, morphine was associated with higher rates of ischemic events in patients with NSTEACS. (EARLY ACS: Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome; NCT00089895)     

The importance of building trust and tailoring interactions when meeting older adults’ health literacy needs

Purpose: Health literacy is the ability to access, understand and use health information. This study qualitatively explored the views and experiences of older adults with varying health literacy levels who had attended a falls clinic on their overall experience of the falls clinic, access to the service and provider–patient interaction.

Methods: Individual semi-structured interviews were conducted with nine older adults using a falls clinic in England. Health literacy was assessed using the REALM and NVS-UK. Interviews were audio-recorded, transcribed verbatim and interrogated using interpretative phenomenological analysis (IPA).

Results: Two superordinate themes emerged from the analysis: The importance of trust and relationship building to achieve effective communication with older adults; and the importance of tailoring education and healthcare to older adults’ individual health literacy needs and preferences.

Conclusions: The findings corroborate previous research emphasising the importance of face-to-face communication in responding to older adults’ individual health literacy needs. Building trust in the relationship and tailoring communication to older adults’ individual attributes and preferred learning styles is essential. Healthcare practitioners and managers should consider how service organisation and communication methods can enhance positive and effective relationships with patients. Improved training could support healthcare providers in meeting patients’ personal communication needs.

• Implications for Rehabilitation

• Rehabilitation professionals should be aware of their patients’ individual health literacy needs and communication/learning preferences.

• It is important to build relationships and trust with older adults attending rehabilitation services.

• Further training for rehabilitation professionals could support them in meeting patients’ personal communication needs.

     

药对“蛇床子一补骨脂”与乳腺癌骨转移裸鼠体重变化与骨代谢的量效关系研究

目的 从调节破骨细胞分化的主要途径护骨素(OPG)/细胞核因子κB受体活化因子配体(RANKL)/细胞核因子κB受体活化因子(RANK)系统研究蛇床子—补骨脂温肾药对抑制乳腺癌骨转移的作用机制.方法 将42只乳腺癌骨转移裸鼠随机分为模型组、唑来磷酸组、蛇床子组、补骨脂组、2:2配比组、1:3配比组、3:1配比组,每组6只;另备正常裸鼠6只作为正常组.分别给予相应的药液灌胃,唑来磷酸组皮下注射,正常组给予生理盐水灌胃,持续6周.观察裸鼠的体重、骨转移灶病理和OPG、RANKL mRNA表达水平变化.结果 3:1配比组和2:2配比组体重下降率明显低于其他配比组,而2:2配比组低于3:1配比组;不同比例配伍组的骨抗酒石酸酸性磷酶(TRAP)(+)细胞数差异均有统计学意义,2:2配比组优于1:3配比组(P＜0.05);不同配比的蛇床子—补骨脂可不同程度地上调OPG基因表达,下调RANKL基因表达,从基因方面调节OPG/RANKL的分泌比例,其中2:2配比组的疗效优于其他配比组.结论 不同配比的蛇床子—补骨脂均具有一定的抑制乳腺癌骨转移作用,其中2:2配比组疗效最突出,其作用机制可能是调节了OPG/RANKL基因分泌比例.     

Transforming growth-beta 1 contributes to isoflurane postconditioning against cerebral ischemia–reperfusion injury by regulating the c-Jun N-terminal kinase signaling pathway

AimCerebral ischemia–reperfusion (I/R) injury is a devastating complication in the perioperative period. Transforming growth factor beta (TGF-β) is a key protein that can participate in the repair and control process responses after I/R injury. Isoflurane is widely used in neurosurgery. Previous studies have shown that isoflurane preconditioning plays an important role in neuroprotection. However, the effects of isoflurane postconditioning on cerebral I/R injury have not yet been elucidated. In the present study, we evaluated the protective effect of isoflurane postconditioning against cerebral I/R injury and investigated the role of the TGF-β signaling pathway and the downstream c-Jun N-terminal kinase (JNK) signaling pathway in neuroprotective mechanism. In particular, the JNK signaling pathway emerges as a possible target for brain repair after stroke.MethodsCerebral I/R injury was produced in SD rat by using the middle cerebral artery occlusion model for 90 min, followed by 24 h reperfusion. Postconditioning by inhalation of isoflurane was performed at different concentrations (1.5%, 3.0%, and 4.5%) for 1 h after ischemia at the starting time point of reperfusion. The protective effect was tested by neurological deficit scoring with 2,3,5-triphenyl tetrazolium chloride and propidium iodide (PI) staining. Apoptosis of CA1 cells in the hippocampus was detected by TUNEL method. Expression levels of TGF-β1, Smad 2/3, p-Smad2/3, JNK, and p-JNK were determined by immunostaining and Western blot.ResultsPostconditioning by isoflurane at 1.5% and 3.0% concentrations significantly decreased the neurobehavioral deficit scores and infarct volume compared with the I/R group, but no significant difference in neurobehavioral deficit score was detected between the I/R and 4.5% isoflurane postconditioning groups. Additionally, 1.5% isoflurane postconditioning decreased the numbers of PI-positive cells at 24 h after reperfusion compared with the I/R group. TGF-β1 and p-Smad2/3 protein gradually increased after I/R injury, with the highest values observed in the 1.5% and 3% isoflurane postconditioning groups. For Smad2/3 protein expression, no differences existed among all groups. After inducing the TGF-β/SMAD3 signaling pathway specific blocker (LY2157299), the neurological deficit scores increased, infarct volumes enlarged, apoptosis increased, and PI-positive CA1 cells in the hippocampus also increased. The expression levels of TGF-β1 and p-Smad2/3 proteins were downregulated. During the pre-injection of LY2157299, the expression levels of TGF-β1 and p-Smad2/3 decreased significantly, but compared with the sham group, the expression level of p-JNK significantly increased. When the injection of LY2157299 was abolished, the expression of p-JNK significantly decreased. The expression levels of p-JNK and TGF-β1 significantly decreased when LY2157299 and SP600125 were injected simultaneously. However, the protective effect mediated by SP600125 completely disappeared, and the role of LY2157299 became dominant. Compared with the sham group, the expression of TGF-β1 was almost unchanged by the injection of SP600125 alone, but the expression of p-JNK significantly decreased.ConclusionsUp to 1.5% isoflurane can upregulate the expression of TGF-β1 and downregulate that of p-JNK, which significantly mitigated I/R injury, leading to cerebral injury. However, this protective effect was abrogated when the TGF-β1 signaling pathway was blocked by LY2157299. Overall, the present results provided valid evidence to demonstrate that TGF-β1 contributes to isoflurane postconditioning against cerebral I/R injury by inhibiting the JNK signaling pathway.     

McCune–Albright syndrome,natural history and multidisciplinary management in a series of 14 pediatric cases

BackgroundMcCune–Albright syndrome is a rare disorder characterized by endocrine disorders, café-au-lait spots and fibrous dysplasia of bone that occurs early in life.MethodsA series of 14 pediatric cases were followed between 1994 and 2013 by the competence center for rare endocrine diseases and constitutional bone diseases at CHU de Nancy (France). The diagnosis is based on the presence of at least two symptoms.ResultsThe mean follow-up was 6 years (1–17 years). The sex ratio was six girls per boy. The incidence was 0.28 cases/million population/year. Mean age at diagnosis was 6 years. A mutation in the GNAS gene was found in 33% of patients tested. Gonadal involvement (13/14 cases), including early peripheral puberty and ovarian cysts in girls (82%) occurred on average at 4 years of age. Bone involvement (10/14 cases) appeared on average at 5 years of age and was most often multiple (80%) with fracture risk, and the skull, with a neurosensory risk.ConclusionClinical definition and methods of screening and monitoring can be improved to allow for an earlier intervention. It must be multidisciplinary and take into account the disability and quality of life of the patient.