Predictors and Clinical Impact of Prosthesis-Patient Mismatch After Self-Expandable TAVR in Small Annuli

ObjectivesThe aim of this study was to define predictors of prosthesis-patient mismatch (PPM) and its impact on mortality after transcatheter aortic valve replacement (TAVR) with self-expandable valves (SEVs) in patients with small annuli.BackgroundTAVR seems to reduce the risk for PPM compared with surgical aortic valve replacement, especially in patients with small aortic annuli. Nevertheless, predictors and impact of PPM in this population have not been clarified yet.MethodsPredictors of PPM and all-cause mortality were investigated using multivariable logistic regression analysis from the cohort of the TAVI-SMALL (International Multicenter Registry to Evaluate the Performance of Self-Expandable Valves in Small Aortic Annuli) registry, which included patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm² on computed tomography) treated with transcatheter SEVs: 445 patients with (n = 129) and without (n = 316) PPM were enrolled.ResultsIntra-annular valves conferred increased risk for PPM (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.16 to 4.81), while post-dilation (OR: 0.46; 95% CI: 0.25–0.84) and valve oversizing (OR: 0.53; 95% CI: 0.28–1.00) seemed to protect against PPM occurrence. At a median follow-up of 354 days, patients with severe PPM, but not those with moderate PPM, had a higher all-cause mortality rate compared with those without PPM (log-rank p = 0.008). Multivariable Cox regression confirmed severe PPM as an independent predictor of all-cause mortality (hazard ratio: 4.27; 95% CI: 1.34 to 13.6).ConclusionsAmong patients with aortic stenosis and small aortic annuli undergoing transcatheter SEV implantation, use of intra-annular valves yielded higher risk for PPM; conversely, post-dilation and valve oversizing protected against PPM occurrence. Severe PPM was independently associated with all-cause mortality.     

Extraintestinal manifestations of granulomatous enterocolitis induced in rabbits by long-term submucosal administration of muramyl dipeptide emulsified with Freund's incomplete adjuvant

We examined whether extraintestinal manifestations of granulomatous enterocolitis in rabbits might be produced by the long-term administration of muramyl dipeptide which represents the basic fragment of the bacterial cell wall, emulsified with Freund's incomplete adjuvant. Muramyl dipeptide emulsion was injected submucosally at six sites in the rectum and colon, 10 cm proximal to the anus, each time with a flexible endoscope. Seven rabbits were injected nine times or more every month, and all were sacrificed 1 month after the last injection. The histological changes in the colon in the seven rabbits were mononuclear cell infiltration, epithelioid granulomas, granulomatous lesion, and denuded and regenerative epithelia, although the changes differed in degree. In five of the seven rabbits, histological examination of the liver showed pericholangitis and periductal fibrosis, findings analogous to sclerosing cholangitis in patients with inflammatory bowel disease. In four of the seven rabbits, fibrosis bridging mainly between portal and portal veins, and, in places, between portal and central veins, was seen. Two of the seven rabbits developed polyarthritis. The histological changes in our model suggest that continuous stimulation with bacterial cell wall fragments may be involved in the extraintestinal manifestations of chronic intestinal inflammation such as that seen in inflammatory bowel disease.     

Impact of intravascular ultrasound for the treatment of calcified infrarenal aortic stenosis: A case report study

We report two cases of heavily calcified infrarenal aortic stenosis that were successfully treated by Intravascular ultrasound‐ (IVUS)‐guided stenting. Two middle‐aged women visited our hospital due to intermittent claudication. Diagnostic arteriography revealed possible infrarenal aortic stenosis even though the findings were equivocal. IVUS demonstrated heavily calcified atherosclerotic lesions and allowed the accurate assessment of the types and extents of the lesions to be treated in both cases. The patients successfully underwent stent implantation according to the findings of IVUS. IVUS significantly contributed to the interventional successes. © 2008 Wiley‐Liss, Inc.     

Acute and chronic cough

Individuals are generally content to self-medicate for acute cough. It is only when the cough becomes persistent that they seek medical assistance. It is not known why patients cough in association with an acute upper respiratory tract infection (URTI), although interest has focused on how viruses may influence airway sensory nerve function and contribute to heightened cough reflex sensitivity. Why some patients develop a persistent cough following a viral URTI is also unclear. Much more is known about the causes and aggravants of chronic cough although there is no broad agreement as to the best way to manage such patients. Asthma, upper gastrointestinal dysfunction and rhinitis are frequently associated with chronic cough, although the impact of cough in suppurative lung disease and interstitial lung fibrosis is rarely considered. The development of effective treatments for cough remains a challenge and will require co-operation between clinicians, scientists and the pharmaceutical industry.     

Increased blood–brain barrier vulnerability to systemic inflammation in an Alzheimer disease mouse model

Behavioral and psychological problems are often observed in patients with dementia such as that associated with Alzheimer disease, and these noncognitive symptoms place an extremely heavy burden on the family and caregivers. Although it is well know that these symptoms often are triggered by infection of peripheral organs, the underlying mechanisms for these pathological conditions are still unclear. In this study, using an Alzheimer amyloid precursor protein (APP)-transgenic mouse, we analyzed behavioral changes and brain inflammatory response induced by peripheral administration of lipopolysaccharide. Application of a unique in vivo microdialysis system revealed that the increase in brain inflammatory cytokine (interleukin-6) level was significantly higher in APP-Tg than in wild-type mice after peripheral lipopolysaccharide injection, which was associated with more severe sickness behaviors. The blood–brain barrier became more permeable in APP-Tg mice during peripherally evoked inflammation, suggesting the increased vulnerability of the blood–brain barrier to inflammation in this animal model of Alzheimer's disease. These findings might provide insight into the pathogenesis of noncognitive symptoms in dementia and a basis to develop new therapeutic treatments for them.     

Enhancement of the antitumor efficacy of the antiprogestin,onapristone, by combination with the antiestrogen,ICI 164384

So far, no combination of endocrine treatments has been routinely used in the therapy of breast Cancer. It was, therefore, our interest to determine whether the combination of the antiprogestin, onapristone (ON), and the pure antiestrogen, ICI 164384 (ICI), might provide a more effective therapy than either monotherapy in experimental mammary tumors containing both estrogen and progesterone receptors. In the MXT-mammary tumor of the mouse, ON (5 mg/kg) administered for 3 weeks exerted an ovariectomy-like antitumor effect (56% inhibition), whereas ICI (30 mg/kg) was weakly effective (28% inhibition). The combination of ON and ICI was, however, distinctly more effective than the monotherapies or ovariectomy, causing 78% inhibition. A similar potentation of antitumor effect by the combination was manifested in the dimethylbenzanthracene-induced mammary tumor of the rat when ON (5 mg/kg) and ICI (30 mg/kg) were administered once daily for 4 weeks (s.c.). The remission rates of tumors found after treatment with ICI, ON, the combination and ovariectomy (complete and partial remission) were 15%, 46%, 71% and 100% respectively. In the animals bearing DMBA-induced tumors, treatment with ON alone significantly increased the serum levels of luteinizing hormone and prolactin, but caused only a slight increase in the peripheral levels of estradiol and progesterone. ON had no appreciable effect on the uterine and ovarian weights. ICI reduced the uterine weight and the serum progesterone level. In the combination with ON, ICI reversed the effect of ON on the progesterone level without influencing the luteinizing harmone and prolactin levels. These findings suggest that the augmentation of antitumor effectiveness by the combination of two antihormones can be ascribed not only to their effects at estrogen- and progester-one-receptor-binding sites, but also to the decrease in the peripheral level of progesterone. Thus, an appropriate combination of antiprogestin and pure antiestrogen may be useful in the management of breast cancer.