Atrial fibrillation and aortic stenosis: impact on clinical outcomes among patients undergoing transcatheter aortic valve implantation

Atrial fibrillation (AF) is an important risk factor for stroke and is common among elderly patients undergoing transcatheter aortic valve implantation. The aim of this study was to assess the impact of AF on clinical outcomes among patients undergoing transcatheter aortic valve implantation.

Prolyl hydroxylase inhibitors increase the production of vascular endothelial growth factor in dental pulp-derived cells

Introduction: Prolyl hydroxylase (PHD) inhibitors can induce a proangiogenic response that stimulates regeneration in soft and hard tissues. However, the effect of PHD inhibitors on the dental pulp is unclear. The purpose of this study was to evaluate the effects of PHD inhibitors on the proangiogenic capacity of human dental pulp–derived cells. Methods: To test the response of dental pulp–derived cells to PHD inhibitors, the cells were exposed to dimethyloxalylglycine, desferrioxamine, L-mimosine, and cobalt chloride. To assess the response of dental pulp cells to a capping material supplemented with PHD inhibitors, the cells were treated with supernatants from calcium hydroxide. Viability, proliferation, and protein synthesis were assessed by formazan formation, 3[H]thymidine, and 3[H]leucine incorporation assays. The effect on the proangiogenic capacity was measured by immunoassays for vascular endothelial growth factor (VEGF). Results: We found that all 4 PHD inhibitors can reduce viability, proliferation, and protein synthesis at high concentrations. At nontoxic concentrations and in the presence of supernatants from calcium hydroxide, PHD inhibitors stimulated the production of VEGF in dental pulp–derived cells. When calcium hydroxide was supplemented with the PHD inhibitors, the supernatants from these preparations did not significantly elevate VEGF levels. Conclusions: These results show that PHD inhibitors can stimulate VEGF production of dental pulp–derived cells, suggesting a corresponding increase in their proangiogenic capacity. Further studies will be required to understand the impact that this might have on pulp regeneration.

Exogenous gonadotropins have little impact on follicular but considerable effect on serum cytokine concentrations – a comparison between Natural Cycle and stimulated IVF using a multiplexed assay platform

Introduction: Throughout follicular growth and subsequent corpus luteum formation the leukocyte number increases and follicular vascularisation changes. These processes are enhanced under exogenous stimulation with gonadotropins. Cytokines released by leukocytes contribute to further recruitment and vascularisation of the follicle, and they play an important role in regulating ovarian steroidogenesis by influencing theca and granulosa–lutein cell function. Changes in cytokine and vascular endothelial growth factor (VEGF) concentrations in the ovary as a consequence of gonadotropin stimulation may negatively influence oocyte quality. In this project we have compared the intrafollicular production of inflammatory cytokines and growth factors between natural IVF cycles (NC) and classical, gonadotropin-stimulated IVF cycles (gsIVF). Material and Methods: Serum on the day of oocyte retrieval and follicular fluid (FF) were collected in 37 NC and 39 gsIVF cycles. Thirteen women within this population underwent one NC and one gsIVF cycle each. A total of 14 cytokines from Bio-Plex panels I and II were determined in matched serum and FF samples using Luminex xMAP technology on the Bio-Plex(R) platform, using the serum protocol. Results: Tumour necrosis factor-alpha, RANTES, eotaxin and interferon-gamma-induced protein-10 levels were lower in FF than in serum, and thus not further investigated. Interleukin (IL)-6, -8, -10, -15, -18, monocyte chemotactic protein-1 (MCP-1), VEGF and leukaemia inhibitory factor (LIF) showed higher median concentrations in FF than in serum, indicating possible ovarian production. Moreover, most of these showed higher evels in the gsIVF than in the NC groups in the serum, but not in the follicular fluid. IL-8 was reduced in gsIVF cycles. Conclusion: The fact that serum but not FF levels of the studied cytokines were higher in the stimulated than in the natural cycles can be attributed to the increased number of active follicles present after controlled ovarian stimulation.

Loss of heterozygosity 1p36 and 19q13 is a prognostic factor for overall survival in patients with diffuse WHO grade 2 gliomas treated without chemotherapy

PURPOSE: This study was conducted to elucidate the impact of loss of heterozygosity (LOH) for chromosomes 1p36 and 19q13 on the overall survival of patients with diffusely infiltrating WHO grade 2 gliomas treated without chemotherapy. PATIENTS AND METHODS: We assessed the LOH status of tumors from patients harboring WHO grade 2 gliomas diagnosed between 1991 and 2000. Patients were either followed after initial biopsy or treated by surgery and/or radiation therapy (RT). Overall survival, time to malignant transformation, and progression-free survival were last updated as of March 2005. RESULTS: Of a total of 79 patients, LOH 1p36 and LOH 19q13 could be assessed in 67 and 66 patients, respectively. The median follow-up after diagnosis was 6 years. Loss of either 1p or 19q, in particular codeletion(s) at both loci, was found to positively impact on both overall survival (log-rank P < .01), progression-free survival, and survival without malignant transformation (P < .05). Tumor volume (P < .0001), neurologic deficits at diagnosis (P < .01), involvement of more than one lobe (P < .01), and absence of an oligodendroglial component (P < .05) were also predictors of shorter overall survival. The extent of surgery was similar in patients with or without LOH 1p and/or 19q; RT was more frequently resorted to for patients without than for patients with LOH 1p/19q (30% v 60%). CONCLUSION: The presence of LOH on either 1p36 or 19q13, and in particular codeletion of both loci is a strong, nontreatment-related, prognostic factor for overall survival in patients with diffusely infiltrating WHO grade 2 gliomas.

Nerve sparing open radical retropubic prostatectomy--does it have an impact on urinary continence?

PURPOSE: We prospectively assessed the role of nerve sparing surgery on urinary continence after open radical retropubic prostatectomy. MATERIALS AND METHODS: We evaluated a consecutive series of 536 patients who underwent open radical retropubic prostatectomy with attempted bilateral, unilateral or no nerve sparing, as defined by the surgeon, without prior radiotherapy at a minimum followup of 1 year with documented assessment of urinary continence status. Because outlet obstruction may influence continence rates, its incidence and management was also evaluated. RESULTS: One year after surgery 505 of 536 patients (94.2%) were continent, 27 (5%) had grade I stress incontinence and 4 (0.8%) had grade II stress incontinence. Incontinence was found in 1 of 75 (1.3%), 11 of 322 (3.4%) and 19 of 139 patients (13.7%) with attempted bilateral, attempted unilateral and without attempted nerve sparing, respectively. The proportional differences were highly significant, favoring a nerve sparing technique (p <0.0001). On multiple logistic regression analysis attempted nerve sparing was the only statistically significant factor influencing urinary continence after open radical retropubic prostatectomy (OR 4.77, 95% CI 2.18 to 10.44, p = 0.0001). Outlet obstruction at the anastomotic site in 33 of the 536 men (6.2%) developed at a median of 8 weeks (IQR 4 to 12) and was managed by dilation or an endoscopic procedure. CONCLUSIONS: The incidence of incontinence after open radical retropubic prostatectomy is low and continence is highly associated with a nerve sparing technique. Therefore, nerve sparing should be attempted in all patients if the principles of oncological surgery are not compromised.

Comparisons of bacterial patterns present at implant and tooth sites in subjects on supportive periodontal therapy. I. Impact of clinical variables, gender and smoking

OBJECTIVE: (I) To compare the oral microflora at implant and tooth sites in subjects participating in a periodontal recall program, (II) to test whether the microflora at implant and tooth sites differ as an effect of gingival bleeding (bleeding on probing (BOP)), or pocket probing depth (PPD), and (III) to test whether smoking and gender had an impact on the microflora. MATERIAL AND METHODS: Data were collected from 127 implants and all teeth in 56 subjects. Microbiological data were identified by the DNA-DNA checkerboard hybridization. RESULTS: PPD> or =4 mm were found in 16.9% of tooth, and at 26.6% of implant sites (P<0.01). Tooth sites with PPD> or =4 mm had a 3.1-fold higher bacterial load than implant sites (mean difference: 66%, 95% confidence interval (CI): 40.7-91.3, P<0.001). No differences were found for the red, orange, green, and yellow complexes. A higher total bacterial load was found at implant sites with PPD> or =4 mm (mean difference 35.7 x 10(5), 95% CI: 5.2 (10(5)) to 66.1 (10(5)), P<0.02 with equal variance not assumed). At implant sites, BOP had no impact on bacterial load but influenced the load at tooth sites (P<0.01). CONCLUSION: BOP, and smoking had no impact on bacteria at implant sites but influenced the bacterial load at tooth sites. Tooth sites harbored more bacteria than implant sites with comparable PPD. The 4 mm PPD cutoff level influenced the distribution and amounts of bacterial loads. The subject factor is explanatory to bacterial load at both tooth and implant sites.

[Impact of tobacco use on the periodontium--an update (I)--Part 1: Epidemiologic und pathogenetic aspects of tobacco-related periodontal diseases]

This literature review represents the second in a series of articles from the Swiss task force "Smoking--Intervention in the private dental office" on the topic "tobacco use and dental medicine". In this article, the epidemiological background as well as some pathogenetic processes are described and discussed critically for tobacco-related periodontal diseases. Earlier publications confirmed tobacco consumption as a risk factor for periodontal diseases. Over the last few years, oral health research has significantly contributed to the understanding of the mechanisms leading to the deterioration of the hard and soft tissues supporting the teeth. With the recording of the number of cigarettes smoked per day and the amount of years tobacco was used, a dose response relationship was established. Various, potentially significant pathogenic effects of tobacco-related substances may exist on the periodontal tissues, the immune response system or the composition of the oral flora. Moreover, there is reference that tobacco consumption may change the genetically determined susceptibility for periodontal diseases.

Climate and human impact during the past 2000 years as recorded in the Lagunas de Yala, Jujuy, northwestern Argentina

210Pb, 137Cs and 14C dated sediments of two late Holocene landslide lakes in the Provincial Park Lagunas de Yala (Laguna Rodeo, Laguna Comedero, 24°06′S, 65°30′W, 2100 m asl, northwestern Argentina) reveal a high-resolution multi-proxy data set of climate change and human impact for the past ca. 2000 years. Comparison of the lake sediment data set for the 20th century (sediment mass accumulation rates MARs, pollen spectra, nutrient and charcoal fluxes) with independent dendroecological data from the catchment (fire scars, tree growth) and long regional precipitation series (from 1934 onwards) show that (1) the lake sediment data set is internally highly consistent and compares well with independent data sets, (2) the chronology of the sediment is reliable, (3) large fires (1940s, 1983/1984–1989) as documented in the local fire scar frequency are recorded in the charcoal flux to the lake sediments and coincide with low wet-season precipitation rates (e.g., 1940s, 1983/1984) and/or high interannual precipitation variability (late 1940s), and (4) the regional increase in precipitation after 1970 is recorded in an increase in the MARs (L. Rodeo from 100 to 390 mg cm−2 yr−1) and in an increase in fern spores reflecting wet vegetation. The most significant change in MARs and nutrient fluxes (Corg and P) of the past 2000 years is observed with the transition from the Inca Empire to the Spanish Conquest around 1600 AD. Compared with the pre-17th century conditions, MARs increased by a factor of ca. 5 to >8 (to 800 +130, −280 mg cm−2 yr−1), PO4 fluxes increased by a factor of 7, and Corg fluxes by a factor of 10.5 for the time between 1640 and 1930 AD. 17th to 19th century MARs and nutrient fluxes also exceed 20th century values. Excess Pb deposition as indicated by a significant increase in Pb/Zr and Pb/Rb ratios in the sediments after the 1950s coincides with a rapid expansion of the regional mining industry. Excess Pb is interpreted as atmospheric deposition and direct human impact due to Pb smelting.

Insulin-like growth factor type-1 receptor down-regulation associated with dwarfism in Holstein calves

Perturbations in endocrine functions can impact normal growth. Endocrine traits were studied in three dwarf calves exhibiting retarded but proportionate growth and four phenotypically normal half-siblings, sired by the same bull, and four unrelated control calves. Plasma 3,5,3'-triiodothyronine and thyroxine concentrations in dwarfs and half-siblings were in the physiological range and responded normally to injected thyroid-releasing hormone. Plasma glucagon concentrations were different (dwarfs, controls>half-siblings; P<0.05). Plasma growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin concentrations in the three groups during an 8-h period were similar, but integrated GH concentrations (areas under concentration curves) were different (dwarfs>controls, P<0.02; half-siblings>controls, P=0.08). Responses of GH to xylazine and to a GH-releasing-factor analogue were similar in dwarfs and half-siblings. Relative gene expression of IGF-1, IGF-2, GH receptor (GHR), insulin receptor, IGF-1 type-1 and -2 receptors (IGF-1R, IGF-2R), and IGF binding proteins were measured in liver and anconeus muscle. GHR mRNA levels were different in liver (dwarfs

Factor XIII in severe sepsis and septic shock

OBJECTIVE: In sepsis, activation of coagulation and inhibition of fibrinolysis lead to microvascular thrombosis. Thus, clot stability might be a critical issue in the development of multiple organ dysfunction syndrome. Activated FXIII (FXIIIa) forms stable fibrin clots by covalently cross-linking fibrin monomers. Therefore, we investigated the impact of FXIII antigen and activity levels on disease severity and fatality in sepsis patients. PATIENTS AND METHODS: FXIII subunit A (FXIIIA) and FXIII cross-linking activity (FXIIICA) were measured in 151 controls, in 32 patients with severe sepsis and 8 with septic shock. In addition, FXIII subunit B (FXIIIB) was measured in the sepsis patients. Moreover, clotting parameters were determined. RESULTS: Patients suffering from sepsis (n=40) had significantly (p<0.005) lower FXIIIA levels (median [range]: 36.5% [8.8-127.4%]) and FXIIICA levels (76.5% [9.4-266%]) as compared to healthy controls (n=151, 119% [31.3-283.2] and 122.4% [40.6-485.3], respectively). No difference in FXIIIA, FXIIIB and FXIIICA levels between survivors and non-survivors, nor between patients with severe sepsis and septic shock was found. The specific activity of FXIII (FXIIICA/FXIIIA, SA(FXIII)) was significantly (p<0.001) higher in sepsis patients (2.0 [0.8-5.3]) as compared to healthy controls (1.0 [0.4-5.1]). SA(FXIII) significantly (p<0.05) increased with fatality (non-survivors [n=13] vs. survivors [n=27]: 3.3 [1.2-5.0] vs. 1.9 [0.8-5.3]) and disease severity (septic shock vs. severe sepsis: 3.4 [1.8-4.3] vs. 1.9 [0.8-5.3]). CONCLUSION: We show decreased FXIIICA and FXIIIA levels, but higher SA(FXIII) in sepsis as compared to controls. Increased SA(FXIII) correlates with disease severity and fatality in sepsis patients.

Cardiovascular risk factor control and outcomes in peripheral artery disease patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry

OBJECTIVES: To examine differences in risk factor (RF) management between peripheral artery disease (PAD) and coronary artery (CAD) or cerebrovascular disease (CVD), as well as the impact of RF control on major 1-year cardiovascular (CV) event rates. METHODS: The REACH Registry recruited >68000 outpatients aged >/=45 years with established atherothrombotic disease or >/=3 RFs for atherothrombosis. The predictors of RF control that were evaluated included: (1) patient demographics, (2) mode of PAD diagnosis, and (3) concomitant CAD and/or CVD. RESULTS: RF control was less frequent in patients with PAD (n=8322), compared with those with CAD or CVD (but no PAD, n=47492) [blood pressure; glycemia; total cholesterol; smoking cessation (each P<0.001)]. Factors independently associated with optimal RF control in patients with PAD were male gender (OR=1.9); residence in North America (OR=3.5), Japan (OR=2.5) or Latin America (OR=1.5); previous coronary revascularization (OR=1.3); and statin use (OR=1.4); whereas prior leg amputation was a negative predictor (OR=0.7) (P<0.001). Optimal RF control was associated with fewer 1-year CV ischemic symptoms or events. CONCLUSIONS: Patients with PAD do not achieve RF control as frequently as individuals with CAD or CVD. Improved RF control is associated with a positive impact on 1-year CV event rates.

Insulin-like growth factor I improves aspects of mycophenolate mofetil-impaired anastomotic healing in an experimental model

BACKGROUND: Patients taking immunosuppressants after transplantation may require intestinal surgery. Mycophenolate mofetil (MMF) has been found to impair the healing of colonic anastomoses in rats. This study examined whether insulin-like growth factor (IGF) I prevents MMF impairment of anastomotic healing. METHODS: Sixty-three rats were divided into three groups (MMF, MMF/IGF and control). Animals underwent a sigmoid colon anastomosis with a 6/0 suture, and were killed on days 2, 4 and 6 after surgery. Investigations included bursting pressure measurement, morphometric analysis, and assessment of mucosal proliferation by 5-bromo-2'-deoxyuridine and Ki67 immunohistochemistry of the anastomoses. RESULTS: The leak rate was three of 21, one of 20 and two of 20 in the MMF, MMF/IGF-I and control groups respectively. Anastomotic bursting pressures were significantly lower in the MMF group than in the control group on days 2 and 4, but there was no significant difference by day 6. Values in the MMF/IGF-I and control groups were similar. Colonic crypt depth was significantly reduced in MMF-treated animals on days 2 and 4, but this impairment was attenuated by IGF-I on day 4. Similarly, IGF-I reduced the negative impact of MMF on mucosal proliferation on days 2 and 6. CONCLUSION: Exogenous IGF-I improves some aspects of MMF-impaired anastomotic healing.

Impact of intraoperative behavior on surgical site infections

BACKGROUND: The aim of this study was to identify intraoperative risk factors for surgical site infections (SSIs), which are accessible to interventions. We evaluated the effect of extensive intraoperative antiseptic measures and the impact of the behavior of members of the surgical team on SSIs. METHODS: Standard versus extensive antiseptic measures were randomly assigned in 1,032 surgical patients. The adherence to principles of asepsis by members of the surgical team was assessed prospectively. RESULTS: The rate of SSI was 14% with standard antiseptic measures and 15% with extensive measures (P = .581). Multivariate analysis identified following independent risk factors: lapses in discipline (odds ratio [OR] 2.02, confidence interval [CI] 1.05-3.88), intestinal anastomosis (OR 6.74, CI 3.42-13.30), duration of operation more than 3 hours (OR 3.34, CI 1.82-6.14), and body mass index >30 kg/m2 (OR 1.98, CI 1.22-3.20). CONCLUSION: Extensive measures of antisepsis did not reduce the incidence of SSI. A lapse to adhere to principles of asepsis was identified as an independent risk factor for the development of SSI (ClinicalTrials.gov number, NCT00555815).

Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial growth factor levels in traumatic wounds

BACKGROUND: Clinical observations are suggesting accelerated granulation tissue formation in traumatic wounds treated with vacuum-assisted closure (VAC). Aim of this study was to determine the impact of VAC therapy versus alternative Epigard application on local inflammation and neovascularization in traumatic soft tissue wounds. METHODS: Thirty-two patients with traumatic wounds requiring temporary coverage (VAC n = 16; Epigard n = 16) were included. At each change of dressing, samples of wound fluid and serum were collected (n = 80). The cytokines interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 were measured by ELISA. Wound biopsies were examined histologically for inflammatory cells and degree of neovascularization present. RESULTS: All cytokines were found to be elevated in wound fluids during both VAC and Epigard treatment, whereas serum concentrations were negligible or not detectable. In wound fluids, significantly higher IL-8 (p < 0.001) and VEGF (p < 0.05) levels were detected during VAC therapy. Furthermore, histologic examination revealed increased neovascularization (p < 0.05) illustrated by CD31 and von Willebrand factor immunohistochemistry in wound biopsies of VAC treatment. In addition, there was an accumulation of neutrophils as well as an augmented expression of VEGF (p < 0.005) in VAC wound biopsies. CONCLUSION: This study suggests that VAC therapy of traumatic wounds leads to increased local IL-8 and VEGF concentrations, which may trigger accumulation of neutrophils and angiogenesis and thus, accelerate neovascularization.

Impact of recommendation updates in well-controlled patients on nonrecommended antiretroviral therapies: the Swiss HIV cohort study

BACKGROUND HIV treatment recommendations are updated as clinical trials are published. Whether recommendations drive clinicians to change antiretroviral therapy in well-controlled patients is unexplored. METHODS We selected patients with undetectable viral loads (VLs) on nonrecommended regimens containing double-boosted protease inhibitors (DBPIs), triple-nucleoside reverse transcriptase inhibitors (NRTIs), or didanosine (ddI) plus stavudine (d4T) at publication of the 2006 International AIDS Society recommendations. We compared demographic and clinical characteristics with those of control patients with undetectable VL not on these regimens and examined clinical outcome and reasons for treatment modification. RESULTS At inclusion, 104 patients were in the DBPI group, 436 in the triple-NRTI group, and 19 in the ddI/d4T group. By 2010, 28 (29%), 204 (52%), and 1 (5%) patient were still on DBPIs, triple-NRTIs, and ddI plus d4T, respectively. 'Physician decision,' excluding toxicity/virological failure, drove 30% of treatment changes. Predictors of recommendation nonobservance included female sex [adjusted odds ratio (aOR) 2.69, 95% confidence interval (CI) 1 to 7.26; P = 0.01] for DPBIs, and undetectable VL (aOR 3.53, 95% CI 1.6 to 7.8; P = 0.002) and lack of cardiovascular events (aOR 2.93, 95% CI 1.23 to 6.97; P = 0.02) for triple-NRTIs. All patients on DBPIs with documented diabetes or a cardiovascular event changed treatment. Recommendation observance resulted in lower cholesterol values in the DBPI group (P = 0.06), and more patients having undetectable VL (P = 0.02) in the triple-NRTI group. CONCLUSION The physician's decision is the main factor driving change from nonrecommended to recommended regimens, whereas virological suppression is associated with not switching. Positive clinical outcomes observed postswitch underline the importance of observing recommendations, even in well-controlled patients.