Dissingevans8025

OBJECTIVES We investigated the diagnostic efficacy of the prostate health index (PHI) and PHI density (PHID) to avoid unnecessary prostate biopsies in 3 urological practices. METHODS In 122 patients, total prostate-specific antigen (PSA), free PSA (f-PSA), the quotient from total PSA and f-PSA (f-PSA%), and [-2]pro-PSA were measured in the serum; PHI, PHID, and PSA density (PSAD) were calculated prior to prostate biopsy. Tissue sampling via transrectal biopsy was indicated in case of suspicious PSA (progression and/or elevation of PSA) and/or suspicious digital rectal examination. PSAD, PHI, and PHID were not used for biopsy indication. The diagnostic efficacy was determined with receiver-operating characteristic (ROC)and decision curve analyses. RESULTS Based on prostate biopsies, 38% (n = 46) of the cases had no prostate carcinoma (PCa), 21% (n = 26) no clinically significant (insignificant) PCa, and 41% (n = 50) had clinically significant PCa. ROC analyses of the PSA parameters showed higher diagnostic efficacy for PHI and PHID (AUC 0.722 and 0.739) than for f-PSA%, PSA, and PSAD (AUC 0.612, 0.595, and 0.698, respectively) regarding carcinoma diagnosis. With a combined use of PHI and PHID (cutoff >40 and >0.9, respectively), only 1 clinically significant PCa would have been missed (sensitivity 98%); in 24 (20%) patients, biopsy could have been avoided. CONCLUSION The integration of PHI and PHID could improve the diagnostic efficacy of risk calculators to avoid unnecessary prostate biopsies. However, as a prerequisite, validation of cutoff values in prospective studies is urgently required. © 2020 S. Karger AG, Basel.INTRODUCTION Although growth hormone (GH) is essential for attainment of peak bone mass, bone health in prepubertal children with GH deficiency is not routinely evaluated. The objective of this study was to evaluate bone microarchitecture in GH-deficient (GHD) boys using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS Fifteen control and fifteen GHD, GH naïve pre-pubertal boys were recruited for a case-control study at a major academic center. Subjects with panhypopituitarism, chromosomal pathology, chronic steroids, or stimulant use were excluded. Volumetric bone mineral density (vBMD; total, cortical, and trabecular), bone geometry (total, cortical and trabecular cross-sectional area, cortical perimeter), bone microarchitecture, and estimated bone strength of the distal radius and tibia were assessed by HR-pQCT. Areal BMD and body composition were assessed by DXA. Insulin-like growth factor 1 (IGF-1), osteocalcin, C telopeptide, and P1NP levels were measured. RESULTS GHD subjects had a significantly smaller cortical perimeter of the distal radius compared to controls (p less then 0.001), with the difference in cortical perimeter persisting after adjusting for height z score, age, lean mass, and 25-hydroxyvitamin D level (p less then 0.05).No significant differences were found in vBMD. No significant differences were found in microarchitecture, estimated strength, areal BMD, body composition, or bone turnover markers. Analysis showed significant positive correlations between IGF-1 levels and cortical parameters. DISCUSSION/CONCLUSIONS Prepubertal GHD boys had deficits in bone geometry not evident with DXA. Larger prospective/longitudinal HR-pQCT studies are needed to determine the extent of these deficits, the need for routine bone evaluation, and the timing of GH replacement for prevention or restoration of these deficits. © 2020 S. Karger AG, Basel.INTRODUCTION Quality of care is an emerging concern, notably in oncology. The aim of the present study was to identify the sociodemographic factors influencing the quality of care in the USA concerning the surgical management of endometrial cancer (EC) through the Surveillance Epidemiology and End Results (SEER) database using already published Belgian quality indicators (QI). click here METHODS Using the SEER database 1988-2013, we identified 151,752 patients treated for EC. Six QI were extracted from a Belgian study on quality of care in EC because of their applicability to the SEER. These QI evaluated only the surgical management. We examined the association between sociodemographic characteristics and quality of care with a logistic regression model. We compared our results with those defined as theoretical target by the Belgian initiative and considered a QI to be accurately met if >80% of the population met the indicator, moderately met between 50 and 80%, and poorly met under 50%. RESULTS Concerning the 6 surgical QIs, one was accurately met, 3 were moderately met, and 2 were poorly met. For example, 73% of the patients with a high-risk EC underwent a pelvic lymphadenectomy. Age over 75 years old, black ethnicity, lower-income group, without partner, and uninsured had a negative impact on adherence to QIs. CONCLUSION Demographic discrepancies persist in the surgical management of EC, impacting evidence-based care. © 2020 S. Karger AG, Basel.OBJECTIVE Studies that investigate predictive factors for spontaneous recovery (reversion) from mild cognitive impairment (MCI) are only beginning to emerge, and the long-term course of MCI is not properly understood. We aimed to investigate stability of the MCI diagnosis, predictors for reversion, as well as the trajectory of MCI over the course of 12 years. MATERIALS AND METHODS Data were drawn from the Swedish population study Good Aging in Skåne with MCI defined according to the expanded Mayo Clinic criteria. A total of 331 participants, aged 60-95 years with MCI, were used to investigate 6-year MCI stability and reversion, and 410 participants were used to inspect 12-year MCI trajectory. Predictors for reversion included demographical factors, psychological status, and factors tied to the cognitive testing session and the operationalization of the MCI criteria. RESULTS Over half (58%, 95% CI 52.7-63.3) of the participants reverted back to normal cognitive functioning at 6-year follow-up. Of those with stable MCI, 56.5% (95% CI 48.2-64.8) changed subtype. A total of 23.9% (95% CI 13.7-34.1) of the 6-year follow-up reverters re-transitioned back to MCI at 12-year follow-up. ORs for reversion were significantly higher in participants with lower age (60-year-olds OR 2.19, 95% CI 1.08-4.43, 70-year-olds OR 3.11, 95% CI 1.27-7.62), better global cognitive functioning (OR 1.15, 95% CI 1.03-1.29), good concentration (OR 2.53, 95% CI 1.06-6.05), and single-domain subtype (OR 2.68, 95% CI 1.51-4.75). CONCLUSION Our findings provide further support that MCI reversion to normal cognitive functioning as well as re-transitioning to MCI is fairly common, suggesting that the MCI trajectory does not necessarily lead straight to dementia. Additionally, assessment of factors associated with reversion can aid clinicians to make accurate MCI progression prognosis. © 2020 The Author(s) Published by S. Karger AG, Basel.INTRODUCTION Distal clot migration (DCM) is a known complication of mechanical thrombectomy (MT), but neither risk factors for DCM nor ways of how it might affect clinical outcomes have been extensively studied to date. METHODS To identify risk factors for and outcomes in the setting of DCM, the records of all patients with acute ischemic stroke due to anterior circulation large vessel occlusion (LVO) treated with MT at a single center between May 2016 and June 2018 were retrospectively reviewed. Uni- and multivariable analyses were performed to evaluate predictors of DCM and good functional outcome (90-day modified Rankin Scale; mRS 0-2). RESULTS A total of 65 patients were included, DCM was identified in 22 patients (33.8%). Patients with DCM had significantly higher pre-procedural intravenous tissue plasminogen activator (IV-tPA) administration (81.8 vs. 53.5%, p = 0.03), stentrievers thrombectomy (95.5 vs. 62.8%, p = 0.006), and longer median puncture to recanalization time (44 [34-97] vs. 30 [20-56] min,0 days. IV-tPA administration and MT with short stentrievers are independent predictors of DCM development. © 2020 S. Karger AG, Basel.The cyanobacterial circadian oscillator can be reconstituted by mixing the purified clock proteins KaiA, KaiB, and KaiC with ATP in vitro, leading to a 24-h oscillation of KaiC phosphorylation. The cyanobacterial mutant pr1 carrying valine instead of alanine at position 422 of KaiC (KaiC-A422V) lost the ability to shift the phase of the circadian rhythm. In this study, we analyzed KaiC-A422V to investigate the effect of this single-residue substitution on the in vitro reconstitution of KaiC oscillation. KaiC-A422V exhibited low amplitude oscillations of phosphorylation with a smaller amount of Kai complex than wild-type KaiC (KaiC-WT). Although KaiA can stimulate KaiC phosphorylation, the phosphorylation level of KaiC-A422V is much lower than that of KaiC-WT even at higher KaiA concentrations. It has been suggested that monomer shuffling of KaiC is involved in entraining the in vitro rhythm. To examine whether KaiC-A422V has the capacity for monomer shuffling, we used the difference in the amplitude of the phosphorylation rhythms between KaiC-WT and KaiC-A422V as the indicator of monomer shuffling. When KaiC-A422V and KaiC-WT were mixed, the amplitude of the phosphorylation rhythm changed according to the mixing ratio. This suggests that KaiC-A422V has a reduced ability to shuffle monomers in hexameric KaiC. In addition, the A422V mutation resulted in a change of the stability of the KaiC protein.Second messenger molecules are crucial components of environmental signaling systems to integrate multiple inputs and elicit physiological responses. Among various kinds of second messengers, cyclic nucleotides cAMP and cyclic di-GMP (c-di-GMP) play pivotal roles in bacterial environmental responses. However, how these signaling systems are interconnected for a concerted regulation of cellular physiology remains elusive. In a thermophilic cyanobacterium Thermosynechococcus vulcanus strain RKN, incident light color is sensed by cyanobacteriochrome photoreceptors to transduce the light information to the levels of c-di-GMP, which induces cellular aggregation probably via cellulose synthase activation. Herein, we identified that Tlr0485, which is composed of a cGMP-specific phosphodiesterases, adenylate cyclases, and FhlA (GAF) domain and an HD-GYP domain, is a cAMP-activated c-di-GMP phosphodiesterase. We also show biochemical evidence that the two class-III nucleotide cyclases, Cya1 and Cya2, are both adenylate cyclases to produce cAMP in T. vulcanus. The prevalence of cAMP-activated c-di-GMP phosphodiesterase genes in cyanobacterial genomes suggests that the direct crosstalk between cAMP and c-di-GMP signaling systems may be crucial for cyanobacterial environmental responses.Anticentriole autoantibodies-positive systemic sclerosis (SSc) has been reported to develop pulmonary arterial hypertension (PAH) at a high rate. In this report, we describe two patients with anticentriole antibodies-positive SSc-PAH who were treated with pulmonary vasodilators. Both cases were elderly women with poor physical conditions and clinical findings of SSc. Case 1 was resistant to combination therapy with pulmonary vasodilators; in Case 2, hemodynamic improvement was obtained by upfront combination therapy at an early stage. Because anticentriole antibodies-positive SSc-PAH rapidly deteriorates, careful hemodynamic observation and timely aggressive use of pulmonary vasodilators should be considered.