OBJECTIVE

The aim of this study was to evaluate the microtensile bond strengths (MTBSs) of porcelain laminate veneers bonded to normal and fluorosed teeth.

METHODS

Forty human incisors, including 20 normal and 20 moderately fluorosed teeth [Thylstrup Fejerskov Index (TFI) = 4 to 6], were collected. The labial surfaces of the teeth were ground up to 1 mm and polished with #600 silicon carbide abrasive paper. The surfaces were bonded to 1-mm-thick ceramic slices (5 x 5 mm(2)) previously made (VitaVM7) using one of two ceramic cement systems (RelyX or Clapearl) following the manufacturers' instructions. A resin composite was added on top of the ceramic slices and built up to 5-mm thickness to serve as grips. The specimens were stored in water (37 degrees C) for 24 hours, and beams of adhesive interface with a surface area of approximately 1.25 mm(2) were obtained. Then the beams were subjected to MTBS tests at a crosshead speed of 1.0 mm/min. The data were analyzed with two-way ANOVA.

RESULTS

The results of the MTBS test (MPa) were 20.55 +/- 5.83 (RelyX/fluorosed), 20.16 +/- 4.61 (RelyX/normal), 18.74 +/- 2.88 (Clapearl/fluorosed), and 21.06 +/- 4.99 (Clapearl/normal). There were no significant differences in the MTBSs among the four groups (p>> 0.05).

CONCLUSIONS

The MTBSs of ceramic cement systems used were not influenced by the moderately fluorosed teeth.

The purpose of this study was to evaluate the micro-shear bond strengths and the etching efficacy of a two-step self-etching adhesive system to fluorosed and non-fluorosed enamel. The extracted teeth, obtained from Australian and Japanese patients, were classified according to the severity of fluorosis, using the Thylstrup & Fejerskov index (TFI). Australian teeth were classified as mildly fluorosed (TFI = 1-3), whereas Japanese teeth were classified as non-fluorosed (TFI = 0). Resin composite was bonded to 20 enamel samples using Clearfil SE bond. The bonded samples were stressed at a crosshead speed of 1 mm min(-1) to determine the micro-shear bond strength. To examine the etching efficacy of primer on fluorosed and non-fluorosed enamel, the enamel-surface pH values were directly measured using a micro pH sensor. The non-fluorosed enamel showed significantly higher bond strengths compared with the fluorosed enamel. There was a statistical difference between fluorosed and non-fluorosed enamel regarding the surface pH change before and after application of the Clearfil SE bond primer. The results from this study suggest that water fluoridation has an effect on the acid resistance of enamel surfaces when treated with a two-step self-etching adhesive system and that this effect leads to reduced bond strengths.

Background: Early detection of frail older people is important. Timely intervention may allow health care professionals to prevent or delay the occurrence of adverse outcomes such as disability, increases in health care utilization, and premature death.

Objectives: We assessed the construct and criterion validity of the SUNFRAIL tool, a questionnaire for measuring frailty among older people.

Design, setting and participants: This cross-sectional study was carried out in a sample of Dutch citizens. A total of 195 community-dwelling persons aged 71 years and older completed the questionnaire.

Measurements: Construct validity was examined by determining the correlation between the SUNFRAIL tool and the Tilburg Frailty Indicator (TFI). Criterion validity for the SUNFRAIL tool was determined by establishing the correlations with chronic diseases and adverse outcomes of frailty (disability, falls, indicators of health care utilization). Disability was measured using the Groningen Activity Restriction Scale. Participants also answered questions regarding falls and health care utilization.

Results: The construct validity of this tool was good and showed significant correlations with the TFI. The correlation between SUNFRAIL total and TFI total was 0.624. The criterion validity of the SUNFRAIL tool was good for chronic diseases and good-to-excellent for adverse outcomes disability, receiving nursing care, and falls. The area under the curve for these outcomes was 0.840 (95% CI 0.781-0.899), 0.782 (95% CI 0.696-0.868), and 0.769 (95% CI 0.686-0.859), respectively.

Conclusions: The results of our study suggest that the SUNFRAIL tool is a valid instrument for assessing frailty in community-dwelling older people. It is an attractive instrument for use in practice because it takes little time for health care professionals and older people to complete the questionnaire, and it expresses the integral functioning of human beings.

Keywords: Frailty; SUNFRAIL tool; disability; health care utilization; validity.

Cushing's disease (CD) is an endocrine disorder originated by a corticotroph tumor. It is linked with high mortality and morbidity due to chronic hypercortisolism. Treatment goals are to control cortisol excess and achieve long-term remission, therefore, reducing both complications and patient's mortality. First-line of treatment for CD is pituitary's surgery. However, 30% of patients who undergo surgery experience recurrence in long-term follow-up. Persistent or recurrent CD demands second-line treatments, such as pituitary radiotherapy, adrenal surgery, and/or pharmacological therapy. The latter plays a key role in cortisol excess control. Its targets are inhibition of adrenocorticotropic hormone (ACTH) production, inhibition of adrenal steroidogenesis, or antagonism of cortisol action at its peripheral receptor. Retinoic acid (RA) is a metabolic product of vitamin A (retinol) and has been studied for its antiproliferative effects on corticotroph tumor cells. It has been shown that this drug regulates the expression of pro-opiomelanocortin (POMC), ACTH secretion, and tumor growth in corticotroph tumor mouse cell lines and in the nude mice experimental model, via inhibition of POMC transcription. It has been shown to result in tumor reduction, normalization of cortisol levels and clinical improvement in dogs treated with RA for 6 months. The orphan nuclear receptor COUP-TFI is expressed in normal corticotroph cells, but not in corticotroph tumoral cells, and inhibits RA pathways. A first clinical human study demonstrated clinical and biochemical effectiveness in 5/7 patients treated with RA for a period of up to 12 months. In a recent second clinical trial, 25% of 16 patients achieved eucortisolemia, and all achieved a cortisol reduction after 6- to 12-month treatment. The goal of this review is to discuss in the context of the available and future pharmacological treatments of CD, RA mechanisms of action on corticotroph tumor cells, and future perspectives, focusing on potential clinical implementation.

This study was to retrospectively analyze the effect of the age of embryos transfer and oocyte retrieval on the clinical pregnancy outcome in patients with simple tubal factor infertility (TFI) who received frozen-thawed embryo transfer. Patients (n = 3619) with simple TFI who underwent in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) frozen-thawed embryo transfer at our hospital were enrolled. Univariate logistic regression analysis, categorical multivariate logistic regression analysis, curve fitting and threshold effect analysis were performed. Age of embryo transfer was a significant (P < 0.05) independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rates. The Clinical pregnancy outcome declined significantly after the age of 34 years. After limiting the female oocyte retrieval age to ≤ 34 years, no significant change was detected in the clinical pregnancy, live birth, or miscarriage rate with increase of transplantation age. In conclusion, in patients with simple TFI undergoing IVF/ICSI frozen-thawed embryo transfer, age is a significant independent risk factor affecting the clinical pregnancy, live birth, and miscarriage rate. Aging of oocytes has a greater impact on the clinical pregnancy in women with simple TFI than the aging of the body. Patients with TFI can freeze embryos in advance to preserve fertility.

This research article describes an approach to modify the thiazolidinedione scaffold to produce test drugs capable of binding to, and inhibit, the in vitro transcriptional activity of the oncogenic protein FOXM1. This approach allowed us to obtain FOXM1 inhibitors that bind directly to the FOXM1-DNA binding domain without targeting the expression levels of Sp1, an upstream transcription factor protein known to activate the expression of FOXM1. Briefly, we modified the chemical structure of the thiazolidinedione scaffold present in anti-diabetic medications such as pioglitazone, rosiglitazone and the former anti-diabetic drug troglitazone, because these drugs have been reported to exert inhibition of FOXM1 but hit other targets as well. After the chemical synthesis of 11 derivatives possessing a modified thiazolidinedione moiety, we screened all test compounds using in vitro protocols to measure their ability to (a) dissociate a FOXM1-DNA complex (EMSA assay); (b) decrease the expression of FOXM1 in triple negative-breast cancer cells (WB assay); (c) downregulate the expression of FOXM1 downstream targets (luciferase reporter assays and qPCR); and inhibit the formation of colonies of MDA-MB-231 cancer cells (colony formation assay). We also identified a potential binding mode associated with these compounds in which compound TFI-10, one of the most active molecules, exerts binding interactions with Arg289, Trp308, and His287. Unlike the parent drug, troglitazone, compound TFI-10 does not target the in vitro expression of Sp1, suggesting that it is possible to design FOXM1 inhibitors with a better selectivity profile.

Keywords: Anticancer; Breast cancer; FOXM1; MDA-MB-231; Thiazolidinediones.; Transcription factors; Troglitazone.

Several European countries have seen major health issues after a switch from one levothyroxine brand to another, as well as following the introduction of several levothyroxine formulation changes. While the relationship between these health issues and brand or formulation changes merits further investigation, the current position statement on behalf of both health-care providers and patients summarizes recent events in several European countries and provides a number of recommendations to limit the burden for patients, so as to prevent increased health-care consumption and health-care expenses in this context.

BACKGROUND

There is growing evidence that transradial (TRI) as compared to transfemoral (TFI) percutaneous coronary intervention (PCI) is associated with improved clinical outcome driven by less hemorrhagic complications, in particular in STEMI patients receiving aggressive antithrombotic treatment. Feasibility rate of TRI in STEMI patients has not yet been evaluated.

RESULTS

Four-hundred seventy-five consecutive STEMI patients (<12h) without cardiogenic shock were prospectively screened for this all-comer single-centre registry between January 2008 and August 2010. Nine patients were excluded for a priori ineligibility for TRI (forearm shunt for dialysis, prior TRI failure). In the 466 patients enrolled, the operator's opinion about ease of radial puncture was assessed in 4 categories, based on radial pulse quality. Operators were advised not to attempt TRI if ease of puncture was judged "probably difficult/impossible". In case of puncture failure the operator switched immediately to TFI. The mean age of patients was 61 ± 14 (range 27-94) years. Seventy-three percent were men, 17% had diabetes. Nine percent had previous PCI. Glycoprotein inhibitors were used in 70%, and thrombectomy was performed in 70% of patients. PCI was performed using 6F and 5F guiding catheters. Procedural success rate was 98.2% (TIMI flow ≥ 2). In 4.1% (n=19) of patients the operator judged ease of radial puncture "probably difficult/impossible" and no TRI attempt was performed (primary TFI). In the 447 patients with TRI attempt, TRI failure requiring switch to TFI (secondary TFI) was necessary in 22 patients (4.7% of total) following radial puncture failure (n=15), dissection of the radial artery (n=1), prohibitive tortuosities or stenosis of the upper limb axis (n=2), or non-selective position or lack of stability of the guiding catheter (n=2). After the start of the angioplasty procedure, switch from TR to TF was not necessary in any patient. In total, the overall feasibility rate of TRI was 91.2%. Independent predictors of final TFI were age ≥ 80 years (adjusted OR: 2.37; 95% CI:1.05-5.34, p=0.037), body weight<60 kg (adjusted OR: 2.84; 95% CI:1.22-6.59, p=0.015); and previous PCI (adjusted OR: 3.42; 95% CI:1.40-8.37, p=0.007); female gender was borderline significant (adjusted OR:2.10; 95% CI:0.97-4.54, p=0.059).

CONCLUSIONS

In STEMI patients without cardiogenic shock and without a priori indication for TFI, PCI can be performed via the radial artery in more than 90% of cases with high procedural success rate. Operator's judgement of eligibility for TRI based on radial pulse quality is predictive of successful TRI in 95% of cases. TR failure is significantly more common in the elderly and in patients with low body weight.

Mindfulness-based therapies have been introduced as a treatment option to reduce the psychological severity of tinnitus, a currently incurable chronic condition. This pilot study of twelve subjects with chronic tinnitus investigates the relationship between measures of both task-based and resting state functional magnetic resonance imaging (fMRI) and measures of tinnitus severity, assessed with the Tinnitus Functional Index (TFI). MRI was measured at three time points: before, after, and at follow-up of an 8-week long mindfulness-based cognitive therapy intervention. During the task-based fMRI with affective sounds, no significant changes were observed between sessions, nor was the activation to emotionally salient compared to neutral stimuli significantly predictive of TFI. Significant results were found using resting state fMRI. There were significant decreases in functional connectivity among the default mode network, cingulo-opercular network, and amygdala across the intervention, but no differences were seen in connectivity with seeds in the dorsal attention network (DAN) or fronto-parietal network and the rest of the brain. Further, only resting state connectivity between the brain and the amygdala, DAN, and fronto-parietal network significantly predicted TFI. These results point to a mostly differentiated landscape of functional brain measures related to tinnitus severity on one hand and mindfulness-based therapy on the other. However, overlapping results of decreased amygdala connectivity with parietal areas and the negative correlation between amygdala-parietal connectivity and TFI is suggestive of a brain imaging marker of successful treatment.

Identifying characteristics associated with transcranial magnetic stimulation (TMS) benefit would offer insight as to why some individuals experience tinnitus relief following TMS treatment, whereas others do not. The purpose of this study was to use the Tinnitus Functional Index (TFI) and its subscales to identify specific factors associated with TMS treatment responsiveness.

Individuals with bothersome tinnitus underwent 2000 pulses of 1-Hz TMS for 10 consecutive business days. The primary outcome measure was the TFI which yields a total score and eight individual subscale scores. Analyses were performed on baseline data from the active arm (n = 35) of a prospective, double-blind, randomized placebo-controlled clinical trial of TMS for tinnitus.

Baseline total TFI score and three of the eight TFI subscales were useful in differentiating between responders and nonresponders to TMS intervention for tinnitus. These findings are not definitive, but suggest potential factors that contribute to perceived benefit following TMS.

Overall, the main factor associated with TMS benefit was a higher tinnitus severity score for responders at baseline. The TFI subscales helped to clarify the factors that contributed to a higher severity score at baseline. Large-scale prospective research using systematic approaches is needed to identify and describe additional factors associated with tinnitus benefit following TMS.

ClinicalTrials.gov, ID: NCT01104207 . Registered on 13 April 2010.

UNASSIGNED

The tinnitus research literature suggests that N-methyl-d-aspartate (NMDA) receptor antagonists may be useful in reducing tinnitus. Nitrous oxide, a member of the NMDA receptor antagonist class, is a widely used general anesthetic and sedative with a proven safety record.

UNASSIGNED

To investigate whether nitrous oxide can reduce bothersome tinnitus.

UNASSIGNED

Randomized, placebo-controlled crossover trial conducted between October 15, 2016, and June 22, 2017. Participants attended 2 interventional sessions separated by at least 14 days and were randomized to receive either placebo first or nitrous oxide first. Participants were followed up through completion of the second arm of the study. The setting was a clinical research unit at an academic medical center. Adults aged 18 to 65 years with subjective, idiopathic, nonpulsatile bothersome tinnitus of 6 months' duration or longer were recruited from 2 clinical research databases. Seventy-one individuals were screened, of whom 40 were enrolled. Of those enrolled, 37 participants completed all components of the study.

UNASSIGNED

The placebo session consisted of 50% nitrogen and 50% oxygen inhaled for 40 minutes, and the treatment session consisted of 50% nitrous oxide and 50% oxygen inhaled for 40 minutes.

UNASSIGNED

Tinnitus was assessed before and after intervention, with the change in the Tinnitus Functional Index (TFI) as the primary outcome measure. Secondary outcome measures included the Patients' Global Impression of Change score and the change in the Global Bothersome Scale score.

UNASSIGNED

Among 40 participants in this intent-to-treat randomized clinical trial with 20 participants randomly assigned to each group, the mean (SD) age of participants was 52.9 (11.1) years, with equal numbers of male and female participants. The TFI after intervention was a mean (SD) of 1.8 (8.8) points lower than before intervention in the placebo arm and a mean (SD) of 2.5 (11.0) points lower than before intervention in the nitrous oxide arm. The within-participant mean difference in the change in the TFI of the placebo arm compared with the nitrous oxide arm was -1.1 points (95% CI, -5.6 to 3.4 points). The difference between the placebo and nitrous oxide arms was neither clinically meaningful nor statistically significant.

UNASSIGNED

Nitrous oxide was no more effective than placebo for the treatment of subjective, idiopathic tinnitus.

UNASSIGNED

ClinicalTrials.gov identifier: NCT03365011.

Sexually transmitted infections (STIs) caused by Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium are a common cause of pelvic inflammatory disease (PID) which can lead to tubal factor infertility (TFI). TFI is one of the most common causes of infertility, accounting for 30% of female fertility problems. STIs can also have an impact on pregnancy, leading to adverse pregnancy outcomes. Escalating antibiotic resistance in Neisseria gonorrhoeae and Mycoplasma genitalium represents a significant problem and can be therapeutically challenging. We present a comprehensive review of the current treatment options, as well as the molecular approach to this subject. We have given special attention to molecular epidemiology, molecular diagnostics, current and new treatments, and drug resistance.

Keywords: STI; fertility; genotyping; pregnancy; resistance mechanisms.

Objectives: The current study examined predictors of outcomes of internet-based cognitive-behavioural therapy (ICBT) for individuals with tinnitus.

Design: Secondary analysis of intervention studies.

Setting: Internet-based guided tinnitus intervention provided in the UK.

Participants: 228 individuals who underwent ICBT.

Interventions: ICBT.

Primary and secondary outcome measures: The key predictor variables included demographic, tinnitus, hearing-related and treatment-related variables as well as clinical factors (eg, anxiety, depression, insomnia), which can have an impact on the treatment outcome. A 13-point reduction in Tinnitus Functional Index (TFI) scores has been defined as a successful outcome.

Results: Of the 228 subjects who were included in the study, 65% had a successful ICBT outcome. As per the univariate analysis, participants with a master's degree or above had the highest odds of having a larger reduction in tinnitus severity (OR 3.47; 95% CI 1.32 to 12.51), compared with the participants who had education only up to high school or less. Additionally, the baseline tinnitus severity was found to be a significant variable (OR 2.65; 95% CI 1.50 to 4.67) contributing to a successful outcome with the intervention. Both linear and logistic regression models have identified education level and baseline tinnitus severity to be significant predictor variables contributing to a reduction in tinnitus severity post-ICBT. As per the linear regression model, participants who had received disability allowance had shown a 25.3-point lower TFI reduction compared with those who did not experience a decrease in their workload due to tinnitus after adjusting for baseline tinnitus severity and their education level.

Conclusions: Predictors of intervention outcome can be used as a means of triaging patients to the most suited form of treatment to achieve optimal outcomes and to make healthcare savings. Future studies should consider including a heterogeneous group of participants as well as other predictor variables not included in the current study.ClinicalTrial.gov Registration: NCT02370810 (completed); NCT02665975 (completed).

Keywords: adult otolaryngology; audiology; depression & mood disorders.

In MONARCH 3, continuous dosing of abemaciclib with an aromatase inhibitor (AI) conferred significant clinical benefit to postmenopausal women with HR+, HER2- advanced breast cancer. We report data for clinically prognostic subgroups: liver metastases, progesterone receptor status, tumor grade, bone-only disease, ECOG performance status, and treatment-free interval (TFI) from an additional 12-month follow-up (after final progression-free survival [PFS] readout). In the intent-to-treat population, after median follow-up of approximately 39 months, the updated PFS was 28.2 versus 14.8 months (hazard ratio [HR], 0.525; 95% confidence interval, 0.415-0.665) in abemaciclib versus placebo arms, respectively. Time to chemotherapy (HR, 0.513), time to second disease progression (HR, 0.637), and duration of response (HR, 0.466) were also statistically significantly prolonged with the addition of abemaciclib to AI. Treatment benefit was observed across all subgroups, as evidenced by objective response rate change from the addition of abemaciclib to AI, with the largest effects observed in patients with liver metastases, progesterone receptor-negative tumors, high-grade tumors, or TFI < 36 months. Extended follow-up in the MONARCH 3 trial further confirmed that the addition of abemaciclib to AI conferred significant treatment benefit to all subgroups, including those with poorer prognosis.

Pycnogenol^® (an extract of the bark of French maritime pine tree) is used for dietary supplement and known to have excellent antioxidative efficacy. However, there are few reports on neuroprotective effect of Pycnogenol^® supplementation and its mechanisms against ischemic injury following transient forebrain ischemia (TFI) in gerbils. Now, we examined neuroprotective effect and its mechanisms of Pycnogenol^® in the gerbils with 5-min TFI, which evokes a significant death (loss) of pyramidal cells located in the cornu ammonis (CA1) region of gerbil hippocampus from 4-5 days post-TFI. Gerbils were pretreated with 30, 40, and 50 mg/kg of Pycnogenol^® once a day for 7 days before TFI surgery. Treatment with 50 mg/kg, not 30 or 40 mg/kg, of Pycnogenol^® potently protected learning and memory, as well as CA1 pyramidal cells, from ischemic injury. Treatment with 50 mg/kg Pycnogenol^® significantly enhanced immunoreactivity of antioxidant enzymes (superoxide dismutases and catalase) in the pyramidal cells before and after TFI induction. Furthermore, the treatment significantly reduced the generation of superoxide anion, ribonucleic acid oxidation and lipid peroxidation in the pyramidal cells. Moreover, interestingly, its neuroprotective effect was abolished by administration of sodium azide (a potent inhibitor of SODs and catalase activities). Taken together, current results clearly indicate that Pycnogenol^® supplementation can prevent neurons from ischemic stroke through its potent antioxidative role.

Keywords: antioxidant enzymes; antioxidation; free radicals; ischemia-reperfusion injury; neuroprotection; oxidative stress.

Chemotherapy for advanced or recurrent endometrial cancer requires further development. Irinotecan hydrochloride (CPT-11) suppresses tumor growth in several endometrial cancer strains. The present study evaluated the anti-tumor activity and toxicity of CPT-11 in patients with advanced or recurrent endometrial cancer.

Enrolled patients had advanced endometrial cancer with measurable lesions and received 2 pretreatment regimens. A 90-minute intravenous infusion of CPT-11 (100 mg/m2) was given on days 1, 8, and 15 of a 4-week cycle, aiming for an effect with ≤2 cycles. Treatment was continued until the primary disease worsened or severe toxicity occurred. The primary endpoint was response rate, and the secondary endpoints were progression-free survival, overall survival, and adverse events. Antitumor effect and adverse events were evaluated according to RECIST version 1.1 and NCI-CTC AE version 3.0, respectively.

Twenty-two patients were registered (11 endometrioid carcinomas and 11 serous carcinomas). The median duration of the treatment-free interval (TFI) was 7.5 months, and the median number of administered cycles per patient was 4. Response rate was 36.4% (complete response: 1 patient, partial response: 7 patients). Clinical benefit rate, including stable disease, was 77.3%. Median progression-free and overall survival was 4.4 and 18.4 months, respectively. Observed adverse events included grade 4 hematotoxicity (neutropenia and thrombocytopenia), and grade 2 or 3 non-hematotoxicity (diarrhea). All adverse events were manageable. Biomarker predictors of therapeutic effectiveness were not observed.

As a single agent, CPT-11 has anti-tumor activity for advanced or recurrent endometrial cancer and has manageable adverse events.

Aim: Screening is one of the most important ways for early frailty detection that contributes to its prevention and timely treatment. The aim of this study was to determine the diagnostic value of the Persian version of the Tilburg Frailty Indicator (P-TFI) in the frailty screening.

Method: This is a diagnostic test accuracy study that uses known group method. It was designed based on a STARD statement and performed on 175 elderly people in the City of Kashan, Iran. The subjects were selected among older people available in health centers affiliated to Kashan University of Medical Sciences using purposive sampling. Data analysis was carried out using SPSS v16. Descriptive statistics were used to describe the characteristics of the research subjects. Independent t-test was used to determine the ability of the P-TFI to discriminate frail and non-frail individuals, and to evaluate the cut-off point and instrument accuracy, the receiver operating characteristic (ROC) curve was used. The best cut-off point was determined among the proposed points using Youden index. At the determined cut-off point, the diagnostic value parameters of the P-TFI (sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, accuracy, and diagnostic odds ratio) were calculated and their range was estimated with 95 % confidence interval.

Findings: A total of 74.3 % of the sample was male and their mean age was 68.6 ± 54.44 years. The area under the ROC curve was calculated 0.922, indicating high accuracy of the instrument. The sensitivity and specificity of this instrument at the cut-off point of 4.5 were 0.95 and 0.86, respectively. Positive and negative predictive values were calculated 0.68 and 0.98, respectively, and the accuracy of the instrument was reported to be 0.88.

Conclusion: The P-TFI can be used as a sensitive and accurate instrument, which is highly applicable to screen frailty in older people.

Keywords: Diagnostic accuracy; Elderly; Frailty; Sensitivity; Specificity; Tilburg Frailty Indicator.

Tandem mass spectral (MS/MS) data in liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis are often contaminated as the selection of precursor ions is based on a low-resolution quadrupole mass filter. In this work, we developed a strategy to differentiate contamination fragment ions (CFIs) from true fragment ions (TFIs) in an MS/MS spectrum. The rationale is that TFIs should coelute with their parent ions, but CFIs should not. To assess coelution, we performed a parallel LC-MS/MS analysis in data-independent acquisition (DIA) with all-ion-fragmentation (AIF) mode. Using the DIA (AIF) data, peak-peak correlation (PPC) score is calculated between the extracted ion chromatogram (EIC) of the fragment ion using the MS/MS scans and the EIC of the precursor ion using the MS1 scans. A high PPC score is an indication of TFIs, and a low PPC score is an indication of CFIs. Tested using metabolomics data generated by high resolution QTOF and Orbitrap MS from various vendors in different LC-MS configurations, we found that more than 70% of the fragment ions have PPC scores < 0.8 and identified three common sources of CFIs, including (1) solvent contamination, (2) adjacent chemical contamination, and (3) undetermined signals from artifacts and noise. Combining PPC scores with other precursor and fragment ion information, we further developed a machine learning model that can robustly and conservatively predict CFIs. Incorporating the machine learning model, we created an R program, MS2Purifier, to automatically recognize CFIs and clean MS/MS spectra of metabolic features in LC-MS/MS data with high sensitivity and specificity.

Keywords: adjacent chemical contamination; contamination fragment ion; data-dependent acquisition; data-independent acquisition; liquid chromatography−mass spectrometry; solvent contamination.

Compared with transradial intervention (TRI), it is unclear whether transfemoral intervention (TFI) with vascular closure device (VCD) improves major adverse cardiocerebrovascular events (MACCE) in patients with acute myocardial infarction (AMI). The aim of this study is to compare TRI versus TFI with or without VCD for reducing MACCEs. We examined 11,596 patients who underwent TRI or TFI from the Korean AMI Registry - National Institute of Health database. The MACCE at 1-year was defined as death, nonfatal MI, repeat revascularization, cerebrovascular accident, hospitalizations, and major bleedings. Because the patients were not randomly assigned to vascular access sites, propensity-score (PS) matching was performed. In the PS-matched cohorts, compared with TFI, TRI significantly reduced 1-year MACCEs (7.1% vs 10.1%; log-rank p < 0.001) through a reduction in major bleeding (0.6% vs 2.2%; p < 0.001). Compared with TRI, 1-year MACCEs (11.3% vs 7.9%, log-rank p < 0.001) and major bleedings (0.6% vs 2.2%; p < 0.001) were significantly greater in TFI without VCD, whereas TFI with VCD was comparable in 1-year MACCEs (7.5% vs 8.1%, log-rank p = 0.437) and major bleeding (0.7% vs 1.0%; p = 0.409). In conclusion, the use of VCD could be an alternative to avoid major bleeding and to improve clinical outcomes, particularly in high-risk patients who are not suitable for TRI.