Tag: pubmed

J Mol Neurosci. 2021 Jun 14. doi: 10.1007/s12031-021-01853-3. Online ahead of print.

ABSTRACT

Parkinson’s disease is a progressive neurodegenerative disorder in which dopaminergic neurons located in the substantia nigra are gradually lost. Currently, combined treatment strategies are receiving increasing attention as potential therapeutic approaches for Parkinson’s disease. This study aimed to evaluate the potential effects of exosomes released from SH-Sy5y cells and the liposomal form of L-dopa on Parkinson’s rat models. Twenty-five male Wistar albino rats, in five groups, were included in this study. Parkinson’s disease was induced through microinjection of 6-OHDA (2.5 mg/mL) into the right substantia nigra. The exosomes released from the SH-Sy5y cell line were isolated and administered (0.2 µg/5 µL) alone or in combination with the liposomal form of L-Dopa (80 mg/kg) to the defined model groups. Behavioral tests and molecular assays were conducted to evaluate the expression levels of tyrosine hydroxylase (TH) and dopamine receptor D2 (DRD2). The rats in the groups receiving the combined liposomal form of L-Dopa and exosome treatment and the liposomal form of L-Dopa alone showed a significant improvement in their movement ability (p < 0.05). At molecular levels, these two groups also exhibited significant increases in Th (0.005 ± 0.001) and Drd2 (0.002 ± 0.0001) expression compared to controls (p < 0.05). The observed alterations of Th and Drd2 expression were not statistically significant in exosome- and L-Dopa-treated groups. The current study shows that exosome-derived neuronal cells and liposomal form of L-Dopa can protect different cells against pathological complications such as Parkinson’s disease.

PMID:34125397 | DOI:10.1007/s12031-021-01853-3

Cardiol J. 2021 Jun 14. doi: 10.5603/CJ.a2021.0058. Online ahead of print.

ABSTRACT

BACKGROUND: Several scoring systems have been described to assess the level of difficulty and to predict the probability of success of percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). The J-CTO score was initially developed to correlate CTO complexity with guidewire time crossing through the lesion within 30 min. Moreover, almost all scoring systems represent procedures performed by seasoned operators. Herein, this study sought to evaluate the predictive capacity of J-CTO for PCI success in a European single-center cohort with growing experience in the approach of CTO.

METHODS: 526 procedures were performed between 2007 and 2020 mainly by a single operator. The predictive power of J-CTO score was assessed by area under the receiver-operator characteristic curve (ROC) in the entire cohort and additionally in two separate periods. The goodness-of-fit of the model was evaluated by the Hosmer and Lemeshow statistic.

RESULTS: Successful procedure in first-attempt PCI was 79.5% and the overall success including 47 repeated procedures was achieved in 85.8%. The retrograde approach was attempted in 14.4%. The score was inversely associated with procedural success and lower success rate in more difficult CTOs (p < 0.001). ROC curve for the entire cohort, and first block (case 1-200) and second block (case 201-526) was 0.696, 0.661 and 0.748, respectively. The model showed good calibration for the entire cohort (X2 = 1.7; p = 0.43).

CONCLUSIONS: J-CTO score showed an acceptable predictive power for procedural success in this cohort although its discriminatory power is better as the level of experience is improved.

PMID:34125431 | DOI:10.5603/CJ.a2021.0058

J Psycholinguist Res. 2021 Jun 14. doi: 10.1007/s10936-021-09784-1. Online ahead of print.

ABSTRACT

It is unknown how self-relevance is dependent on emotional salience. Emotional salience encompasses an individual’s degree of attraction or aversion to emotionally-valenced information. The current study investigated the interconnection between self and salience through the evaluation of emotional valence and self-relevance. 56 native Dutch participants completed a questionnaire assessing valence, intensity, and self-relevance of 552 Dutch nouns and verbs. One-way repeated-measures ANCOVA investigated the relationship between valence and self, age and gender. Repeated-measures ANCOVA also tested the relationship between valence and self with intensity ratings and effects of gender and age. Results showed a significant main effect of valence for self-relevant words. Intensity analyses showed a main effect of valence but not of self-relevance. There were no significant effects of gender and age. The most important finding presents that self-relevance is dependent on valence. These findings concerning the relationship between self and salience opens avenues to study an individual’s self-definition.

PMID:34125312 | DOI:10.1007/s10936-021-09784-1

Ann Surg Oncol. 2021 Jun 14. doi: 10.1245/s10434-021-10148-1. Online ahead of print.

ABSTRACT

BACKGROUND: Nearly one-third of patients with inflammatory breast cancer (IBC) present with de novo stage IV disease. There are limited data on frequency and clinical outcomes of contralateral axillary metastasis (CAM) in IBC with no consensus diagnostic and treatment guidelines.

PATIENTS AND METHODS: Frequency of synchronous CAM was calculated in unilateral IBC patients at a single center (10/2004-6/2019). Clinicopathologic variables, diagnostic evaluation, treatment received, and overall survival (OS) were assessed and compared.

RESULTS: Of 588 unilateral IBC patients, 49 (8.3%) had synchronous CAM. Of these, 32 (65.3%) also presented with metastatic disease at another distant site. CAM was not associated with age, tumor laterality, breast cancer subtype, grade, or cN stage (p > 0.05). The sensitivity/specificity to detect CAM was as follows: mammography (18.2%/99.2%), ultrasound (92.3%/95.5%), PET (90.1/99.1%), and MRI (76.0%/98.6%). Following systemic therapy, 22 patients had contralateral axillary surgery, and 18 received adjuvant contralateral nodal radiation. On multivariable analysis including tumor receptor subtypes, patients with stage IV-isolated CAM has statistically similar survival to stage III patients (HR 1.37, 95% CI 0.70-2.69, p = 0.36). Patients with Stage IV non-CAM (HR 2.18, 95% CI 1.66-2.85, p < 0.001) and stage IV-CAM plus other distant metastasis (HR 2.57, 95% CI 1.59-4.16, p < 0.001) had higher risk of death (reference: stage III disease).

CONCLUSIONS: CAM in IBC was diagnosed in 8.3% of patients at presentation and was best identified by ultrasound and PET. We recommend routine contralateral axillary ultrasound as part of staging for all IBC patients. Diagnosis of CAM is a key first step toward much-needed prospective clinical trials evaluating management and outcomes of CAM in IBC.

PMID:34125346 | DOI:10.1245/s10434-021-10148-1

Cardiovasc Drugs Ther. 2021 Jun 14. doi: 10.1007/s10557-021-07210-1. Online ahead of print.

ABSTRACT

PURPOSE: In PARADIGM-HF, sacubitril/valsartan showed a significant reduction in mortality and hospitalization for patients with heart failure with reduced ejection fraction. Despite proven efficacy, sacubitril/valsartan has moderate uptake in clinical practice. This study explores the safety profile of sacubitril/valsartan by comparing adverse events in RCT and real-world use.

METHODS: We studied hypotension, renal dysfunction, hyperkalemia, and angioedema associated with sacubitril/valsartan in RCTs and pharmacovigilance databases. A random-effects meta-analysis was performed with six RCTs investigating sacubitril/valsartan vs. control/comparators in heart failure patients. WHO’s VigiBase, FAERS, and EMA’s EudraVigilance were mined to obtain spontaneously reported real-world adverse events. Disproportionality analysis was performed with the FDA’s OpenVigil 2.0.

RESULTS: Six RCTs enrolled 15,538 patients with heart failure with reduced and preserved ejection fractions. There was no statistical difference for the composite of hypotension, renal dysfunction, hyperkalemia, and angioedema between sacubitril/valsartan and its comparators viz. ACEi or ARBs (OR 1.23, CI 0.98-1.56; p = 0.08). A total of 103,038 adverse events were registered in the spontaneous reporting systems. Hypotension was the most reported adverse event. Proportions of composite adverse events were 20% in VigiBase, 17% in FAERS, and 39% with EudraVigilance. Disproportionality analysis showed a lower risk of adverse events with sacubitril/valsartan than other guideline-directed heart failure medications used in clinical practice.

CONCLUSION: With increased uptake of sacubitril/valsartan, risks of hypotension, renal dysfunction, hyperkalemia, and angioedema appear low and acceptable in RCTs and global clinical practice.

PMID:34125356 | DOI:10.1007/s10557-021-07210-1

CVIR Endovasc. 2021 Jun 14;4(1):51. doi: 10.1186/s42155-021-00234-6.

ABSTRACT

BACKGROUND: This study aimed to assess the error of different registration techniques and imaging modalities for fusion imaging of the aorta in a standardized setting using a anthropomorphic body phantom.

MATERIALS AND METHODS: A phantom with the 3D printed vasculature of a patient suffering from an infrarenal aortic aneurysm was constructed. Pulsatile flow was generated via an external pump. CTA/MRA of the phantom was performed, and a virtual 3D vascular model was computed. Subsequently, fusion imaging was performed employing 3D-3D and 2D-3D registration techniques. Accuracy of the registration was evaluated from 7 right/left anterior oblique c-arm angulations using the agreement of centerlines and landmarks between the phantom vessels and the virtual 3D virtual vascular model. Differences between imaging modalities were assessed in a head-to-head comparison based on centerline deviation. Statistics included the comparison of means ± standard deviations, student’s t-test, Bland-Altman analysis, and intraclass correlation coefficient for intra- and inter-reader analysis.

RESULTS: 3D-3D registration was superior to 2D-3D registration, with the highest mean centerline deviation being 1.67 ± 0.24 mm compared to 4.47 ± 0.92 mm. The highest absolute deviation was 3.25 mm for 3D-3D and 6.25 mm for 2D-3D registration. Differences for all angulations between registration techniques reached statistical significance. A decrease in registration accuracy was observed for c-arm angulations beyond 30° right anterior oblique/left anterior oblique. All landmarks (100%) were correctly positioned using 3D-3D registration compared to 81% using 2D-3D registration. Differences in accuracy between CT and MRI were acceptably small. Intra- and inter-reader reliability was excellent.

CONCLUSION: In the realm of registration techniques, the 3D-3D method proved more accurate than did the 2D-3D method. Based on our data, the use of 2D-3D registration for interventions with high registration quality requirements (e.g., fenestrated aortic repair procedures) cannot be fully recommended. Regarding imaging modalities, CTA and MRA can be used equivalently.

PMID:34125287 | DOI:10.1186/s42155-021-00234-6

Graefes Arch Clin Exp Ophthalmol. 2021 Jun 14. doi: 10.1007/s00417-021-05257-2. Online ahead of print.

ABSTRACT

PURPOSE: To compare surgical outcomes between patients who underwent Baerveldt glaucoma implantation versus trabeculectomy (TLE) for the treatment of neovascular glaucoma.

METHODS: We performed a prospective, randomized, controlled clinical trial at Hiroshima University and Tsukazaki Hospital, Japan. Patients were randomized to Baerveldt glaucoma implantation (23 patients) or TLE (27 patients). The primary outcome measure was the rate of intraocular-pressure control. Secondary outcome measures included complications and interventions. We defined “failure” as intraocular pressure ≥ 22 mmHg or < 20% reduction from baseline pressure, on two consecutive follow-up visits; need for additional glaucoma surgery; vision-threatening complications; or loss of light perception. Kaplan-Meier analysis was used to determine surgical success rates. Postoperative complications and interventions were compared between the two groups with Pearson Chi-square tests.

RESULTS: There were no significant differences in demographic or ocular characteristics between the treatment groups at baseline. The postoperative follow-up was 26.6 ± 19.4 months in the Baerveldt group and 27.3 ± 20.1 months in the TLE group. There were no statistical differences (Mann-Whitney nonparametric tests with Bonferroni correction) in postoperative intraocular pressure measured at 6-month intervals. Success rates were 59.1 and 61.6% at 1-year after Baerveldt glaucoma implantation and TLE, respectively. Kaplan-Meier analysis showed no significant difference in success between groups (P = 0.71, log-rank test). Medication use, visual acuity, and interventions were similar between groups. Thirteen late postoperative complications developed in the Baerveldt glaucoma implantation group and four complications developed in the TLE group. Tube exposure was the most common late complication.

CONCLUSION: These two procedures produced similar surgical success, intraocular-pressure reductions, visual acuity, and number of medications at the last visit. The TLE group showed smaller numbers of late complications and patients who lost more than two lines of visual acuity. Therefore, TLE might be a safer and better way to treat patients with neovascular glaucoma.

PMID:34125289 | DOI:10.1007/s00417-021-05257-2

Arch Orthop Trauma Surg. 2021 Jun 14. doi: 10.1007/s00402-021-03991-0. Online ahead of print.

ABSTRACT

INTRODUCTION: The risk factors for a second nonsimultaneous hip fracture are unclear, and in general, it is empirically assumed that they are similar to those associated with the first hip fracture. We aimed to determine the incidence of a second hip fracture and define the characteristics of the patients sustaining the event in a prospective cohort study in a Spanish population.

MATERIALS AND METHODS: We conducted a multicentric, prospective cohort study in a representative sample of 45 hospitals from 15 autonomic regions in Spain. In total, the study included 994 patients. One hundred and one patients presented a nonsimultaneous contralateral hip fracture, constituting the intervention group. The remaining 893 patients presenting with a hip fracture formed the control group. The main outcome measures of this study were sociodemographic characteristics of the patient, comorbid conditions, and baseline and postfracture clinical outcomes (inpatient complications and acute mortality).

RESULTS: The key fracture risk factors were a history of fragility fractures, the need for assistance when walking outdoors and a history of falls. There were no associations between the groups in any of the common fragility risk factors, including rheumatoid arthritis, secondary osteoporosis, or steroid consumption. The results showed that patients suffering a nonsimultaneous hip fracture had an increased risk of mortality after discharge compared with the control group.

CONCLUSION: A nonsimultaneous second hip fracture leads to a near-significant increase in four-month mortality. In our study, this fracture was associated with a history of falls, prior fragility fractures, and the need for a walking aid.

PMID:34125250 | DOI:10.1007/s00402-021-03991-0

J Neurol. 2021 Jun 14. doi: 10.1007/s00415-021-10635-1. Online ahead of print.

ABSTRACT

OBJECTIVE: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare disease characterized by rapid neuropathic progression. In pivotal studies of gene-silencing treatments, the modified Neuropathy Impairment Score + 7 tests (mNIS + 7) and Norfolk-Quality of Life (QOL)-Diabetic Neuropathy (DN) questionnaire assessed treatment impact on neuropathic progression. Establishing responder definition (RD) thresholds for these measures would enable evaluation of clinically meaningful treatment benefit.

METHODS: mNIS + 7 and Norfolk-QOL-DN were administered at baseline and week 65 to 165 adults with ATTRv-PN receiving inotersen (n = 106) or placebo (n = 59) in the NEURO-TTR study. Anchor-based approaches for estimating RD thresholds were used for Norfolk QOL-DN, while distribution-based approaches were used for both measures. Responders were patients with a score change < RD, indicating improvement or stabilization (i.e., no clinically meaningful progression). Odds ratios (ORs) and Fisher’s exact tests compared proportions of responders by treatment.

RESULTS: The mean RD estimates were 12.2 points and 8.8 points for mNIS + 7 and Norfolk QOL-DN, respectively. The proportions of patients whose change in score indicated improvement or stabilization were statistically significantly larger for inotersen than placebo for all estimated RD thresholds for mNIS + 7 (64-86% responders for inotersen vs. 27-46% for placebo, ORs = 3.8-7.2, ps < 0.001) and Norfolk QOL-DN (66-81% vs. 35-56%, ORs = 2.4-3.6, ps < 0.05).

DISCUSSION: Establishing RD thresholds for these instruments enables evaluation of clinically relevant and individual-level treatment benefit on neuropathic progression. Across RDs estimated using multiple methods, a higher proportion of patients receiving inotersen than placebo showed improved or stabilized neuropathic progression at week 65.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01737398; Date of registration: November 29, 2012.

PMID:34125267 | DOI:10.1007/s00415-021-10635-1

Eur Arch Otorhinolaryngol. 2021 Jun 14. doi: 10.1007/s00405-021-06937-9. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to investigate the changes in voice nasality after septoplasty and turbinate hypertrophy reduction and to evaluate the effect of these changes on patients’ voice-related quality of life.

METHODS: Sixty patients with nasal obstruction symptoms caused by septal deviation and inferior turbinate hypertrophy who underwent septoplasty and inferior turbinate hypertrophy reduction and 25 healthy controls were included. Active anterior rhinomanometry and acoustic rhinometry were utilized for the evaluation of nasal patency and nasometry was used for quantitative assessment of nasalance. All participants completed validated questionnaires for assessing nasal obstruction symptom severity, psychological status and the impact of voice performance on their quality of life preoperatively and 6 months after septoplasty.

RESULTS: Patients presented preoperatively statistically significantly lower nasalance scores and higher VHI scores than controls (p < 0.05). Septoplasty and inferior turbinate hypertrophy reduction led to improvement of nasalance for the nasal text and the physical subscale of the VHI scores. Postoperatively, there were no statistically significant differences in nasalance and VHI scores between patients and controls. Significant correlations were found only for the baseline and the postoperative nasalance scores for the nasal text and the total nasal cavity volume (p < 0.05). Postoperatively, patients who presented significant improvement of nasal obstruction symptoms and resolution of stress levels were more likely to positively evaluate the impact of their voice quality on their daily life (OR: 2.32, 95% CI 1.08-5.15, p = 0.041 and OR: 3.06, 95% CI 1.15-7.04, p = 0.038, respectively).

CONCLUSION: Septoplasty and inferior turbinate hypertrophy reduction may increase the nasal resonance, but in the long term, this change appears not to be significant enough. The severity of nasal obstruction symptoms and psychological status mainly affect the patients’ perceptual assessment regarding the effect of voice performance on their quality of life.

PMID:34125283 | DOI:10.1007/s00405-021-06937-9