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Nevin Manimala Statistics

Radiofrequency ablation turbinoplasty improves the sense of smell in pediatric patients: A prospective study

Int J Pediatr Otorhinolaryngol. 2021 Oct 5;150:110935. doi: 10.1016/j.ijporl.2021.110935. Online ahead of print.

ABSTRACT

INTRODUCTION: The olfactory sense is of paramount importance for the adequate development of a child. Olfactory loss in children might have different origins. One of the most common is conductive, when nasal obstruction prevents odorants from reaching the olfactory epithelium. Rhinitis and turbinate enlargement have been proven to diminish the sense of smell in pediatric patients. A common treatment for resistant rhinitis in these patients is turbinate radiofrequency ablation (TRA). However, despite an increasing research effort in this field, there are no studies instrumentally assessing olfaction in children undergoing turbinate surgery to date. This study was designed with the aim of assessing changes in olfaction through validated instrumental tools in pediatric patients undergoing TRA for the first time.

METHODS: A prospective uncontrolled intervention clinical trial design was conducted. Two cohorts of children ranging 4-15 years old were consecutively selected from a third level referral Hospital and subjected to the universal sniff test (U-Sniff), alcohol sniff test (AST), and sniffin sticks threshold test (SST) before and 1, 3 and 6 months after surgery. Cohort A consisted of children solely undergoing TRA. Cohort B consisted of children on whom adenoidectomy and TRA had been performed. Additionally, a cohort of Spanish healthy controls, paired by sex and age, were asked to perform the U-Sniff.

RESULTS: A total of 81 participants with a mean age of 10.31 ± 2.56 years were included. Fifty-three patients underwent TRA exclusively and 28 were subjected to associated adenoidectomy. Despite a tendency toward improvement in the U-sniff scores, there were no statistically significant differences after surgery. However, statistically significant differences were obtained for threshold tasks measured with SST and AST, revealing differences at 1, 3 and 6 months after surgery compared to preoperative scores.

CONCLUSIONS: In summary, this research demonstrated adequate levels in the sense of smell regarding identification tasks, but decreased olfactory threshold scores in pediatric patients suffering from TE. TRA, alone or with adenoidectomy, improved smell threshold scores, but had no significant effect on identification tasks.

PMID:34649156 | DOI:10.1016/j.ijporl.2021.110935

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Plasma acyl-carnitines, bilirubin, tyramine and tetrahydro-21-deoxycortisol in Parkinson’s disease and essential tremor. A case control biomarker study

Parkinsonism Relat Disord. 2021 Sep 21;91:167-172. doi: 10.1016/j.parkreldis.2021.09.014. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Given the overlapping clinical manifestations and pathology, the differentiation between essential tremor (ET) and Parkinson’s disease (PD) is difficult. Our aims were to examine the plasma metabolomics profiling and their association with motor and non-motor symptoms (NMS) in patients with PD, and to determine differences between de novo PD compared to moderate-advanced PD vs. controls and patients with ET.

METHODS: Plasma samples were collected from 137 subjects including 35 age matched controls, 29 NOVO-PD, 35 PD and 38 ET patients. PD severity, motor and NMS including cognitive function were assessed using the UPDRS, NMS and PD cognitive rating scales, respectively. Metabolomics analysis was performed by UPLC-ESI-QToF-MS followed by unsupervised multivariate statistics. The area under the curve of the biomarkers according to distribution of their concentrations and the diagnosis of PD (NOVO-PD, advanced PD) vs ET and healthy controls was used as a measurement of diagnostic ability.

RESULTS: Several acyl-carnitines, bilirubin, tyramine and tetrahydro-21-deoxycortisol (THS) presented good predictive accuracy (AUC higher than 0.8) for differentiating de novo PD and advanced PD from controls and ET, suggesting an alteration in the lipid oxidation pathway. In multivariate regression analysis, metabolite levels were not significantly associated with motor and NMS severity in PD.

CONCLUSIONS: Diverse acyl-carnitines, bilirubin, tyramine and some adrenal gland derived metabolites are suggested as potential biomarkers able to distinguish between PD from controls and ET.

PMID:34649109 | DOI:10.1016/j.parkreldis.2021.09.014

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A risk score for prediction of symptomatic intracerebral haemorrhage following thrombolysis

Int J Med Inform. 2021 Sep 21;156:104586. doi: 10.1016/j.ijmedinf.2021.104586. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Intravenous recombinant tissue plasminogen activator (rt-PA) remains the only FDA approved pharmacological therapy for acute ischemic stroke (AIS), but this treatment is associated with symptomatic intracerebral haemorrhage (SICH). The aim of this study was to derive and validate an accurate measure of SICH risk in ischemic stroke patients treated with rt-PA using data readily available from patient clinical records.

METHODS: Demographics, physiological parameters, and clinical data were obtained from 1,270 ischemic stroke patients treated with thrombolysis at 20 hospitals. This included age, sex, weight, blood pressure, glucose levels, smoking preferences, and presence of previous clinical conditions. Using a bivariate analysis on a training dataset of 890 patients, SICH cases were compared against SICH-free patients and key risk factors associated with SICH were identified. Continuous variables were stratified using k-means clustering, and odds ratios computed for each of the categorical risk factors employed in the risk score. The SICH risk score, which was assessed using an independent validation dataset comprising 380 patients, was defined between 0 and 53, and stratified into 4 categories: very low risk (0-6), low risk (7-12), moderate risk (13-19), and high risk (>20).

RESULTS: Older age (age > 75 years), higher blood pressure, higher severity of stroke, pre-treatment antithrombotic and history of hypertension and hyperlipidaemia, were shown to be significant risk factors for SICH following rt-PA treatment (p < 0.05). A number of interaction effects with age produced greater overall SICH risk than that of individual variables alone, including age*weight, age*NIHSS, age*diastolic blood pressure, and age*hypertension. The SICH prediction tool demonstrated a C-statistic of 0.75 for continuous risk scoring (0-53) and 0.71 for stratified risk levels.

CONCLUSION: A novel, computationally efficient risk score utilising data readily available from patient clinical records was shown to predict SICH risk following thrombolysis treatment with high accuracy. This tool may be useful for pre-screening patients for SICH risk to reduce the morbidity and mortality associated with thrombolysis treatment.

PMID:34649112 | DOI:10.1016/j.ijmedinf.2021.104586

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Pattern-based colorimetric sensor array to monitor food spoilage using automated high-throughput analysis

Biosens Bioelectron. 2021 Oct 6;196:113687. doi: 10.1016/j.bios.2021.113687. Online ahead of print.

ABSTRACT

Despite the existing rapid and reliable analytical methods for determining biogenic amine in food matrices, recently special efforts have been devoted for development of portable and inexpensive devices for discrimination of biogenic amines (BAs) in food products to achieve onsite detection of food-spoilage. Thus, in this context, a field deployable cross-reactive sensor array and a field-portable array reader has been developed for determination of food quality. The sensor array consisting of metal complexes (C1 – C11) of single azophenol dye-based receptor generated a unique visible response on interaction with different amines (A1 – A7). Further, the colorimetric pattern and discrimination efficacy of the sensor array was evaluated using multivariate statistical techniques such as principal component analysis and linear discriminant analysis. Motivated by outstanding discriminatory power of sensor array, titration experiment was performed with BAs, and colorimetric response of array was linearly corelated to concentrations of BAs such as tryptamine and spermine with R2 values of 0.9596 and 0.967 respectively. Finally, for practical utility and the field analysis, a portable reader was developed and utilized for quantification of biogenic amines in meat and cottage cheese samples spiked with spermine and tryptamine up to the concentrations of 40 μM; therefore, apparently proving the potential applicability of the designed sensing method for food quality monitoring.

PMID:34649095 | DOI:10.1016/j.bios.2021.113687

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Increased functional connectivity in a population at risk of developing Parkinson’s disease

Parkinsonism Relat Disord. 2021 Oct 6;92:1-6. doi: 10.1016/j.parkreldis.2021.09.026. Online ahead of print.

ABSTRACT

BACKGROUND: While the concept of prodromal Parkinson’s disease (PD) is well established, reliable markers for the diagnosis of this disease stage are still lacking. We investigated the functional connectivity of the putamina in a resting-state functional MRI analysis in persons with at least two prodromal factors for PD, which is considered a high risk for PD (HRPD) group, in comparison to PD patients and controls.

METHODS: We included 16 PD patients, 20 healthy controls and 20 HRPD subjects. Resting state echo planar images and anatomical T1-weighted images were acquired with a Siemens Prisma 3 T scanner. The computation of correlation maps of the left and the right putamen to the rest of the brain was done in a voxel-wise approach using the REST toolbox. Finally, group differences in the correlation maps were compared on voxel-level and summarized in cluster z-statistics.

RESULTS: Compared to both PD patients and healthy controls, the HRPD group showed higher functional connectivity of both putamina to brain regions involved in execution of motion and coordination (cerebellum, vermis, pre- and postcentral gyrus, supplementary motor area) as well as the planning of movement (precuneus, cuneus, superior medial frontal lobe).

CONCLUSIONS: Higher functional connectivity of the putamina of HRPD subjects to other brain regions involved in motor execution and planning may indicate a compensatory mechanism. Follow-up evaluation and independent longitudinal studies should test whether our results reflect a dynamic process associated with a prodromal PD state.

PMID:34649107 | DOI:10.1016/j.parkreldis.2021.09.026

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Superficial placement of endotracheal tubes associated with unplanned extubation: A case-control study

J Crit Care. 2021 Oct 11;67:39-43. doi: 10.1016/j.jcrc.2021.09.010. Online ahead of print.

ABSTRACT

INTRODUCTION: Unplanned extubations (UEs) refer to the inadvertent removal of endotracheal tubes (ETTs). Superficially placed ETTs anecdotally increases the risk of UEs. This study aims to assess the impact of ETT position as well as other factors that could be associated with risk of UEs.

METHOD: A retrospective case-control study was conducted at NewYork-Presbyterian Queens Hospital from January 2017 to February 2020. All adults admitted to intensive care units (ICUs) who received mechanical ventilation (MV) through ETTs were screened to identify UEs. For each case with UE, two controls with planned extubation were identified. A multivariate logistic regression was conducted to identify risk factors associated with UEs.

RESULTS: 1100 patients received MV through ETTs during the time period. The incidence of UE was 4.9%. 53 patients with UEs and 106 patients with planned extubation were included for statistical analysis. Overall, patients with UE had higher in-hospital mortality rates (26.4% versus 11.3%, P = 0.02) and reintubation rates (28.3% versus 6.6%, P < 0.001). Within the UE group, patients who required reintubation had significantly higher in-hospital mortality rates than those who did not require reintubation (53.3% versus 15.8%, P = 0.005). Multivariate logistic regression showed higher APACHE II scores (Odds ratios (OR) 1.07; 95% Confidence interval (CI), 1 to 1.13), distance of ETT tips to carina ≥6 cm (OR 6.41; 95% CI, 1.1 to 37.3), physical restraint use (OR 2.98; 95% CI, 1.28 to 6.95) and continuous infusions of sedatives and/or analgesics (OR 10.72, 95% CI, 4.19 to 27.43) were associated with UE.

CONCLUSION: UE and the need for reintubation is associated with worse outcomes. Distance of ETT tips to carina ≥6 cm may be associated with higher risks of UE. Further prospective studies are needed to establish the optimal position of ETT to prevent UE.

PMID:34649093 | DOI:10.1016/j.jcrc.2021.09.010

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Comparing the performance of the palliative prognostic (PaP) score with clinical predictions of survival: A systematic review

Eur J Cancer. 2021 Oct 11;158:27-35. doi: 10.1016/j.ejca.2021.08.049. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with advanced cancer, prognosis is usually determined using clinicians’ predictions of survival (CPS). The palliative prognostic (PaP) score is a prognostic algorithm that was developed to predict survival in patients with advanced cancer. The score categorises patients into three risk groups in accordance with their probability of surviving for 30 days. The relative accuracy of PaP and CPS is unclear.

DESIGN: This was a systematic review of MEDLINE, Embase, AMED, CINAHL Plus and the Cochrane Database of Systematic Reviews and Trials from inception up to June 2021. The inclusion criteria were studies in adults with advanced cancer reporting data on performance of both PaP and CPS. Data were extracted on accuracy of prognoses and where available on discrimination (area under the receiver operating characteristic curve or C-index) and/or diagnostic performance (sensitivity, specificity).

RESULTS: Eleven studies were included. One study reported a direct comparison between PaP risk groups and equivalent risk groups defined by CPS and found that PaP was as accurate as CPS. Five studies reported discrimination of PaP as a continuous total score (rather than using the previously validated risk categories) and reported C-statistics that ranged from 0.64 (95% confidence interval [CI] 0.54, 0.74) up to 0.90 (95% CI 0.87, 0.92). Other studies compared PaP against CPS using non-equivalent metrics (e.g. comparing probability estimates against length of survival estimates).

CONCLUSIONS: PaP risk categories and CPS are equally able to discriminate between patients with different survival probabilities. Total PaP scores show good discrimination between patients in accordance with their length of survival. The role of PaP in clinical practice still needs to be defined.

TRIAL REGISTRATION: PROSPERO (CRD42021241074, 5th March 2021).

PMID:34649086 | DOI:10.1016/j.ejca.2021.08.049

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High RSK4 expression constitutes a predictor of poor prognosis for patients with clear cell renal carcinoma

Pathol Res Pract. 2021 Oct 2;227:153642. doi: 10.1016/j.prp.2021.153642. Online ahead of print.

ABSTRACT

BACKGROUND: This research focuses on exploring RSK4 protein expression within Clear Cell Renal Cell Carcinoma (ccRCC), based on these investigations on level of expressions coupled with the relevance to clinicopathologic features and clinical outcomes.

METHODS: The expression of RSK4 in 48 ccRCC and 20 hydronephrosis samples were under the detection of immunohistochemistry; besides, its relevance to the combination of clinicopathologic features with prognosis was committed in virtue of statistical approaches.

RESULTS: The 48 ccRCC samples included 36 (75%, 36/48) positive for RSK4, while the positive rate in hydronephrosis samples were 5 (25%, 5/20). Statistical analysis showed that RSK4 in ccRCC samples express higher expression the hydronephrosis samples (P < 0.05). Furthermore, the expression of RSK4 in ccRCC samples weren’t correlated with ages and genders (P > 0.05), while WHO/ISUP nucleolar grade harboured relevance to low survival rate (P = 0.018). Molecular researches demonstrated that over-expression of RSK4 was able to upgrade the proliferation capability of ccRCC cell lines.

CONCLUSIONS: According to the expression pattern and molecular systems featured RSK4 in ccRCCs, it performed the function of a latent independent prognostic factor performing the function of a newly built latent therapeutic aim oriented with the patients undergoing RCC. Moreover, the specific mechanism of action is expected to be revealed in the future research.

PMID:34649054 | DOI:10.1016/j.prp.2021.153642

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Toward Å-fs-meV resolution in electron microscopy: systematic simulation of the temporal spread of single-electron packets

Phys Chem Chem Phys. 2021 Oct 14. doi: 10.1039/d1cp03518e. Online ahead of print.

ABSTRACT

Though efforts to improve the temporal resolution of transmission electron microscopes (TEMs) have waxed and waned for decades, with relatively recent advances routinely reaching sub-picosecond scales, fundamental and practical challenges have hindered the advance of combined Å-fs-meV resolutions, particularly for core-loss spectroscopy and real-space imaging. This is due in no small part to the complexity of the approach required to access timescales upon which electrons, atoms, molecules, and materials first begin to respond and transform – attoseconds to picoseconds. Here we present part of a larger effort devoted to systematically mapping the instrument parameter space of a TEM modified to reach ultrafast timescales. With General Particle Tracer, we studied the statistical temporal distributions of single-electron packets as a function of various fs pulsed-laser parameters and electron-gun configurations and fields for the exact architecture and dimensions of a Thermo Fisher Tecnai Femto ultrafast electron microscope. We focused on easily-adjustable parameters, such as laser pulse duration, laser spot size, photon energy, Wehnelt aperture diameter, and photocathode size. In addition to establishing trends and dispersion behaviors, we identify regimes within which packet duration can be 100s of fs and approach the 300 fs laser limit employed here. Overall, the results provide a detailed picture of the temporal behavior of single-electron packets in the Tecnai Femto gun region, forming the initial contribution of a larger effort.

PMID:34648611 | DOI:10.1039/d1cp03518e

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Making a science out of preanalytics: An analytical method to determine optimal tissue fixation in real-time

PLoS One. 2021 Oct 14;16(10):e0258495. doi: 10.1371/journal.pone.0258495. eCollection 2021.

ABSTRACT

Modern histopathology is built on the cornerstone principle of tissue fixation, however there are currently no analytical methods of detecting fixation and as a result, in clinical practice fixation is highly variable and a persistent source of error. We have previously shown that immersion in cold formalin followed by heated formalin is beneficial for preservation of histomorphology and have combined two-temperature fixation with ultra-sensitive acoustic monitoring technology that can actively detect formalin diffusing into a tissue. Here we expand on our previous work by developing a predictive statistical model to determine when a tissue is properly diffused based on the real-time acoustic signal. We trained the model based on the morphology and characteristic diffusion curves of 30 tonsil cores. To test our model, a set of 87 different tonsil samples were fixed with four different protocols: dynamic fixation according to our predictive algorithm (C/H:Dynamic, N = 18), gold-standard 24 hour room temperature (RT:24hr, N = 24), 6 hours in cold formalin followed by 1 hour in heated formalin (C/H:6+1, N = 21), and 2 hours in cold formalin followed by 1 hour in heated formalin (C/H:2+1, N = 24). Digital pathology analysis revealed that the C/H:Dynamic samples had FOXP3 staining that was spatially uniform and statistically equivalent to RT:24hr and C/H:6+1 fixation protocols. For comparison, the intentionally underfixed C/H:2+1 samples had significantly suppressed FOXP3 staining (p<0.002). Furthermore, our dynamic fixation protocol produced bcl-2 staining concordant with standard fixation techniques. The dynamically fixed samples were on average only submerged in cold formalin for 4.2 hours, representing a significant workflow improvement. We have successfully demonstrated a first-of-its-kind analytical method to assess the quality of fixation in real-time and have confirmed its performance with quantitative analysis of downstream staining. This innovative technology could be used to ensure high-quality and standardized staining as part of an expedited and fully documented preanalytical workflow.

PMID:34648597 | DOI:10.1371/journal.pone.0258495