Nevin Manimala Statistics

Increased alpha-band connectivity during tic suppression in children with Tourette syndrome revealed by source EEG analyses

Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 May 12:S2451-9022(21)00140-3. doi: 10.1016/j.bpsc.2021.05.001. Online ahead of print.


BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder involving chronic motor and phonic tics. Most individuals with Tourette syndrome can suppress their tics for at least a short period of time. Yet, the brain correlates of tic suppression are still poorly understood.

METHODS: In the current study, high-density electroencephalography (EEG) was recorded during a resting-state and a tic suppression session in 72 children with TS. Functional connectivity between cortical regions was assessed in the alpha band (8-13 Hz) using an EEG source connectivity method. Graph theory and network-based statistics were used to assess the global network topology and to identify brain regions showing increased connectivity during tic suppression.

RESULTS: Graph theoretical analyses revealed distinctive global network topology during tic suppression, relative to rest. Using network-based statistics, we found a subnetwork of increased connectivity during tic suppression (p < .001). That subnetwork encompassed many cortical areas, including the right superior frontal gyrus and the left precuneus, which are involved in the default mode network. We also found a condition by age interaction, suggesting age-mediated increases in connectivity during tic suppression.

CONCLUSIONS: These results suggest that children with TS suppress their tics through a brain circuit involving distributed cortical regions, many of which are part of the default mode network. Brain connectivity during tic suppression also increases as youths with TS mature. These results highlight a mechanism by which children with TS may control their tics, which could be relevant for future treatment studies.

PMID:33991741 | DOI:10.1016/j.bpsc.2021.05.001

Nevin Manimala Statistics

Identification of differential DNA methylation associated with multiple sclerosis: A family-based study

J Neuroimmunol. 2021 Apr 30;356:577600. doi: 10.1016/j.jneuroim.2021.577600. Online ahead of print.


Multiple Sclerosis (MS) is caused by a still unknown interplay between genetic and environmental factors. Epigenetics, including DNA methylation, represents a model for environmental factors to influence MS risk. Twenty-six affected and 26 unaffected relatives from 8 MS multiplex families were analysed in a multicentric Italian study using MeDIP-Seq, followed by technical validation and biological replication in two additional families of differentially methylated regions (DMRs) using SeqCap Epi Choice Enrichment kit (Roche®). Associations from MeDIP-Seq across families were combined with aggregation statistics, yielding 162 DMRs at FDR ≤ 0.1. Technical validation and biological replication led to 2 hypo-methylated regions, which point to NTM and BAI3 genes, and to 2 hyper-methylated regions in PIK3R1 and CAPN13. These 4 novel regions contain genes of potential interest that need to be tested in larger cohorts of patients.

PMID:33991750 | DOI:10.1016/j.jneuroim.2021.577600

Nevin Manimala Statistics

Metabolites from mid-trimester plasma of pregnant patients at high-risk for preterm birth

Am J Obstet Gynecol MFM. 2021 May 12:100393. doi: 10.1016/j.ajogmf.2021.100393. Online ahead of print.


BACKGROUND: There is an increased awareness regarding the association between exposure to environmental contaminants and adverse pregnancy outcomes including preterm birth. Whether an individual’s metabolic profile can be utilized during pregnancy to differentiate the subset of patients who are ultimately destined to deliver preterm remains uncertain but could have significant clinical implications.

OBJECTIVE: We sought to objectively quantify metabolomic profiles of patients at high risk for preterm birth by evaluating mid-trimester maternal plasma, and to measure whether endogenous metabolites and exogenous environmental substances differ among those who ultimately deliver preterm compared to those who deliver at term.

STUDY DESIGN: This was a case-control analysis from a prospective cohort of patients carrying a singleton, non-anomalous gestation who were at high risk for spontaneous preterm birth. Subjects with a plasma blood sample drawn <28 weeks’ gestation and no evidence of preterm labor at the time of enrollment were included. Metabolites were extracted from frozen samples and metabolomic analysis was performed using liquid chromatography/mass spectrometry. The primary outcome was preterm birth 16.0-36.9 weeks’ gestation.

RESULTS: 42 patients met inclusion criteria. Of these, 25 (59.5%) delivered preterm <37 weeks’ gestation, at a median 30.14 [interquartile range 28.14 – 34.14] weeks’ gestation. Eight-hundred and twelve molecular features differed between preterm birth cases and term controls with a minimum fold change of 1.2 and p-value <0.05. Of these, 570/812 (70.1%) were found in higher abundances in preterm birth cases; the other 242/812 (29.9%) were in higher abundance in term birth controls. The identity of the small molecule/compound represented by the molecular features differing statistically between preterm birth cases and term controls were identified as ranging from those involved with endogenous metabolic pathways (including lipid catabolism, steroids, and steroid-related molecules) to exogenous exposures (including avocadyne, diosgenin, polycyclic aromatic hydrocarbons, acetaminophen metabolites, aspartame, and caffeine). Random forest analyses evaluating the relative contribution of each of the top 30 compounds in differentiating preterm birth and term controls accurately classified 21/25 (84%) of preterm birth cases.

CONCLUSION: Both endogenous metabolites and exogenous exposures differ in maternal plasma in the mid-trimester among patients who ultimately delivered preterm compared with those who deliver at term.

PMID:33991707 | DOI:10.1016/j.ajogmf.2021.100393

Nevin Manimala Statistics

Relapse protection following early CMV reactivation after HSCT is limited to HLA-C KIR ligand homozygous recipients

Transplant Cell Ther. 2021 May 12:S2666-6367(21)00889-7. doi: 10.1016/j.jtct.2021.04.028. Online ahead of print.


BACKGROUND: While the risk for non-relapse mortality (NRM) associated with early cytomegalovirus (CMV) reactivation (CMVR) after allogeneic hematopoietic stem cell transplantation (HSCT) is well established, debate is ongoing on whether CMVR may reduce the risk of primary disease relapse.

OBJECTIVE: Relapse protection following early CMV reactivation after HSCT in the context of the HLA-C KIR ligands of the recipients.

STUDY DESIGN: In this retrospective, bi-centric study, 406 matched-related or unrelated transplants for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) were stratified by HLA-C KIRL groups (homozygous versus heterozygous) and were separately analyzed for the impact of early CMVR on the cumulative incidence of relapse, non-relapse mortality (NRM), acute and chronic graft-versus-host-disease (GVHD), using landmark and multi-state analyses.

RESULTS: By landmark analysis of patients alive and relapse-free 45 days post-HSCT, HLA-C KIRL homozygous recipients (C1/1 or C2/2) had a lower risk of subsequent relapse if CMVR occurred before this landmark (sub-hazard ratio (sHR) 0.36; P=0.002). By contrast, in HLA-C KIRL heterozygous (C1/2) recipients, early CMVR had no impact on subsequent relapse (sHR 0.88; P=0.63). In the homozygous cohort, NRM (sHR 3.31; P<0.001), and aGVHD 3-4 (sHR 2.60; P=0.04) were significantly increased after early CMVR, but not so in the heterozygous group (sHR 1.23; P=0.53, and sHR 1.40; P=0.50). Multivariable landmark analyses and a multi-state model confirmed the limitation of the relapse-protective effect of early CMVR to the homozygous cohort. Chronic GVHD and overall survival were not influenced in neither cohort.

CONCLUSION: An antileukemic effect of early CMVR after HSCT for AML/MDS was significant, but strictly limited to recipients homozygous for HLA-C KIRL. However, particularly in this cohort, CMVR had an adverse impact on aGVHD and NRM.

PMID:33991724 | DOI:10.1016/j.jtct.2021.04.028

Nevin Manimala Statistics

Use of the angiogenic biomarker profile to risk stratify patients with fetal growth restriction

Am J Obstet Gynecol MFM. 2021 May 12:100394. doi: 10.1016/j.ajogmf.2021.100394. Online ahead of print.


BACKGROUND: Novel angiogenic biomarker profiles have demonstrated emerging evidence for predicting preeclampsia onset, severity, and adverse outcomes. Limited data exists in screening patients with fetal growth restriction for preeclampsia development using angiogenic biomarkers.

OBJECTIVE: The objective of this study was to risk stratify patients with fetal growth restriction using a soluble fms-like tyrosine kinase-1 (sFlt1) to placental growth factor (PlGF) ratio. Previously published cutoff of 38 was used to predict preeclampsia development and severity as well as adverse maternal or neonatal outcomes within a two-week time period.

STUDY DESIGN: This was a prospective observational cohort study carried out in a single tertiary hospital. Patients with a singleton fetal growth restriction pregnancy between 24 and 37 weeks gestation were evaluated using serial two-week encounters from the time of enrollment until delivery. Pregnancies with proven genetic or infectious etiology of fetal growth restriction or congenital anomalies were excluded. Ultrasound growth and Doppler measurements were obtained at the start of every encounter with routine preeclampsia labs and blood pressure checks when clinically indicated. Maternal serum was collected for all serial encounters and measured for sFlt1 and PlGF after delivery in a double blinded fashion. Maternal charts were reviewed for baseline demographic characteristics, pregnancy diagnoses and outcomes, and neonatal outcomes.

RESULTS: A total of 45 patients were enrolled for a total of 77 encounters, with the median (quartile 1, quartile 3) gestational age of the study enrolled at 31.43 (28.14, 33.57) weeks. Patients were divided into low risk (ratio < 38) and high risk (ratio ≥ 38) groups. Baseline characteristics of patients did not show any significant differences, including preeclampsia labs or ultrasound parameters, between the two groups. Systolic and diastolic blood pressures upon enrollment were statistically elevated when sFlt1/PlGF ≥ 38 (p = 0.02 and p = 0.01, respectively). Compared to patients with a low ratio, patients with a high ratio had a greater proportion of preeclampsia diagnosis, higher rates of preterm delivery under 34 and 37 weeks of gestation, smaller neonatal birthweight, and a smaller time to delivery from testing to delivery.

CONCLUSIONS: Among patients with fetal growth restriction, the sFlt1/PlGF ratio may serve as a potential biomarker for identifying at risk patients for developing preeclampsia and subsequently preterm delivery.

PMID:33991706 | DOI:10.1016/j.ajogmf.2021.100394

Nevin Manimala Statistics

State of the art in breast intraoperative electron radiation therapy after intraoperative ultrasound introduction

Radiol Oncol. 2021 May 16. doi: 10.2478/raon-2021-0023. Online ahead of print.


BACKGROUND: Breast intraoperative electron radiation therapy (B-IOERT) can be used in clinical practice both as elective irradiation (partial breast irradiation – APBI) in low risk breast cancer patients, and as an anticipated boost. The procedure generally includes the use of a shielding disk between the residual breast and the pectoralis fascia for the protection of the tissues underneath the target volume. The aim of the study was to evaluate the role of intraoperative ultrasound (IOUS) in improving the quality of B-IOERT.

PATIENTS AND METHODS: B-IOERT was introduced in Trieste in 2012 and its technique was improved in 2014 with IOUS. Both, needle and IOUS were used to measure target thickness and the latter was used even to check the correct position of the shielding disk. The primary endpoint of the study was the evaluation of the effectiveness of IOUS in reducing the risk of a disk misalignment related to B-IOERT and the secondary endpoint was the analysis of acute and late toxicity, by comparing two groups of patients treated with IOERT as a boost, either measured with IOUS and needle (Group 1) or with needle alone (Group 2). Acute and late toxicity were evaluated by validated scoring systems.

RESULTS: From the institutional patients who were treated between June 2012 and October 2019, 109 were eligible for this study (corresponding to 110 cases, as one patients underwent bilateral conservative surgery and bilateral B-IOERT). Of these, 38 were allocated to group 1 and 72 to group 2. The target thickness measured with the IOUS probe and with the needle were similar (mean difference of 0.1 mm, p = 0.38). The percentage of patients in which the shield was perfectly aligned after IOUS introduction increased from 23% to more than 70%. Moreover, patients treated after IOUS guidance had less acute toxicity (36.8% vs. 48.6%, p = 0.33) from radiation therapy, which reached no statistical significance. Late toxicity turned out to be similar regardless of the use of IOUS guidance: 39.5% vs. 37.5% (p = 0.99).

CONCLUSIONS: IOUS showed to be accurate in measuring the target depth and decrease the misalignment between collimator and disk. Furthermore there was an absolute decrease in acute toxicity, even though not statistically significant, in the group of women who underwent B-IOERT with IOUS guidance.

PMID:33991470 | DOI:10.2478/raon-2021-0023

Nevin Manimala Statistics

Sex Differences Among Patients With High Risk Receiving Ticagrelor With or Without Aspirin After Percutaneous Coronary Intervention: A Subgroup Analysis of the TWILIGHT Randomized Clinical Trial

JAMA Cardiol. 2021 May 15. doi: 10.1001/jamacardio.2021.1720. Online ahead of print.


IMPORTANCE: Shortened dual antiplatelet therapy followed by potent P2Y12 receptor inhibitor monotherapy reduces bleeding without increasing ischemic events after percutaneous coronary intervention (PCI).

OBJECTIVE: To explore sex differences and evaluate the association of sex with outcomes among patients treated with ticagrelor monotherapy vs ticagrelor plus aspirin.

DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of TWILIGHT, an investigator-initiated, placebo-controlled randomized clinical trial conducted at 187 sites across 11 countries. Study participants included patients who underwent successful PCI with drug-eluting stents, were planned for discharge with ticagrelor plus aspirin, and who had at least 1 clinical and at least 1 angiographic feature associated with high risk of ischemic or bleeding events. Data were analyzed from May to July 2020.

INTERVENTIONS: At 3 months after PCI, patients adherent to ticagrelor and aspirin without major adverse event were randomized to either aspirin or placebo for an additional 12 months along with ticagrelor.

MAIN OUTCOMES AND MEASURES: The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 12 months after randomization. The primary ischemic end point was a composite of death, myocardial infarction, or stroke.

RESULTS: Of 9006 enrolled patients, 7119 underwent randomization (mean [SD] age, 63.9 [10.2] years; 5421 [76.1%] men). Women were older (mean [SD] age, 65.5 [9.6] years in women vs 63.4 [10.3] years in men) with higher prevalence of chronic kidney disease (347 women [21.2%] vs 764 men [14.7%]). The primary bleeding end point occurred more often in women than men (hazard ratio [HR], 1.32; 95% CI, 1.06-1.64; P = .01). After multivariate adjustment, incremental bleeding risk associated with female sex was no longer significant (adjusted HR, 1.20; 95% CI, 0.95-1.52; P = .12). Ischemic end points were similar between sexes. Ticagrelor plus placebo vs ticagrelor plus aspirin was associated with lower risk of BARC type 2, 3, or 5 bleeding in women (adjusted HR, 0.62; 95% CI, 0.42-0.92; P = .02) and men (adjusted HR, 0.57; 95% CI, 0.44-0.73; P < .001; P for interaction = .69). Ischemic end points were similar between treatment groups in both sexes.

CONCLUSIONS AND RELEVANCE: These findings suggest that the higher bleeding risk in women compared with men was mostly attributable to baseline differences, whereas ischemic events were similar between sexes. In this high-risk PCI population, the benefits of early aspirin withdrawal with continuation of ticagrelor were generally comparable in women and men.

TRIAL REGISTRATION: Identifier: NCT02270242.

PMID:33991416 | DOI:10.1001/jamacardio.2021.1720

Nevin Manimala Statistics

The use of statistical modelling to identify important parameters for the shape of the torso following surgery for adolescent idiopathic scoliosis

J Anat. 2021 May 15. doi: 10.1111/joa.13454. Online ahead of print.


The surgical strategy in adolescent idiopathic scoliosis (AIS) aims to recreate the symmetry of the torso. This requires the minimisation of both the size of the scoliosis and the angulation between the sides of the torso, along with the recreation of a normal thoracic kyphosis. This study uses predictive modelling to identify the significance of the value of the pre-operative parameters, and the change in the magnitude of the parameters as a result of an operation on the shape of the torso using the ‘most prominent points’; two areas of maximum prominence on either side of the spine with x, y and z coordinates. The pre-operative values, and the change in magnitude between the pre and post-operative values, for scoliosis, kyphosis and skin angulation from a group of Lenke 1 convex to the right AIS were analysed with measures collected using Integrated Spine Imaging System 2 surface topography and compared with those without visible spinal deformity. The models best explained the z coordinate and least well explained the x coordinate, although there was a contribution to all of the models that remained unexplained. The parameters that affected the position of the coordinates in the model differed between the models. This confirms that surgically altering the shape of the spine and torso whilst correcting an AIS does not lead to a symmetrical torso. There are as yet, undefined factors which contribute to the shape of the torso and which if identified and corrected surgically would lead to greater symmetry post-operatively.

PMID:33991430 | DOI:10.1111/joa.13454

Nevin Manimala Statistics

COVID-19 among children with cancer in Greece (2020): Results from the Nationwide Registry of Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)

Pediatr Blood Cancer. 2021 May 15:e29079. doi: 10.1002/pbc.29079. Online ahead of print.


PMID:33991383 | DOI:10.1002/pbc.29079

Nevin Manimala Statistics

Do natural ingredients in a dentifrice contribute to prevention of plaque and gingivitis?

Int J Dent Hyg. 2021 May 15. doi: 10.1111/idh.12517. Online ahead of print.


OBJECTIVE: To test the effectiveness of a dentifrice containing the turmeric and licorice extract compared to a control for preventing plaque and gingivitis over a four-month period.

MATERIAL AND METHODS: Ninety (non-dental) participants with moderate gingival inflammation(≥40%) were selected. The triple blind study consisted of two phases, namely at first a 3-week pre-experimental phase of using an oxygenating and chlorhexidine (CHX) mouthrinse. Secondly, a 4-months experimental period in which participants were randomly assigned to a test or control group. All were instructed to brush their teeth twice daily for 2 minutes with their assigned dentifrice. Gingival bleeding(BI), plaque(PI) and gingivitis(GI) were assessed.

RESULTS: Eighty participants completed the protocol. At the first assessment in the pre-experimental phase, the mean scores of all indices showed no differences for the two groups. At the second session, the values of all three parameters had decreased significantly (p<0.001). At the last session the BI values were 0.52(0.25) for the test group and 0.56(0.25) for the control, the mean GI was 0.27(0.17) for the test group and 0.31 0.16) for the control, and for PI the scores were 1.89(0.46) for the test group and 1.98(0.43) for the control group. Statistical comparison of the scores for the two groups at each stage of the study showed no significant difference for any of the parameters.

CONCLUSION: Within the limits of the current study design, dentifrice formulation and concentration of turmeric/licorice extracts the results show that the adjuvant effect of the natural ingredients in the test dentifrice was not evident on clinical parameters of gingivitis and plaque.

PMID:33991392 | DOI:10.1111/idh.12517