Category: Nevin Manimala

Epilepsia. 2021 Jul 12. doi: 10.1111/epi.16998. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to determine whether two commonly prescribed antiseizure medications (ASMs), levetiracetam (LEV) and oxcarbazepine (OXC), were associated with an increased risk of fragility fracture in children with epilepsy when initiating therapy during a crucial period of bone development, namely, pre- and midpuberty.

METHODS: Claims data from January 1, 2009 to December 31, 2018 were extracted from the Optum Clinformatics Data Mart. Children aged 4-13 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1-year baseline (e.g., pre-ASM exposure) and 4 years of follow-up. Children with epilepsy who were ASM naïve were grouped based on whether ASM treatment initiation included LEV or OXC. The comparison group included children without epilepsy and without ASM exposure. Crude incidence rate (IR; n per 1000 person-years) and IR ratio (IRR; with 95% confidence interval [CI]) were estimated for nontrauma fracture (NTFx), a claims-based proxy for fragility fracture, for up to 4 years of follow-up. Cox proportional hazards regression estimated the hazard ratio (HR; with 95% CI) after adjusting for demographic variables, motor impairment, and baseline fracture.

RESULTS: The crude IR (95% CI) of NTFx was 21.5 (21.2-21.8) for non-ASM-users without epilepsy (n = 271 346), 19.8 (12.3-27.2) for LEV (n = 358), and 34.4 (21.1-47.7) for OXC (n = 203). Compared to non-ASM-users, the crude IRR of NTFx was similar for LEV (IRR = .92, 95% CI = .63-1.34) and elevated for OXC (IRR = 1.60, 95% CI = 1.09-2.35); the crude IRR of NTFx was elevated for OXC compared to LEV (IRR = 1.74, 95% CI = 1.02-2.99). The findings were consistent after adjusting for covariates, except when comparing OXC to LEV (HR = 1.71, 95% CI = .99-2.93), which was marginally statistically insignificant (p = .053).

SIGNIFICANCE: Initiating OXC, but not LEV, therapy among 4-13-year-olds with epilepsy is associated with an elevated risk of fragility fracture. Studies are needed to determine whether these children could benefit from adjunct bone fragility therapies.

PMID:34250606 | DOI:10.1111/epi.16998

Eur J Neurosci. 2021 Jul 11. doi: 10.1111/ejn.15386. Online ahead of print.

ABSTRACT

Recent studies have proposed that one can summarize brain activity into dynamics among a relatively small number of hidden states and that such an approach is a promising tool for revealing brain function. Hidden Markov models (HMMs) are a prevalent approach to inferring such neural dynamics among discrete brain states. However, the impact of assuming Markovian structure in neural time series data has not been sufficiently examined. Here, to address this situation and examine the performance of the HMM, we compare the model with the Gaussian mixture model (GMM), which is with no temporal regularization and thus a statistically simpler model than the HMM, by applying both models to synthetic time series generated from empirical resting-state functional magnetic resonance imaging (fMRI) data. We compared the GMM and HMM for various sampling frequencies, lengths of recording per participant, numbers of participants, and numbers of independent component signals. We find that the HMM attains a better accuracy of estimating the hidden state than the GMM in a majority of cases. However, we also find that the accuracy of the GMM is comparable to that of the HMM under the condition that the sampling frequency is reasonably low (e.g., TR = 2.88 or 3.60 s) or the data is relatively short. These results suggest that the GMM can be a viable alternative to the HMM for investigating hidden-state dynamics under this condition.

PMID:34250639 | DOI:10.1111/ejn.15386

J Forensic Sci. 2021 Jul 12. doi: 10.1111/1556-4029.14791. Online ahead of print.

ABSTRACT

The current standard technique for cardiopulmonary resuscitation (CPR), initially described in the early 1960s, has quickly become the expected response for all persons found without a pulse or respiration. Despite the potentially lifesaving properties of external cardiac massage, the mainstay of resuscitation, it consists of repeated blunt force trauma to the chest, which can lead to extensive traumatic skeletal and nonskeletal injuries. Numerous autopsy-based studies have documented the incidence and patterns of rib and sternal fractures associated with attempted CPR, but there is relatively little data on the incidence and severity of nonskeletal CPR-related injuries. We reviewed reports from 1878 autopsies performed between September 2017 and December 2019 (inclusive), for documentation of CPR-related injuries. Among these cases, there were 93 cases with resuscitation-related nonskeletal injuries. The most common type of injury identified were visceral contusions, documented in 57.0% of cases. These contusions predominantly involved the heart, lungs, neck soft tissue, and surrounding structures. Resuscitation-related lacerations were seen in 17.2% of the cases, most predominantly involving the pericardium, heart, and liver. Statistical analysis of the data demonstrated that lacerations were more likely to be seen in females and with associated sternal fractures. Additionally, hemothoraces were present in 34.4% of cases and hemopericardium was seen in 8.6% of cases. This study provides additional documentation of the range, severity, and incidence of various types of resuscitation-related visceral injuries to better assist autopsy pathologists in distinguishing these injuries from other antecedent traumatic injuries.

PMID:34250595 | DOI:10.1111/1556-4029.14791

Adv Ther. 2021 Jul 12. doi: 10.1007/s12325-021-01846-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Both radiofrequency (RF) and cryoballoon (CB) ablation are treatment options for persistent atrial fibrillation (PsAF). An important recent innovation in RF ablation is Ablation Index (AI), known also as the VISITAG SURPOINT™ Module, a composite lesion quality marker whose use has been shown to significantly reduce the incidence of acute and late pulmonary vein (PV) reconnection and the recurrence of atrial arrhythmias in PsAF. Due to a lack of direct comparative evidence between the latest generations of technologies, there is uncertainty regarding the best treatment option in PsAF. The objective of the present study was to conduct a matching-adjusted indirect treatment comparison (MAIC) using individual patient-level data (IPD) to assess the comparative effectiveness of the THERMOCOOL SMARTTOUCH™ Catheter or the THERMOCOOL SMARTTOUCH™ SF Catheter with AI/VISITAG SURPOINT™ Module (STAI) versus the second-generation CB catheter (Arctic Front Advance™; herein referred to as CB) with respect to 12-month atrial arrhythmia recurrence, fluoroscopy time, and procedural efficiency.

METHODS: IPD for STAI were obtained from four investigator-initiated studies and were pooled. Comparable CB studies identified from a systematic literature review were also pooled. In the absence of a common treatment arm between STAI and CB studies, an unanchored MAIC was conducted. The primary analysis compared the pooled STAI IPD to the pooled CB cohort, with corrections for differences across trials, including eligibility criteria and patient baseline characteristics. Scenario and sensitivity analyses were conducted to assess the robustness of the primary analysis.

RESULTS: In the primary analysis, which was adjusted for left atrial diameter (LAD), age, diabetes, and sex, STAI was associated with a statistically significant 65% relative reduction in the rate of arrhythmia recurrence compared to CB at 12-month follow-up (HR 0.35; 95% CI 0.23, 0.52). STAI was associated with shorter total fluoroscopy time than CB but longer procedure time. Results were consistent across scenario and sensitivity analyses.

CONCLUSION: Radiofrequency ablation with AI significantly reduced atrial arrhythmia recurrence at 12-month follow-up and fluoroscopy time compared to CB, with longer procedure times.

PMID:34250584 | DOI:10.1007/s12325-021-01846-z

J Relig Health. 2021 Jul 11. doi: 10.1007/s10943-021-01335-1. Online ahead of print.

ABSTRACT

Studying Alzheimer’s disease with the fluctuating environmental, individual, and cultural factors in pertinence to the Diagnostic Statistical Manual (DSM-5) requires information, awareness, and understanding of the disease. Studies have calibrated sociocultural factors to be imperative in the expression of functional symptomology of Alzheimer’s disease. Pakistan as a sociocentric, predominantly Muslim country, calls for such efforts. The current research was conducted to study the functional symptomology and experiences of Alzheimer’s disease. A qualitative approach was adopted in which in-depth interviews of three dyads of patients with Alzheimer’s disease and their caregivers (N = 6) were conducted. Interpretative Phenomenological Analysis was applied to acquire the thematic analysis of data. Results showed sociocentricism as a forefront factor. Cognition, behavior, and emotions were found to be functionally expressed by religion, unawareness, respect of older people, stigmatization, and isolation within family dynamics. The study could be an instigator for further culture-oriented assessment and management providing services.

PMID:34250570 | DOI:10.1007/s10943-021-01335-1

Curr Med Sci. 2021 Jun;41(3):565-571. doi: 10.1007/s11596-021-2392-4. Epub 2021 Jul 11.

ABSTRACT

There are few studies regarding imaging markers for predicting postoperative rebleeding after stereotactic minimally invasive surgery (MIS) for hypertensive intracerebral haemorrhage (ICH), and little is known about the relationship between satellite sign on computed tomography (CT) scans and postoperative rebleeding after MIS. This study aimed to determine the value of the CT satellite sign in predicting postoperative rebleeding in patients with hypertensive ICH who undergo stereotactic MIS. We retrospectively examined and analysed 105 patients with hypertensive ICH who underwent standard stereotactic MIS for hematoma evacuation within 72 h following admission. Postoperative rebleeding occurred in 14 of 65 (21.5%) patients with the satellite sign on baseline CT, and in 5 of the 40 (12.5%) patients without the satellite sign. This difference was statistically significant. Positive and negative values of the satellite sign for predicting postoperative rebleeding were 21.5% and 87.5%, respectively. Multivariate logistic regression analysis verified that baseline ICH volume and intraventricular rupture were independent predictors of postoperative rebleeding. In conclusion, the satellite sign on baseline CT scans may not predict postoperative rebleeding following stereotactic MIS for hypertensive ICH.

PMID:34250575 | DOI:10.1007/s11596-021-2392-4

J Natl Cancer Inst. 2021 Jul 12:djab128. doi: 10.1093/jnci/djab128. Online ahead of print.

ABSTRACT

BACKGROUND: Although an immunosuppressive tumor microenvironment (TME) is key for tumor progression, the molecular characteristics associated with the immunosuppressive TME remain unknown in triple-negative breast cancer (TNBC). Our previous functional proteomic study of TNBC tumors identified that C-JUN N-terminal kinase (JNK) pathway-related molecules were enriched in a cluster associated with the inflammatory pathway. However, the role of the JNK pathway in the TNBC TME is still unclear.

METHODS: Transcriptomic analysis was conducted using The Cancer Genome Atlas (TCGA) datasets. The effect of JNK-IN-8, a covalent pan-JNK inhibitor, on TNBC tumor growth, lung metastasis, and the TME was measured in TNBC syngeneic mouse models (n = 13 per group). Tumor (n = 43) or serum (n = 46) samples from TNBC patients were analyzed using multiplex immunohistochemistry or Luminex assay. All statistical tests were 2-sided.

RESULTS: CIBERSORT analysis revealed that TNBC patients with high pJNK level (n = 47) had more regulatory T cell (Treg) infiltration than those with low pJNK level (n = 47) (P = .02). Inhibition of JNK signaling statistically significantly reduced tumor growth (P < .001) and tumor-infiltrating Tregs (P = .02) while increasing the infiltration of CD8+ T cells in TNBC mouse models through the reduction of C-C motif ligand 2 (CCL2). Tumor-associated macrophages (TAMs) were the predominant cells secreting CCL2, and inhibition of JNK signaling reduced CCL2 secretion of human primary macrophages. Moreover, in patients with TNBC (n = 43), those with high levels of CCL2+ TAMs had more Treg and less CD8+ T cell infiltration (P = .04), and serum CCL2 level was associated with poor overall survival (hazard ratio = 2.65, 95% confidence interval = 1.29 to 5.44; P = .008) in TNBC patients (n = 46).

CONCLUSIONS: The JNK/C-JUN/CCL2 axis contributes to TNBC aggressiveness via forming an immunosuppressive TME and can offer novel therapeutic strategies for TNBC.

PMID:34250544 | DOI:10.1093/jnci/djab128

CVIR Endovasc. 2021 Jul 12;4(1):59. doi: 10.1186/s42155-021-00246-2.

ABSTRACT

AIM: To describe a 3 years experience of peripheral arterial embolization with Micro Vascular Plug (MVP) (Medtronic, USA).

MATERIALS AND METHODS: The following parameters were investigated: type of vascular injury, anticoagulation therapy at time of procedure, anatomical district, caliper of the target artery, course of the landing zone, additional embolics, technical and clinical success, device related clinical complications. Technical success was defined as complete embolization without deployment of additional embolics after MVP release. Primary clinical success was considered as hemodynamic stability in emergency setting and resolution of the underlying vascular pathology in elective cases; secondary clinical success was considered clinical success after a second embolization session.

RESULTS: 116 MVP have been released in 104 patients (67 males and 37 females; mean age 61.3 years). The pullback release technique was adopted in each case. 85 patients were treated in emergent settings while in 19 patients the procedure was scheduled. The overall technical success was 75%. Primary clinical success was 96.1%, secondary clinical success 3% and clinical failure 0.9%. No statistical differences in terms of effectiveness were observed among patients assuming anticoagulation (p-value = 0.6). A straight and longer landing zone were statistically associated with higher technical success compared to curved and shorter ones, (p-values < 0.001 and = 0.048 respectively). MVP-3 and MVP-5 were the most frequently adopted models in this sample, in 29.8% and 49% of the patients respectively. No clinically adverse events directly related to MVP occurred; in 3 cases device migration was registered without clinical complications.

CONCLUSION: MVP is a safe and effective embolic agent. While eventual concomitant anticoagulation therapy did not influence the technical outcome, straight course and length of the landing zone are essential parameters to evaluate before deployment.

PMID:34250548 | DOI:10.1186/s42155-021-00246-2

Lancet Microbe. 2021 Jul 6. doi: 10.1016/S2666-5247(21)00146-4. Online ahead of print.

ABSTRACT

BACKGROUND: We hypothesised that host-response biomarkers of viral infections might contribute to early identification of individuals infected with SARS-CoV-2, which is critical to breaking the chains of transmission. We aimed to evaluate the diagnostic accuracy of existing candidate whole-blood transcriptomic signatures for viral infection to predict positivity of nasopharyngeal SARS-CoV-2 PCR testing.

METHODS: We did a nested case-control diagnostic accuracy study among a prospective cohort of health-care workers (aged ≥18 years) at St Bartholomew’s Hospital (London, UK) undergoing weekly blood and nasopharyngeal swab sampling for whole-blood RNA sequencing and SARS-CoV-2 PCR testing, when fit to attend work. We identified candidate blood transcriptomic signatures for viral infection through a systematic literature search. We searched MEDLINE for articles published between database inception and Oct 12, 2020, using comprehensive MeSH and keyword terms for “viral infection”, “transcriptome”, “biomarker”, and “blood”. We reconstructed signature scores in blood RNA sequencing data and evaluated their diagnostic accuracy for contemporaneous SARS-CoV-2 infection, compared with the gold standard of SARS-CoV-2 PCR testing, by quantifying the area under the receiver operating characteristic curve (AUROC), sensitivities, and specificities at a standardised Z score of at least 2 based on the distribution of signature scores in test-negative controls. We used pairwise DeLong tests compared with the most discriminating signature to identify the subset of best performing biomarkers. We evaluated associations between signature expression, viral load (using PCR cycle thresholds), and symptom status visually and using Spearman rank correlation. The primary outcome was the AUROC for discriminating between samples from participants who tested negative throughout the study (test-negative controls) and samples from participants with PCR-confirmed SARS-CoV-2 infection (test-positive participants) during their first week of PCR positivity.

FINDINGS: We identified 20 candidate blood transcriptomic signatures of viral infection from 18 studies and evaluated their accuracy among 169 blood RNA samples from 96 participants over 24 weeks. Participants were recruited between March 23 and March 31, 2020. 114 samples were from 41 participants with SARS-CoV-2 infection, and 55 samples were from 55 test-negative controls. The median age of participants was 36 years (IQR 27-47) and 69 (72%) of 96 were women. Signatures had little overlap of component genes, but were mostly correlated as components of type I interferon responses. A single blood transcript for IFI27 provided the highest accuracy for discriminating between test-negative controls and test-positive individuals at the time of their first positive SARS-CoV-2 PCR result, with AUROC of 0·95 (95% CI 0·91-0·99), sensitivity 0·84 (0·70-0·93), and specificity 0·95 (0·85-0·98) at a predefined threshold (Z score >2). The transcript performed equally well in individuals with and without symptoms. Three other candidate signatures (including two to 48 transcripts) had statistically equivalent discrimination to IFI27 (AUROCs 0·91-0·95).

INTERPRETATION: Our findings support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection for screening individuals at high risk of infection, such as contacts of index cases, to facilitate early case isolation and early use of antiviral treatments as they emerge.

FUNDING: Barts Charity, Wellcome Trust, and National Institute of Health Research.

PMID:34250515 | PMC:PMC8260104 | DOI:10.1016/S2666-5247(21)00146-4

J Infect Dis. 2021 Jul 12:jiab198. doi: 10.1093/infdis/jiab198. Online ahead of print.

NO ABSTRACT

PMID:34250540 | DOI:10.1093/infdis/jiab198