Category: Nevin Manimala

Br J Dermatol. 2021 Mar 2. doi: 10.1111/bjd.19885. Online ahead of print.

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity.

OBJECTIVE: To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables.

METHODS: We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14. We regressed identified subtypes on non-genetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete-case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results.

RESULTS: 11,866 children contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%); Moderate-Frequent (7%); Moderate-Declining (11%); and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin null mutations (FLG), an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other.

CONCLUSIONS: Considering severity and AD trajectories leads to four well-defined and recognisable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.

PMID:33655501 | DOI:10.1111/bjd.19885

Pharmacotherapy. 2021 Mar 2. doi: 10.1002/phar.2516. Online ahead of print.

ABSTRACT

INTRODUCTION: Two case reports describe a possible interaction between levetiracetam and high-dose methotrexate (HDMTX). Only two small retrospective studies have evaluated the interaction, and it remains unclear if concomitant use should be avoided.

METHODS: This single-center, retrospective study evaluated adult lymphoma patients who received HDMTX as a 4-hour infusion with or without concomitant levetiracetam for a difference in incidence of delayed MTX elimination (MTX level > 1µmol/L at 48 hours). Secondary outcomes included incidence of acute kidney injury (AKI) and hospital length of stay (LOS). Generalized estimating equations clustered on patient were used to assess each outcome.

RESULTS: The 430 included patients receiving 1993 doses of HDMTX had a median (IQR) age of 66 (57.5, 72.6) years, 88 (20.5%) received concomitant levetiracetam with at least one dose of MTX, 267 (62.1%) were male, and 397 (92.3%) were Caucasian. HDMTX doses ranged from 1-8 g/m² . The most common lymphoma diagnoses were systemic diffuse large B-cell lymphoma (DLBCL) (58.5%) and systemic DLBCL with central nervous system (CNS) involvement (32.8%). Rates of delayed elimination with and without levetiracetam were 13.4% and 16.3%, respectively (OR = 0.80, 95% CI 0.47-1.34, p=0.39). AKI occurred in 15.6% and 17.0% of patients with and without concomitant levetiracetam, respectively (OR=0.83, 95% CI 0.52-1.33, p=0.28). The median LOS with and without levetiracetam was 4.2 and 4.1 days, respectively (p=0.039). On multivariable analyses, only age, body surface area, diagnosis of systemic DLBCL with CNS involvement, serum creatinine, hemoglobin, total bilirubin, and dose of HDMTX were associated with delayed elimination.

CONCLUSIONS: HDMTX administered with concomitant levetiracetam was not associated with increased risk for delayed MTX elimination or AKI. These results support that levetiracetam and HDMTX are safe for coadministration.

PMID:33655525 | DOI:10.1002/phar.2516

Med Phys. 2021 Mar 2. doi: 10.1002/mp.14810. Online ahead of print.

ABSTRACT

PURPOSE: Radiation dose to specific cardiac substructures, such as the atria and ventricles, has been linked to post-treatment toxicity and has shown to be more predictive of these toxicities than dose to the whole heart. A deep learning-based algorithm for automatic generation of these contours is proposed to aid in either retrospective or prospective dosimetric studies to better understand the relationship between radiation dose and toxicities.

METHODS: The proposed method uses a mask-scoring regional convolutional neural network (R-CNN) which consists of five major subnetworks: backbone, regional proposal network (RPN), regional convolutional neural network (RCNN) head, mask head, and mask-scoring head. Multi-scale feature maps are learned from CT via the backbone network. The RPN utilizes these feature maps to detect the location and region-of-interest (ROI) of all substructures, and the final three subnetworks work in series to extract structural information from these ROIs. The network is trained using 55 patient CT datasets, with 22 patients having contrast scans. Three-fold cross validation (CV) is used for evaluation on 45 datasets, and a separate cohort of 10 patients are used for holdout evaluation. The proposed method is compared to a 3D UNet.

RESULTS: The proposed method produces contours that are qualitatively similar to the ground truth contours. Quantitatively, the proposed method achieved average Dice score coefficients (DSC) for the whole heart, chambers, great vessels, coronary arteries, the valves of the heart of 0.96, 0.94, 0.93, 0.66, and 0.77 respectively, outperforming the 3D UNet, which achieved DSCs of 0.92, 0.87, 0.88, 0.48, 0.59 for the corresponding substructure groups. Mean surface distances (MSD) between substructures segmented by the proposed method and the ground truth were less than 2 mm except for the left anterior descending coronary artery and the mitral and tricuspid valves, and less than 5 mm for all substructures. When dividing results into non-contrast and contrast datasets, the model performed statistically significantly better in terms of DSC, MSD, centroid mean distance (CMD), and volume difference for the chambers and whole heart with contrast. Notably, the presence of contrast did not statistically significantly affect coronary artery segmentation DSC or MSD. After network training, all substructures and the whole heart can be segmented on new datasets in less than five seconds.

CONCLUSIONS: A deep-learning network was trained for automatic delineation of cardiac substructures based on CT alone. The proposed method can be used as a tool to investigate the relationship between cardiac substructure dose and treatment toxicities.

PMID:33655548 | DOI:10.1002/mp.14810

J Nucl Cardiol. 2021 Mar 2. doi: 10.1007/s12350-021-02555-4. Online ahead of print.

ABSTRACT

BACKGROUND: A variety of temporal sampling protocols is used worldwide to measure myocardial blood flow (MBF). Both the length and number of time frames in these protocols may alter MBF and myocardial flow reserve (MFR) measurements. We aimed to assess the effect of different clinically used temporal sampling protocols on MBF and MFR quantification in Rubidium-82 (Rb-82) PET imaging.

METHODS: We retrospectively included 20 patients referred for myocardial perfusion imaging using Rb-82 PET. A literature search was performed to identify appropriate sampling protocols. PET data were reconstructed using 14 selected temporal sampling protocols with time frames of 5-10 seconds in the first-pass phase and 30-120 seconds in the tissue phase. Rest and stress MBF and MFR were calculated for all protocols and compared to the reference protocol with 26 time frames.

RESULTS: MBF measurements differed (P ≤ 0.003) in six (43%) protocols in comparison to the reference protocol, with mean absolute relative differences up to 16% (range 5%-31%). Statistically significant differences were most frequently found for protocols with tissue phase time frames < 90 seconds. MFR did not differ (P ≥ 0.11) for any of the protocols.

CONCLUSIONS: Various temporal sampling protocols result in different MBF values using Rb-82 PET. MFR measurements were more robust to different temporal sampling protocols.

PMID:33655444 | DOI:10.1007/s12350-021-02555-4

Acad Psychiatry. 2021 Mar 2. doi: 10.1007/s40596-021-01425-y. Online ahead of print.

ABSTRACT

OBJECTIVE: Patient suicide is a common experience in psychiatry residency, and its effects on trainees can be profound. There are currently no ACGME Common Program Requirements for education about patient suicide, and a need exists for evidence-based curricula to prepare residents for this difficult outcome.

METHODS: A comprehensive patient suicide curriculum was developed utilizing multiple modes of delivering content, including a training designed to foster built-in support among peers in the healthcare workplace. The content was delivered at intervals over the course of the 2019-2020 academic year for 43 psychiatry residents at The Ohio State University Wexner Medical Center. Pre- and post-curriculum surveys were obtained to assess the resident experience of the new curriculum.

RESULTS: Twenty-seven residents completed the pre-curriculum survey and 25 completed the post-curriculum survey. Results demonstrated statistically significant improvements in ratings of preparedness to deal with the loss of a patient by suicide, preparedness to support a co-resident who has experienced the death of a patient by suicide, program-level support for residents, understanding systems-level and quality processes, and knowledge of what steps to take if finding out a patient has completed suicide.

CONCLUSIONS: A multimodal approach incorporating understanding emotional reactions, provision of support, delineation of procedural issues, and education regarding quality and risk management considerations was effective at improving resident preparedness to cope following a patient suicide.

PMID:33655455 | DOI:10.1007/s40596-021-01425-y

Surg Endosc. 2021 Mar 2. doi: 10.1007/s00464-021-08353-w. Online ahead of print.

ABSTRACT

BACKGROUND: Achalasia is a rare, chronic, and morbid condition with evolving treatment. Peroral endoscopic myotomy (POEM) has gained considerable popularity, but its comparative effectiveness is uncertain. We aim to evaluate the literature comparing POEM to Heller myotomy (HM) and pneumatic dilation (PD) for the treatment of achalasia.

METHODS: We conducted a systematic review of comparative studies between POEM and HM or PD. A priori outcomes pertained to efficacy, perioperative metrics, and safety. Internal validity of observational studies and randomized trials (RCTs) was judged using the Newcastle Ottawa Scale and the Cochrane Risk of Bias 2.0 tool, respectively.

RESULTS: From 1379 unique literature citations, we included 28 studies comparing POEM and HM (n = 21) or PD (n = 8), with only 1 RCT addressing each. Aside from two 4-year observational studies, POEM follow-up averaged ≤ 2 years. While POEM had similar efficacy to HM, POEM treated dysphagia better than PD both in an RCT (treatment “success” RR 1.71, 95% CI 1.34-2.17; 126 patients) and in observational studies (Eckardt score MD – 0.43, 95% CI – 0.71 to – 0.16; 5 studies; I² 21%; 405 patients). POEM needed reintervention less than PD in an RCT (RR 0.19, 95% CI 0.08-0.47; 126 patients) and HM in an observational study (RR 0.33, 95% CI 0.16, 0.68; 98 patients). Though 6-12 months patient-reported reflux was worse than PD in 3 observational studies (RR 2.67, 95% CI 1.02-7.00; I² 0%; 164 patients), post-intervention reflux was inconsistently measured and not statistically different in measures ≥ 1 year. POEM had similar safety outcomes to both HM and PD, including treatment-related serious adverse events.

CONCLUSIONS: POEM has similar outcomes to HM and greater efficacy than PD. Reflux remains a critical outcome with unknown long-term clinical significance due to insufficient data and inconsistent reporting.

PMID:33655443 | DOI:10.1007/s00464-021-08353-w

Phys Med Biol. 2021 Mar 2. doi: 10.1088/1361-6560/abeb32. Online ahead of print.

ABSTRACT

Virtual imaging trials (VITs), defined as the process of conducting clinical imaging trials using computer simulations, offer a time- and cost-effective alternative to traditional imaging trials for CT. The clinical potential of VITs hinges on the realism of simulations modeling the image acquisition process, where the accurate scanner-specific simulation of scatter in a time- feasible manner poses a particular challenge. To meet this need, this study proposes, develops, and validates a rapid scatter estimation framework, based on GPU-accelerated Monte Carlo (MC) simulations and denoising methods, for estimating scatter in single source, dual-source, and photon-counting CT. A CT simulator was developed to incorporate parametric models for an anti-scatter grid and a curved energy integrating detector (EID) with an energy-dependent response. The scatter estimates from the simulator were validated using physical measurements acquired on a clinical CT system using the standard single-blocker method. The MC simulator was further extended to incorporate a pre-validated model for a photon-counting detector and an additional source-detector pair to model cross scatter in dual-source configurations. To estimate scatter with desirable levels of statistical noise using a manageable computational load, two denoising methods using a (1) convolutional neural network and an (2) optimized Gaussian filter were further deployed. The viability of this framework for clinical VITs was assessed by integrating it with a scanner-specific ray-tracer program to simulate images for an image quality (Mercury) and an anthropomorphic phantom (XCAT). The simulated scatter-to-primary ratios agreed with physical measurements within 4.4%10.8% across all projection angles and kVs. The differences of ~121 HU between images with and without scatter, signifying the importance of scatter for simulating clinical images. The denoising methods preserved the magnitudes and trends observed in the reference scatter distributions, with an averaged rRMSE value of 0.91 and 0.97 for the two methods, respectively. The execution time of ~30 seconds for simulating scatter in a single projection with a desirable level of statistical noise indicates a major improvement in performance, making our tool an eligible candidate for conducting extensive VITs spanning multiple patients and scan protocols.

PMID:33652421 | DOI:10.1088/1361-6560/abeb32

Chin Med J (Engl). 2021 Feb 9;134(5):564-572. doi: 10.1097/CM9.0000000000001400.

ABSTRACT

BACKGROUND: The pathogenesis of osteosarcoma (OS) is still unclear, and it is still necessary to find new targets and drugs for anti-OS. This study aimed to investigate the role and mechanism of the anti-OS effects of miR-296-5p.

METHODS: We measured the expression of miR-296-5p in human OS cell lines and tissues. The effect of miR-296-5p and its target gene staphylococcal nuclease and tudor domain containing 1 on proliferation, migration, and invasion of human OS lines was examined. The Student’s t test was used for statistical analysis.

RESULTS: We found that microRNA (miR)-296-5p was significantly downregulated in OS cell lines and tissues (control vs. OS, 1.802 ± 0.313 vs. 0.618 ± 0.235, t = 6.402, P < 0.01). Overexpression of miR-296-5p suppressed proliferation, migration, and invasion of OA cells. SND1 was identified as a target of miR-296-5p by bioinformatic analysis and dual-luciferase reporter assay. Overexpression of SND1 abrogated the effects induced by miR-296-5p upregulation (miRNA-296-5p vs. miRNA-296-5p + SND1, 0.294 ± 0.159 vs. 2.300 ± 0.277, t = 12.68, P = 0.003).

CONCLUSION: Our study indicates that miR-296-5p may function as a tumor suppressor by targeting SND1 in OS.

PMID:33652459 | DOI:10.1097/CM9.0000000000001400

Sci Total Environ. 2021 Feb 18;776:145935. doi: 10.1016/j.scitotenv.2021.145935. Online ahead of print.

ABSTRACT

Data-driven landslide susceptibility models formally integrate spatial landslide information with explanatory environmental variables that describe predisposing factors of slope instability. Well-performing models are commonly utilized to identify landslide-prone terrain or to understand the causes of slope instability. In most cases, however, the available landslide data is affected by spatial biases (e.g. underrepresentation of landslides far from infrastructure or in forests) and does therefore not perfectly represent the spatial distribution of past slope instabilities. Literature shows that implications of such data flaws are frequently ignored. This study was built upon landslide information that systematically relates to damage-causing and infrastructure-threatening events in South Tyrol, Italy (7400 km²). The created models represent three conceptually different strategies to deal with biased landslide information. The aims were to demonstrate why an inference of geomorphic causation from apparently well-performing models is invalid under common landslide data bias conditions (Model 1), to test a novel bias-adjustment approach (Model 2) and to exploit the underlying data bias to model areas likely affected by potentially damaging landslides (Model 3; intervention index), instead of landslide susceptibility. The study offers a novel perspective on how biases in landslide data can be considered within data-driven models by focusing not only on the process under investigation (landsliding), but also on the circumstances that led to the registration of landslide information (data collection effects). The results were evaluated in terms of statistical relationships, variable importance, predictive performance, and geomorphic plausibility. The results revealed that none of the models reflected landslide susceptibility. Despite partly high predictive performances, the models were unable to create geomorphically plausible spatial predictions. The impact-oriented intervention index, however, enabled to identify damage-causing landslides with high accuracy. We conclude that the frequent practice of inferring geomorphic causation from well-performing models without accounting for data limitations is invalid.

PMID:33652311 | DOI:10.1016/j.scitotenv.2021.145935

J Stroke Cerebrovasc Dis. 2021 Feb 27;30(5):105680. doi: 10.1016/j.jstrokecerebrovasdis.2021.105680. Online ahead of print.

ABSTRACT

INTRODUCTION: Body lateropulsion (BLP) is seen in neurological lesions involving the pathways responsible for body position and verticality. We report a case of isolated body lateropulsion (iBLP) as the presentation of lateral medullary infarction and conducted a systematic literature review.

METHODS: MEDLINE and EMBASE databases were searched up to December 3, 2020.

INCLUSION CRITERIA: age ≥ 18, presence of BLP, confirmed stroke on imaging.

EXCLUSION CRITERIA: age < 18, qualitative reviews, studies with inadequate patient data. Statistical analysis was performed using IBM® SPSS® Statistics 20.

RESULTS: A 64-year-old man presented with acute-onset iBLP. Brain MRI demonstrated acute infarction in the right caudolateral medulla. His symptoms progressed with ipsilateral Horner syndrome over the next 24 hours and contralateral hemisensory loss 10 days later. Repeat MRI showed an increase in infarct size. BLP resolved partially at discharge. Systematic review: 418 abstracts were screened; 59 studies were selected reporting 103 patients. Thirty-three patients had iBLP (32%). BLP was ipsilateral to stroke in 70 (68%) and contralateral in 32 (32%). The most common stroke locations were medulla (n = 63, 59%), pons (n = 16, 15%), and cerebellum (n = 16, 15%). Four strokes were cortical, 3 frontal and 1 temporoparietal (3%). The most common etiology was large-artery atherosclerosis (LAA) in 20 patients (32%), followed by small-vessel occlusion in 12 (19%). Seventeen (27%) had large-vessel occlusion (LVO), 12 involving the vertebral artery. Sixty (98%) had some degree of resolution of BLP; complete in 41 (70%). Median time-to-resolution was 14 days (IQR 10-21). There was no relationship between time-to-resolution and age, sex, side of BLP or side of stroke.

CONCLUSION: BLP was commonly seen with medullary infarction and was the isolated finding in one-third. LAA and LVO were the most common etiologies. Recovery of BLP was early and complete in most cases.

PMID:33652344 | DOI:10.1016/j.jstrokecerebrovasdis.2021.105680