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Background . There is growing evidence that social and behavioral determinants of health (SBDH) play a substantial effect in a wide range of health outcomes. Electronic health records (EHRs) have been widely employed to conduct observational studies in the age of artificial intelligence (AI). However, there has been limited review into how to make the most of SBDH information from EHRs using AI approaches. Methods . A systematic search was conducted in six databases to find relevant peer-reviewed publications that had recently been published. Relevance was determined by screening and evaluating the articles. Based on selected relevant studies, a methodological analysis of AI algorithms leveraging SBDH information in EHR data was provided. Results . Our synthesis was driven by an analysis of SBDH categories, the relationship between SBDH and healthcare-related statuses, natural language processing (NLP) approaches for extracting SBDH from clinical notes, and predictive models using SBDH for health outcomes. Discussion . The associations between SBDH and health outcomes are complicated and diverse; several pathways may be involved. Using NLP technology to support the extraction of SBDH and other clinical ideas simplifies the identification and extraction of essential concepts from clinical data, efficiently unlocks unstructured data, and aids in the resolution of unstructured data-related issues. Conclusion . Despite known associations between SBDH and diseases, SBDH factors are rarely investigated as interventions to improve patient outcomes. Gaining knowledge about SBDH and how SBDH data can be collected from EHRs using NLP approaches and predictive models improves the chances of influencing health policy change for patient wellness, ultimately promoting health and health equity.

The NCCN Guidelines for Wilms Tumor focus on the screening, diagnosis, staging, treatment, and management of Wilms tumor (WT, also known as nephroblastoma). WT is the most common primary renal tumor in children. Five-year survival is more than 90% for children with all stages of favorable histology WT who receive appropriate treatment. All patients with WT should be managed by a multidisciplinary team with experience in managing renal tumors; consulting a pediatric oncologist is strongly encouraged. Treatment of WT includes surgery, neoadjuvant or adjuvant chemotherapy, and radiation therapy (RT) if needed. Careful use of available therapies is necessary to maximize cure and minimize long-term toxicities. This article discusses the NCCN Guidelines recommendations for favorable histology WT.

Abstract Aims The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems‐level analysis. Methods Imaging‐based cortical structural maps from a large‐scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell‐type deconvolution, differential expression analysis and cell‐type enrichment analyses were used to identify differences in cell‐type distribution. These differences were followed up in post‐mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell‐type‐specific depletion was used in a murine model of acquired epilepsy. Results We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post‐mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non‐spatial memory test seen in epileptic mice not depleted of microglia. Conclusions These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Rationale: Anthracycline-induced cardiotoxicity (AIC) is a major side effect that limits the use of anthracyclines as effective chemotherapeutics. No mechanism-based therapy is available when cardiac function deteriorates. Objective: We aim to elucidate the dynamic autophagic defects in AIC and to identify a mechanism-based therapy via both genetic and pharmacological studies. Method and Results: Through phenotyping an adult AIC zebrafish model, we detected a biphasic response in autophagy: activation in the early stage and suppression in the later phase that is characterized by a decline in cardiac function. We conducted conditional genetic studies with atg7 , which encodes a rate-limiting autophagy core protein, and found that atg7 overexpression leads to therapeutic effects in the late phase but deleterious effects in the early phase of adult AIC. We then assessed the therapeutic effects of 37 Food and Drug Administration–approved autophagy activators using an embryonic AIC zebrafish model and identified spironolactone, pravastatin, and minoxidil as top-ranking drugs. We demonstrated the therapeutic efficacy of these Food and Drug Administration–approved autophagy activators in the adult AIC model and confirmed that these drugs exert therapeutic effects in the late phase but not in the early AIC phase. Finally, we demonstrated that the time-dependent therapeutic effects are conserved in a mouse AIC model and that spironolactone and rapamycin activated autophagy in an Atg7-dependent fashion. Conclusions: Our findings suggest that atg7-based autophagy activation is an effective therapeutic avenue to reversing the decline in cardiac function in AIC, highlighting the time-dependent nature of autophagy-based therapy.

Mechanical thrombectomy (MT) represents the mainstay of treatment for patients with acute ischemic stroke due to large-vessel occlusion (LVO). Intravenous thrombolysis has been associated with worse clinical outcome in patients presenting with high blood glucose levels at admission; to date the true effect of hyperglycemia in the setting of MT has not been fully elucidated. In this meta-analysis, we analyzed the influence of high blood glucose levels at admission on clinical outcome after MT. Ovid EMBASE, PubMed, Scopus, and Cochrane Library databases were searched from their dates of inception up to March 2021. An initial search identified 2118 articles representing 1235 unique studies. After applying selection criteria, three prospective and five retrospective studies were analyzed, yielding a pooled cohort of 5861 patients (2041 who presented with hyperglycemia, and 3820 who presented with normal blood glucose levels). Patients in the hyperglycemia group were less likely to have a modified Ranking Scale (mRS) score <3 (risk ratio (RR): 0.65; 95% CI 0.59 to 0.72; p<0.0001; I 2=13%), and had an increased risk of symptomatic intracranial hemorrhage (sICH) (RR: 2.07; 95% CI 1.65 to 2.60; p<0.0001; I 2=0%) and mortality (RR: 1.73; 95% CI 1.57 to 1.91; p<0.0001; I 2=0%). Patients who present with hyperglycemia and undergo MT for treatment of LVO have an increased risk of unfavorable clinical outcome, sICH, and mortality. Glucose levels at admission appear to be a prognostic factor in this subset of patients. Further studies should focus on evaluating control of the glucose level at admission as a modifiable risk factor in patients undergoing MT for LVO.

Objective Observational studies utilising diffusion tractography have suggested a common mechanism for tremor alleviation in deep brain stimulation for essential tremor: the decussating portion of the dentato-rubro-thalamic tract. We hypothesised that directional stimulation of the dentato-rubro-thalamic tract would result in greater tremor improvement compared to sham programming, as well as comparable improvement as more tedious standard-of-care programming. Methods A prospective, blinded crossover trial was performed to assess the feasibility, safety and outcomes of programming based solely on dentato-rubro-thalamic tract anatomy. Using magnetic resonance imaging diffusion-tractography, the dentato-rubro-thalamic tract was identified and a connectivity-based treatment setting was derived by modelling a volume of tissue activated using directional current steering oriented towards the dentato-rubro-thalamic tract centre. A sham setting was created at approximately 180° opposite the connectivity-based treatment. Standard-of-care programming at 3 months was compared to connectivity-based treatment and sham settings that were blinded to the programmer. The primary outcome measure was percentage improvement in the Fahn–Tolosa–Marín tremor rating score compared to the preoperative baseline. Results Among the six patients, tremor rating scores differed significantly among the three experimental conditions ( P=0.030). The mean tremor rating score improvement was greater with the connectivity-based treatment settings (64.6% ± 14.3%) than with sham (44.8% ± 18.6%; P=0.031) and standard-of-care programming (50.7% ± 19.2%; P=0.062). The distance between the centre of the dentato-rubro-thalamic tract and the volume of tissue activated inversely correlated with the percentage improvement in the tremor rating score (R 2 =0.24; P=0.04). No significant adverse events were encountered. Conclusions Using a blinded, crossover trial design, we have shown the technical feasibility, safety and potential efficacy of connectivity-based stimulation settings in deep brain stimulation for treatment of essential tremor.

Abstract Objective This study aims to evaluate the role of scalp electroencephalography (EEG; ictal and interictal patterns) in predicting resective epilepsy surgery outcomes. We use the data to further develop a nomogram to predict seizure freedom. Methods We retrospectively reviewed the scalp EEG findings and clinical data of patients who underwent surgical resection at three epilepsy centers. Using both EEG and clinical variables categorized into 13 isolated candidate predictors and 6 interaction terms, we built a multivariable Cox proportional hazards model to predict seizure freedom 2 years after surgery. Harrell's step‐down procedure was used to sequentially eliminate the least‐informative variables from the model until the change in the concordance index (c‐index) with variable removal was less than 0.01. We created a separate model using only clinical variables. Discrimination of the two models was compared to evaluate the role of scalp EEG in seizure‐freedom prediction. Results Four hundred seventy patient records were analyzed. Following internal validation, the full Clinical + EEG model achieved an optimism‐corrected c‐index of 0.65, whereas the c‐index of the model without EEG data was 0.59. The presence of focal to bilateral tonic‐clonic seizures (FBTCS), high preoperative seizure frequency, absence of hippocampal sclerosis, and presence of nonlocalizable seizures predicted worse outcome. The presence of FBTCS had the largest impact for predicting outcome. The analysis of the models’ interactions showed that in patients with unilateral interictal epileptiform discharges (IEDs), temporal lobe surgery cases had a better outcome. In cases with bilateral IEDs, abnormal magnetic resonance imaging (MRI) predicted worse outcomes, and in cases without IEDs, patients with extratemporal epilepsy and abnormal MRI had better outcomes. Significance This study highlights the value of scalp EEG, particularly the significance of IEDs, in predicting surgical outcome. The nomogram delivers an individualized prediction of postoperative outcome, and provides a unique assessment of the relationship between the outcome and preoperative findings.

Purpose: The availability of an objective outcome measure for facial reconstructive surgery remains elusive. Evaluations submitted by external raters or by patient self-report are subjective, and may unreliably convey how one is perceived by others. We are interested in observers’ instantaneous responses to the human face. The goal of modern facelift and associated procedures for facial rejuvenation are to achieved subtle differences that lead to the perception of youth and attractiveness, yet the observer cannot pinpoint what exactly have been done to the patient’s face. We explored the visual markers that lead to differential perception of patients before and after facial rejuvenation surgery (high SMAS facelift, neck lift, fat grafting, brow lifts and blepharoplasty). Methods: 40 images were obtained which portrayed pre and post operative photos of patients who underwent high SMAS facelift, fat grafting, and browlifts and blepharoplasty for facial rejuvenation. Photographs were obtained before and after surgical correction (>3 months postop). 40 observers examined the images while an infrared eye-tracking camera recorded their eye movements. The observers were then asked to rate the image for character attributes (attractiveness, trustworthiness, sociability, healthy, and capability, 1-7 scale, and also estimate the age of the patient). Results: (i) The surgical intervention was found to decrease observers’ attention to the cervical region, but did not change how other areas are perceived significantly.(ii) The surgical intervention was found to significantly increase the character ratings for all five attributes compared to pre op controls: (sociable 3.53 to 4.18, trustworthy 3.85 to 4.20, attractive 3.34 to 3.3.90, health 4.07 to 4.61, capable 3.91 to 4.43.(iii) Average age estimate of the photos decreased significantly from 54 years (SD 6) to 48.6 years (SD 5.2), with true average age of 57.4 (7.6). Conclusion: We provide data illustrating a novel and objective technique to evaluate the effect of reconstructive intervention for facial rejuvenation. Consistent with the goals of subtle facial rejuvenation, the observers did not detect any particular areas of difference post operatively, but gain a more favorable impression of the person, and also perceived them as younger by a decade compared to their true age.