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Tuberous sclerosis complex (TSC) is a genetic disorder that is manifested in multiple body systems. A mammalian target of rapamycin (mTOR) inhibitor (mTORi), either everolimus or sirolimus, is now routinely prescribed for multiple clinical manifestations of TSC, including subependymal giant cell astrocytoma and epilepsy. These medications are generally well tolerated. Side effects previously identified in well-designed clinical trials tend to be mild and readily manageable. Regulatory approvals for the treatment of TSC have expanded the use of everolimus and sirolimus clinically, enlarging clinician experience and enabling identification of potential treatment-related effects that are rarer than could be identified or recognized in previous clinical trials.

The medical records of clinical patients from our TSC center who were treated with an mTORi and later developed diabetes mellitus (DM) were analyzed and compared with those who were not treated with an mTORi. Eight individuals received detailed analysis, including laboratory results, concomitant medications, and body mass indices.

Among the 1576 individuals with TSC, 4% taking an mTORi developed diabetes compared with 0.6% of those not on mTORi, showing a significant interaction between DM and mTORi (chi-square=18.1, P<0.001). Details of eight patients who developed DM were presented.

The long-term use of mTORi agents in TSC may contribute to a risk of diabetes. Early detection can be critical in management. Additional studies are need to further investigate a causal relationship, but clinicians should be aware of this possible association when initiating and monitoring ongoing treatment.

The long-term use of mTORi agents in TSC may contribute to a risk of diabetes. Early detection can be critical in management. Additional studies are need to further investigate a causal relationship, but clinicians should be aware of this possible association when initiating and monitoring ongoing treatment.

Given the expanding evidence of clinico-radiological differences between moyamoya disease (MMD) and moyamoya syndrome (MMS), we compared the clinical and radiographic features of childhood MMD and MMS to identify predictors of ischemic event recurrence.

We reviewed a pediatric moyamoya cohort followed between 2003 and 2019. Clinical and radiographic characteristics at diagnosis and follow-up were abstracted. Comparisons between MMD and MMS as well as between MMD and two MMS subgroups (neurofibromatosis [MMS-NF1] and sickle cell disease [MMS-SCD]) were performed.

A total of 111 patients were identified. Patients with MMD presented commonly with transient ischemic attacks (TIAs) (35 % MMD versus 13% MMS-NF1 versus 9.5% MMS-SCD; P=0.047). Symptomatic stroke presentation (MMD 37% versus MMS-NF1 4% versus 33%; P=0.0147) and bilateral disease at diagnosis (MMD 73% versus MMS-NF1 22 % versus MMS-SCD 67%; P=0.0002) were uncommon in MMS-NF1. TIA recurrence was common in MMD (hazard ratio 2.86; P=0.001). The ivy sign was absent on neuroimaging in a majority of patients with MMS-SCD (MMD 67% versus MMS-NF1 52% versus MMS-SCD 9.5%; P=0.0002). Predictors of poor motor outcome included early age at diagnosis (odds ratio [OR] 8.45; P=0.0014), symptomatic stroke presentation (OR 6.6; P= 0.019), and advanced Suzuki stage (OR 3.59; P=0.019).

Moyamoya exhibits different phenotypes based on underlying etiologies. Frequent TIAs is a common phenotype of MMD and symptomatic stroke presentation a common feature of MMD and MMS-SCD, whereas unilateral disease and low infarct burden are common in MMS-NF1. In addition, absence of ivy sign is a common phenotype in MMS-SCD.

Moyamoya exhibits different phenotypes based on underlying etiologies. Frequent TIAs is a common phenotype of MMD and symptomatic stroke presentation a common feature of MMD and MMS-SCD, whereas unilateral disease and low infarct burden are common in MMS-NF1. In addition, absence of ivy sign is a common phenotype in MMS-SCD.

Neurological manifestations are commonly reported in patients with celiac disease (CD). We aimed to characterize epilepsy features in a pediatric population with CD and the effect of a gluten-free diet (GFD) on seizure burden.

A retrospective chart review was performed on pediatric patients treated at the University of Utah and Primary Children's Hospital in Salt Lake City, Utah, with both epilepsy and CD and compared with a control group with epilepsy only.

We identified 56 patients with epilepsy and biopsy-confirmed CD (n= 36, 64%) or elevated tissue transglutaminase antibodies (tTG-Ab) without biopsy-confirmed CD (n= 20, 36%). Age- and gender-matched controls were selected from patients with epilepsy only (n= 168). Patients with biopsy-proven CD or positive tTG-Ab had high percentage of drug-resistant epilepsy (DRE) compared with the control group (P < 0.05). Age at seizure onset preceded the diagnosis of CD on average by 5.9 years for patients with DRE (P < 0.01) compared with 2.2 years for those with drug-responsive epilepsy. Adhering to a GFD reduced seizure frequency or resulted in weaning dosage or weaning off of one or more antiseizure medications in a majority of patients with DRE.

DRE was more prevalent in pediatric patients with biopsy-confirmed CD and positive tTG-Ab compared with the control group (which included childhood epilepsy syndromes), but comparable with the prevalence of DRE in the general population. Adherence to a GFD in combination with antiseizure medications appears to reduce seizure burden for those with CD and DRE.

DRE was more prevalent in pediatric patients with biopsy-confirmed CD and positive tTG-Ab compared with the control group (which included childhood epilepsy syndromes), but comparable with the prevalence of DRE in the general population. Adherence to a GFD in combination with antiseizure medications appears to reduce seizure burden for those with CD and DRE.This paper proposes natural drug candidate compounds for the treatment of coronavirus disease 2019 (COVID-19). We investigated the binding properties between the compounds in the Moringa oleifera plant and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 using molecular docking and ab initio fragment molecular orbital calculations. Among the 12 compounds, niaziminin was found to bind the strongest to Mpro. We furthermore proposed novel compounds based on niaziminin and investigated their binding properties to Mpro. The results reveal that the introduction of a hydroxyl group into niaziminin enhances its binding affinity to Mpro. These niaziminin derivatives can be promising candidate drugs for the treatment of COVID-19.

This study aimed to assess if a forearm (FA) intravenous regional anesthesia (IVRA) with a lower, less toxic, local anesthetic dosage is non-inferior to an upper arm (UA) IVRA in providing a surgical block in patients undergoing hand and wrist surgery.

Observer-blinded, randomized non-inferiority study.

Operating room.

280 patients undergoing hand surgery were randomly assigned to UA IVRA (n=140) or FA IVRA (n=140).

Forearm IVRA or upper arm IVRA in patients undergoing hand and wrist surgery.

The primary outcome was block success rate of both techniques. Block success was defined as no need of additional analgesics. A second, alternative non-inferiority outcome was defined as no need of conversion to general anesthesia. A difference in success rate of <5% was considered non-inferior. Secondary endpoints were tourniquet pain measured with a Numerical Rating Scale (0-10), satisfaction of patients and surgeons, onset time, surgical time and total OR time.

Non-inferiority of block success rate, da was confirmed.

Viscoelastic point-of-care (POC) tests are commonly used to provide prompt diagnosis of coagulopathy and allow targeted treatments in bleeding patients on ECMO. We evaluated the clinical effectiveness of point-of-care (POC) testing for anticoagulation management in patients on extracorporeal membrane oxygenation (ECMO).

Systematic review and meta-analysis. Eligible studies evaluating the use of thromboelastography- or thromboelastometry-guided algorithms, anti-factor Xa and platelet function testing were selected after screening the literature from July 1975 to January 2020.

Patients on ECMO support.

Anticoagulation management on ECMO patients.

Rotational thromboelastometry, thromboelastography, alone or combined with platelet function testing. Trials monitoring the anticoagulation effects during ECMO using an anti-factor Xa assay were included in the systematic review.

The primary outcomes were bleeding events, surgical revisions, thrombosis events and ECMO circuit change/failure. Secondary outcoes beyond suggesting a diagnosis of surgical bleeding in ECMO patients.

To identify whether adding intrathecal ketamine to intrathecal bupivacaine prolongs the time to first analgesic request in adult humans.

A meta-analysis of randomized controlled trials in humans.

The majority of data was obtained in an operating room and postoperative recovery area.

A total of 750 ASA physical status I and II patients were included in the study. Procedures performed include cesarean section, lower abdominal surgery, lower limb surgery, and urologic surgery.

Databases including PubMed, Embase, Web of Science, and Cochrane were searched. NVP-BHG712 chemical structure Google Scholar was also queried. Multiple reviewers screened the papers for inclusion.

The primary outcome assessed was time to first analgesic request. Secondary outcomes included onset of sensory blockade, onset of motor blockade, duration of sensory blockade, and duration of motor blockade. Data were extracted to include means, 95% confidence intervals, tests for heterogeneity, and use of the Cochrane Collaboration guidelines to assess for publicto optimize dosing, clarify the safety and efficacy of this intrathecal drug combination, and examine the various ketamine formulations as intrathecal bupivacaine adjuvants.

The studies analyzed suggest there may be a benefit to using intrathecal ketamine as an adjunct to bupivacaine. Additional studies are warranted to optimize dosing, clarify the safety and efficacy of this intrathecal drug combination, and examine the various ketamine formulations as intrathecal bupivacaine adjuvants.Neurofilament light chain (NfL) is an axonal protein that when measured in cerebrospinal fluid (CSF) serves as a biomarker of neurodegeneration. We aimed at investigating the association among CSF NfL, presence of Subjective Cognitive Decline (SCD) and hippocampal volume, and how CSF amyloid-β (Aβ) modifies these associations. We included 278 cognitively unimpaired participants from the Alfa+ cohort (78 SCD and 200 Controls). Linear models accounting for covariates (age, gender, and mood) were used to test the association between CSF NfL and SCD status, and between CSF NfL and bilateral hippocampal volumes. Interactions with Aβ were also explored. Individuals with SCD had higher CSF NfL and lower CSF Aβ42/40 than Controls. There was a significant interaction between SCD and CSF-Aβ42/40 levels. Stratified analyses showed a significant association between SCD and NfL only in Aβ+ individuals. Higher CSF NfL was significantly associated with lower hippocampal volume specifically in Aβ+ individuals with SCD. The presence of SCD in Aβ+ individuals may represent an early symptom in the Alzheimer's continuum related to incipient neurodegeneration.

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