Effects of folic acid supplementation on C-reactive protein: A systematic review and meta-analysis of randomized controlled trials

Background and aim

Given the contradictory results of previous randomized controlled trials (RCTs), we performed a systematic review and meta-analysis to quantify and summarize the effects of folic acid supplementation on C-reactive protein (CRP).

Influence of Prior Psychiatric Disorders on the Treatment Course of Gynaecological Cancer – A Nationwide Cohort Study

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

Effects of Mu-Opiate Receptor Gene Polymorphism rs1799971 (A118G) on the Antidepressant and Dissociation Responses in Esketamine Nasal Spray Clinical Trials

BackgroundAt ketamine and esketamine doses at which antidepressant doses are achieved, these agents are relatively selective, noncompetitive, N-methyl-D-aspartate receptor antagonists. However, at substantially higher doses, ketamine has shown mu-opioid receptor (MOR–gene symbol: OPRM1) agonist effects. Preliminary clinical studies showed conflicting results on whether naltrexone, a MOR antagonist, blocks the antidepressant action of ketamine. We examined drug-induced or endogenous MOR involvement in the antidepressant and dissociative responses to esketamine by assessing the effects of a functional single nucleotide polymorphism rs1799971 (A118G) of OPRM1, which is known to alter MOR agonist-mediated responses.MethodsParticipants with treatment-resistant depression from 2 phase III, double-blind, controlled trials of esketamine (or placebo) nasal spray plus an oral antidepressant were genotyped for rs1799971. Participants received the experimental agents twice weekly for 4 weeks. Antidepressant responses were rated using the change in Montgomery–Åsberg Depression Rating Scale (MADRS) score on days 2 and 28 post-dose initiation, and dissociative side effects were assessed using the Clinician-Administered Dissociative-States Scale at 40 minutes post-dose on days 1 and 25.ResultsIn the esketamine + antidepressant arm, no significant genotype effect of single nucleotide polymorphism rs1799971 (A118G) on MADRS score reductions was detected on either day 2 or 28. By contrast, in the antidepressant + placebo arm, there was a significant genotype effect on MADRS score reductions on day 2 and a nonsignificant trend on day 28 towards an improvement in depression symptoms in G-allele carriers. No significant genotype effects on dissociative responses were detected.ConclusionsVariation in rs1799971 (A118G) did not affect the antidepressant response to esketamine + antidepressant. Antidepressant response to antidepressant + placebo was increased in G-allele carriers, compatible with previous reports that release of endorphins/enkephalins may play a role in mediating placebo effect.Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT02417064","term_id":"NCT02417064"}}NCT02417064 and {"type":"clinical-trial","attrs":{"text":"NCT02418585","term_id":"NCT02418585"}}NCT02418585; www.clinicaltrials.gov     

Long-term Implications of Tracheostomy in Cardiac Surgery Patients: Decannulation and Mortality

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Adherence to the Mediterranean diet and weight status in children: the role of parental feeding practices

Abstract

The study examines Parental Feeding Practices (PFP) in relation to adherence to the Mediterranean Diet (MD) and children’s weight status. It’s a cross-sectional study of 402 parents (68.4% mothers), with children aged 2–12 years. Parents completed the Comprehensive Parental Feeding Questionnaire and the Mediterranean Diet Quality Index for children and adolescents (KIDMED), evaluating children’s adherence to the MD. Logistic regression showed that in children aged 2–<6 years, “emotion regulation/food as reward” and “pressure” decrease MD adherence (OR?=?0.186, p?<?0.0001 and OR?=?0.496, p?=?0.004), and “monitoring” decrease excess body weight (OR?=?0.284, p?=?0.009). In older children (6–12 years), “healthy eating guidance” and “monitoring” increase MD adherence (OR?=?3.262, p?=?0.001 and OR?=?3.147, p?<?0.0001), “child control” decreases MD adherence (OR?=?0.587, p?=?0.049), “pressure” decrease excess body weight (OR?=?0.495, p?<?0.0001) and “restriction” increase excess body weight (OR?=?1.784, p?=?0.015). “Healthy eating guidance” and “monitoring” seem to be the best PFP employed, in terms of children’s MD adherence and weight status.     

Tractography of the Cerebellar Peduncles in Second- and Third-Trimester Fetuses

BACKGROUND AND PURPOSE:Little is known about microstructural development of cerebellar white matter in vivo. This study aimed to investigate developmental changes of the cerebellar peduncles in second- and third-trimester healthy fetuses using motion-corrected DTI and tractography.MATERIALS AND METHODS:3T data of 81 healthy fetuses were reviewed. Structural imaging consisted of multiplanar T2-single-shot sequences; DTI consisted of a series of 12-direction diffusion. A robust motion-tracked section-to-volume registration algorithm reconstructed images. ROI-based deterministic tractography was performed using anatomic landmarks described in postnatal tractography. Asymmetry was evaluated qualitatively with a perceived difference of >25% between sides. Linear regression evaluated gestational age as a predictor of tract volume, ADC, and fractional anisotropy.RESULTS:Twenty-four cases were excluded due to low-quality reconstructions. Fifty-eight fetuses with a median gestational age of 30.6 weeks (interquartile range, 7 weeks) were analyzed. The superior cerebellar peduncle was identified in 39 subjects (69%), and it was symmetric in 15 (38%). The middle cerebellar peduncle was identified in all subjects and appeared symmetric; in 13 subjects (22%), two distinct subcomponents were identified. The inferior cerebellar peduncle was not found in any subject. There was a significant increase in volume for the superior cerebellar peduncle and middle cerebellar peduncle (both, P < .05), an increase in fractional anisotropy (both, P < .001), and a decrease in ADC (both, P < .001) with gestational age. The middle cerebellar peduncle had higher volume (P < .001) and fractional anisotropy (P = .002) and lower ADC (P < .001) than the superior cerebellar peduncle after controlling for gestational age.CONCLUSIONS:A robust motion-tracked section-to-volume registration algorithm enabled deterministic tractography of the superior cerebellar peduncle and middle cerebellar peduncle in vivo and allowed characterization of developmental changes.

In the second half of pregnancy, the cerebellum is growing rapidly and is extremely vulnerable.¹ Despite the increasingly recognized association of antenatal and perinatal cerebellar injury with adverse motor and neurologic outcomes later in life,^2-5 little is known about normal cerebellar developmental in the later part of gestation, in particular with regard to changes in microstructure. In fact, most existing fetal MR imaging data addresses primarily changes in cerebellar volume with gestational age (GA) or changes in volume and their association with specific diseases such as congenital heart disease.^6-8In vivo evaluation of cerebellar microstructure using fetal MR imaging has been limited by the technical challenges related to imaging the gravid abdomen, particularly patient motion. However, data from ex vivo MR imaging studies are promising. For instance, Takahashi et al^9,10 performed high-resolution ex vivo DTI of fetal specimens and demonstrated the feasibility of using tractography to outline the cerebellar peduncles prenatally. Even though tractography of the cerebellar peduncles has been sporadically reported in vivo in technical articles or general review articles on fetal DTI,¹¹ the GA-related microstructural changes that occur in the cerebellar peduncles in the second half of pregnancy remain largely unexplored.Recent advances in hardware and software have improved fetal MR imaging substantially. The use of 3T magnets, which have been shown to be safe, results in improvement of the SNR and spatial resolution, which is advantageous to image the small structures of the fetal brain.^12,13 In addition, postprocessing algorithms that enable reconstruction of motion-corrected fetal DTI data are increasingly available and have been used by several groups to characterize the development of the supratentorial white matter tracts in vivo.^14-16 We hypothesize that fetal DTI performed at 3T and processed with a robust section-to-volume motion-correction and registration¹⁴ algorithm will enable tractography of the cerebellar peduncles in fetuses in the second and third trimesters of pregnancy. We aimed to characterize fetal cerebellar tract microstructure and to investigate tract-specific developmental changes.     

Postprocedural Antiplatelet Treatment after Emergent Carotid Stenting in Tandem Lesions Stroke: Impact on Stent Patency beyond Day 1

BACKGROUND AND PURPOSE:Postprocedural dual-antiplatelet therapy is frequently withheld after emergent carotid stent placement during stroke thrombectomy. We aimed to assess whether antiplatelet regimen variations increase the risk of stent thrombosis beyond postprocedural day 1.MATERIALS AND METHODS:Retrospective review was undertaken of all consecutive thrombectomies for acute stroke with tandem lesions in the anterior circulation performed in a single comprehensive stroke center between January 9, 2011 and March 30, 2020. Patients were included if carotid stent patency was confirmed at day 1 postprocedure. The group of patients with continuous dual-antiplatelet therapy from day 1 was compared with the group of patients with absent/discontinued dual-antiplatelet therapy.RESULTS:Of a total of 109 tandem lesion thrombectomies, 96 patients had patent carotid stents at the end of the procedure. The early postprocedural stent thrombosis rate during the first 24 hours was 14/96 (14.5%). Of 82 patients with patent stents at day 1, in 28 (34.1%), dual-antiplatelet therapy was either not initiated at day 1 or was discontinued thereafter. After exclusion of cases without further controls of stent patency, there was no significant difference in the rate of subacute/late stent thrombosis between the 2 groups: 1/50 (2%) in patients with continuous dual-antiplatelet therapy versus 0/22 (0%) in patients with absent/discontinued dual-antiplatelet therapy (P = 1.000). In total, we observed 88 patient days without any antiplatelet treatment and 471 patient days with single antiplatelet treatment.CONCLUSIONS:Discontinuation of dual-antiplatelet therapy was not associated with an increased risk of stent thrombosis beyond postprocedural day 1. Further studies are warranted to better assess the additional benefit and optimal duration of dual-antiplatelet therapy after tandem lesion stroke thrombectomy.

In around 15% of endovascular procedures for anterior circulation stroke,¹ there is a tight stenosis or occlusion of the cervical carotid artery in addition to the intracranial artery occlusion. The optimal endovascular management of tandem lesions has yet to be defined; however, there is mounting evidence^2,3 that emergent stent placement in the carotid artery associated with at least 1 antiplatelet agent could lead to better recanalization rates and improved clinical outcomes. A more definitive answer should be provided by the Thrombectomy In TANdem lesions (TITAN) randomized multicenter trial,⁴ designed to assess the safety and efficacy of emergent internal carotid artery stent placement in tandem lesion thrombectomy. This study recently enrolled the first patient in early 2020.In patients undergoing emergent carotid stent placement, there is no consensus regarding the optimal periprocedural antiplatelet therapy. Many groups^5,6 chose to avoid dual-antiplatelet therapy (DAPT) during the first 24 hours in an attempt to reduce the risk of hemorrhagic transformation. Conversely, less aggressive antiplatelet regimens might increase the risk of carotid stent thrombosis.Stent thrombosis was recently identified as a predictor of unfavorable clinical outcome.^7,8 To date, available data regarding stent patency rates remain scarce. Most case series of endovascular management for tandem lesions^5,9-11 do not report postprocedural stent patency, while some publications^12-15 offer partial data for a subgroup of patients for whom carotid imaging controls were available. Reported rates of stent thrombosis ranged between 1.2% and 22.0%.^{6-8,12-14,16,17}To date, no study has attempted to differentiate between early (first 24 hours) and subacute/late postprocedural stent thrombosis. During the first 24 hours, protection against stent thrombosis is conferred by antiplatelet agents administered during the procedure (periprocedural antiplatelets). Beyond 24 hours, the recommended antiplatelet regimen is DAPT for 4–12 weeks,^9,17 but in reality, antiplatelets are often tailored in view of neurological and extra-neurological hemorrhagic events. It is currently unknown whether discontinuation of DAPT is associated with an increased risk of late stent thrombosis.Thus, we aimed to describe the variations in the postprocedural antiplatelet regimen in a large consecutive cohort of tandem lesion thrombectomies with emergent carotid artery stent placement and to assess whether discontinuation of DAPT was associated with an increased risk of carotid stent thrombosis.     

Pituitary Adenylate Cyclase-Activating Polypeptide Attenuates Brain Edema by Protecting Blood–Brain Barrier and Glymphatic System After Subarachnoid Hemorrhage in Rats

Brain edema is a vital contributor to early brain injury after subarachnoid hemorrhage (SAH), which is responsible for prolonged hospitalization and poor outcomes. Pharmacological therapeutic targets on edema formation have been the focus of research for decades. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to participate in neural development and brain injury. Here, we used PACAP knockout CRISPR to demonstrate that endogenous PACAP plays an endogenous neuroprotective role against brain edema formation after SAH in rats. The exogenous PACAP treatment provided both short- and long-term neurological benefits by preserving the function of the blood–brain barrier and glymphatic system after SAH. Pretreatment of inhibitors of PACAP receptors showed that the PACAP-involved anti-edema effect and neuroprotection after SAH was facilitated by the selective PACAP receptor (PAC1). Further administration of adenylyl cyclase (AC) inhibitor and sulfonylurea receptor 1 (SUR1) CRISPR activator suggested that the AC–cyclic adenosine monophosphate (cAMP)–protein kinase A (PKA) axis participated in PACAP signaling after SAH, which inhibited the expression of edema-related proteins, SUR1 and aquaporin-4 (AQP4), through SUR1 phosphorylation. Thus, PACAP may serve as a potential clinical treatment to alleviate brain edema in patients with SAH.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00925-3) contains supplementary material, which is available to authorized users.Key Words: Subarachnoid hemorrhage, brain edema, pituitary adenylate cyclase-activating polypeptide, blood–brain barrier, glymphatic system     

Can MRI differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma? A systematic review

Background and purpose — Adequate staging of chondroid tumors at diagnosis is important as it determines both treatment and outcome. This systematic review provides an overview of MRI criteria used to differentiate between atypical cartilaginous tumors (ACT) and high-grade chondrosarcoma (HGCS).Patients and methods — For this systematic review PubMed and Embase were searched, from inception of the databases to July 12, 2018. All original articles describing MRI characteristics of pathologically proven primary central chondrosarcoma and ACT were included. A quality appraisal of the included papers was performed. Data on MRI characteristics and histological grade were extracted by 2 reviewers. Meta-analysis was performed if possible. The study is registered with PROSPERO, CRD42018067959.Results — Our search identified 2,132 unique records, of which 14 studies were included. 239 ACT and 140 HGCS were identified. The quality assessment showed great variability in consensus criteria used for both pathologic and radiologic diagnosis. Due to substantial heterogeneity we refrained from pooling the results in a meta-analysis and reported non-statistical syntheses. Loss of entrapped fatty marrow, cortical breakthrough, and extraosseous soft tissue expansion appeared to be present more often in HGCS compared with ACT.Interpretation — This systematic review provides an overview of MRI characteristics used to differentiate between ACT and HGCS. Future studies are needed to develop and assess more reliable imaging methods and/or features to differentiate ACT from HGCS.

The incidence of chondrosarcoma of bone appears to have been increasing during the last decade and is now reported to be the most common primary malignant bone tumor in several countries (Thorkildsen et al. 2018, van Praag et al. 2018). Conventional chondrosarcoma is the most common subtype of chondrosarcoma. Other subtypes of chondrosarcoma (e.g., juxtacortical, mesenchymal, or secondary chondrosarcoma) are rare and show different radiologic appearance and clinical behavior (Bindiganavile et al. 2015).Conventional chondrosarcoma is classified into the histological grades 1 (currently known as atypical cartilaginous tumor [ACT]), 2, and 3. The metastatic potential, and therefore the disease-specific survival, correlates with the histological grade (Fletcher et al. 2013, Laitinen et al. 2018, Thorkildsen et al. 2018). ACTs rarely metastasize and are therefore reclassified as an intermediate type of tumor, not a malignancy (Fletcher et al. 2013). Due to the increase in patients undergoing MRI examinations for joint-related complaints, the incidental detection of ACT has increased substantially (van Praag et al. 2018).With the increasing incidence of ACT, clear radiologic criteria to differentiate ACT from high-grade chondrosarcoma (i.e., grades 2 and 3) become more and more important. Adequate staging of chondroid tumors at diagnosis is important as it determines both treatment and prognosis. High-grade chondrosarcomas behave aggressively. Between 10% and 30% of grade 2 and about 70% of grade 3 chondrosarcomas metastasize (Evans et al. 1977). Hence, high-grade chondrosarcoma (HGCS) requires wide en bloc resection with free surgical margins. In contrast, ACTs are intermediate tumors and can be treated either with intralesional curettage and local adjuvant or nonoperatively with regular follow-up when located in the long bones (Deckers et al. 2016).Due to the heterogenous composition of chondroid tumors, diagnostic biopsy is unreliable in assessing the genuine histological grade and malignant potential of chondrosarcomas (Laitinen et al. 2018). Therefore, physicians need to rely on imaging and clinical findings (e.g., pain is more common in HGCS) to differentiate ACT from HGCS. Imaging evaluation of cartilaginous and other bone tumors is generally based on multimodal assessment including at least conventional radiography and MRI (Nascimento et al. 2014).During the most recent decades research has focused mainly on differentiating enchondroma from chondrosarcoma (Choi et al. 2013, Douis et al. 2014, Crim et al. 2015, Lisson et al. 2018). New insights have shown that both enchondroma and ACT located in the long bones can be observed without treatment (Deckers et al. 2016, Sampath Kumar et al. 2016, Chung et al. 2018). These insights make the differentiation between ACT and HGCS clinically relevant. Currently, literature on differentiating ACT from HGCS is sparse and clear radiologic criteria are lacking. Therefore, we performed a systematic review to provide an overview of MRI characteristics used to date to differentiate between ACT and HGCS.