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Τετάρτη 9 Νοεμβρίου 2022

Obesity-related SNPs and weight gain following first-line antiretroviral therapy

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Abstract
Background
We studied the association of obesity-related SNPs (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with HIV (PWH).
Methods
Participants were ART-naïve PWH from the Spanish HIV Research Cohort who started ART from 2014 onwards and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of GWAS body mass index (B MI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models (A-LMM).
Results
A total of 1,021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% CI: 2.54–3.26) Kg. Factors associated with higher weight gain were female sex, birth in Sub-Saharan Africa, prior AIDS, CD4+ < 200 cells/uL, HIV-RNA > 100,000 copies/mL, negative HCV serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotypes polymorphisms and weight and BMI increase. The estimated adjusted mean (SE) of weight gains were 4.26 (0.56) Kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) Kg in AA/AG carriers (P = 0.007). Likewise, the estimated means (SE) weight gain at 96 weeks were 3.35 (0.29) Kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) Kg in AG/AA carriers (P = 0.020).
Conclusions
Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.
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Radiomics‐based machine learning for the diagnosis of lymph node metastases in patients with head and neck cancer: Systematic review

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Abstract

Machine learning (ML) is increasingly used to detect lymph node (LN) metastases in head and neck (H&N) carcinoma. We systematically reviewed the literature on radiomic-based ML for the detection of pathological LNs in H&N cancer. A systematic review was conducted in PubMed, EMBASE, and the Cochrane Library. Baseline study characteristics and methodological quality items (modeling, performance evaluation, clinical utility, and transparency items) were extracted and evaluated. The qualitative synthesis is presented using descriptive statistics. Seven studies were included in this study. Overall, the methodological quality items were generally favorable for modeling (57% of studies). The studies were mostly unsuccessful in terms of transparency (85.7%), evaluation of clinical utility (71.3%), and assessment of generalizability employing independent or external validation (72.5%). ML may be able to predict LN metastases in H&N cancer. Further studies are warranted to impro ve the generalizability assessment, clinical utility evaluation, and transparency items.

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Clinical trials on the pharmacological treatment of long COVID: a systematic review

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Abstract

Background

The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), also known as post-acute coronavirus disease 19 (COVID-19) or the long COVID syndrome (long COVID) is an emerging public health concern. A substantial proportion of individuals may remain symptomatic months after initial recovery. An updated review of published and ongoing trials focusing on managing long COVID will help identify gaps and address the unmet needs of patients suffering from this potentially debilitating syndrome.

Methods

A comprehensive literature search was conducted on the international databases and clinical trial registries from inception to 31 July 2022.

Results

This review included 6 published trials and 54 trial registration records. There is significant heterogeneity in the characterization of long COVID and ascertainment of primary outcomes. Most of the trials are focused on individual symptoms of long COVI D or isolated organ dysfunction, classified according to cardiovascular, respiratory and functional capacity, neurological and psychological, fatigue, and olfactory dysfunction. Most of the interventions are related to the mechanisms causing the individual symptoms. Although the 6 published trials showed significant improvement in the symptoms or organ dysfunction studied, these initial studies lack internal and external validity limiting the generalizability.

Conclusions

This review provides an update of the pharmacological agents that could be used to treat long COVID. Further standardization of the diagnostic criteria, inclusion of participants with concomitant chronic cardiometabolic diseases and standardization of outcomes will be essential in future clinical trials.

This article is protected by copyright. All rights reserved.

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Comprehensive analysis of HHV‐6 and HHV‐7‐related gene signature in prognosis and response to temozolomide of glioma

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Abstract

Background

Human herpesvirus (HHV)-6 and HHV-7 have been detected in central nervous system and glioma tissue, while their exact role in glioma remains uncertain.

Methods

Omics profiles and clinical information were downloaded from public databases, including TCGA cohort for training set and the CGGA cohorts for validation sets. Differentially expressed genes between HHV-6 and HHV-7 infected or non-infected glioma patients were screened for establishing the HHV-6 and HHV-7 infection (HI) model through Lasso regression analysis. Bioinformatics methods were used to analyze the correlation between HI scores and prognosis, metastasis in glioma patients. Predictable efficacy of HI in temozolomide-resistance and HI-related genetic signatures were also explored.

Results

The HI model was constructed as: Risk score = (0.014709*DIRAS3) + (0.029787*TEX26) + (0.223492*FBXO39) + (0.074951*MYBL1) + (0.060202*HILS1). The 5 gene signature showed good perfor mance in predicting survival time for glioma patients, while higher HI score is correlated with malignant features. Moreover, DNA mismatch repair genes were augmented in glioma patients with higher HI score as well as non-response to temozolomide treatment, which was in parallel with the transcriptomic result of temozolomide-resistant glioma cell.

Conclusions

Targeting the five gene signature is beneficial for prognosis of glioma patients, especially in glioma patients underwent temozolomide treatment.

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Ocular survival after intra‐arterial chemotherapy for retinoblastoma improves with accrual of experience and programmatic evolution

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Abstract

Background

Intra-arterial chemotherapy (IAC) for the treatment of intraocular retinoblastoma has gained recognition as a method to improve ocular salvage; however, there is a paucity of evidence supporting treatment factors prognosticating ocular survival.

Methods

All patients with retinoblastoma treated with IAC at a single institution between December 2008 and December 2019 were evaluated. Patient demographics, tumor classification, prior treatments, procedural data, other non-IAC therapies, adverse reactions, procedural complications, ocular outcomes, and overall survival were assessed via retrospective chart review. Factors suggestive of increased ocular survival were identified via univariate and multivariate analyses. The impact of accrued treatment experience was evaluated by grouping eyes by the respective year, IAC treatment was initiated.

Results

Forty-nine eyes of 43 patients were treated for retinoblastoma with IAC (256 total procedures). At least grade 3 neutropenia was observed following 19% of IAC procedures. The risk of neutropenia was not statistically different between single or multidrug IAC. Comparing those who received balloon-assisted intra-arterial chemotherapy (bIAC) in more than two-thirds of cycles to those who did not, the risk of arterial access site complications was not statistically different. Multivariate analysis revealed a significantly lower risk of enucleation associated with treatment era in years (hazard ratio [HR] = 0.52–1.00, p < .05) and laser therapies (HR = 0.02–0.60, p < .05).

Conclusions

Ocular survival rates in patients treated with IAC for retinoblastoma at our institution have increased over time. Accrued treatment experience and programmatic changes have likely contributed. Larger, prospective series may lead to a better understanding of factors that consistently contribute to better ocular salvage.

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RANDOMISED CLINICAL TRIAL TO ASSESS THE IMPACT OF ORAL INTERVENTION WITH CETYLPYRIDINIUM CHLORIDE (CPC) TO REDUCE SALIVARY SARS‐CoV‐2 VIRAL LOAD

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Aerosols released from the oral cavity help spread the SARS-CoV-2 virus. The use of a mouthwash formulated with an antiviral agent could reduce the viral load in saliva, helping to lower the spread of the virus.

Aim

The aim of this study was to assess the efficacy of a mouthwash with 0.07% cetylpyridinium chloride to reduce the viral load in saliva of COVID-19 patients.

Material and Methods

In this multi-centre, single-blind, randomised, parallel group clinical trial, 80 COVID-19 patients were enrolled and randomised to two groups, test (N=40) and placebo (N=40). Saliva samples were collected at baseline and 2 hours after rinsing. The samples were analysed by RT-qPCR and an ELISA test specific for the nucleocapsid (N) protein of SARS-CoV-2.

Results

By means of RT-qPCR, no significant differences were observed between the placebo group and the test group. However, 2 hours after a single rinse N protein concentration in saliva was significantly higher in the test group, indicating an increase in lysed virus.

Conclusions

The use of 0.07% CPC mouthwash induced a significant increase in N protein detection in the saliva of COVID-19 patients. Lysis of the virus in the mouth could help reduce the transmission of SARS-CoV-2. However, more studies are required to prove this.

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A 53‐year‐old woman with a rapidly progressive, non‐enhancing left frontotemporal lesion

alexandrossfakianakis shared this article with you from Inoreader

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Brain Pathology
Brain Pathology
CASE IMAGE
Open Access
A 53-year-old woman with a rapidly progressive, non-enhancing left frontotemporal lesion
Michael L. Miller,Daniel W. Griepp,Yu Sun,Sean Tamir,Rebecca Straus Farber,Marc L. Otten,Osama Al-Dalahmah
First published: 08 November 2022 https://doi.org/10.1111/bpa.13125
Michael L. Miller and Daniel W. Griepp contributed equally to this study.
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Abstract
Fifty-three-year-old woman presented with chronic, episodic headache.

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1 CLINICAL HISTORY AND IMAGING
A 53-year-old woman presented with chronic, episodic headache. The patient's headache was first noted several years prior to presentation and would occur for weeks to months, then remit for several weeks to months. More recently, the severity of the headache worsened which prompted a referral to neurology. The patient's past medical history included bilateral knee arthralgia and swelling about 6 years prior to presentation, which since resolved. While the symptoms raised the possibility of Lyme disease or rheumatoid arthritis (RA), neither diagnosis was confirmed. Given the patient's intractable headache, magnetic resonance imaging (MRI) was performed which revealed a non-enhancing left frontal white matter lesion (Figure 1A). On evaluation by neurosurgery, observation was initially recommended with the possibility of open biopsy. At follow-up, despite resolution of the patient's presenting symptom of headache, the patient began to show signs of subjective neurocognitive impairment s, including word-finding difficulty, poor performance playing chess, and fear of driving. Repeat imaging 3 months since presentation revealed progression of the lesion (Figure 1B) with expansion into the temporal lobe (not shown). Given the relatively rapid radiographic progression, the lesion was biopsied with concern for a neoplastic process (Box 1).

Details are in the caption following the image
FIGURE 1
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PowerPoint
Brain magnetic resonance imaging. Axial plane FLAIR sequences at initial presentation (A) and at follow up 3–4 months later (B) revealed relatively rapid progression of the left frontal lobe.
BOX 1. Slide scan
Access the whole slide scan at https://isn-slidearchive.org/?col=ISN&fol=Archive&file=BPA-21-12-302.svs

2 FINDINGS
Hematoxylin and eosin (H&E)-stained sections revealed gliotic brain. Mixed chronic- and focally acute-appearing inflammatory infiltrates composed primarily of histiocytes and multinucleated giant cells, with scant lymphocytes and occasional eosinophils, involved most cortical vessels (Figure 2A–C). Transmural disruption and focal necrosis were also identified (Figure 2A), as were scattered well-formed granulomas. Cortical and leptomeningeal vessels appeared thickened and occasionally produced a double-barreled appearance. Focally exuberant perivascular hemosiderin deposits were identified. Within the vessel walls, deposition of amorphous, congophilic material was identified that appeared green-red birefringent under polarized light (Figure 2D,E). Immunohistochemistry with beta-amyloid revealed intense circumferential staining in the leptomeningeal and cortical blood vessels (Figure 2F).

Details are in the caption following the image
FIGURE 2
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PowerPoint
Histology of brain biopsy. Gliotic brain parenchyma with focal fibrinous exudate of vessels (A) and angiocentric inflammation composed of monocytes, lymphocytes, and prominent giant cells (B). (C) Giant cells were highlighted with CD68 immunostain. (D) Congophilic material within vascular walls, which appeared apple-green when viewed under polarized light (inset). (E and F) Intense, circumferential accumulation of beta-amyloid around intraparenchymal vessel, including vessels with prominent transmural inflammation (for all, scale bar = 50 μm)
3 FINAL DIAGNOSIS
Amyloid beta-related angiitis (ABRA).

4 DISCUSSION
A defining feature of ABRAis the presence of cerebral amyloid angiopathy (CAA) in association with vasculitis [1]. Given prognostic and predictive differences of ABRA when compared to CNS vasculitis in the absence of CAA and CAA in the absence of vasculitis, accurate distinction is clinically meaningful [2]. For instance, in contrast to ABRA, primary CNS vasculitis without CAA generally results in a less favorable outcome [2]. While CAA is primarily the result of imbalanced amyloid production and clearance, ABRA is thought to occur when beta-amyloid vascular deposits are recognized as foreign antigens [1]. Although ABRA generally occurs earlier in life compared to CAA, most studies describe presentation of ABRA in the sixth or seventh decades of life [1, 3]. Predisposing factors to the development of ABRA are not clearly defined, although it is associated with preexisting autoimmune processes, prior radiation treatment, and ApoE4 genotype. It is notable that the present patient was r elatively young and had a possible history of rheumatoid arthritis.

The inflammatory process of ABRA results in the destruction of vessels. Previously reported cases of ABRA were typically characterized by severe leptomeningeal and parenchymal amyloid angiopathy, along with chronic inflammation within the leptomeninges and in and around vessel walls [3]. Granulomatous inflammatory infiltrates and large multinucleated macrophages are also characteristic findings [1, 3]. Extensive fibrinoid necrosis of vessels may be identified [3]. Features characteristic of CAA may also be observed, such as hemosiderin-laden macrophages suggestive of prior hemorrhage [3]. Many of these histopathological features were appreciated in the present case.

Diagnosis of ABRA is difficult given the generally non-specific clinical presentation and broad radiographic diagnosis. While the signs of CAA are more likely to manifest as spontaneous lobar intracerebral hematoma or progressive dementia, the presenting signs of ABRA may include seizure, mental status change, headache, or newly recognized focal neurological deficits. Radiographic changes are also nonspecific, but typically include asymmetric subcortical white matter lesions, evidence of microhemorrhages, and leptomeningeal enhancement. The present patient's clinical presentation was non-specific and consisted of headache that progressed to word-finding difficulty. The radiographic presentation showed a non-enhancing white matter lesion as well as several punctate areas of susceptibility outside of the lesion. Thus overall, prior to biopsy, there was a concern for malignancy although a diverse differential including inflammatory processes was considered.

Definitive diagnosis of ABRA is rendered through microscopic examination of a targeted brain biopsy. The most successful treatments reported include immunosuppression with prednisone and/or cyclophosphamide, although other immunosuppressive agents have been successful [1, 3]. With treatment, approximately three quarters of patients recover to some degree while approximately one quarter develops relapses [1]. While in our case, the patient's young age and the rapid radiologic progression of the lesion prompted a biopsy—which was diagnostic—it is important to remember that when ABRA/CAA is clinically suspected, the diagnosis can be made without surgery when imaging is supportive.

AUTHOR CONTRIBUTIONS
Michael L. Miller, Daniel W. Griepp and Osama Al-Dalahmah wrote the original draft. Yu Sun, Sean Tamir, Rebecca Straus Farber and Marc L. Otten reviewed and edited the draft.

CONFLICT OF INTEREST
The authors declare no conflict of interest.

ETHICS STATEMENT
All data related to this case are deidentified.

Open Research
REFERENCES

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A 53-year-old woman with a rapidly progressive, non-enhancing left frontotemporal lesion

Fifty-three-year-old woman presented with chronic, episodic headache.


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Uprighting a Mesially Tilted Molar Using Customized Titanium Healing Abutment of an Adjacent Osseointegrated Implant

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Abstract

This case report evaluates the use of a customized healing abutment of a dental implant to upright a mesially tilted molar using elastic separating rings. The external surface of the healing abutment was roughened by air particle abrasion, and a flowable composite was applied as a collar around it. The size of the resin collar was increased several times during the molar uprighting treatment by replacing the elastic ring. The uprighting procedure was evaluated after 2 months using radiographic and clinical evaluations. After treatment, the mesiodistal space above the implant was increased from 6 mm to 9 mm as follows: 2 mm by uprighting the second molar and 1 mm by mesial shifting the second premolar, and then a screw-retained zirconia crown was placed to restore the implant. The healing abutment of the implant can be modified by adding a resin collar and used as orthodontic anchorage for uprighting the adjacent tilted molar to facilitate the prosthetic procedure. Neither special instruments nor an orthodontic background are required for this minor tooth movement.

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Maternal age and the risk of low birthweight and pre-term delivery: a pan-Nordic comparison

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Abstract
BackgroundAdvanced maternal age at birth is considered a risk factor for adverse birth outcomes. A recent study applying a sibling design has shown, however, that the association might be confounded by unobserved maternal characteristics.
Methods
Using total population register data on all live singleton births during the period 1999–2012 in Denmark (N = 580 133; 90% population coverage), Norway (N = 540 890) and Sweden (N = 941 403) and from 2001–2014 in Finland (N = 568 026), we test whether advanced maternal age at birth independently increases the risk of low birthweight (LBW) (<2500 g) and pre-term birth (<37 weeks gestation). We estimated within-family models to reduce confounding by unobserved maternal characteristics shared by siblings using three model specifications: Model 0 ex amines the bivariate association; Model 1 adjusts for parity and sex; Model 2 for parity, sex and birth year.
Results
The main results (Model 1) show an increased risk in LBW and pre-term delivery with increasing maternal ages. For example, compared with maternal ages of 26–27 years, maternal ages of 38–39 years display a 2.2, 0.9, 2.1 and 2.4 percentage point increase in the risk of LBW in Denmark, Finland, Norway and Sweden, respectively. The same patterns hold for pre-term delivery.
Conclusions
Advanced maternal age is independently associated with higher risk of poor perinatal health outcomes even after adjusting for all observed and unobserved factors shared between siblings.
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