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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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Maternal Antibody Response and Transplacental Transfer Following SARS-CoV-2 Infection or Vaccination in Pregnancy

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Abstract
Background
Pregnant persons are at increased risk of severe COVID-19 and adverse obstetric outcomes. Understanding maternal antibody response, duration, and transplacental transfer after SARS-CoV-2 infection and COVID-19 vaccination is important to inform public health recommendations.
Methods
This prospective observational cohort study included 351 pregnant people who had SARS-CoV-2 infection or COVID-19 vaccination during pregnancy. IgG and IgM to SAR S-CoV-2 S1 receptor binding domain were measured in maternal and cord blood. Antibody levels and transplacental transfer ratios were compared across 1) disease severity for those with SARS-CoV-2 infection and 2) infection versus vaccination.
Results
There were 252 individuals with SARS-CoV-2 infection and 99 who received COVID-19 vaccination during pregnancy. Birthing people with more severe SARS-CoV-2 infection had higher maternal and cord blood IgG levels (p = 0.0001, p = 0.0001). Median IgG transfer ratio was 0.87-1.2. Maternal and cord blood IgG were higher after vaccination than infection (p = 0.001, p = 0.001). Transfer ratio was higher after 90 days in the vaccinated group (p < 0.001). Modeling showed higher amplitude and half-life of maternal IgG following vaccination (p < 0.0001). There were no significant differences by fetal sex.
Conclusions
COVID-19 vaccination in pregnancy leads to higher and longer lasting maternal IgG le vels, higher cord blood IgG, and higher transfer ratio after 90 days compared to SARS-CoV-2 infection. Greater infection severity leads to higher maternal and cord blood antibodies. Maternal IgG decreases over time following both vaccination and infection, reinforcing the importance of vaccination, even after infection, and vaccine boosters for pregnant patients.
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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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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.
SECTIONSPDFPDFTOOLS SHARE
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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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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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

alexandrossfakianakis shared this article with you from Inoreader

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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Expression of Ki-67 and P16 are related with HPV in squamous cell carcinoma of the external auditory canal

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Squamous cell carcinoma of the external auditory canal (EACSCC) is an uncommon tumor and responsible for no more than 0.2% of all the head and neck malignancies. Although there is remarkable research evidence ...
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