Comparative analysis of SARS‐CoV‐2 Omicron BA.2.12.1 and BA.5.2 variants

alexandrossfakianakis shared this article with you from Inoreader Comparative analysis of SARS‐CoV‐2 Omicron BA.2.12.1 and BA.5.2 variants via Journal of Medical Virology Abstract The initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants, BA.1 and BA.2, are being progressively displaced by BA.5 in many countries. To provide insight on the replacement of BA.2 by BA.5 as the dominant SARS-CoV-2 variant, we performed a comparative analysis of Omicron BA.2.12.1 and BA.5.2 variants in cell culture and hamster models. We found that BA.5.2 exhibited enhanced replicative kinetics over BA.2.12.1 in vitro and in vivo, which is evidenced by the dominant BA.5.2 viral genome detected at different time points, regardless of immune selection pressure with vaccine-induced serum antibodies. Utilising reverse genetics, we constructed a mutant SARS-CoV-2 carrying spike F486V substitution, which is an uncharacterized mutation that concurrently discriminates Omicron BA.5.2 from BA.2.12.1 variant. We noticed that the 486th residue does not confer viral replication advantage to the virus. We also f ound that 486V displayed generally reduced immune evasion capacity when compared with its predecessor, 486F. However, the surge of fitness in BA.5.2 over BA.2.12.1 was not due to stand-alone F486V substitution but as a result of combination of multiple mutations. Our study upholds the urgency for continuous monitoring of SARS-CoV-2 Omicron variants with enhanced replication fitness. This article is protected by copyright. All rights reserved. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Asparaginase‐related diabetic ketoacidosis: Analysis of the FDA Adverse Event Reporting System (FAERS) data and literature review

alexandrossfakianakis shared this article with you from Inoreader Asparaginase‐related diabetic ketoacidosis: Analysis of the FDA Adverse Event Reporting System (FAERS) data and literature review via Journal of Clinical Pharmacy and Therapeutics This study investigated the association between asparaginase and diabetic ketoacidosis from the perspective of adverse reaction signal detection and literature review. The reporting odd ratio (ROR) of diabetic ketoacidosis (DKA) caused by l-asparaginase was statistically significant, but there was not a statistical association for DKA caused by pegaspargase. Combined with the results of literature review, we speculated that the asparaginase dosage form may affect the occurrence of DKA. Abstract What is Known and Objective Diabetic ketoacidosis (DKA) may occur during asparaginase use. However, limited by the study population, the association between asparaginase and DKA has not been elucidated. The purpose of this study was to determine the potential association between asparaginase and DKA and analyse related clinical characteristics and possible risk factor. Methods Disproportionality analysis with the reporting odd ratio (ROR) was used to detect the adverse reaction signals of asparaginase-associated DKA in Food and Drug Administration Adverse Event Reporting System (FAERS). A literature review was conducted to further analyse clinical characteristics, possible risk factor and something noteworthy in asparaginase-associated DKA. Results and Discussion A total of 12 reports of DKA associated with l-asparaginase (l-asp) and 6 reports associated with pegaspargase (PEG-asp) were extracted in FAERS, more than 50% of the cases were classified as serious adverse events. DKA was a positive signal of l-asp (ROR = 2.397, 95% CI 1.360–4.226), while not closely related to the use of PEG-asp (ROR = 1.602, 95% CI 0.719–3.570). Searched in PubMed, Embase and Web of Science, a total of eight patients were collected. The patients were mainly adolescent patients, aged between 11 and 25 years old with a median age of 16 years. Drug dosage form distribution is unbalanced, 7 patients received l-asp and only 1 received PEG-asp. What is New and Conclusions The ROR of KDA caused by l-asp was statistically significant, but there was not a statistical association for DKA caused by PEG-asp. Asparaginase dosage form may affect the occurrence of DKA, but further research is needed. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Response assessment by positron emission tomography‐computed tomography as compared with contrast‐enhanced computed tomography in childhood Hodgkin lymphoma can reduce the need for radiotherapy in low‐ and middle‐income countries

alexandrossfakianakis shared this article with you from Inoreader Response assessment by positron emission tomography‐computed tomography as compared with contrast‐enhanced computed tomography in childhood Hodgkin lymphoma can reduce the need for radiotherapy in low‐ and middle‐income countries via Pediatric Blood & Cancer Abstract Introduction The InPOG-HL-15-01, a multicentric prospective study, used a risk-stratified and response-based approach with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) backbone to treat children and adolescents with newly diagnosed Hodgkin lymphoma (HL) and reduce the use of radiation therapy (RT). Children/adolescents with bulky disease or inadequate response at early response assessment (ERA) after two cycles of chemotherapy were assigned to receive RT. For ERA, positron emission tomography computed tomography (PET-CT) was recommended but not mandatory in view of limited access. This study aimed to compare the impact of using contrast-enhanced computed tomography (CECT) and PET-CT on treatment decisions and outcomes. Methodology 396 patients were enrolled and 382 had an ERA at the assigned time point. Satisfactory response was defined as Deauville score 3 or less for patients undergoing PET-CT and complete response (CR)/very good partial response (VGPR) for patients undergoing CECT. Outcomes of interest incorporate 5 year event-free survival (EFS), EFS including abandonment (EFSa), and overall survival (OS). Results At ERA, satisfactory response was documented in 277 out of 382 (72.5%) participants and this was significantly higher in PET-CT (151 out of 186, 81.2%) as compared with CECT-based assessments (126 out of 196, 64.3%) respectively (p value < .001). Amongst the 203 patients with nonbulky disease (wherein the indication for RT was entirely dependent on ERA), 96 out of 114 (84.2%) and 61 out of 89 (68.5%) patients achieved a satisfactory response according to the PET-CT and CECT (p value = .008) respectively and hence a lesser proportion of patients in the PET-CT arm received RT. Despite a lower usage of RT the 5 year OS of both groups, ERA based on CECT (91.8%) versus PET-CT (94.1%) was comparable (p value = .391) and so was the 5 year EFS (86.7 vs. 85.5%, p value = .724). Conclusion Use of PET-CT as the modality for ERA is more likely to indicate a satisfactory response as compared with CECT and thereby decreases the need for RT in response-based treatment algorithm for HL-afflicted children. The reduction in the application of RT did not impact the overall outcome and plausibly would lower the risk of delayed toxic effects. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Relapse after non‐metastatic rhabdomyosarcoma: The impact of routine surveillance imaging on early detection and post‐relapse survival

alexandrossfakianakis shared this article with you from Inoreader Relapse after non‐metastatic rhabdomyosarcoma: The impact of routine surveillance imaging on early detection and post‐relapse survival via Pediatric Blood & Cancer Abstract Background Patients with rhabdomyosarcoma (RMS) whose disease relapses have little chance of being cured, so front-line treatments are usually followed up with surveillance imaging in an effort to detect any recurrences as early as possible, and thereby improve post-relapse outcomes. The real benefit of such routine surveillance imaging in RMS remains to be demonstrated, however. This retrospective, single-center study examines how well surveillance imaging identifies recurrent tumors and its impact on post-relapse survival. Methods The analysis concerned 79 patients <21 years old treated between 1985 and 2020 whose initially localized RMS relapsed. Clinical findings, treatment modalities, and survival were analyzed, comparing patients whose relapse was first suspected from symptoms they developed (clinical symptoms group) with those whose relapse was identified by radiological surveillance (routine imaging group). Results Tumor relapses came to light because of clinical symptoms in 42 cases, and on routine imaging in 37. The time to relapse was much the same in the two groups. The median overall survival (OS) and 5-year OS rate were, respectively, 10 months and 12.6% in the clinical symptoms group, and 11 months and 27.5% in the routine imaging group (p-value .327). Among patients with favorable prognostic scores, survival was better for those in the routine imaging group (5-year OS 75.0% vs. 33.0%, p-value .047). Conclusion It remains doubtful whether surveillance imaging has any real impact on RMS relapse detection and patients' post-relapse survival. Further studies are needed to establish the most appropriate follow-up recommendations, taking the potentially negative effects of regular radiological exams into account. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Marginal bone loss around dental implants: comparison between matched groups of bruxer and non‐bruxer patients: A retrospective case–control study

alexandrossfakianakis shared this article with you from Inoreader Marginal bone loss around dental implants: comparison between matched groups of bruxer and non‐bruxer patients: A retrospective case–control study via Clinical Implant Dentistry and Related Research Abstract Purpose To compare marginal bone loss (MBL) around dental implants in a group of bruxers in relation to a matched group of non-bruxers. Methods The present record-based retrospective study included patients selected from individuals treated with dental implants at one specialist clinic in Malmö. Only implants not lost and with baseline radiographs taken within 12 months after implant placement and with a minimum of 36 months of radiological follow-up were considered for inclusion. Univariate linear regression models and a linear mixed-effects model were performed. Results Two hundred and four patients (104 bruxers, 100 non-bruxers), with a total of 811 implants (416 in bruxers, 395 in non-bruxers) were included in the study. The results of the linear mixed-effects model suggested that bruxism, smoking, age, region of the jaws, implant diameter, and prosthesis type had a statistically significant influence on MBL over time. Individuals who are both bruxers and smokers showed greater MBL when compared to individuals who are either a bruxer or smoker, or neither (p < 0.001). Conclusions Bruxism is suggested to increase the risk of MBL over time, as well as higher age, smoking, and the combination of bruxism and smoking. Other factors that showed a correlation with increased MBL were implant diameter, region of the jaws, and prosthesis type, but it is not possible to draw robust conclusions for these factors, as the categories of these variables were very unbalanced. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Evaluation of guidelines for diagnosis and treatment of Helicobacter pylori infection

alexandrossfakianakis shared this article with you from Inoreader Evaluation of guidelines for diagnosis and treatment of Helicobacter pylori infection via Helicobacter Abstract Background To systematically evaluate the quality of the guidelines for the diagnosis and treatment of Helicobacter pylori infection and to analyze the differences and reasons for the key recommendations in the guidelines. Methods Databases and websites were systematically searched to obtain guidelines for the diagnosis and treatment of Helicobacter pylori infection. Four independent reviewers used the Guideline Evaluation Tool (AGREE II) to evaluate the included guidelines. The intraclass correlation coefficient (ICC) and Fleiss' kappa coefficient were used to measure the consistency of evaluation guidelines between guide reviewers. Differences between guidelines and the reasons for the differences were analyzed by comparing the recommendations of different guidelines and the evidence supporting the recommendations. Results A total of 17 guidelines for Helicobacter pylori infection were included in this study. The AGREE II scores of these guidelines were low overall, with 4 of them had a score of over 60%, which indicates that the guidelines are recommended, and 13 of them having a score ranging from 30 to 60%, which indicates that the guidelines are recommended but need to be revised, while no guideline had a score of 30% or less, which indicates that they were not recommended. The analysis of these guidelines found that there were some differences in the main recommendations. Not all guidelines recommend sequential therapy as the recommended therapy. Whether bismuth quadruple therapy should be used as the recommended first-line therapy is unclear. The antibiotic resistance rate is different in different regions. Combined with the local antibiotic sensitivity test, the eradication rate of Helicobacter pylori can be improved. Conclusion There are significant differences in the quality of Helicobacter pylori infection guidelines and the key recommendations. Improving the deficiencies of existing guidelines is an effective way to develop high-quality guidelines and make reasonable recommendations for the treatment of Helicobacter pylori infection in the future. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

ABRACADABRA literacy instruction for children with Down syndrome via telepractice during COVID‐19: A pilot study

alexandrossfakianakis shared this article with you from Inoreader ABRACADABRA literacy instruction for children with Down syndrome via telepractice during COVID‐19: A pilot study via British Journal of Educational Psychology Abstract Background COVID-19 has resulted in some educators and allied health practitioners transitioning to online delivery of literacy instruction. As far as we are aware, no studies have investigated online delivery of comprehensive literacy instruction for children with Down syndrome. Aims In this pilot study, we explore the efficacy of online delivery of ABRACADABRA (a free literacy web application) for children with Down syndrome, alongside supplementary parent-led shared book reading, during the COVID-19 pandemic. Sample Six children with Down syndrome, aged 8–12 years, participated in this within-participants design study. Methods Participants acted as their own controls with outcome variables measured at three timepoints: baseline, pre-instruction and post-instruction. Children participated in 16–18 hrs of one-to-one literacy instruction online over a 6-week instruction phase, along with twice weekly parent-led shared book reading activities. Results Outcomes from standardized assessments revealed statistically significant improvements in word- and passage-level reading accuracy skills over the instruction phase (pre-instruction to post-instruction) compared with the no-instruction control phase (baseline to pre-instruction). Improvements in reading comprehension skills were inconsistent across assessment measures and statistical analyses. Conclusion Children with Down syndrome can benefit from comprehensive literacy instruction delivered via telepractice. Our study provides critical initial evidence of successful service delivery during a global pandemic and beyond. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The fate of interneurons, GABAA receptor sub‐types and perineuronal nets in Alzheimer's disease

alexandrossfakianakis shared this article with you from Inoreader The fate of interneurons, GABAA receptor sub‐types and perineuronal nets in Alzheimer's disease via Brain Pathology Abstract Alzheimer's disease (AD) is the most common neurological disease, which is associated with gradual memory loss and correlated with synaptic hyperactivity and abnormal oscillatory rhythmic brain activity that precedes phenotypic alterations and is partly responsible for the spread of the disease pathology. Synaptic hyperactivity is thought to be because of alteration in the homeostasis of phasic and tonic synaptic inhibition, which is orchestrated by the GABAA inhibitory system, encompassing subclasses of interneurons and GABAA receptors, which play a vital role in cognitive functions, including learning and memory. Furthermore, the extracellular matrix, the perineuronal nets (PNNs) which often go unnoticed in considerations of AD pathology, encapsulate the inhibitory cells and neurites in critical brain regions and have recently come under the light for their crucial role in synaptic stabilisation and excitatory-inhibitory balance and when disrupted, serve as a potential trigger for AD-associated synaptic imbalance. Therefore, in this review, we summarise the current understanding of the selective vulnerability of distinct interneuron subtypes, their synaptic and extrasynaptic GABAAR subtypes as well as the changes in PNNs in AD, detailing their contribution to the mechanisms of disease development. We aim to highlight how seemingly unique malfunction in each component of the interneuronal GABA inhibitory system can be tied together to result in critical circuit dysfunction, leading to the irreversible symptomatic damage observed in AD. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

High‐frequency (10 kHz) Spinal Cord Stimulation (SCS) as a Salvage Therapy for Failed Traditional SCS: A Narrative Review of the Available Evidence

alexandrossfakianakis shared this article with you from Inoreader High‐frequency (10 kHz) Spinal Cord Stimulation (SCS) as a Salvage Therapy for Failed Traditional SCS: A Narrative Review of the Available Evidence via Pain Practice Abstract Introduction Traditional spinal cord stimulation (t-SCS) has been used to treat chronic pain for over 50 years. However, up to 30% of patients undergo explant, with the main indication being loss of efficacy (LoE), and few alternative treatment options exist for these patients. Strategies to mitigate LoE commonly include conversion to another type of SCS (termed 'salvage' or 'rescue'). This review summarizes the existing literature concerning the efficacy and safety of 10 kHz SCS as a salvage therapy. Methods We searched PubMed, the Cochrane Library, ClinicalTrials.gov, and other sources between January 2009 and April 2021. Records were retained if the authors reported clinical outcomes with a minimum of ≥3 months of follow-up in patients implanted with a Senza® 10 kHz SCS system in an effort to treat t-SCS LoE. Results Ten articles were eligible for inclusion, reporting 3 prospective studies and 7 retrospective reviews. In the single study that salvaged patients without a repeat trial prior to surgery, 81% of patients were responders (≥50% pain relief from baseline), with mean pain relief of 60%. Among repeat-trial studies, the responder rate ranged from 46% to 80%, and mean pain relief from 47% to 68%. No unanticipated therapy-related safety issues were reported among the included articles. Conclusion Preliminary data suggest that chronic back and/or leg pain patients with t-SCS LoE can experience improved and durable pain relief after conversion to 10 kHz SCS. However, additional research is needed to define predictors of success and establish whether salvage without a repeat trial is a viable conversion method. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Use of antihypertensive drugs and risk of cutaneous melanoma: a nationwide nested case-control study

alexandrossfakianakis shared this article with you from Inoreader Use of antihypertensive drugs and risk of cutaneous melanoma: a nationwide nested case-control study via International Journal of Epidemiology - Advance Access Abstract Background Most antihypertensives can induce dermal photosensitivity, which may increase melanoma risk. However, corroborating evidence is limited. We examined the associations between use of antihypertensives and melanoma risk. Methods A nationwide nested case-control study was conducted using data from the Cancer Registry of Norway, the National Registry and the Norwegian Prescription Database in 2004–15. Ten controls were randomly selected for each melanoma case, matched on sex and birth year. The study included 12 048 cases and 117 895 controls. We estimated rate ratios (RRs) with 95% confidence intervals (CIs). All analyses were adjusted for ambient ultraviolet radiation (UVR). We additionally performed active comparator analyses, and sensitivity analyses by only including new users, distinguishing between exclusive and mixed users, allowing for different latency periods, and subgroup analyses by melanoma subtype and clinical stage. Results Compared with non-use, we observed a slightly increased melanoma risk in users of diuretics (RR 1.08, CI 1.01–1.15), calcium-channel blockers (RR 1.10, CI 1.04–1.18) and drugs affecting the renin-angiotensin system (RR 1.10, CI 1.04–1.16), but not for beta blockers (RR 0.97, CI 0.92–1.03). We found no heterogeneity of associations by melanoma subtype or clinical stage and no dose-response relationship between the cumulative defined daily doses (DDDs) and melanoma. No interaction was found between cumulative DDDs and ambient UVR. Conclusions Weak associations, with lack of a dose-response relationship and lack of interactions with ambient UVR, in the DDD analysis in this nationwide study do not support a causal relationship between antihypertensives and melanoma risk. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.