Τρίτη 31 Ιανουαρίου 2023

Detect and suppress future zoonotic‐derived outbreaks: A lesson from last two decades

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Abstract

COVID-19 pandemic has revealed how vulnerable and inexperienced we are when dealing with an unprecedented global infectious threat. Looking back on the last few decades, there has been a surge in zoonotic-derived viruses globally. Notably, these outbreaks emerged as harmless zoonotic diseases within a favorable environment, then spilled over to humans and widely spread to become outbreaks. Most of these are respiratory viruses (particularly Orthomyxoviridae Orthomyxoviridae or Coronaviridae Coronaviridae family), with high transmissibility and can be easily spread. Low- and middle-income countries, particularly those with tropical climates, provide ideal environments for the growth and evolution of these zoonotic viruses. Nevertheless, a lot of our advanced centers for infectious diseases are located in high-income countries (HIC) and focus on human pathogens only (e.g., influenza, RSV, adenovirus). We should critically think about reallocating health resources in th e near-term. It is an urge for a few surveillance centers aim to detect surges in cases of respiratory pathogens or any spikes in cases, and suppress the transmission chain from an early stage. In this article, we digest lessons learned from the previous spillover pandemics and suggest actionable tactics to deal with future pandemics properly.

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Genetic characteristics and treatment outcome in infants with KMT2A germline B‐cell precursor acute lymphoblastic leukemia: Results of MLL‐Baby protocol

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Abstract

The aim of this study was to present the diagnostic and outcome characteristics of infants with germline status of KMT2A gene (KMT2A-g) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treated consistently according to the MLL-Baby protocol, a moderate-intensity protocol. Of the 139 patients enrolled in the MLL-Baby study, 100 (71.9%) carried different types of rearranged KMT2A (KMT2A-r), while the remaining 39 infants (28.1%) had KMT2A-g. KMT2A-g patients were generally older (77% older than 6 months), less likely to have a very high white blood cell count (greater than 100 × 109/L), less likely to be central nervous system (CNS)-positive, and more likely to be CD10-positive. The 6-year event-free survival and overall survival rates for all 39 patients were 0.74 (standard error [SE] 0.07) and 0.80 (SE 0.07), respectively. Relapse was the most common adverse event (n = 5), with a cumulativ e incidence of relapse (CIR) of 0.13 (SE 0.06), while the incidence of a second malignancy (n = 1) and death in remission (n = 3) was 0.03 (SE 0.04) and 0.08 (SE 0.04), respectively. None of the initial parameters, including genetics and the presence of recently described fusions of NUTM1 and PAX5 genes, was able to distinguish patients with different outcomes. Only rapidity of response, measured as minimal residual disease (MRD) by flow cytometry, showed a statistically significant impact. Moderate-intensity therapy, as used in the MLL-Baby protocol in infants with KMT2A-g BCP-ALL, yields results comparable to other infant studies. Patients with a slow multicolor flow cytometry (MFC)-MRD response should be subjected to advanced therapies, such as targeted or immunotherapies.

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Δευτέρα 30 Ιανουαρίου 2023

Severe Fatigue and Persistent Symptoms at Three Months Following SARS-CoV-2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study

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ABSTRACT
Background
Most research on SARS-CoV-2 variants focuses on initial symptomatology with limited data on longer-term sequelae. We sought to characterize the prevalence and differences in prolonged symptoms at three months post SARS-CoV-2-infection across the three major variant time-periods (pre-Delta, Delta, and Omicron).
Methods
This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, individual and organ system-based symptoms, and presence of ≥3 total symptoms across variants among COVID-positive and COVID-negative participants 3 months after their initial SARS-CoV-2 diagnosis. Variant periods were defined by dates with ≥50% dominant strain. We performed a sensitivity analysis using ≥90% dominance threshold and multivariable logistic regression modeling to estimate the independent effects of each variant adjusting for socio-demographic chara cteristics, baseline health, and vaccine status.
Results
The study included 3,223 participants (2,402 COVID-positive and 821 COVID-negative). Among the COVID-positive cohort, 463 (19.3%) were pre-Delta, 1,198 (49.9%) during Delta, and 741 (30.8%) during Omicron. Prolonged severe fatigue was highest in the pre-Delta COVID-positive cohort compared with Delta and Omicron cohorts (16.7% vs 11.5% vs 12.3%, respectively; p = 0.017), as was presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; p < 0.001). No difference was seen in the COVID-negative cohort between variant time-periods. In multivariable models, there was no difference in severe fatigue between variants. There was decreased odds of having ≥3 symptoms in Omicron compared with other variants; this was not significant after adjusting for vaccination status.
Conclusions
Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during the pre-Delta period compared with Delta and Omicron periods; however, these differences were no longer significant after adjusting for vaccination status. This suggests a potential beneficial effect of vaccination on the risk of developing long-term symptoms.
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Πέμπτη 26 Ιανουαρίου 2023

The association among insomnia symptom severity, comorbid symptoms, and suicidal ideation in two veteran cohorts meeting diagnostic criteria for insomnia disorder

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Abstract

Objective

Examine the association between insomnia symptom severity and suicidal ideation (SI), after adjusting for clinical comorbidity in veterans meeting diagnostic criteria for insomnia disorder.

Methods

Secondary data analyses of psychometrically validated baseline assessments of depression, posttraumatic stress disorder (PTSD), and anxiety symptoms from two online insomnia intervention randomized clinical trials (n = 232; n = 80) were conducted. Multiple linear regression was used to determine the association between insomnia symptom severity and SI, after controlling for clinical comorbidity and demographics.

Results

Insomnia symptom severity was significantly correlated with comorbid depression, PTSD, and anxiety symptoms in both cohorts and significantly correlated with SI in one. After controlling for demographics and clinical comorbidity, insomnia symptom severity was not significantly associated with SI in linear regression models.

Conclusion

Findings extend insomnia-suicide research by providing evidence that insomnia symptom severity may not confer a unique risk for SI above comorbid mental health symptoms in veterans meeting diagnostic criteria for insomnia disorder.

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Association between inflammatory bowel disease and periodontitis: A bidirectional 2‐Sample Mendelian randomization study

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Abstract

Aim

This Mendelian randomization (MR) study was performed to explore the potential bidirectional causal association between inflammatory bowel disease (IBD) and periodontitis.

Materials and methods

We used genetic instruments from the genome-wide association study (GWAS) summary statistics of European descent for IBD (12,882 cases, 21,770 controls) to investigate the association with periodontitis (3,046 cases, 195,395 controls) and vice versa. The radial inverse-variance weighted (IVW) method was carried out to obtain the primary causal estimates, and the robustness of the results was assessed by a series of sensitivity analyses. Due to multiple testing, associations with P values < 0.008 were considered as statistically significant, and P values ≥ 0.008 and < 0.05 were considered as suggestively significant.

Results

In the primary causal estimates, IBD as a whole was associated with an increased risk of periodontitis (odds ratio [OR], 1.060; 95% confidence interval [CI], 1.017; 1.105; P = 0.006). Subtype analyses showed that ulcerative colitis (UC) was associated with periodontitis (OR, 1.074; 95% CI 1.029; 1.122; P=0.001), while Crohn's disease (CD) was not. Regarding the reverse direction, periodontitis showed a suggestive association with IBD as a whole (OR, 1.065; 95% CI 1.013; 1.119; P=0.014). Subtype analyses revealed that periodontitis was associated with CD (OR, 1.100; 95% CI 1.038; 1.167; P=0.001) but not UC. The final models after outlier removal showed no obvious pleiotropy, indicating that our primary analysis results were reliable.

Conclusions

The present MR study provides moderate evidence on the bidirectional causal relationship between IBD and periodontitis. The bidirectional increased risk found in our study was marginal and, possibly, of limited clinical relevance. More studies are needed to support the findings of our current study.

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Τετάρτη 25 Ιανουαρίου 2023

Surveillance, Isolation and Genomic Characterization of Pteropine orthoreovirus of Probable Bat Origin Among Patients with Acute Respiratory Infection in Malaysia

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Abstract

Pteropine orthoreovirus (PRV), an emerging bat-borne virus, has been linked to cases of acute respiratory infections (ARI) in humans. The prevalence, epidemiology and genomic diversity of PRV among ARI of unknown origin were studied. Among 632 urban outpatients tested negative for all known respiratory viruses, 2.2% were PRV-positive. Patients mainly presented with moderate to severe forms of cough, sore throat and muscle ache, but rarely with fever. Phylogenetic analysis revealed that over 90% of patients infected with the Melaka virus (MelV)-like PRV, while one patient infected with the Pulau virus previously found only in fruit bats. Human oral keratinocytes and nasopharyngeal epithelial cells were susceptible to clinical isolates of PRV, including the newly isolated MelV-like 12MYKLU1034. Whole genome sequence of 12MYKLU1034 using Nanopore technique revealed a novel reassortant strain. Evolutionary analysis of the global PRV strains suggests the continuous evolution of PRV through genetic reassortment among PRV strains circulating in human, bats and non-human primate hosts, creating a spectrum of reassortant lineages with complex evolutionary characteristics. In summary, the role of PRV as a common etiologic agent of ARI is evident. Continuous monitoring of PRV prevalence, pathogenicity and diversity among human and animal hosts is important to trace the emergence of novel reassortants.

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Use of gemcitabine, oxaliplatin, and anti‐CD20 therapy in children and adolescents with non‐Hodgkin lymphoma unfit for intensive therapy

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Abstract

Multiagent immunochemotherapy affords excellent outcomes in pediatric non-Hodgkin lymphoma (NHL); however, scarce data exist for patients unfit for intensive treatment. Rituximab, gemcitabine, and oxaliplatin (R-GemOx) is well tolerated and efficacious in elderly adults with NHL; however, its use has not been described in pediatrics. In this retrospective, single-center study, six children with mature B-cell NHL and significant comorbidities received anti-CD20 therapy with GemOx (rituximab or obinutuzumab or ofatumumab with gemcitabine and oxaliplatin [R/O-GemOx]). R/O-GemOx was well tolerated and resulted in complete response in two of three patients with newly diagnosed NHL and one of three patients with primary refractory NHL. R/O-GemOx is a viable treatment option for children with NHL who cannot tolerate intensive therapy.

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Compression of the Vertebral Artery by the Thyroid Cartilage Causing Vertebrobasilar Insufficiency

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Compression of the Vertebral Artery by the Thyroid Cartilage Causing Vertebrobasilar Insufficiency

Mechanical compression of the vertebral artery during mouth opening by the thyroid cartilage. Successfully resolved by resection of the thyroid cartilage.


Background

This retrospective case report describes a rare presentation of VBI in a young male patient.

Aims

Share a rare cause of VBI in a young patient.

Materials & Methods

The patient presented with recurrent episodes of dizziness and a history of several cerebellar infarcts. Imaging revealed the right vertebral artery was being mechanically compressed by the right superior cornu of the thyroid cartilage during mouth opening. Surgical resection of the right superior cornu of the thyroid cartilage was performed.

Results

Intraoperative angiography revealed a right vertebral artery without compression during mouth opening.

Discussion

Clinicians should consider the thyroid cartilage as a potential source of recurrent VBI due to mechanical compression of the VA.

Conclusion

Resection of the causative portion of the thyroid cartilage resolved the compression in this case, and should be employed in similar cases. Laryngoscope, 2023

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Τρίτη 24 Ιανουαρίου 2023

Peri‐implantitis: A bibliometric network analysis of top 100 most‐cited research articles

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Abstract

Background

Over the past decades, there has been an increase in research publications focusing on peri-implantitis. When facing limited healthcare resources, bibliometric analyses can guide researchers and funding parties toward areas where reallocation or more focus on research activity is warranted. The main objective of this study was to identify the trends of the top 100 cited articles on peri-implantitis research as the first study of its kind.

Methods

A Web of Science search, using the keywords "peri-implantitis or periimplantitis" was built to create a database of the most-cited articles. Articles were ranked by citation count and screened by two independent reviewers. The bibliometric characteristics of the studies were gathered and analyzed using several bibliometric software. Author collaborations, author clusters, and keyword co-occurrence network analyses were also performed. The correlation between the citation count and the age of each article was tested.

Results

The top 100 cited papers were published from 1994 to 2018 and the total citation counts ranged from 119 to 972 with 244.5 citations/paper on average. There was no correlation between the age of the articles and the citation count (p-value = 0.67). 21% of the studies consisted of prospective clinical studies. 35% of the papers focused on treatment and prevention of peri-implantitis while 65% concerned epidemiology. The top three most prolific countries were Sweden (n = 31), Germany (n = 15), and Switzerland (n = 13). We found 12 authors who had greater than five publications on the list. Also, the most published journal was Clinical Oral Implants Research.

Conclusion

This study provides insight into the characteristics and quality of the most highly cited peri-implantitis literature. This revealed a deficiency in terms of the number of studies on treatment strategies as well as a higher level of evidence studies among the most- impactful papers on peri-implantitis at the moment.

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Perspectives on Adherence from the ACTG 5360 MINMON Trial: A Minimum Monitoring Approach with 12 Weeks of Sofosbuvir/Velpatasvir in Chronic Hepatitis C Treatment

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Abstract
Background
With the advent of efficacious oral Direct-acting antivirals (DAAs) for hepatitis C virus(HCV), identification of characteristics associated with adherence is critical to treatment success. We examined correlates of sub-optimal adherence to HCV therapy in a single-arm, multinational, clinical trial.
Methods
ACTG A5360 enrolled HCV treatment-naïve persons without decompensated cirrhosis from 5 countries. All participants received a 12-weeks course of sofosbuvir/velpatasvir at entry. In-person visits occurred at initiation and week 24, sustained virologic response (SVR) assessment. Adherence at week 4 was collected remotely and was dichotomized optimal (100%, no missed doses) versus sub-optimal (<100%). Correlates of sub-optimal adherence were explored using logistic regression.
Results
400 participants enrolled; 399 initiated treatment; 395/397 (99%) reported completing at week 24.. Median age was 47 year s with 35% female. Among the 368 reporting optimal adherence at week 4 SVR was 96.5% (95% CI [94.1%, 97.9%]) vs. 77.8% (95% CI [59.2%, 89.4%]) p-value < 0.001. In the multivariate model age < 30 years and being a US participant were independently associated with early sub-optimal adherence. Participants < 30 years were 7.1 times more likely to have early sub-optimal adherence compared to their older counterparts.
Conclusion
Self-reported optimal adherence at week 4 was associated with SVR. Early self-reported adherence could be used to identify those at higher risk of treatment failure and may benefit from additional support. Younger individuals < 30 years may also be prioritized for additional adherence support.
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