Πέμπτη 22 Δεκεμβρίου 2022

Is Mpox an STI? Why narrowing the scope of this disease may be harmful

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ABSTRACT
The 2022 multi-national Mpox outbreak has been characterized by unprecedented spread among men who have sex with men outside of sub-Saharan Africa. Close contact during sex and intimacy has been well established as a key pathway for human-to-human transmission in the current outbreak. Discussions on whether to assign this illness as a sexually transmitted infection (STI) have been ongoing since the initiation of the outbreak. While sexual contact certainly appears to be a primary means of spread, classifying Mpox as an STI is inaccurate based on its known transmission dynamics, yields potential unintended consequences, and ignores the historical impact of the disease in Central and West Africa. Rather than focusing our energy on disease categorization, more effort should be placed on destigmatizing this illness and empowering communities at risk to protect themselves from Mpox.
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mTOR Signaling Regulates Zika Virus Replication Bidirectionally through Autophagy and Protein Translation

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Abstract

Zika virus (ZIKV) reemerged in 2016 and attracted much more attention worldwide. To date, the limited knowledge of ZIKV interactions with host cells in the early stages of infection impedes the prevention of viral epidemics and the treatment of ZIKV disease. The Mammalian target of rapamycin (mTOR) signaling pathway plays an essential role in the regulation of autophagy and protein synthesis during multiple viral infections. This study aimed to investigate the functional role of mTOR signaling in ZIKV replication in human umbilical vein endothelial cells (HUVECs). Immunoblotting demonstrated that ZIKV infection inhibited mTORC1 signaling, enhancing autophagy but obstructing protein translation. Drugs or siRNA for interfering with mTOR signaling molecules were utilized to demonstrate that AKT/TSC2/mTORC1 signaling was involved in ZIKV infection and that autophagy promoted ZIKV production, but viral protein expression was regulated by mTORC1 signaling. Moreover, confocal microscopy indicated a robust correlation between autophagy and viral RNA transcription. This study clarifies the dual functions of mTOR signaling during ZIKV infection and provides theoretical support for developing potential anti-ZIKV drugs based on mTOR signaling molecules and deeper insights to better understand the mechanism between ZIKV and host cells.

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Clinical severity of Omicron sub‐variants BA.1, BA.2 and BA.5 in a population‐based cohort study in British Columbia, Canada

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Abstract

The SARS-CoV-2 variant Omicron emerged in late 2021. In British Columbia (BC), Canada, and globally, three genetically distinct sub-variants of Omicron, BA.1, BA.2 and BA.5, emerged and became dominant successively within an 8-month period. SARS-CoV-2 sub-variants continue to circulate in the population, acquiring new mutations that have the potential to alter infectivity, immunity and disease severity. Here, we report a propensity-matched severity analysis from residents of BC over the course of the Omicron wave, including 39,237 individuals infected with BA.1, BA.2 or BA.5 based on paired high-quality sequence data and linked to comprehensive clinical outcomes data between Dec. 23, 2021 and August 31, 2022. Relative to BA.1, BA.2 cases were associated with a 15% and 28% lower risk of hospitalization and Intensive Care Unit (ICU) admission (aHRhospital=1.17; 95%CI=1.096-1.252; aHRICU=1.368; 95%CI=1.152-1.624), whereas BA.5 infections were associated with a 1 8% higher risk of hospitalization (aHRhospital=1.18; 95%CI=1.133-1.224) after accounting for age, sex, co-morbidities, vaccination status, geography and social determinants of health. Phylogenetic analysis revealed no specific sub-clades associated with more severe clinical outcomes for any Omicron sub-variant. In summary, BA.1, BA.2 and BA.5 sub-variants were associated with differences in clinical severity, emphasizing how variant-specific monitoring programs remain critical components of patient and population-level public health responses as the pandemic continues.

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Infection evaluation in the early period after liver transplantation: a single‐center exploration

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Abstract

Background

Infection is a significant risk factor that impacts for perioperative morbidity and mortality in liver transplantation (LTx) patients and is difficult to evaluate quantitatively in the early posttransplantation period. Thus, a biomarker to assess the risk of infection and the prognosis of the recipient is highly desirable.

Methods

One hundred and twenty-eight consecutive patients with end-stage liver diseases undergoing LTx between January 1, 2020, and December 31, 2021, at the First Affiliated Hospital of Zhejiang University School of Medicine were screened retrospectively. Graft preservation fluid and blood samples were collected for culture, and other perioperative laboratory examination results were recorded, for assessment of infection status.

Results

After a follow-up period of 30 days, the survival rate among the 128 LTx recipients was 94.5%. Multivariable regression analysis showed that the logarithmically transformed neutrophil-to-lymphocyte ratio (NLR) (HR = 3.548, 95% CI: ; p = 0.041) on post-LTx day 1 and graft preservation fluid culture positivity (HR = 12.032, 95% CI: ; p = 0.006) were independent predictive factors for early prognosis after LTx.

Conclusions

Positive graft preservation fluid culture and the logarithmically transformed NLR on post-LTx day 1 were independent predictive factors for early prognosis after LTx. The logarithmically transformed NLR could provide an earlier indication than culture results in clinical practice.

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Omicron infection increases IgG binding to spike protein of predecessor variants

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Abstract

Background

SARS-CoV-2 transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1and D614G), Delta, and Omicron variants. The aim of this study was to examine the effect of infections on the humoral immune response and cross-reactivity to spike proteins of Wuhan-Hu-1, Delta, C.1.2., and Omicron.

Objectives

Residual archival sera (N=81) received between January 2020 and March 2022 were included. Infection status was inferred by a positive SARS-CoV-2 RT-PCR and/or serology (anti-N and anti-S antibodies) and sequencing of contemporaneous samples (N=18) to infer lineage. We estimated the levels and cross-reactivity of infection-induced sera including Wild, Delta, Omicron as well as vaccine breakthrough infections (Delta and Omicron).

Results

We found ~2-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared to the pre-Omicron period, whilst the change in pre- and post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of cross-reactive antibodies against predecessor variants, in spite of weaker degree of humoral response compared to Wuhan-Hu-1 and Delta infection. Intriguingly, Omicron vaccine-breakthrough infections when compared with primary infections, exhibited increased humoral responses against RBD (7.7-fold) and Trimeric S (Trimeric form of spike protein) (34.6-fold) in addition to increased binding of IgGs towards previously circulating variants (4.2 - 6.5-fold). Despite Delta breakthrough infections showing a higher level of humoral response against RBD (2.9-fold) and Trimeric S (5.7-fold) compared to primary Delta sera, a demonstrably reduced binding (36-49%) was observed to Omicron spike protein.

Conclusions

Omicron vaccine breakthrough infection results in increased intensity of humoral response and wider breadth of IgG binding to spike proteins of antigenically-distinct, predecessor variants.

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HTLV‐1 persistent infection and ATLL oncogenesis

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Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus; whereas HTLV-1 mainly persists in the infected host cell as a provirus, it also causes a malignancy called adult T-cell leukemia/lymphoma (ATLL) in about 5% of infection. HTLV-1 replication is in most cases silent in vivo and viral de novo infection rarely occurs; HTLV-1 rather relies on clonal proliferation of infected T cells for viral propagation as it multiplies the number of the provirus copies. It is mechanistically elusive how leukemic clones emerge during the course of HTLV-1 infection in vivo and eventually cause the onset of ATLL. This review summarizes our current understanding of HTLV-1 persistence and oncogenesis, with the incorporation of recent cutting-edge discoveries obtained by high-throughput sequencing.

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Imaging of pediatric hematopoietic stem cell transplant recipients: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

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Abstract

Imaging in hematopoietic stem cell transplantation patients is not targeted at evaluating the transplant per se. Rather, imaging is largely confined to evaluating peri-procedural and post-procedural complications. Alternatively, imaging may be performed to establish a baseline study for comparison should the patient develop certain post-procedural complications. This article looks to describe the various imaging modalities available with recommendations for which imaging study should be performed in specific complications. We also provide select imaging protocols for different indications and modalities for the purpose of establishing a set minimal standard for imaging in these complex patients.
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Caring for a child with retinoblastoma: Experience of Ethiopian parents

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Abstract

Objective

This study explored the lived experience of parents of children with retinoblastoma.

Design and method

A phenomenological qualitative study design was used, and a purposive sampling technique to recruit parents of children with retinoblastoma. Semi-structured interviews were conducted to document the lived experience of participants, who were asked to narrate their experiences caring for a child with retinoblastoma, thinking back to the day they learned about their child's condition, as well as their thoughts about the future. The interviews were conducted in Amharic and Oromo language, and audio recordings were transcribed and translated to English. Data were analyzed using thematic analysis.

Results

Thirteen parents (seven mothers, six fathers) participated in the study. Collectively, the children of the participants represented all the stages of the retinoblastoma journey (i.e., diagnosis, treatment, remission, and recurrence). Five major themes emerged from the thematic data analysis: (a) reactions when learning the child's condition; (b) receiving health care; (c) costs of caregiving; (d) support; and (e) uncertainties.

Conclusion

The lived experiences of parents of children with retinoblastoma revealed a significant mental health and psychosocial burden. The sources of mental distress were found to be complex and varied. Holistic care for retinoblastoma should include programs that address the biopsychosocial needs of caregivers.
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The varied spectrum of nephroblastomatosis, nephrogenic rests, and Wilms tumors: Review of current definitions and challenges of the field

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Abstract

The diagnosis of multiple or diffuse renal lesions in a child is challenging by imaging and/or pathology. Optimal management requires distinguishing benign lesions such as nephrogenic rests from cancerous lesions such as Wilms tumor, but this is often difficult or impossible. This difficulty is compounded by the overlapping nature of our current radiologic and pathologic definitions of lesions along the spectrum of nephrogenic rests/nephroblastomatosis. We provide a review of these issues, as a collaborative effort between the Children's Oncology Group Renal Tumor Committee and International Society of Pediatric Oncology Renal Tumor Study Group. Our aim is to discuss current challenges in diagnosis and management of these renal lesions, encouraging future work toward consensus definitions for research and patient care.
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Ninety‐day mortality following transoral robotic surgery or radiation at Commission on Cancer‐accredited facilities

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Abstract

Background

Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown.

Methods

NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson–Deyo score 0–1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities.

Results

3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality.

Conclusions

There is minimal difference between 90-day mortality in patients treated with TORS or radiotherapy for early-stage OPSCC. While overall rates are low, for patients with expectation of cure, work is needed to identify optimal treatment.
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