Identification of HPV genotypes causing cervical precancer using tissue-based genotyping

Identification of high-risk human papillomavirus genotypes causing cervical precancer is crucial for informing HPV vaccine development and efficacy studies, and for determining which types to include in next-generation genotyping assays. Co-occurrence of hrHPV infections is common and complicates carcinogenicity assessment; accurate attribution requires tissue-based genotyping of precancers. We included all women with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) from the Biopsy Study, an observational study of 690 women enrolled between 2009 and 2012 at the University of Oklahoma. Tissue-based genotyping, including whole tissue sections (WTS) and laser-capture microdissection (LCM), was performed on all precancers with multiple hrHPV infections detected in cytology, totaling over 1,800 HPV genotyping assays. Genotype attribution was compared to hierarchical and proportional hrHPV-type attribution models. Of 276 women with CIN2+, 122 (44.2%) had multiple hrHPV genotypes in cytology. Of 114 women with genotyping data, 94 had one or more hrHPV detected in tissue. Seventy-one women (75.5%) had a single causal hrHPV genotype, while 23 women had multiple hrHPV genotypes causing CIN2+. Ten women had multiple causal infections in a single biopsy, contrary to the previous notion that each lesion is caused by a single type only. While HPV16 was the predominant causal hrHPV genotype using all approaches, the hierarchical model overattributed HPV16, whereas other causal hrHPV genotypes, particularly HPV18 and HPV35, were underattributed. Understanding true causal genotypes is important for the evaluation of vaccine efficacy, to estimate the extent of unmasking, and for type-specific risk assessment in screening and management.     

Readability of Online Information on Celiac Disease: A Brief Report

Abstract

Celiac disease (CD) is an autoimmune condition characterized by an intolerance to dietary gluten for those with a genetic predisposition. The Internet has become a key source of information about CD as well as a gluten-free diet (GFD), although the quality is varied. There has been little investigation into the readability of online CD information. Keyword “celiac disease” was used for a search in the browser, Google Chrome. URLs of the first 100 English websites were recorded; sponsored or advertised websites were not included in the sample. Five recommended tests generated by Readable.io were utilized to assess the sample’s readability scores. Only one of the 100 websites received an acceptable reading score on two of the five reading assessments. Websites with extensions of .com or .org were equally likely to be written at the same unacceptable level. Informational websites on celiac disease may serve as an unintentional barrier for consumers seeking readable, online material on this health topic.     

Persistent Musculoskeletal Deficits in Pediatric,Adolescent and Young Adult Survivors of Allogeneic Hematopoietic Stem-Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a common therapy for pediatric hematologic malignancies. With improved supportive care, addressing treatment-related late effects is at the forefront of survivor long-term health and quality of life. We previously demonstrated that alloHSCT survivors had increased adiposity, decreased lean mass, and lower bone density and strength, 7 years (median) from alloHSCT compared to their healthy peers. Yet it is unknown whether these deficits persist. Our longitudinal study characterized changes in muscle and bone over a period of 3.4 (range, 2.0 to 4.9) years in 47 childhood alloHSCT survivors, age 5–26 years at baseline (34% female). Tibia cortical bone geometry and volumetric density and lower leg muscle cross-sectional area (MCSA) were assessed via peripheral quantitative computed tomography (pQCT). Anthropometric and pQCT measurements were converted to age, sex, and ancestry-specific standard deviation scores, adjusted for leg length. Muscle-specific force was assessed as strength relative to MCSA adjusted for leg length (strength Z-score). Measurements were compared to a healthy reference cohort (n = 921), age 5–30 years (52% female). At baseline and follow-up, alloHSCT survivors demonstrated lower height Z-scores, weight Z-scores, and leg length Z-scores compared to the healthy reference cohort. Deficits in MCSA, trabecular volumetric bone density, and cortical bone size and estimated strength (section modulus) were evident in survivors (all p < 0.05). Between the two study time points, anthropometric, muscle, and bone Z-scores did not change significantly in alloHSCT survivors. Approximately 15% and 17% of alloHSCT survivors had MCSA and section modulus Z-score < −2.0, at baseline and follow-up, respectively. Furthermore, those with a history of total body irradiation compared to those without demonstrated lower MCSA at follow-up. The persistent muscle and bone deficits in pediatric alloHSCT survivors support the need for strategies to improve bone and muscle health in this at-risk population. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Complications and reoperations after surgery for 647 patients with spine metastatic disease

Background Context

Postoperative morbidity may offset the potential benefits of surgical treatment for spine metastatic disease; hence, risk factors for postoperative complications and reoperations should be taken into considerations during surgical decision-making. In addition, it remains unknown whether complications and reoperations shorten these patients' survival.

Burden of illness among patients with severe aplastic anemia who have had insufficient response to immunosuppressive therapy: a multicenter retrospective chart review study

Annals of Hematology - This study assessed treatment patterns and healthcare resource utilization (HRU) of patients with severe aplastic anemia (SAA) with insufficient response to immunosuppressive...     

When to consider targeted therapies in thrombotic microangiopathies in the modern era: walking the tightrope between cost,safety, and efficacy

Journal of Thrombosis and Thrombolysis - Thrombotic Microangiopathy (TMA) is a heterogeneous collection of syndromes that encompasses TTP, HUS, and other processes characterized by...