Increased incidence and unusual presentations of CMV disease in kidney transplant recipients after conversion to belatacept

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4–68.5]) were converted to belatacept (median of 11.5 months [2.5–37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R− CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.     

Reply to: ‘Liposuction-assisted brachioplasty in breast cancer-related lymphedema: Impact on volume reduction and quality of life’

BackgroundNecrotizing fasciitis (NF) is a rapid infectious process involving the fascia and subcutaneous tissue. Current standards of care rely on surgical debridement, resulting in large defects, with limited reconstructive options. Wound management has evolved over the last decade, including use of bilayer wound matrices (BWM). The authors sought to assess the use of collagen-GAG bilayer wound matrices on STSG take for NF wounds.MethodsA qualitative clinical evaluation (2016–2018) was performed to analyze the efficacy of BWM to aide in STSG take. Primary outcomes were 180-day bilayer matrix success, defined by progressing to split-thickness skin graft (STSG) and STSG take, determined by clinical evaluation. Wounds without a diagnosis of NF or reconstruction with BWM were excluded.ResultsTen patients with 11 NF wounds were identified. Average BMI was 32 kg/m². Comorbidities included hypertension (70%), diabetes (40%), and peripheral vascular disease (40%). Average wound size was 542cm² (range: 49cm² -1050cm²) and average wound age was 19 days at BWM placement. Matrices were applied to the lower extremity (64%), upper extremity (27%), and perineum (9%). One-hundred percent (n = 11) of wounds were deemed successful by receiving a STSG. Average time to STSG was 44 days (21d –108d). Complications consisted of delayed healing (n = 1, 8%) and partial necrosis (n = 1). No instances of infection or STSG graft loss occurred.ConclusionComplex defects caused by soft tissue necrotizing infections remain a reconstructive challenge. We highlight the benefit of a BWM as a treatment modality for reconstruction by priming the wound bed for a definitive STSG.     

Fertility and digital technology: narratives of using smartphone app ‘Natural Cycles’ while trying to conceive

Fertility awareness apps, which help to identify the ‘fertile window’ when conception is most likely, have been hailed as ‘revolutionising’ women’s reproductive health. Despite rapidly growing popularity, little research has explored how people use these apps when trying to conceive and what these apps mean to them. We draw on in‐depth, qualitative interviews, adopting a critical digital health studies lens (a sub‐field of science and technology studies), to explore the experiences of cisgender women and partners with one such app, Natural Cycles, in the context of their daily lives. We found that many women valued the technology as a ‘natural’, inobtrusive alternative to biomedical intervention, and a means of controlling and knowing their bodies, amid a dearth of fertility‐related education and care. Yet this technology also intervened materially and affectively into the spaces of their lives and relationships and privileged disembodied metrics (temperature) over embodied knowledge. Meanwhile, app language, advertising and cost have contributed to characterising ‘typical’ users as white, heterosexual, affluent, cisgender women without disabilities. In the context of neoliberal shifts towards bodily self‐tracking, technologies appealing as novel, liberating and ‘natural’ to individuals who can access them may nevertheless reproduce highly gendered reproductive responsibilities, anxieties and broader health and social inequalities.     

Small animal jet injection technique results in enhanced immunogenicity of hantavirus DNA vaccines

DNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine delivery might be adapted to successfully deliver a DNA vaccine to small animals. Disposable syringe jet injection (DSJI) does not currently exist for small animals. However, a commercialized, human intradermal device used to to administer medicines to the human dermis in a 0.1 mL volume was evaluated in Syrian hamsters. Here, we found that hantavirus DNA vaccines administered to hamsters using DSJI were substantially more immunogenic than the same vaccines delivered by needle/syringe or particle mediated epidermal delivery (gene gun) vaccination. By adjusting how the device was used we could deliver vaccine to either subcutaneous tissues, or through the skin into the muscle. RNA and/or antigen expression was detected in epidermal, subepidermal and fibroblast cells. We directly compared six optimized and non-optimized hantavirus DNA vaccines in hamsters. Optimization, including codon-usage and mRNA stability, did not necessarily result in increased immunogenicity for all vaccines tested; however, optimization of the Andes virus (ANDV) DNA vaccine protected vaccinated hamsters from lethal disease. This is the first time active vaccination with an ANDV DNA vaccine has shown protective efficacy in the hamster model. The adaptation of a human intradermal jet injection device for use as a method of subcutaneous and intramuscular jet injection of DNA vaccines will advance the development of nucleic acid based medical countermeasures for diseases modeled in hamsters.     

Psycholinguistic features,design attributes,and respondent-reported cognition predict response time to patient-reported outcome measure items

Purpose

Patient-reported outcome measures (PROMs) vary in their psycholinguistic complexity. This study examined whether response time to PROM items is related to psycholinguistic attributes of the item and/or the self-reported cognitive ability of the respondent.

Methods

Baseline data from Wave 2 of the Quality of Life in Neurological Disorders (Neuro-QoL) development study were reanalyzed. That sample contained 581 adults with neurological disorders and whose self-reported cognitive abilities were quantified by the Neuro-QoL v2.0 Cognitive Function Item Bank. 185 Neuro-QoL items were coded for several psycholinguistic variables and design attributes: number of words and syllables, mean imageability of words, mean word frequency, mean age of word acquisition, and response format (e.g., about symptom frequency or task difficulty). Data were analyzed with linear and generalized linear mixed models.

Results

Main effects models revealed that slower response times were associated with respondents with lower self-reported cognitive abilities and with PROM items that contained more syllables, less imageable (e.g., more abstract) words, and that asked about task difficulty rather than symptom frequency. Interaction effects were found between self-reported cognition and those same PROM attributes such that people with worse self-reported cognitive abilities were disproportionately slow when responding to items that were longer (more syllables), contained less imageable words, and asked about task difficulty.

Conclusion

Completing a PROM requires multiple cognitive skills (e.g., memory, executive functioning) and appraisal processes. Response time is a means of operationalizing the amount or difficulty of cognitive processing, and this report indicates several aspects of PROM design that relate to a measure’s cognitive burden. However, future research with better experimental control is needed.