Byrnebjerring1424
Chimeric antigen receptor (CAR) T-cell therapy is a promising therapeutic strategy against lymphoma. However, post-treatment relapses due to antigen loss remain a challenge. Here the authors designed a novel bicistronic CAR construct and tested its functions in vitro and in vivo. The CAR construct consisted of individual anti-CD19 and anti-CD20 single-chain fragment variables equipped with ICOS-CD3ζ and 4-1BB-CD3ζ intracellular domains, respectively. The CD19 and CD20 bicistronic CAR T cells exhibited tumor lytic capacities equivalent to corresponding monospecific CAR T cells. Moreover, when stimulated with CD19 and CD20 simultaneously, the bicistronic CAR T cells showed prolonged persistence and enhanced cytokine generation compared with single stimulations. Interestingly, the authors found that the 4-1BB signal was predominant in the signaling profiles of ICOS and 4-1BB doubly activated CAR T cells. In vivo study using a CD19/CD20 double-positive tumor model revealed that the bicistronic CAR T cells were more efficient than monospecific CD19 CAR T cells in eradicating tumors and prolonging mouse survival. The authors' novel bicistronic CD19/CD20 CAR T cells demonstrate improved anti-tumor efficacy in response to dual antigen stimulations. These data provide optimism that this novel bicistronic CAR construct can improve treatment outcomes in patients with relapsed/refractory B cell malignancy.
Mesenchymal stem/stromal cells (MSCs) are multipotent and self-renewing cells that are extensively used in tissue engineering. Adipose tissues are known to be the source of two types of MSCs; namely, adipose tissue-derived MSCs (ASCs) and dedifferentiated fat (DFAT) cells. Although ASCs are sometimes transplanted for clinical cytotherapy, the effects of DFAT cell transplantation on mandibular bone healing remain unclear.
The authors assessed whether DFAT cells have osteogenerative potential compared with ASCs in rats in vitro. In addition, to elucidate the ability of DFAT cells to regenerate the jaw bone, the authors examined the effects of DFAT cells on new bone formation in a mandibular defect model in (i) 30-week-old rats and (ii) ovariectomy-induced osteoporotic rats in vivo.
Osteoblast differentiation with bone morphogenetic protein 2 (BMP-2) or osteogenesis-induced medium upregulated the osteogenesis-related molecules in DFAT cells compared with those in ASCs. Cathepsin Inhibitor 1 nmr BMP-2 activated the phosphorylation sy.
Antipsychotics are often used for the first-line management of behavioral and psychological symptoms of dementia despite their limited efficacy and the risk of serious adverse drug events, compounded with disregard for guidelines recommending prioritizing non-pharmacological interventions. Some innovative interventions promote the deprescription of antipsychotics in long term care (LTC) settings.
The objective of this article is to present the conditions leading to the scale-up of an innovative program on the appropriate use of antipsychotics in LTC centers.
The Optimizing Practices, Use, Care and Services-Antipsychotics (OPUS-AP) program is a mixed-method project that aims to improve LTC residents' care through increased knowledge and competency among staff, resident-centered approaches, nonpharmacologic interventions, and by deprescribing antipsychotics when appropriate. This article consists of a qualitative study focused on exploring the implementation conditions of the OPUS-AP program. This study w scaling up efforts. Hence, this study underscores the need to further examine conditions for scaling up medication usage programs in real life contexts.
Despite advances in technology and type 1 diabetes (T1D) care, children from low-income families continue to have suboptimal outcomes and increased health-care utilization. In this study, we describe social determinants of health (SDOH) in high-risk children with T1D, as well as their SDOH-related priority goals, and assess the correlation between SDOH, glycemic control and health-care utilization.
Caregivers of children aged 4 to 18 years with a diagnosis of T1D of >1 year, poor glycemic control (glycated hemoglobin [A1C] ≥9.5%) or high health-care utilization (≥2 diabetes-related hospitalizations, emergency department attendances or missed outpatient appointments in the previous year) were included. Primary caregiver health-related quality of life (HRQOL), self-efficacy (Maternal Self-Efficacy in Diabetes [MSED] scale) and SDOH were assessed. Goals were identified after assessment by a community health worker.
Fifty-three families were included, most (n=48, 91%) of whom had government insurance. Cha modifiable factor to improve outcomes in this patient population.
The French Department of Health published on October 23, 2020 a decree governing acts associated with mid-urethral sling (MUS) operations. The aim of this study was to evaluate the changes in practice following this new legislation.
A cross-sectional study was carried out among French urologists and gynecologists using an online survey to collect changes in practices since the publication of the decree.
From January to February 2021, 436 surgeons participated in the survey. Among these surgeons, 87% were aware of the new legislation and 56% of them considered the decree as useless. The order resulted in an increase in working time in 81% of cases. Among these surgeons, 66% of the surgeons worked in tertiary referral centers for the management of incontinence, of which 55% had a multidisciplinary meeting in urogynecology. Among the surgeons, 31% considered this meeting to be useful but 80% considered that it did not lead to any change in surgical indications, even though 33% of complications of BSU were discussed there. In conclusion, 61% of surgeons felt more reluctant to schedule a BSU placement with this new legislation.
The majority of questioned surgeons considered the decree as useless. It generated few changes in practices which already respected the law on information, consultation, consent, experience and training. Most urologists and gynecologists are more reluctant to offer MUS after this new legislation.
4.
4.
The incidence of median nerve injuries in pediatric elbow dislocations is approximately 3% and avulsion of the open medial epicondylar epiphysis in the pediatric population is one predisposing factor that may explain this age predilection. These lesions can be difficult to diagnose in the acute phase because symptoms tend to be mild or delayed, consequently their management can be challenging and functional outcome poorer.
We present the case of an unrecognized median nerve entrapment in a 16-year-old boy with posterior dislocation of the elbow and a medial epicondyle fracture, treated initially with close reduction and open stabilization with a cannulated screw. Assessment is supported by a review of similar reported cases available in literature.
We discuss the diagnostic approach and the surgical options that can be used for this type of injury.
High clinical suspicion of entrapment is imperative in presence of signs of damage to the median nerve in the pediatric patient immediately after the reduction of an elbow dislocation. If diagnosis of entrapment is made the therapeutic choice between neurolysis and nerve graft depends on the lesion severity. In the presence of a Fourrier's type 4 lesion, neurolysis should be avoided, while nerve resection and grafting are recommended.
High clinical suspicion of entrapment is imperative in presence of signs of damage to the median nerve in the pediatric patient immediately after the reduction of an elbow dislocation. If diagnosis of entrapment is made the therapeutic choice between neurolysis and nerve graft depends on the lesion severity. In the presence of a Fourrier's type 4 lesion, neurolysis should be avoided, while nerve resection and grafting are recommended.
Nephrotoxicity remains a major long-standing concern for colistin, and it is critical to find agents that can prevent it. The present study aims to investigate the effect of vitamin E on the prevention of colistin-induced nephrotoxicity based on its antioxidant and free radical scavenging properties.
A randomized clinical trial was designed for 52 patients taking colistin. These patients were categorized into two groups of equal size, receiving colistin or colistin plus vitamin E (α-Tocopherol). Vitamin E with doses of 400 units was administrated daily either orally or by a nasogastric tube if needed. The incidence of Acute Kidney Injury (AKI) and its duration was recorded based on RIFLE criteria.
The Incidence of AKI based on RIFLE criteria was 42.3% and 46.2% in intervention and control groups, respectively. The analysis showed no significant difference in the prevalence of AKI for the two groups (P=0.78). There was no significant difference in the duration of AKI neither (P=0.83).
Although vitamin E is a powerful biological antioxidant, the effects of Vitamin E prophylaxis on colistin-induced nephrotoxicity was not taken into consideration in this study.
Although vitamin E is a powerful biological antioxidant, the effects of Vitamin E prophylaxis on colistin-induced nephrotoxicity was not taken into consideration in this study.
The aim of this study was to monitor the development of drug-resistant bacteria isolated from acute uncomplicated cystitis (AUC) and to evaluate methodology of the survey conducted by collecting only clinical data.
We enrolled female patients at least 16 years of age diagnosed with AUC in 2018. Patient information including age, menopausal status, and results of bacteriological examination were collected and analyzed regardless of bacterial identification, antimicrobial susceptibility testing or extended-spectrum β-lactamase (ESBL) detection method.
A total of 847 eligible cases were collected. Escherichia coli (E.coli) was the most frequently isolated bacterial species at about 70%, with proportions of fluoroquinolone-resistant E.coli (QREC) and ESBL-producing E.coli isolates at 15.6% and 9.5% of all E.coli isolates, respectively. The proportion of Staphylococcus saprophyticus (S.saprophyticus) was significantly higher in premenopausal women. Regarding the drug susceptibility of E.coli, isolates from EIt is expected to be continuously performed as an alternative survey to conventional one collecting bacterial strains.
Our study aimed to evaluate the cytokine levels in pediatric chronic non-bacterial osteomyelitis (CNO) patients and compare these with other immune-mediated diseases and healthy controls.
In this prospective study, we included 42 children with CNO, 28 patients with non-systemic juvenile idiopathic arthritis (JIA), 17 children with insulin-dependent diabetes mellitus (IDDM), and 30 healthy age-matched controls. In each of the CNO patients and comparison groups, the levels of 14-3-3-η protein, S100A8/A9 protein, interleukin-4 (IL-4), interleukin-17 (IL-17), interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) were measured by ELISA assay.
All studied cytokines in the CNO patients were significantly higher than controls, and IDDM, 14-3-3-η protein, IL-18, IL-4, IL-17, IL-1β, and TNF-α were less than in JIA patients. In the discriminant analysis, ESR, 14-3-3 protein, S100A8/A9, IL-18, IL-4, and TNF-α can discriminate CNO from JIA, and 14-3-3 protein, S100A8/A9, IL-18, IL-17, IL-4, and TNF-α can distinguish CNO from other diseases and HC.
