Functionalized microcarriers for Enhanced CAR T cell manufacturing

Adoptive cell therapy using chimeric antigen receptor (CAR) T cells has shown immense promise in treating cancer. In 2017, Novartis and Kite Pharma both acquired FDA approval for their CAR T cell therapies targeted toward B cell malignancies. Despite these successes, manufacturing high-quality T cells at scale has proven challenging. Notably, current processes rely on bead-based expansion and suspension-cell bioreactors, which do not recapitulate the high cell density and robust signaling found in the lymph nodes. Please click Additional Files below to see the full abstract

Spinal manipulation and mobilisation in the treatment of infants, children, and adolescents: a systematic scoping review

PURPOSE: To i) identify and map the available evidence regarding effectiveness and harms of spinal manipulation and mobilisation for infants, children and adolescents with a broad range of conditions; ii) identify and synthesise policies, regulations, position statements and practice guidelines informing their clinical use. DESIGN: Systematic scoping review, utilising four electronic databases (PubMed, Embase, CINHAL and Cochrane) and grey literature from root to 4(th) February 2021. PARTICIPANTS: Infants, children and adolescents (birth to < 18 years) with any childhood disorder/condition. INTERVENTION: Spinal manipulation and mobilisation OUTCOME MEASURES: Outcomes relating to common childhood conditions were explored. METHOD: Two reviewers (A.P., L.L.) independently screened and selected studies, extracted key findings and assessed methodological quality of included papers using Joanna Briggs Institute Checklist for Systematic Reviews and Research Synthesis, Joanna Briggs Institute Critical Appraisal Checklist for Text and Opinion Papers, Mixed Methods Appraisal Tool and International Centre for Allied Health Evidence Guideline Quality Checklist. A descriptive synthesis of reported findings was undertaken using a levels of evidence approach. RESULTS: Eighty-seven articles were included. Methodological quality of articles varied. Spinal manipulation and mobilisation are being utilised clinically by a variety of health professionals to manage paediatric populations with adolescent idiopathic scoliosis (AIS), asthma, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), back/neck pain, breastfeeding difficulties, cerebral palsy (CP), dysfunctional voiding, excessive crying, headaches, infantile colic, kinetic imbalances due to suboccipital strain (KISS), nocturnal enuresis, otitis media, torticollis and plagiocephaly. The descriptive synthesis revealed: no evidence to explicitly support the effectiveness of spinal manipulation or mobilisation for any condition in paediatric populations. Mild transient symptoms were commonly described in randomised controlled trials and on occasion, moderate-to-severe adverse events were reported in systematic reviews of randomised controlled trials and other lower quality studies. There was strong to very strong evidence for ‘no significant effect’ of spinal manipulation for managing asthma (pulmonary function), headache and nocturnal enuresis, and inconclusive or insufficient evidence for all other conditions explored. There is insufficient evidence to draw conclusions regarding spinal mobilisation to treat paediatric populations with any condition. CONCLUSION: Whilst some individual high-quality studies demonstrate positive results for some conditions, our descriptive synthesis of the collective findings does not provide support for spinal manipulation or mobilisation in paediatric populations for any condition. Increased reporting of adverse events is required to determine true risks. Randomised controlled trials examining effectiveness of spinal manipulation and mobilisation in paediatric populations are warranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12887-022-03781-6

Cutaneous squamous cell carcinoma staging may influence management in users: A survey study.

PURPOSE: This study aims to determine whether there is consensus regarding staging and management of cutaneous squamous cell carcinoma (CSCC) across the various specialties that manage this disease. MATERIALS AND METHODS: A survey regarding CSCC high-risk features, staging, and management was created and emailed to cutaneous oncology experts including dermatology, head and neck surgery/surgical oncology, radiation oncology, and medical oncology. RESULTS: One hundred fifty-six (46%) of 357 invited physicians completed the survey. Depth of invasion (92%), perineural invasion (99%), histologic differentiation (85%), and patient immunosuppression (90%) achieved consensus (\u3e80%) as high-risk features of CSCC. Dermatologists were more likely to also choose clinical tumor diameter (79% vs. 54%) and histology (99% vs. 66%) as a high-risk feature. Dermatologists were also more likely to utilize the Brigham and Women\u27s Hospital (BWH) staging system alone or in conjunction with American Joint Committee on Cancer (AJCC) (71%), whereas other cancer specialists (OCS) tend to use only AJCC (71%). Respondents considered AJCC T3 and higher (90%) and BWH T2b and higher (100%) to be high risk and when they consider radiologic imaging, sentinel lymph node biopsy, post-operative radiation therapy, and increased follow-up. Notably, a large number of respondents do not use staging systems or tumor stage to determine treatment options beyond surgery in high-risk CSCC. CONCLUSION: This survey study highlights areas of consensus and differences regarding the definition of high-risk features of CSCC, staging approaches, and management patterns between dermatologists and OCS. High-risk CSCC is defined as, but not limited to, BWH T2b and higher and AJCC T3 and higher, and these thresholds can be used to identify cases for which treatment beyond surgery may be considered. Dermatologists are more likely to utilize BWH staging, likely because BWH validation studies showing advantages over AJCC were published in dermatology journals and discussed at dermatology meetings. Additional data are necessary to develop a comprehensive risk-based management approach for CSCC

Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States

IMPORTANCE Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population-based incidence in the United States. OBJECTIVE To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008. DESIGN, SETTING, AND PARTICIPANTS This multicenter retrospective cohort study examined 10 649 adult recipients of a primary transplant performed at 26 centers across the United States in the Transplant Skin Cancer Network during 1 of 2 calendar years (either 2003 or 2008) identified through the Organ Procurement and Transplantation Network (OPTN) database. Recipients of all organs except intestine were included, and the follow-up periods were 5 and 10 years. MAIN OUTCOMES AND MEASURES Incident skin cancerwas determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates for posttransplant skin cancer overall and for SCC, MM, and MCC were calculated per 100 000 person-years. Potential risk factors for posttransplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR). RESULTS Overall, 10 649 organ transplant recipients (mean [SD] age, 51 [12] years; 3873 women [36%] and 6776 men [64%]) contributed 59 923 years of follow-up. The incidence rates for posttransplant skin cancer was 1437 per 100 000 person-years. Specific subtype rates for SCC, MM, and MCC were 812, 75, and 2 per 100 000 person-years, respectively. Statistically significant risk factors for posttransplant skin cancer included pretransplant skin cancer (HR, 4.69; 95% CI, 3.26-6.73), male sex (HR, 1.56; 95% CI, 1.34-1.81), white race (HR, 9.04; 95% CI, 6.20-13.18), age at transplant 50 years or older (HR, 2.77; 95% CI, 2.20-3.48), and being transplanted in 2008 vs 2003 (HR, 1.53; 95% CI, 1.22-1.94). CONCLUSIONS AND RELEVANCE Posttransplant skin cancer is common, with elevated risk imparted by increased age, white race, male sex, and thoracic organ transplantation. A temporal cohort effect was present. Understanding the risk factors and trends in posttransplant skin cancer is fundamental to targeted screening and prevention in this population.American Academy of Dermatology and Galderma12 month embargo; Published Online: January 11, 2017.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]