Quantitative interpretation of utterances and movements from videoed interactions between rheumatology nurses and patients commencing methotrexate: a pilot study

Clinical Rheumatology - Educating patients about methotrexate is a core role of rheumatology nurses. We have previously reported the scoring of videoed interviews of rheumatology nurses educating...     

Rosmarinus plants: Key farm concepts towards food applications

Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti‐inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications.     

B-cell maturation antigen-specific chimeric antigen receptor T cells for multiple myeloma: Clinical experience and future perspectives

Despite major advances in the treatment of multiple myeloma (MM), it remains a largely incurable disease with long-term control often dependent on continuous therapy. More effective, better tolerated treatments are therefore required to achieve durable remissions and to improve the quality of life of MM patients. Adoptive immunotherapy employing T cells expressing chimeric antigen receptors (CAR) is currently among the most promising treatment approaches in cancer. Within the target portfolio for MM immunotherapy, B-cell maturation antigen (BCMA) is among the most widely studied target antigens. BCMA is consistently expressed on MM cells and, importantly, is not expressed in critical healthy tissue. For this reason, it is an ideal target for MM immunotherapy. Several clinical trials evaluating different BCMA-targeting CAR constructs have been initiated and early results are very promising. However, in this rapidly developing clinical landscape, the ultimate role of BCMA-specific CAR-T cell therapy remains unclear. In this review, we will summarize currently available clinical data on BCMA-directed CAR-T cells and discuss potential future perspective for this promising treatment approach in MM.     

Re-interpretation of PAM50 gene expression as quantitative tumor dimensions shows utility for clinical trials: application to prognosis and response to paclitaxel in breast cancer

Background

We recently showed PAM50 gene expression data can be represented by five quantitative, orthogonal, multi-gene breast tumor traits. These novel tumor ‘dimensions’ were superior to categorical intrinsic subtypes for clustering in high-risk breast cancer pedigrees, indicating potential to represent underlying genetic susceptibilities and biological pathways. Here we explore the prognostic and predictive utility of these dimensions in a sub-study of GEICAM/9906, a Phase III randomized prospective clinical trial of paclitaxel in breast cancer.

Methods

Tumor dimensions, PC1–PC5, were calculated using pre-defined coefficients. Univariable and multivariable Cox proportional hazards (PH) models for disease-free survival (DFS) were used to identify associations between quantitative dimensions and prognosis or response to the addition of paclitaxel. Results were illustrated using Kaplan–Meier curves.

Results

Dimensions PC1 and PC5 were associated with DFS (Cox PH p = 6.7 \(\times\) 10⁻⁷ and p = 0.036), remaining significant after correction for standard clinical–pathological prognostic characteristics. Both dimensions were selected in the optimal multivariable model, together with nodal status and tumor size (Cox PH p = 1.4 \(\times\) 10⁻¹²). Interactions with treatment were identified for PC3 and PC4. Response to paclitaxel was restricted to tumors with low PC3 and PC4 (log-rank p = 0.0021). Women with tumors high for PC3 or PC4 showed no survival advantage.

Conclusions

Our proof-of-concept application of quantitative dimensions illustrated novel findings and clinical utility beyond standard clinical–pathological characteristics and categorical intrinsic subtypes for prognosis and predicting chemotherapy response. Consideration of expression data as quantitative tumor dimensions offers new potential to identify clinically important patient subsets in clinical trials and advance precision medicine.

     

Experiences and psychological distress of fertility treatment and employment

Purpose: This study examined experiences and psychological distress about fertility treatment in people combining work and treatment.

Methods: Five hundred and sixty-three participants in the UK completed an online survey asking about difficulties in combining work and treatment; workplace disclosure, support, absence and policy; and psychological distress about treatment.

Results: Absence from work and perceptions that treatment has an impact on work and career prospects were reported by the majority of participants and this was related to the psychological distress of treatment. Around three quarters of participants disclosed to their employer and colleagues. The key reason for disclosure was needing to ask for absence from work and the main reason for non-disclosure was privacy. Workplace policy relating to managing fertility treatment and support from colleagues and their employer was related to reduced psychological distress but workplace policy was reported by less than one quarter of participants.

Conclusion: Difficulties experienced in combining work and treatment suggest that support is needed. Specific workplace policy, guidance for supervisors and flexibility in fertility clinic times should help support employees during treatment and reduce psychological distress, thereby potentially influencing physical health and treatment outcomes.     

Insights into the pathogenesis of ATP1A1‐related CMT disease using patient‐specific iPSCs

The development of patient‐specific induced pluripotent stem cells (iPSCs) offered interesting insights in modeling the pathogenesis of Charcot‐Marie‐Tooth (CMT) disease and thus we decided to explore the phenotypes of iPSCs derived from a single CMT patient carrying a mutant ATP1A1 allele (p.Pro600Ala). iPSCs clones generated from CMT and control fibroblasts, were induced to differentiate into neural precursors and then into post‐mitotic neurons. Control iPSCs differentiated into neuronal precursors and then into post‐mitotic neurons within 6‐8 days. On the contrary, the differentiation of CMT iPSCs was clearly defective. Electrophysiological properties confirmed that post‐mitotic neurons were less mature compared to the normal counterpart. The impairment of in vitro differentiation of CMT iPSCs only concerned with the neuronal pathway, because they were able to differentiate into mesendodermal cells and other ectodermal derivatives. ATP1A1 was undetectable in the few neuronal cells derived from CMT iPSCs. ATP1A1 gene mutation (p.Pro600Ala), responsible for a form of axonal CMT disease, is associated in vitro with a dramatic alteration of the differentiation of patient‐derived iPSCs into post‐mitotic neurons. Thus, the defect in neuronal cell development might lead in vivo to a decreased number of mature neurons in ATP1A1‐CMT disease.     

Periodization in Anterior Cruciate Ligament Rehabilitation: A Novel Framework

More than 250,000 anterior cruciate ligament (ACL) injuries occur each year in the USA, and approximately 65% of these injuries undergo reconstructive surgery. Appropriate rehabilitation after ACL reconstruction can yield predictably good outcomes, with return to previous levels of activity and high knee function. At present, periodization is used at all levels of sports training. Whether conceptualized and directed by coaches, or by athletes themselves, competitors structure their training in a cyclic fashion, enabling athletes to best realize their performance goals. In practical application, sport physical therapists use periodization: postoperative “protocols” serve as rudimentary forms of periodization, albeit implemented over shorter time frames than that typically employed in preparation for competition. An ACL injury should not be considered a “simple” musculoskeletal pathology with only local mechanical or motor dysfunctions. Together with the psychological trauma and reduction in physical capacity, there is a cascade of events, including neurological insult to the central nervous system and reduction in afferences to the sensorimotor system. Rehabilitation should consider all these issues, and periodization would allow to better define and to plan aims and objectives to return athletes to their sport. Technological resources including advanced neuroimaging methods, virtual reality for injury risk screening and return to sport assessment, and interactive artificial reality-based neuromuscular training methods offer new approaches and tools to address this important biomedical problem. The cost and availability of many of these technologies will continue to decrease, providing greater availability, scientific rigor, and ultimately, utility for cost-effective and data-driven assessments.     

COVID-19 in the endoscopy unit: How likely is transmission of infection? Results from an international,multicenter study

BACKGROUND Coronavirus disease 2019(COVID-19) significantly affected endoscopy practice,as gastrointestinal endoscopy is considered a risky procedure for transmission of infection to patients and personnel of endoscopy units(PEU).AIM To assess the impact of COVID-19 on endoscopy during the first European lockdown(March-May 2020).METHODS Patients undergoing endoscopy in nine endoscopy units across six European countries during the period of the first European lockdown for COVID-19(MarchMay 2020) were included. Prior to the endoscopy procedure, participants were stratified as low-or high-risk for potential COVID-19 infection according to the European Society of Gastrointestinal Endoscopy(ESGE) and the European Society of Gastroenterology and Endoscopy Nurses and Associates(ESGENA) joint statement, and contacted 7-14 d later to assess COVID-19 infection status. PEU were questioned regarding COVID-19 symptoms and/or infection via questionnaire, while information regarding hospitalizations, intensive care unitadmissions and COVID-19-related deaths were collected. The number of weekly endoscopies at each center during the lockdown period was also recorded.RESULTS A total of 1267 endoscopies were performed in 1222 individuals across nine European endoscopy departments in six countries. Eighty-seven(7%) were excluded because of initial positive testing. Of the 1135 pre-endoscopy low risk or polymerase chain reaction negative for COVID-19, 254(22.4%) were tested post endoscopy and 8 were eventually found positive, resulting in an infection rate of 0.7% [(95%CI: 0.2-0.12]. The majority(6 of the 8 patients, 75%) had undergone esophagogastroduodenoscopy. Of the 163 PEU, 5 [3%;(95%CI: 0.4-5.7)] tested positive during the study period. A decrease of 68.7%(95%CI: 64.8-72.7) in the number of weekly endoscopies was recorded in all centers after March 2020. All centers implemented appropriate personal protective measures(PPM) from the initial phases of the lockdown.CONCLUSION COVID-19 transmission in endoscopy units is highly unlikely in a lockdown setting, provided endoscopies are restricted to emergency cases and PPM are implemented.