Evaluation of cartilage repair in the distal femur after autologous chondrocyte transplantation using T2 relaxation time and dGEMRIC

OBJECTIVES: To investigate the potential of combining T2 relaxation time and delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) measurements after autologous chondrocyte transplantation (ACT). MATERIALS AND METHODS: T2 and dGEMRIC maps were measured in the sagittal and coronal directions in 12 patients 10-15 months after ACT surgery. Grafts were assessed for bulk full thickness, superficial and deep tissue T2 and dGEMRIC values, and were compared to control cartilage. RESULTS: All ACT grafts showed filling of the repair area to the level of or above the articular surface. Matrix of the grafts lacked the classical laminar structure and appeared more heterogenous on T2 maps than control cartilage. As compared to control cartilage, ACT grafts showed significantly longer T2 values for bulk tissue as well as for the superficial 50% and deep 50% of tissue except for superficial cartilage in the coronal direction. dGEMRIC assessment in the sagittal and coronal directions did not show a significant difference between bulk, superficial or deep tissue as compared to the control cartilage. Superficial and deep ACT tissue did not differ statistically in terms of their T2 or dGEMRIC values. CONCLUSIONS: These preliminary results suggest that, according to T2 measurements, ACT repair tissue at 10-15 months differs from normal cartilage and probably lacks the preferential collagen arrangement of normal cartilage, while according to dGEMRIC a varying degree of proteoglycan replenishment takes place. Combining these two quantitative magnetic resonance imaging techniques enables a more comprehensive characterization of cartilage repair than before.     

Effect of a vigorous aerobic regimen on physical performance in breast cancer patients - a randomized controlled pilot trial

This randomized, controlled pilot trial was carried out to assess the feasibility and efficacy of an aerobic exercise in enhancing physical performance of breast cancer patients after adjuvant treatments. The potential of the training regimen to prevent accompanying bone loss was also assessed. Thirty patients, 41-65 years of age, were randomly assigned into training or control groups shortly after adjuvant chemo- or radiotherapy. The 12-week training included a guided aerobic exercise session once a week (the effective part being either step aerobic- or circuit-training in alternate weeks) and similar home exercise sessions twice a week. Adherence to the guided sessions was 78%, while home training was performed an average 2.1 times per week. Agility assessed with figure-8 running test and peak jumping power showed significant between-group treatment-effects (∼5% and ∼10%, respectively). Judged from the accelerometer data, reaction forces up to six times body weight occurred during the training, which implies that the training could also have potential to affect bone mass. The present exercise regimen turned out to be feasible and effective among breast cancer patients in terms of physical performance. Large controlled trials are necessary to confirm these findings.     

The effect of small doses of botulinum toxin a on neck-shoulder myofascial pain syndrome: a double-blind, randomized, and controlled crossover trial

OBJECTIVES: Myofascial pain syndrome is a common cause of muscular pain in the shoulder-neck region. Injections of large amounts of botulinum toxin A have been found to be beneficial for the alleviation of myofascial pain, but large doses of this toxin may cause paresis of the muscle and other adverse events. The aim of this work was to determine the effect of small doses (5 U) of botulinum toxin A (BTA) injected directly into the painful trigger points of the muscles, using a double-blind crossover technique. METHODS: On the basis of the empirical criteria proposed for diagnosis of myofascial pain syndrome, 31 patients suffering from myofascial pain in the neck-shoulder region were studied. The patients received either botulinum toxin A or physiological saline injections on 2 occasions 4 weeks apart. The total dose varied from 15 to 35 U of botulinum toxin A [28+/- 6 U (mean+/- SD)]. The follow-up measurements were carried out at 4 weeks after each treatment. Neck pain and result of treatment were assessed with questionnaires. The pressure pain threshold was determined using a dolorimeter. RESULTS: Neck pain values decreased from 4.3+/- 2.4 to 3.3+/- 2.0 after saline injections and from 4.1+/- 2.1 to 3.3+/- 2.2 after botulinum toxin A. The pressure pain threshold values increased from 5.2+/-1.6 to 5.9+/-1.5 and from 5.7+/-1.6 to 5.9+/-1.6 after injections with saline and botulinum toxin A, respectively. No statistically significant changes in the neck pain and pressure pain threshold values occurred between the botulinum toxin A and saline groups. After the first injections, the subjective result of treatment was significantly (P=0.008) in favor of botulinum toxin A, and after the second injections, the subjective result was better for saline, but the difference was not statistically significant (P=0.098). There was no significant difference in the prevalence of side effects between saline and botulinum toxin A. CONCLUSIONS: Our study shows that there was no difference between the effect of small doses of botulinum toxin A and those of physiological saline in the treatment of myofascial pain syndrome.     

DNA flow cytometry in surgically treated lung cancer--prognostic significance.

Although DNA aneuploidy and high proliferative activity (S-phase fraction, SPF) of tumour cells, measured by flow cytometry, have proved to be indicators of poor prognosis in most solid tumours, there have been conflicting results in lung cancer studies. During a four-year period we studied the prognostic significance of DNA ploidy and SPF in 99 surgically treated lung cancer patients. Flow cytometric analysis was done from archival, formalin-fixed, paraffin-embedded tumour specimens. DNA index and SPF were determined, using MultiCycle software with sliced nuclear correction to compensate for debris. There were 61 DNA diploid and 38 DNA aneuploid tumours. The median SPF was 10.2%. Neither ploidy nor SPF was associated with previously known prognostic factors. Survival was poorer in patients with aneuploid tumours than in the other patients, but the difference was not statistically significant. DNA ploidy and SPF thus do not seem to be useful prognostic indicators in surgically treated lung cancer.     

Risk of venous thromboembolism in COVID-19 infection

The incidence of venous thromboembolism (VTE) for non-hospitalised patients with coronavirus disease-2019 infection has not been very widely studied. 13 019 persons with a positive SARS-CoV-2 nucleic acid amplification test were identified. In total, 447 (0.2%) VTEs were identified in the study population, 293 (66%) of these were pulmonary embolisms. A positive SARS-CoV-2 test did not increase the risk for VTE in the univariate analysis (odds ratio (OR): 1.0, 95% confidence interval (CI): 0.69–1.4) or multivariable analysis (OR: 1.36, 95% CI: 0.93–1.97).     

‘I became more aware of my actions’—A qualitative longitudinal study of a health psychological group intervention for patients with myalgic encephalomyelitis/chronic fatigue syndrome

Objectives

To explore myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients' experiences of a health psychological group intervention and its usefulness, non-usefulness or harmfulness for illness management and adjustment.

Design

A qualitative longitudinal study using inductive content analysis.

Methods

Semistructured interviews were conducted with 10 adults. Interviews were conducted before the 16-week intervention, immediately after its completion, and at 3 months after completion.

Results

Participants reported that the intervention was useful and not harmful. The model improved their ability to cope with ME/CFS by providing them with useful information about the illness along with peer support and professional guidance. Participants reported improved illness management and adjustment, which they perceived as an outcome of achieving new ways of thinking, feeling and acting.

Conclusions

Participants viewed the health psychological approach to group intervention as meeting their needs. To achieve better illness management and adjustment, more consideration should be given to supportive interactional processes with peers and healthcare professionals.

Patient or Public Contribution

The intervention was developed to meet patients' needs of finding ways to manage their illness. The research team consulted eight patients with ME/CFS and three clinical centres working with ME/CFS treatment and rehabilitation at the intervention planning stage. Their comments influenced the planning and content of the intervention as well as ethical issues that should be considered, such as potential harm to participants. All participants were informed about the theoretical foundations of the study and the principles guiding the intervention. Participants were not involved in the data analysis.

Clinical Trial Registration

NCT04151693     

Experiences of dialectical behaviour therapy for adolescents: A qualitative analysis

Objectives

To explore how former patients in dialectical behaviour therapy for adolescents (DBT-A) experience their treatment, and specifically if there were aspects of the treatment that they retrospectively identify as particularly meaningful, helpful or unhelpful.

Design

From a larger sample of 75 former DBT-A patients 19 were selected for a qualitative semi-structured interview study.

Methods

Young adults (N = 19; 18 females, one male), who as adolescents had been enrolled in DBT-A due to self-harming behaviours and features of borderline personality disorder, were interviewed up to 8 years (median 6.0; min 1.3; max 8.2) after end of treatment, at mean age 23 years (SD 2.5). Reflexive thematic analysis was implemented.

Results

Six key themes were revealed; (1) The need to be seen, listened to and believed in, (2) the importance of teamwork between patient and therapist, (3) the value of group and structure, (4) therapy as lifesaving and life-changing, (5) the risks of feeling misplaced and (6) the risks of abrupt endings.

Conclusion

A trusting relationship with the therapist promoted commitment and motivation for treatment. This relationship was facilitated by the therapist showing explicit care and belief in the patient's own competence in changing their destructive behaviours. Meeting peers in group skill training offered a salient form of validation and was reported to be of particular value. The format of meeting peers and the importance of the dialectical therapeutic stance need to be studied further. Not all youth experienced DBT-A as suitable and the need for sufficient treatment dose was emphasized.     

FURIN regulates cytotoxic T-lymphocyte effector function and memory cell transition in mice

The proprotein convertase subtilisin/kexins (PCSKs) regulate biological actions by cleaving immature substrate proteins. The archetype PCSK, FURIN, promotes the pathogenicity of viruses by proteolytically processing viral proteins. FURIN has also important regulatory functions in both innate and adaptive immune responses but its role in the CD8⁺ CTLs remains enigmatic. We used a T-cell-specific FURIN deletion in vivo to demonstrate that FURIN promotes host response against the CTL-dependent lymphocytic choriomeningitis virus by virtue of restricting viral burden and augmenting interferon gamma (IFNG) production. We also characterized Furin KO CD8⁺ T cells ex vivo, including after their activation with FURIN regulating cytokines IL12 or TGFB1. Furin KO CD8⁺ T cells show an inherently activated phenotype characterized by the upregulation of effector genes and increased frequencies of CD44⁺, TNF⁺, and IFNG⁺ cells. In the activated CTLs, FURIN regulates the productions of IL2, TNF, and GZMB and the genes associated with the TGFBR-signaling pathway. FURIN also controls the expression of Eomes, Foxo1, and Bcl6 and the levels of ITGAE and CD62L, which implies a role in the development of CTL memory. Collectively, our data suggest that the T-cell expressed FURIN is important for host responses in viral infections, CTL homeostasis/activation, and memory development.