Summary Background The malignant mechanisms that control the development of cutaneous T‐cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS–mitogen‐activated protein kinase, T‐cell receptor (TCR)–phospholipase C gamma 1 (PLCG1)–nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)–signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. Objectives To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. Methods We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin‐fixed paraffin‐embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR–PLCG1–NFAT, JAK–STAT and NF‐κB pathways. Folliculotropism and large‐cell transformation were also examined. Results NFAT and nuclear factor kappa B (NF‐κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large‐cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF‐negative cases. A significant association of NFAT with NF‐κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T‐cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell‐survival pathways. A higher mutational allele frequency was detected in advanced stages. Conclusions Our results show that STAT3 is activated in advanced cases and is associated with large‐cell transformation, while the activation of NFAT and NF‐κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large‐cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T‐cell lymphoma‐associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in ...
Background and Aims Hemiplegic shoulder pain (HSP) is a very common complaint among patients affected with cerebrovascular accident (CVA). This type of pathology is related with a neuropathic type of pain. Ultrasound-guided percutaneous neuromodulation (US-guided PNM) is a physical therapy technique consisting of low-frequency electric stimulation of peripheral nerves via an acupuncture needle under ultrasound guidance. Because of the relationship between the suprascapular and axillary nerves with the shoulder joint, these represent the target structure for US-guided PNM. This study aimed to observe the effects of the application of US-guided PNM in HSP and to evaluate the possible changes in variables such as pain, functionality and quality of life of patients. Material and Methods This study was a case series. Patients with HSP were selected between the months of April and June 2018 in the Hospital of Denia. Seven patients were interviewed, after which the experimental group was reduced to five participants. These patients received weekly PNM treatment during three weeks. The parameters used were: frequency (10Hz), pulse width (250 μs), intensity (pain threshold) and time (10 min). The main clinical variables examined were pain, measured using the VAS scale, functionality, via the SPADI scale and physical and mental components of quality of life using the SF12 scale. Results The results of the VAS scale, expressed as the mean (SD) was 7.2 (1.3) pre-intervention; 3.6 (0.89) post-intervention week 3; and 4 (1.23) post intervention week 5. The results revealed significant changes in the VAS scale which continued until week 5 (p < 0.05). The mean obtained in the SPADI scale, expressed as the mean (SD) was 72.4 (1.3) pre-intervention, 55.7 (19.72) post-intervention in week 3 and 59.8 (20.66) post intervention week 5. The changes observed between the pre-intervention sample and the measurements obtained in week 3 and 5 were significant (p < 0.05). Conclusions The US-guided PNM technique was effective in the sample under study for improvement of the patient's sensation of pain. The US-guided PNM technique improves functionality of HSP, as well as the emotional status of patients.
Background and Aim The use of prosthetic knee replacements currently represent an alternative for patients who suffer from severe gonarthrosis. Treatment via the technique of ultrasound-guided percutaneous neuromodulation (US-guided PNM) is a therapeutic alternative worth considering as a new tool in physical therapy for the post-surgical recovery of total knee arthroplasty (TKA). The aim of this study was to evaluate the effectiveness of treatment with US-guided PNM in the post-surgical stage among patients intervened with TKA. Material and Methods Patients were selected between February and May 2017 at the Hospital of Denia and were randomly assigned into two groups. The initial sample was 13 patients. The experimental group (n = 7) received treatment with US-guided PNM plus conventional treatment. The control group (n = 6) only received conventional physiotherapy treatment. Patients in the experimental group received an application of PNM, which consisted of an alternate low frequency current at 10 Hz¸ pulse width 250 μs, with an intensity to the pain threshold. The intervention was performed during four consecutive weeks after hospital discharge. The control group received conventional treatment based on manual therapy, active mobilization and the use of the arthromotor until 115° of knee flexion and 0° knee extension was achieved. The main clinical variables evaluated were pain, measured using the Visual Analog Scale (VAS), quality of life, based on physical and mental components, using the SF12 scale and functional assessment using the Oxford Knee Score. Lastly, pain, stiffness and functional capacity was measured using the WOMAC scale. Results Both groups obtained statistically significant results in the four variables evaluated compared to the pre-surgery stage, however, the changes were more evident in the intervention group (p < 0.05). Furthermore, no significant differences were found in the variables evaluated regarding quality of life between the experimental and control group except for the emotional component of the SF-12 scale, where the result was only significant in the experimental group treated with US-guided PNM (P < 0.05). Regarding the improvement in the health status and decreased pain in the postoperative stage after TKA, no significant differences were observed between groups (p > 0.05). Conclusion The application of the US-guided PNM technique provides greater benefits than conventional therapy for decreasing the post-surgical pain in patients who have undergone knee arthroplasty and for emotional function, evaluated using the SF-12 questionnaire.
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