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Background/Objectives: Radiculopathy leads to pain, consequently reducing patient’s quality of life (QoL). Research indicates that certain nucleotides, such as cytidine and uridine, along with vitamins B1 and B12, may help alleviate pain and enhance QoL. This study assessed the impact of adding a supplement containing cytidine and uridine nucleotides and vitamins B1 and B12, alongside standard treatment, on radiculopathy-associated pain. Methods: A multicenter, prospective, two-cohort, randomized, open-label study was conducted. The control group received standard treatment, while the experimental group received standard treatment plus the supplement. The primary endpoint was pain reduction measured by a Visual Analog Scale (VAS). Secondary endpoints included functional improvement (Roland Morris questionnaire), clinical improvement (Clinical Global Impression [CGI] scale), and QoL improvement (EQ-5D-5L questionnaire). Results: A total of 122 patients were included from 17 centers across Spain. Both groups showed pain improvement, but the VAS reduction (control: 24.58 vs. experimental: 31.35) was not statistically significant. The Roland Morris score decreased significantly in the experimental group (estimate: −1.70, 95% CI −3.29 to −0.10; p = 0.038), and these patients were 5 times more likely to progress to a better CGI category (OR = 0.20, 95% CI 0.07 to 0.57; p = 0.003). No significant differences were observed in EQ-5D-5L scores or analgesic consumption. Conclusions: The addition of supplemental pyrimidine nucleotides and vitamins B1 and B12 to standard of care treatment improved radiculopathy functional and clinical outcomes. Regarding pain, however, although there was a numerical improvement, it did not reach statistical significance.

Purpose: To assess the efficacy and safety of a single injection of a new formulation of hyaluronic acid (MPS-HA2%) in patients with symptomatic knee osteoarthritis after 12 months' follow-up. Patients and Methods: Prospective, single-arm, multicentre, open-label, 12-month follow-up study. Patients with Kellgren-Lawrence (KL) 2-3 and visual analogue scale (VA.S) pain scores of [greater than or equal to]40-< 80 mm received a single injection of MPS-HA2%. The primary outcome was the reduction in VAS pain scores from baseline, and the secondary outcomes were the Western Ontario and McMaster (WOMAC) Universities Osteoarthritis Index, the minimum clinically important improvement (MCII), and patient and investigator global assessments (PGA, IGA) measured on 5-point Likert scale. Adverse events were recorded throughout the study for safety purposes. Results: A total of 101 patients (mean age: 68 years; 74% female; and 78% overweight) were included. The mean reduction in pain at 12 months was 37.7%; the total WOMAC score improved by 36.5% and the pain, stiffness and physical function subscores returned improvements of 32.1%, 34.1% and 32.7%, respectively (p=0.0001 with respect to baseline). At 12 months, a statistically significant 62.2% of patients obtained an improvement equal to or greater than the MCII. The mean PGA score at baseline was 2.44 and 1.46 at 12 months (p<0.05), and the mean IGA scores at equivalent timepoints were 2.29 and 1.48 (p<0.05). Fourteen patients received a second injection at the 6-month follow-up visit. Eight patients reported a total of 12 treatment-related adverse events that were local, non-serious and of mild-to-moderate intensity. Conclusion: With just a single intra-articular injection, this not controlled trial suggests that MPS-HA2% is effective 12 months after the procedure in most cases. Patient tolerability and safety were both optimal (NCT03852914). Keywords: osteoarthritis, pain, hyaluronic acid, viscosupplementation

Patients with rheumatoid arthritis (RA) have a significantly increased risk of sexual dysfunction. However, it is not properly included in commonly used questionnaires to assess health-related quality of life in RA. Qualisex is a questionnaire developed in France to assess the impact of RA on patients´ sexual function. Our aim was to adapt and validate this questionnaire for use with Spanish RA patients. Two independent translations and a backward translation were obtained. The final version was tested in a pilot study with 10 RA patients to detect any aspects that could hinder interpretation. The validity and reliability of the linguistically validated questionnaire were studied in a multicenter cross-sectional study, with a longitudinal component for reliability estimation. 125 RA patients were included. The response process, discrimination, internal consistency, internal structure, convergent validity (correlation with MGH-SFQ questionnaire, DAS-28, physician global assessment, patient global health assessment, RAID, HAQ, HADS and SF-12©) and reliability were analyzed. The inclusion of two extra items was proposed in the pilot study. The validity analysis detected responses for item 10 that were not coherent with responses for the rest of items. The Cronbach alpha coefficient was 0.971. The highest correlation (0.665) was obtained with MGH-SFQ (questionnaire measuring sexual functioning), followed by RAID (0.516). The intra-class correlation was 0.880 (95% CI 0.815; 0.923), higher than 0.85, which indicates excellent reliability. All parameters used to assess this questionnaire show highly acceptable values. Qualisex allows for a global score of RA patients’ sexual functioning and can be self-administered.

U-shaped plantar cushions could help reduce stress affecting the central forefoot without the need for an orthosis, but they are yet to be integrated as an element in socks. The objective of this study was to verify the effectiveness of a sock with a central discharge element in terms of plantar temperature and comfort. The sample comprised 38 subjects (13 men and 25 women). Their plantar temperatures were measured with a thermographic camera in a basal situation and after each of two 10-minute walks around an indoor circuit during which they wore either control or experimental socks at random (the same design, weight, and fiber, but with the plantar cushioning element added). After the walks, each subject responded to a comfort questionnaire (five-point Likert scale), blindly scoring the two socks. The highest temperatures (28.3 ± 2.7 °C) were recorded in the zone of the second and third metatarsal heads. With the experimental socks, the observed temperature increase in the central forefoot zone was significantly less than with the control socks (31.6 vs. 30.6 °C, p = 0.001). The subjects found the experimental socks to be more comfortable than the controls (4.63 ± 0.5 vs. 4.03 ± 0.5, p < 0.001). The discharge element included in the experimental socks was effective since it reduced the contact zones and excess friction with the ground, thereby lessening overheating by more than 1 °C. Furthermore, the experimental socks were perceived as being more comfortable by the subjects who had mild and occasional foot discomfort.

IntroductionRefractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation.MethodsIn this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA-) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells’ cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality.ResultsIn vitro , we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo , NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo , they exhibited functional properties of leukemia initiating cells.DiscussionThe data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL.

The prevalence of people over 60 years of age with cognitive impairment has increased in recent decades. As a consequence, numerous computerized cognitive trainings (CCT) have been developed. This pilot study aimed to determine the effectiveness of the CCT with VIRTRAEL in improving older adults’ cognition. Fifty-five participants (x¯ = 72.7 years; SD = 6.5) underwent CCT, and twenty participants (x¯ = 76.1 years; SD = 7.6) received face-to-face cognitive stimulation with a paper-and-pencil methodology. Both trainings were conducted in nine sessions (45–60 min each). Participants completed a pre-post training neuropsychological assessment. ANCOVAs and the standardized clinical change were performed. VIRTRAEL’s group showed a significant and greater improvement in verbal learning (p < 0.006) and delayed recall (p ≤ 0.001), working memory (p < 0.005), abstract (p < 0.002) and semantic reasoning (p < 0.015), and planning (p < 0.021). Additionally, more large clinical changes (d > 0.8) were found in the VIRTRAEL condition (in verbal learning and delayed free and cued recall) than in the standard group. Here we show that the CCT with VIRTRAEL is effective in improving cognitive function in older adults and is superior to the standard format. These preliminary findings indicate that CCT is a useful tool potentially applicable in the fight against cognitive symptomatology associated with aging and neurodegenerative diseases. VIRTRAEL represents a breakthrough in this field as it is inexpensive and easily accessible to any older person, regardless of whether they live far from health care resources.

Approximately 20–30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine diagnosis. The aim of this study was to establish and compare the MMR status using various approaches. Immunohistochemistry (IHC), PCR-based MSI, and the detection of defects in the four key MMR genes (MLH1, PMS2, MSH2, and MSH6) via methylation-specific multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) were performed. MSH3 expression was also evaluated. A set of 126 early-stage EC samples were analyzed, 53.2% of which were dMMR and 46.8% of which were proficient MMR (pMMR) as determined using IHC, whereas 69.3% were classified as microsatellite stable, while 8.8% and 21.9% were classified MSI-low (MSI-L) and MSI-high (MSI-H), respectively. In total, 44.3% of the samples showed genetic or epigenetic alterations in one or more genes; MLH1 promoter methylation was the most common event. Although acceptable concordance was observed, there were overall discrepancies between the three testing approaches, mainly associated with the dMMR group. IHC had a better correlation with MMR genomic status than the MSI status determined using PCR. Further studies are needed to establish solid conclusions regarding the best MMR assessment technique for EC.

Despite being infrequent tumors, the incidence and prevalence of pancreatic neuroendocrine tumors (P-NETs) has been rising over the past few decades. In recent years, rigorous phase III clinical trials have been conducted, allowing the approval of several drugs that have become the standard of care in these patients. Although various treatments are used in clinical practice, including somatostatin analogues (SSAs), biological therapies like sunitinib or everolimus, peptide receptor radionuclide therapy (PRRT) or even chemotherapy, a consensus regarding the optimal sequence of treatment has not yet been reached. Notwithstanding, sunitinib is largely used in these patients after the promising results shown in SUN111 phase III clinical trial. However, both prompt progression as well as tumor recurrence after initial response have been reported, suggesting the existence of primary and acquired resistances to this antiangiogenic drug. In this review, we aim to summarize the most relevant mechanisms of angiogenesis resistance that are key contributors of tumor progression and dissemination. Furthermore, several targeted molecules acting selectively against these pathways have shown promising results in preclinical models, and preliminary results from ongoing clinical trials are awaited.

Background/Objectives: This study aims to validate the tests in the VIRTRAEL assessment module for individuals in the chronic stage of Acquired Brain Injury (ABI). Methods: A total of 32 participants (81.3% male) were assessed, including 20 individuals who had experienced a stroke (62.5%) and 12 who had experienced a traumatic brain injury (TBI). Cognitive functions such as attention (d2 Attention Test and Digit Subscale of the WAIS-III), learning-memory (HVLT-R and Letters and Numbers Subscale of the WAIS-III), and executive function (Similarities and Matrices Subscales of the WAIS-III and the Zoo Map Test, version 1 of the BADS Battery) were evaluated using standardized paper-and-pencil tests and computerized tests from the VIRTRAEL online platform. Convergent and divergent correlation analyses were conducted using SPSS version 28. Results: Significant correlations were observed between scores in both formats (ranging from r = 0.408 in planning to r = 0.818 in delayed verbal recall), except in reasoning and verbal memory recognition. Conclusions: The tests from the free online platform VIRTRAEL demonstrate adequate validity for the cognitive assessment of individuals with ABI. This suggests that VIRTRAEL is a valuable, accessible tool for monitoring cognitive status, potentially benefiting health, education, and social and occupational reintegration.