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Oncogene-immortalized bone marrow-derived macrophages are considered to be a good model for the study of immune cell functions, but the factors required for their survival and proliferation are still unknown. Although the effect of the thyroid hormones on global metabolic and transcriptional responses in macrophages has not yet been examined, there is increasing evidence that they could modulate macrophage functions. We show here that the thyroid hormone T3 is an absolute requirement for the growth of immortal macrophages. The hormone regulates the activity of the main signaling pathways required for proliferation and anabolic processes, including the phosphorylation of ERK and p38 MAPKs, AKT, ribosomal S6 protein, AMPK and Sirtuin-1. T3 also alters the levels of metabolites controlling transcriptional and post-transcriptional actions in macrophages, and causes widespread transcriptomic changes, up-regulating genes needed for protein synthesis and cell proliferation, while down-regulating genes involved in immune responses and endocytosis, among others. This is not observed in primary bone marrow-derived macrophages, where only p38 and AMPK activation is regulated by T3 and in which the metabolic and transcriptomic effects of the hormone are much weaker. However, the response to IFN-γ is reduced by T3 similarly in immortalized macrophages and in the primary cells, confirming previous results showing that the thyroid hormones can antagonize JAK/STAT-mediated signaling. These results provide new perspectives on the relevant pathways involved in proliferation and survival of macrophage cell culture models and on the crosstalk between the thyroid hormones and the immune system.

BAF57 is a core subunit present in all mammalian SWI/SNF ATP-dependent chromatin remodeling complexes, which regulates important biological processes including gene transcription, DNA recombination, DNA repair, and DNA replication. Among other functions, BAF57 mediates the recruitment of SWI/SNF to sequence-specific transcription factors. Thus, BAF57 plays a crucial role in regulating estrogen-dependent gene expression and proliferation in human cell lines derived from breast tumors. Increasing genetic and biochemical evidences suggest that mutations in BAF57 or alterations in its expression could play an oncogenic role in the mammary gland. Here, we describe two novel mutations in the BAF57 gene found in a breast cancer patient. Both mutations originate premature stop codons, leading to truncated proteins, structurally similar to another BAF57 mutant previously found in a human cell line derived from a breast tumor (BT-549). The expression of these novel BAF57 mutants has abnormally high estrogen receptor alpha (ERα) coactivating potential, suggesting that they might be involved in the aberrant estrogen-dependent proliferation that occur in the majority of breast tumors that retain ERα expression. In addition, the mutations in BAF57 affect its functional interaction with the androgen receptor and ETS2, two transcription factors that play an important role in breast cell biology. Therefore, mutations in BAF57 could impinge on several oncogenic signaling pathways contributing to the origin and/or development of breast cancer.

BAF57 is a core subunit present in all mammalian SWI/SNF ATP-dependent chromatin remodeling complexes, which regulates important biological processes including gene transcription, DNA recombination, DNA repair, and DNA replication. Among other functions, BAF57 mediates the recruitment of SWI/SNF to sequence-specific transcription factors. Thus, BAF57 plays a crucial role in regulating estrogen-dependent gene expression and proliferation in human cell lines derived from breast tumors. Increasing genetic and biochemical evidences suggest that mutations in BAF57 or alterations in its expression could play an oncogenic role in the mammary gland. Here, we describe two novel mutations in the gene found in a breast cancer patient. Both mutations originate premature stop codons, leading to truncated proteins, structurally similar to another BAF57 mutant previously found in a human cell line derived from a breast tumor (BT-549). The expression of these novel BAF57 mutants has abnormally high estrogen receptor alpha (ERα) coactivating potential, suggesting that they might be involved in the aberrant estrogen-dependent proliferation that occur in the majority of breast tumors that retain ERα expression. In addition, the mutations in BAF57 affect its functional interaction with the androgen receptor and ETS2, two transcription factors that play an important role in breast cell biology. Therefore, mutations in BAF57 could impinge on several oncogenic signaling pathways contributing to the origin and/or development of breast cancer.

Objective: To develop and validate a ResNet-50-based deep learning model for automatic detection of osteomyelitis (DFO) in plain radiographs of patients with diabetic foot ulcers (DFUs). Research Design and Methods: This retrospective study included 168 patients with type one or type two diabetes and clinical suspicion of DFO confirmed via a surgical bone biopsy. An experienced clinician and a pretrained ResNet-50 model independently interpreted the radiographs. The model was developed using Python-based frameworks with ChatGPT assistance for coding. The diagnostic performance was assessed against the histopathological findings, calculating sensitivity, specificity, the positive predictive value (PPV), the negative predictive value (NPV), and the likelihood ratios. Agreement between the AI model and the clinician was evaluated using Cohen’s kappa coefficient. Results: The AI model demonstrated high sensitivity (92.8%) and PPV (0.97), but low-level specificity (4.4%). The clinician showed 90.2% sensitivity and 37.8% specificity. The Cohen’s kappa coefficient between the AI model and the clinician was −0.105 (p = 0.117), indicating weak agreement. Both the methods tended to classify many cases as DFO-positive, with 81.5% agreement in the positive cases. Conclusions: This study demonstrates the potential of IA to support the radiographic diagnosis of DFO using a ResNet-50-based deep learning model. AI-assisted radiographic interpretation could enhance early DFO detection, particularly in high-prevalence settings. However, further validation is necessary to improve its specificity and assess its utility in primary care.

Background/Objectives: diabetic foot osteomyelitis (DFO) is a serious complication characterized by bone infection that can involve cortical structures, bone marrow, and surrounding soft tissues. Its prevalence ranges from 20% in moderate diabetic foot infections to over 50% in severe cases, making accurate diagnosis essential in guiding timely and effective management. in this study, we aimed to evaluate the diagnostic accuracy achieved by combining the probe-to-bone (PTB) test, plain radiography, and blood biomarkers—including the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)—in the diagnosis of DFO. Methods: we conducted a diagnostic accuracy study involving 128 patients with diabetic foot ulcers and clinical suspicion of DFO. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for individual tests and for their diagnostic combinations. Results: the combination of PTB and biomarkers yielded a sensitivity of 75%, a specificity of 24%, a positive predictive value of 69%, and a negative predictive value of 29%. Similarly, the combination of PTB and plain radiography showed a sensitivity of 76%, a specificity of 23%, a positive predictive value of 62%, and a negative predictive value of 38%. When the three diagnostic modalities were analyzed together, the sensitivity reached 75%, and the specificity reached 23%. Conclusions: the combination of PTB and inflammatory biomarkers demonstrated moderate effectiveness and diagnostic performance comparable to PTB combined with radiography. These findings suggest that biomarkers may serve as a practical and accessible diagnostic adjunct in settings where imaging availability is limited or radiographic interpretation is challenging.

Aim: To compare the healing time in patients with diabetic foot osteomyelitis according to the presence or absence of clinical signs of infection, variation of blood parameters, the presence of different radiological signs, and the treatment received for the management of osteomyelitis. Methods: A prospective observational study was carried out in a specialised Diabetic Foot Unit between November 2014 and November 2018. A total of 116 patients with osteomyelitis were included in the study (treated by either a surgical or medical approach). During the baseline visit, we assessed the diagnosis of osteomyelitis, demographic characteristics and medical history, vascular and neurological examination, clinical signs of infection, increased blood parameters, radiological signs of osteomyelitis, and the treatment to manage osteomyelitis. We analysed the association between the presence of clinical signs of infection, variation of blood parameters, presence of radiological signs, and treatment received for management of osteomyelitis with the healing time. Results: The mean time to ulcer healing was 15.8 ± 9.7 weeks. Concerning healing times, we did not find an association with the presence of clinical signs of infection or with the increase in blood parameters, except in the case of eosinophils, which with higher values appear to increase the healing time (U = 66, z = −2.880, p = 0.004). Likewise, no relationship has been found between healing time and the appearance of the different radiological signs of osteomyelitis, nor depending on the treatment administered for the management of osteomyelitis. Conclusion: High levels of eosinophils are associated with a longer healing time of diabetic foot ulcers complicated with osteomyelitis, finding no other factors related to increased healing time.

Aim: To compare long-term complications according to the treatment received for management of diabetic foot osteomyelitis (surgical or medical) at 1 year follow up. Design and Participants: A prospective observational study was conducted involving 116 patients with diabetic foot osteomyelitis. The patients received surgical or medical treatment based on the principles described in the literature. To register the development of a complication, both groups of treatments were followed-up 1 year after the ulcer had healed. Results: Ninety-six (82.8%) patients received surgical treatment and 20 (17.2%) medical treatment. No differences were found in the time to healing between both groups of treatment, 15.7 ± 9.2 weeks in the surgical group versus 16.4 ± 12.1 weeks in the medical group; p = 0.103. During follow up, 85 (73.3%) patients developed complications without differences between both groups, 68 (70.8%) in the surgical group versus 17 (85%) in the medical group (p = 0.193). The most common complication in both groups was re-ulceration. We did not observe significant differences comparing complication-free time survival between both treatments (p = 0.665). Conclusion: The onset of complications after healing in patients who suffered from diabetic foot osteomyelitis was not associated with the treatment received. Surgical and medical approaches to the management of diabetic foot osteomyelitis produced similar results in long-term follow up.

Background: To identify differences in radiographic outcomes in weight-bearing lateral X-ray to predict the probability of ulceration in patients with midfoot Charcot neuroarthropathy (CN) differentiated by lateral and medial column deformities. Methods: Thirty-five patients who suffered from CN midfoot deformity participated in this 1 year prospective study in a specialized diabetic foot unit. Lateral talar-first metatarsal angle, calcaneal pitch, and cuboid height were performed by digital radiographs in the weight-bearing lateral view. Patients were followed up for 1 year or until an ulcer ulceration event occurred in the midfoot region. Results: ROC analyses showed that all patients with medial pattern deformity that developed a midfoot ulcer had a lateral talar-first metatarsal angle greater (negative) than −27.5 degrees (°). All patients with lateral pattern deformity that developed a midfoot ulcer had a calcaneal pitch greater (more negative) than −5° and a cuboid height greater (more negative) than −1.5°. Conclusions: Lateral talar-first metatarsal angle was the greatest predictor of midfoot ulceration, with greater than −27.5° measurement correlating with ulceration occurrence in patients with medial deformity. Calcaneal pitch and cuboid height were the greatest predictors of midfoot ulceration with greater than −5 and −1.5°, respectively in patients with CN lateral deformity.

Background: To assess long-term clinical outcomes of patients who underwent isolated versus several percutaneous flexor tenotomies for the treatment of toe deformities and previous diabetic foot ulcers; Methods: Twenty-three patients (mean age 66.26 ± 11.20, years) who underwent prophylactic percutaneous flexor tenotomies secondary to tip-toe ulcers participated in this 1-year prospective study. The study was stratified into two groups for analyses: (1) isolated tenotomies patients, and (2) several tenotomies patients (two or more tenotomies). Outcome measures were toe reulceration and recurrence, minor lesions, digital deformities, and peak plantar pressure (PPP—N/cm2) and pressure/time Integral (PTI—N/cm2/s) in the hallux and minor toes after a 1-year follow-up period; Results: Patients with isolated tenotomies (n = 11, 35.48%) showed a higher rate of reulceration (n = 8, 72.7%, p < 0.001) in the adjacent toes, additionally, we found more prevalence of hyperkeratosis (n = 11, 100%), minor lesions (n = 9, 81%), and claw toes (n = 11, 100%) (p < 0.001). In several tenotomies patients (n = 20, 64.52%), we found a higher rate of floating toes (n = 16, 80%) in comparison with isolated tenotomies patients (p < 0.001). PPP and PTI in the non-tenotomy toes were higher in the group of patients who underwent isolated tenotomies (p < 0.001); Conclusions: Patients who underwent several tenotomies had better clinical outcomes after a 1-year follow-up period compared to isolated tenotomies.