Search Results (955)

Background: Recalcitrant plantar fasciitis (RPF) is a common cause of chronic heel pain, resistant to conservative treatment in up to 10% of cases. A biomechanical association exists between isolated gastrocnemius contracture and increased tension on the plantar fascia. In this context, gastrocnemius recession (GR) has emerged as a surgical intervention aimed at reducing fascial strain and improving functional outcomes. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD420251028862). Randomized controlled trials evaluating the efficacy of GR in patients with RPF were included. Searches were performed in PubMed, Cochrane Library, and Web of Science. Risk of bias was assessed using the RoB 2 tool, and the certainty of evidence was evaluated using the GRADE approach. Primary outcomes included foot function (AOFAS), pain (VAS), and ankle dorsiflexion range (FDTPA). Results: Five studies encompassing 150 patients were included. Meta-analysis revealed statistically significant improvements in foot function (AOFAS, standardized mean difference [SMD] = 0.81; 95% CI: 0.26–1.36), pain reduction (VAS, SMD = −1.17; 95% CI: −1.99 to −0.36), and ankle dorsiflexion (FDTPA, SMD = 0.74; 95% CI: 0.26–1.22). GR demonstrated advantages over plantar fasciotomy in terms of postoperative recovery and preservation of fascial structure. No major complications were reported, and some studies documented sustained benefits up to six years postoperatively. Moderate to high heterogeneity was observed, largely due to variations in surgical technique and follow-up durations. Conclusions: Gastrocnemius recession is a safe and effective surgical option for treating RPF, particularly in patients with isolated gastrocnemius contracture and failure of conservative therapies. It significantly improves foot function, reduces pain, and enhances ankle mobility, with durable long-term outcomes. Trial Registration: This systematic review is registered with PROSPERO (CRD420251028862). Full article

Transanal Irrigation (TAI) and Colon Hydrotherapy (CHT) represent emerging therapeutic options that may complement first-line interventions or serve as rescue treatments for chronic constipation and fecal incontinence. Their clinical utility depends on patient characteristics, specific therapeutic goals, device features, and probe type, as well as the procedural setting. This review presents the various pathophysiological contexts in which these techniques can be applied, analyzing their specific characteristics and potential pros and cons. Moreover, these interventions are also considered within a Psycho-Neuro-Endocrino-Immunological (PNEI) framework, given the potential influence of intestinal function and microbiota modulation on the bidirectional communication pathways linking the enteric nervous system, neuroendocrine regulation, immune activity, and global patient well-being. Since there is not yet enough scientific data on this topic, future research should prioritize randomized controlled trials comparing these techniques with other standard treatments (e.g., laxatives or dietary fiber) in defined patient populations. Longitudinal studies will also be essential to clarify long-term safety, potential effects on microbiota, and both risks and benefits. Standardization of technical procedures also remains a critical need, especially regarding professional competencies, operating parameters (e.g., instilled volumes and pressure ranges), and reproducible protocols. Moreover, future investigations should incorporate objective outcome measures, as colonic transit time, stool form and frequency, indices of inflammation or intestinal wall integrity, and changes to microbiome composition. In conclusion, TAI and CHT have the potential to serve as important interventions for the treatment and prevention of chronic constipation and intestinal dysbiosis, as well as their broader systemic correlates, in the setting of bio-integrated medicine. Full article

The increasing adoption of highly glazed façades in contemporary office building has improved daylight penetration but has also intensified glare risk and sunlight overexposure in Mediterranean climates, with direct implications for occupant visual comfort and environmental sustainability. While daylight optimization has been widely discussed, fewer studies have examined how façade morphology systematically shapes the balance between daylight sufficiency and visual comfort in Mediterranean island contexts. This study investigates the relationship between façade configuration, daylight availability, and glare performance in office buildings in Northern Cyprus using climate-based daylight simulation. Six façade morphologies are evaluated across a range of window-to-wall ratios (WWR) using EN 17037-aligned criteria and metrics, including spatial daylight autonomy (sDA), annual sunlight exposure (ASE), and daylight glare probability (DGP). Usable daylight is not simply a function of more glass. As WWR increases, fully glazed façades in Mediterranean conditions tend to admit excessive direct sun and intensify glare, so daylight becomes less workable even when illuminance is high. Instead, hybrid and adaptive morphologies that control lighting through a combined approach of shade, diffusion, and redirection provide the most dependable performance, reducing both overexposure and glare while ensuring sufficient daylight sufficiency. The findings also indicate a distinct turning point at about 50–55% WWR, beyond which performance is mostly dependent on the façade’s ability to modulate its morphology and further glass offers minimal advantage. Based on this, the article suggests a contextual framework to encourage façade options for Mediterranean office environments that are more sustainable, aesthetically pleasing, and climate-responsive. Full article

Background: Traumatic injuries of the duodenum are generally rare but when they occur, they can result in serious complications. Inaccurate injury classification, delayed diagnosis, or late treatment can significantly raise morbidity and mortality. A multidisciplinary approach is often necessary. Mechanisms of injury: Isolated duodenal injuries are relatively uncommon due to the duodenum’s proximity to pancreas and major vascular structures. Duodenal injuries can result from blunt or penetrating trauma. Classification: The 2019 World Society of Emergency Surgery (WSES)-American Association for the Surgery of Trauma (AAST) guidelines recommend incorporating both the AAST-OIS grading and the patient’s hemodynamic status to stratify duodenal injuries into four categories: Minor injuries WSES class I, Moderate injuries WSES class II, Severe injuries WSES class III, and WSES class IV. Diagnosis: The diagnostic approach involves a combination of clinical assessment, laboratory investigations, radiological imaging and, in particular situations, surgery. Prompt diagnosis is critical because delays exceeding 24 h are associated with a higher incidence of postoperative complications and a significant rise in mortality. Contrast-enhanced abdominal computed tomography (CT) represents the gold standard for diagnosis in patients who are hemodynamically stable. Management: Duodenal trauma requires a multimodal approach that considers hemodynamic stability, the severity of the injury and the presence of associated lesions. Non-operative management (NOM) is reserved for hemodynamically stable patients with minor duodenal injuries without perforation (AAST I/WSES I), as well as all duodenal hematomas (WSES I–II/AAST I–II) in the absence of associated abdominal organ injuries requiring surgical intervention. All hemodynamically unstable patients, those with peritonitis, or with CT findings consistent with duodenal perforations or AAST grade III or higher injuries are candidates for emergency surgery. If intervention is required, primary repair should be the preferred option whenever feasible, while damage control surgery is the best choice in cases of hemodynamic instability, severe associated injuries, or complex duodenal lesions. Definitive reconstructive surgery should be postponed until the patient has been adequately resuscitated. The role of endoscopic techniques in the treatment of duodenal injuries and their complications is expanding. Conclusions: Duodenal trauma is burdened by potentially high mortality. Among the possible complications, duodenal fistula is the most common, followed by duodenal obstruction, bile duct fistula, abscess, and pancreatitis. The overall mortality rate for duodenal trauma persists to be significant with an average rate of 17%. Future prospective research needed to reduce the risk of complications following duodenal trauma. Full article

The global cancer burden continues to increase worldwide. Among the various treatment options, radiotherapy (RT), which employs high-energy ionizing radiation to destroy cancer cells, is one of the primary modalities for cancer. However, increasing the absorbed dose to the target volume also increases the risk of damage to surrounding healthy tissues. This radiation-induced toxicity to normal tissues limits the desirable dosage that can be delivered to the tumor, thereby constraining the effectiveness of radiation therapy in achieving tumor control. FLASH radiotherapy (FLASH-RT) has emerged as a promising technique due to its biological advantages. FLASH-RT involves the delivery of radiation at an ultra-high dose rate (≥40 Gy/s). Unlike conventional RT, FLASH-RT achieves comparable tumor control rates while significantly reducing damage to surrounding normal tissues, a phenomenon known as the FLASH effect. Although the mechanism behind the FLASH effect is not fully understood, this approach shows considerable promise for future cancer treatment. The development of specialized treatment planning systems (TPS) becomes imperative to facilitate the clinical implementation of FLASH-RT from experimental studies. These systems must account for the unique characteristics of FLASH-RT, including ultra-high dose rate delivery and its distinctive radiobiological effects. Critical reassessment and optimization of treatment planning protocols are essential to fully leverage the therapeutic potential of the FLASH effect. This review examines key considerations for the TPS development of electron and proton FLASH-RT, including electron and proton FLASH techniques, biological models, crucial beam parameters, and dosimetry, providing essential insights for optimizing TPS and advancing the clinical implementation of this promising therapeutic modality. Full article

Background/Objectives: The resin infiltration protocol was introduced as a minimally invasive approach for the treatment of incipient carious lesions using low-viscosity resins with high penetration coefficient. This study aimed to determine the effectiveness of resin infiltration in hypomineralized anterior teeth of paediatric patients, based on aesthetic improvement, colour change (ΔE), and visual perception. The risk of bias was assessed using the Newcastle–Ottawa and physiotherapy evidence database scales. The level of evidence was assessed using the grading of recommendations, assessment, development and evaluation tool. Methods: The following five databases were searched: Web of Science, Scopus, Embase, Cochrane, and PubMed. The review protocol was registered in PROSPERO (registration number: CRD42023405299). Results: The search identified 130 preliminary references related to the population, intervention, control, and outcome question, identified from the PubMed, Scopus, Embase, Web of Science, and Cochrane databases, respectively. In addition, two items were added from the grey literature. Ten articles met the eligibility criteria and were included in the qualitative analyses, and only three studies were included in the quantitative analyses. Positive results regarding stain-size reduction and colour improvement with resin infiltration (Icon^®; DMG, Hamburg, Germany), were reported in moderately severe lesions. Luminosity increased immediately after treatment, and the mean difference in total color change (ΔE), T0–T1 was significant (ΔE, 5.45; confidence interval, 1.94 to 8.96; p < 0.01). The most favourable clinical outcomes were observed following the initial resin infiltration. Moreover, the results were maintained at the 6 month follow-up. Conclusions: Infiltration resin can successfully mask white or white/creamy opacities characteristic MIH affected enamel, similar to those in carious enamel for which it was designed. It yields acceptable aesthetic results in anterior teeth with mild to moderate MIH lesions. Lack of predictability is the main limitation of this therapeutic option. Full article

Osteoarthritis (OA) is a prevalent chronic pain syndrome and a leading cause of disability worldwide, characterized by progressive deterioration of articular cartilage. This degradation leads to pain, swelling, inflammation, and eventual stiffness as the cartilage wears down, causing bone-on-bone friction. Current medical treatments primarily aim at pain relief; however, many interventions, especially invasive or surgical ones, carry risks of adverse outcomes. Consequently, intra-articular (IA) therapy, particularly hyaluronic acid (HA) injections, is widely adopted as a conservative treatment option. HA plays a crucial role in maintaining joint homeostasis by supporting proteoglycan synthesis and scaffolding, restoring optimal HA concentrations in synovial fluid, and providing chondroprotective and anti-inflammatory effects. In recent years, hydrogels composed of natural and synthetic materials have emerged as promising candidates for OA treatment. Our research focuses on the biosynthesis and characterization of novel hydrogel composites combining short peptide hydrogelators with aminated graphene oxide (a-GO) nanosheets functionalized with HA (a-GO-HA@Hgel). These a-GO-HA@Hgel nanocomposites are designed to facilitate the controlled release of HA into the extracellular matrix, aiming to promote cartilage regeneration and mitigate inflammation. The strategy is to exploit the oxygen-containing functional groups of GO nanosheets to enable covalent coupling or physical adsorption of HA molecules through various chemical approaches. The resulting a-GO-HA are incorporated within hydrogel matrices to achieve sustained and controlled HA release. We study the influence of a-GO-HA on the native hydrogel structure and its viscoelastic properties, which are critical for mimicking the mechanical environment of native cartilage tissue. Through this multidisciplinary approach combining advanced materials science and cellular biology, this work aims to develop innovative nanocomposite hydrogels capable of delivering HA in a controlled manner, enhancing cartilage repair and providing a potential therapeutic strategy for OA management. Full article

Background: Peritoneal metastasis represents an aggressive disease pattern in pancreatic ductal adenocarcinoma (PDAC), traditionally associated with poor survival and limited therapeutic options. Emerging intraperitoneal chemotherapy strategies—including hyperthermic intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal paclitaxel (NIPEC/IP-PTX), and pressurized intraperitoneal aerosol chemotherapy (PIPAC)—have been investigated to improve local tumor control and survival outcomes. Methods: We systematically reviewed published studies evaluating HIPEC, NIPEC/IP-PTX, and PIPAC in PDAC, including adjuvant, cytoreductive, and palliative settings. Study characteristics, feasibility, perioperative outcomes, oncologic outcomes, and risk of bias were analyzed. Results: Across modalities, intraperitoneal treatment strategies demonstrated acceptable feasibility and safety profiles in appropriately selected patients. Adjuvant HIPEC following pancreatectomy showed reduced local–regional recurrence signals in limited cohorts. CRS + HIPEC among patients with isolated peritoneal metastases yielded encouraging multi-year survival in highly selected candidates achieving complete cytoreduction. NIPEC/IP-PTX demonstrated favorable ascites control, symptom relief, and potential conversion to resection in select patients. PIPAC was primarily used in unresectable, heavily pretreated, palliative peritoneal metastasis settings, with goals centered on disease stabilization, histologic regression, and symptom control rather than curative intent. Conclusions: Intraperitoneal chemotherapy strategies in PDAC appear feasible with signals of meaningful clinical benefit in select settings. While CRS + HIPEC may benefit carefully selected metastatic patients, NIPEC/IP-PTX and PIPAC hold value primarily in symptom control and disease stabilization. Larger prospective trials are needed to define patient selection, optimize treatment protocols, and clarify survival benefit. Full article

Background/Objectives: Fever and pain are among the most common symptoms in pediatric infections and chronic diseases, causing significant discomfort for children and concern for caregivers. Effective management is essential to relieve distress while avoiding overtreatment or undertreatment. Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs), particularly ibuprofen, are the primary antipyretic and analgesic agents in pediatric care, but their use in children with chronic conditions might be challenging. Methods: A narrative review and clinical expert judgment were used to synthesize current evidence on the use of paracetamol and NSAIDs (especially ibuprofen) in children with some common chronic diseases. Results: Paracetamol is often considered a first-line option in several chronic conditions. Caution is warranted in children with pre-existing malnutrition, obesity, and neuromuscular disorders as these factors might increase the risk of hepatotoxicity. NSAIDs provide additional anti-inflammatory effects and comparable analgesic efficacy but should be used cautiously in some high-risk populations due to potential gastrointestinal, renal, and bleeding complications. Their use is contraindicated in children with dehydration, renal impairment, nephrotic syndrome relapses, while careful risk-benefit assessment is required in small and vulnerable neonates. Some data also suggests NSAIDs may worsen outcomes in certain acute bacterial and viral infections. Data on chronic infections such as tuberculosis, HIV, and viral hepatitis are limited, highlighting the need for further research. Combination therapy with paracetamol and ibuprofen may enhance analgesia in postoperative settings without significantly increasing adverse events. Overall, available evidence is limited and largely observational. Conclusions: This narrative review synthesizes current evidence and clinical expertise to provide practical guidance on the rational use of paracetamol and NSAIDs in children, emphasizing individualized therapy according to comorbidities, risk factors, and clinical context, particularly in vulnerable populations. A risk-adapted, evidence-based approach ensures optimal symptom control while minimizing harm, supporting safer, more effective, and family-centered care for children with fever and pain. Full article

Root-knot nematodes (RKNs) of the Meloidogyne genus impact various plants, including crops, fruits, and vegetables. Few chemical control options exist globally, and many nematicides are banned due to health and environmental risks. This study tested a new nematicidal agent, the symbiotic bacterium Xenorhabdus indica, which was molecularly identified (PV845100). Cell-free culture supernatants of Xenorhabdus spp. and their biogenic Ag-NPs were used in nematicidal assays. Meloidogyne incognita showed high mortality rates of 95.3%, 74.6%, and 72.6% after 72 h of treatment with the X. indica filtrate at three concentrations. At the same concentrations, biogenic Ag-NPs resulted in 82.0%, 90.0%, and 85.3% mortality rates, respectively. After 72 h, hatchability decreased by 53%, 74.6%, and 72.6% for the X. indica filtrate and 82.0%, 90.0%, and 85.3% for Ag-NPs. Quantitative real-time PCR (Q-PCR) revealed that Mi-Ache1 expression was lower in M. incognita second-stage juveniles (J2s) treated with the filtrate and Ag-NPs after 72 h compared to controls. Mi-Ache2 expression was also decreased, but only slightly. Furthermore, both the X. indica filtrate and biogenic Ag-NPs were safe in human lung (WI-38) and skin (HFB4) cell lines. These findings suggest that bacterial filtrates and their biogenic Ag-NPs could serve as cost-effective, environmentally friendly alternatives to commercial nematicides. Full article

Axillary management in early-stage, HER2-negative, hormone receptor-positive breast cancer has undergone major changes in recent years. While axillary lymph node dissection (ALND) was once considered essential for staging and regional control, increasing evidence supports the safety of surgical de-escalation in selected patients. At the same time, systemic therapies such as CDK4/6 and PARP inhibitors rely on nodal burden to define eligibility, raising new challenges in balancing oncologic benefit with treatment-related morbidity. This narrative review summarizes current strategies in axillary management for patients undergoing upfront surgery for HR-positive, HER2-negative early breast cancer. It explores the role of sentinel lymph node biopsy (SLNB), the indications for ALND, the integration of adjuvant systemic therapy, and the emerging role of radiotherapy and predictive tools in guiding individualized treatment decisions. Key randomized trials including Z0011, AMAROS, SENOMAC, SOUND, and INSEMA have demonstrated that omission of ALND is safe in patients with limited nodal involvement, especially when combined with whole-breast or regional nodal radiotherapy. However, trials such as MonarchE and OlympiA have introduced systemic therapies whose indications are closely tied to nodal status, prompting reconsideration of the extent of axillary staging. Advances in imaging and risk stratification tools offer new avenues for safely limiting surgical intervention while preserving access to systemic options. In conclusion, modern axillary management in HR-positive, HER2-negative breast cancer involves navigating the intersection between de-escalated surgery and risk-adapted systemic therapy. Future strategies should prioritize individualized care, incorporating tumor biology, imaging findings, and patient preferences, with multidisciplinary collaboration playing a central role in optimizing outcomes. Full article

Background and Aims: Diabetes mellitus and chronic hepatitis B/C infection are risk factors for liver cirrhosis and hepatocellular carcinoma (HCC). This study aimed to evaluate whether sodium-glucose cotransporter-2 inhibitors (SGLT2i) improved liver-related outcomes in patients with chronic viral hepatitis and co-existing diabetes. Methods: Using data from the Korean nationwide cohort, this study included 37,629 patients with concurrent diabetes and chronic hepatitis B/C infection, without prior HCC, who were treated with oral hypoglycemic agents. Patients who were treated with SGLT2is for over 90 days were allocated to the SGLT2i group, whereas those who never received SGLT2is comprised the non-SGLT2i group. The primary outcome was the occurrence of liver-related events, including HCC. Results: After 1:2 propensity score matching, the SGLT2i group comprised 12,543 patients (chronic hepatitis B, CHB: n = 9392; chronic hepatitis C, CHC: n = 4300, CHB & CHC: n = 1149), while the non-SGLT2i group included 25,086 patients (CHB: n = 18,806; CHC: n = 8553, CHB & CHC: 2273). The incidence rate of composite liver-related complications was lower in the SGLT2i group than that in the non-SGLT2i group (6.67 per 1000 vs. 8.99 per 1000). Moreover, SGLT2i therapy was associated with a reduced risk of HCC development (subdistribution hazard ratio [sHR] = 0.77, 95% confidence interval [CI] = 0.66–0.91; p = 0.002) and developing cirrhosis (sHR = 0.67, 95% CI = 0.54–0.83; p < 0.001). Conclusions: SGLT2is should be considered a therapeutic option for controlling diabetes, reducing the metabolic burden, and improving liver outcomes in patients with concurrent diabetes and chronic viral hepatitis. Full article

Background/Objectives: Systemic sclerosis (SSc) is a rare and severe autoimmune disease with limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) and mesenchymal stem cell transplantation (MSCT) have emerged as promising therapeutic strategies, especially for patients with refractory or rapidly progressive forms of the disease. However, no comparative synthesis has yet evaluated the clinical outcomes, safety, and applicability of these two distinct stem-cell-based interventions. This systematic review aimed to perform a comparative qualitative synthesis of clinical outcomes, safety profiles, and evidence quality for HSCT and MSCT in patients with systemic sclerosis, focusing on survival, skin fibrosis, pulmonary function, and adverse events. Methods: A comprehensive search was conducted in PubMed, ScienceDirect, Cochrane Library, and Google Scholar for the period between 2015 and May 2025. Studies were included if they reported on adult patients with a confirmed diagnosis of SSc treated with either autologous HSCT or MSCT and provided clinical outcome data. Risk of bias was assessed using the Newcastle-Ottawa Scale. Due to heterogeneity across studies, results were synthesized qualitatively. Results: Eleven studies met the inclusion criteria, comprising 504 patients (316 HSCT, 188 MSCT). HSCT showed consistent improvement in survival (1-, 5-, and 10-year), reduction in modified Rodnan skin scores (mRSS), and s ilization or improvement in pulmonary function (DLCO, FVC), albeit with a higher incidence of serious adverse events, including transplant-related mortality (up to 10%) and infectious complications. MSCT demonstrated favorable effects on skin fibrosis and lung involvement with a significantly lower toxicity profile. However, long-term survival data and methodological robustness were limited were more limited. HSCT was supported by multiple randomized controlled trials and international guidelines, while MSCT remains under clinical investigation with promising but still preliminary evidence. Conclusions: Both HSCT and MSCT demonstrate potential clinical benefits in systemic sclerosis, but they differ substantially in evidence strength and risk profiles. HSCT provides the most robust evidence for long-term disease modification in carefully selected patients, whereas MSCT represents a promising and safer investigational option, particularly for patients ineligible for intensive therapy. Further well-designed comparative studies are required to define their optimal clinical roles. Full article

Haemoglobinopathies, including β-thalassaemia and sickle cell disease (SCD), are among the most common monogenic disorders worldwide and remain major causes of morbidity and early mortality. Historically, management of these life-altering diseases has relied on supportive treatment and symptom management and, although these treatments reduce symptoms and ease disease burden, they do not correct the underlying genetic defect. Allogenic haematopoietic stem cell transplantation (HSCT) has been the only established curative option; however, it comes with substantial risks that significantly restrict its applicability. Over the past two decades, haematopoietic stem cell (HSC) gene therapy for haemoglobinopathies has rapidly progressed from experimental proof-of-concept to approved therapies. Lentiviral gene addition approaches have demonstrated durable expression of functional β-like globin transgenes, achieving transfusion independence in β-thalassaemia patients and significant reductions in vaso-occlusive events in SCD patients. Alternative therapeutic approaches to promote HbF expression have proved to be highly successful. Gene silencing strategies targeting BCL11A have been successful clinically and, more recently, gene editing technologies such as CRISPR/Cas9 have enabled precise disruption of regulatory elements controlling γ-globin repression, leading to the approval of the first CRISPR-based therapy for SCD and β-thalassaemia. Emerging base editing technologies promise even more precise genetic modification and are advancing through clinical evaluation. Despite these advances, access to gene therapy remains restricted due to the need for highly specialised manufacturing, toxic myeloablative conditioning regimens, and high treatment costs. Ongoing improvements and adaptations in these areas are essential to ensure that gene therapies fulfil their potential as accessible, curative treatments for patients suffering from haemoglobinopathies worldwide. Full article

Diabetic foot ulcers (DFUs) represent 6.3% of the various complications of type 2 diabetes mellitus, with a risk of development of up to 34%. Several factors contribute to the formation of ulcers, which are very difficult to treat as they hinder efficient wound healing. Patients experience persistent pain, which leads to the consumption of various medications (polypharmacy) due to the lesions not resolving. Conversely, this can increase the risk of various factors, including a chronic inflammatory state, which hinders the body’s own regenerative processes. Until now, treatment options have been limited to washing the wound and stimulating new tissue growth, but this is a painful and unsuccessful process. One of the treatment options is therefore cell therapy with mesenchymal stem cells, which have immunomodulatory characteristics and allow tissue regeneration, although the effect directly in pain is not totally clear. We have previously reported in our working group that patients with ulcers treated with mesenchymal stem cells (MSCs) have been able to integrate into their daily lives, although the pain related to the inflammatory state and polypharmacy has not been studied. Objective: This study investigates how the local administration of MSCs improves the condition of an ulcer by inducing tissue regeneration. It also shows how the concentration of systemic inflammatory biomarkers is modified in direct correlation with pain and the consumption of medications over time. Methods: Local administration of MSCs at 7 and 14 days, measuring pro- and anti-inflammatory cytokines relative to the healthy control group, evaluating wound healing, and monitoring the medications taken by the patient in conjunction with pain perception. Results: Cell administration showed that inflammatory molecules were reduced and anti-inflammatory molecules increased. This is reflected in the consumption of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in relation to wound improvement, with a decrease in pain medication consumption of less than 50%. We provide evidence that locally administered mesenchymal stem cells influence systemic inflammatory processes necessary for tissue recovery, impacting patients’ polypharmacy consumption due to reduced perceived pain. Conclusions: This report establishes a direct link between mesenchymal stem cells and pain relief in type 2 diabetes ulcers, potentially paving the way for new pain therapies. Full article