Evaluating [225Ac]Ac-FAPI-46 for the treatment of soft-tissue sarcoma in mice.

PURPOSE: Fibroblast Activation Protein (FAP) is an emerging theranostic target that is highly expressed on cancer-associated fibroblasts and on certain tumor cells including sarcoma. We investigated the anti-tumor efficacy of [225Ac]Ac-FAPI-46 as monotherapy or in combination with immune checkpoint blockade (ICB) in immunocompetent murine models of sarcoma sensitive or resistant to ICB. METHODS: [68Ga]Ga- and [225Ac]Ac-FAPI-46 were tested in subcutaneous FAP+ FSA fibrosarcoma bearing C3H/Sed/Kam mice. The efficacy of up to three cycles of 60 kBq [225Ac]Ac-FAPI-46 was evaluated as monotherapy and in combination with an anti-PD-1 antibody. Efficacy of [225Ac]Ac-FAPI-46 and/or ICB was further compared in FAP-overexpressing FSA (FSA-F) tumors that were sensitive to ICB or rendered ICB-resistant by tumor-induction in the presence of Abatacept. RESULTS: [225Ac]Ac-FAPI-46 was well tolerated up to 3 × 60 kBq but had minimal effect on FSA tumor growth. The combination of three cycles [225Ac]Ac-FAPI-46 and ICB resulted in growth delay in 55% of mice (6/11) and partial tumor regression in 18% (2/11) of mice. In FSA-F tumors with FAP overexpression, both [225Ac]Ac-FAPI-46 and ICB were effective without additional benefits from the combination. In locally immunosuppressed and ICB resistant FAP-F tumors, however, [225Ac]Ac-FAPI-46 restored responsiveness to ICB, resulting in significant tumor regression and tumor-free survival of 56% of mice in the combination group up to 60 days post treatment. CONCLUSION: [225Ac]Ac-FAPI-46 efficacy is correlated with tumoral FAP expression levels and can restore responsiveness to PD-1 ICB. These data illustrate that careful patient selection based on target expression and rationally designed combination therapies are critically important to maximize the therapeutic impact of FAP-targeting radioligands.

Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Use of semi-constrained total knee arthroplasty in gonarthrosis with collateral ligament insufficiency: Clinical and functional outcomes.

INTRODUCTION: Achieving stability in total knee arthroplasty (TKA) is crucial for long-term implant survival. In cases of severe deformity or ligament laxity, constrained implants may be required. Traditionally, increasing constraint involved intramedullary stems. However, there are intermediary alternatives, including employing a constrained polyethylene insert without stems, thereby avoiding complications related to them. The study aims to evaluate our experience with a non-modular constrained (NMC) implant in primary TKA. MATERIAL AND METHODS: We conducted a retrospective review of the clinical and radiographic outcomes of 108 non-stemmed primary TKAs performed at our institution between 2013 and 2021 in patients with at least 10° deformity or 10mm ligament laxity. Data included demographics, preoperative and postoperative deformities, clinical outcomes and revision rates. RESULTS: A total of 103 patients (108 knees) with a mean age of 74 were followed up for a minimum of 2 years. The mean postoperative range of motion was 105°/0°. The median Oxford Knee Score, Knee Society Score and Knee Society Function Score were 43.5, 92 and 90, respectively. 17 knees had varus deformity (mean tibiofemoral angle of 2.7°), and 87 knees had excessive valgus deformity (mean tibiofemoral angle of 15.1°). The remaining 4 knees had a neutral alignment. The mean postoperative tibiofemoral angle was 6.8°. The overall revision rate was 6.5% (7 patients): 3 deep periprosthetic infections, 2 patellar dislocations, 1 stiffness and 1 aseptic loosening. CONCLUSION: Our experience demonstrates favorable mid-term outcomes with the NMC implant, providing a safe alternative to stemmed implants in primary TKA, particularly in cases of severe deformity or ligament laxity.

Understanding limb necrotizing infections: A comprehensive approach.

INTRODUCTION: Necrotizing soft tissue infections (NSTI) are increasing, posing a significant risk of morbidity and mortality. Due to nonspecific symptoms, a high index of suspicion is crucial. Treatment involves a multidisciplinary approach, with broad-spectrum antibiotics, early surgical debridement, and life support. This study analyzes the characteristics, demographics, complications, and treatment of NSTI in a hospital in Madrid, Spain. METHODS: A retrospective observational study was conducted, including all surgically treated NSTI patients at our center from January 2016 to December 2022, examining epidemiological and clinical data. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) was prospectively calculated for all patients. RESULTS: Twenty-two patients (16 men, 6 women, mean age 54.8) were included. Median time from symptom onset to emergency room visit was 3.5 days. All reported severe treatment-resistant pain; sixteen had fever exceeding 37.8°C (72.7%). Skin lesions occurred in twelve (54.5%), and thirteen had hypotension and tachycardia (59.1%). Treatment involved resuscitative support, antibiotherapy, and radical debridement. Median time to surgery was 8.25h. Intraoperative cultures were positive in twenty patients: twelve Streptococcus pyogenes, four Staphylococcus aureus, one Escherichia coli, and four polymicrobial infection. In-hospital mortality rate was 22.73%. CONCLUSIONS: We examined the correlation between our results, amputation rates and mortality with LRINEC score and time to surgery. However, we found no significant relationship unlike some other studies. Nevertheless, a multidisciplinary approach with radical debridement and antibiotic therapy remains the treatment cornerstone. Our hospital stays, outcomes and mortality rates align with our literature review, confirming high morbimortality despite early and appropriate intervention.

TB drug susceptibility testing in high fluoroquinolone resistance settings.

BACKGROUND: The insurgence of resistance to key drugs of the BPaLM (bedaquiline + pretomanid + moxifloxacin) regimen is a major concern. In settings with widespread resistance to fluoroquinolones (FQs), like Pakistan, new technologies, such as Xpert® MTB/XDR, may ensure drug resistance upfront screening. This study aims to assess MTB/XDR's performance in detecting FQs and isoniazid resistance, proposing a renewed diagnostic algorithm for drug-resistant TB (DR-TB). METHODS: This cross-sectional prospective study, approved by the local ethical committee, collected samples from people newly and previously diagnosed with TB over 6 months. Xpert® MTB/RIF Ultra, MTB/XDR, Genotype® MTBDRplus, Genotype® MTBDRsl, culture, and phenotypic drug susceptibility testing (pDST) for relevant drugs (including bedaquiline and levofloxacin) were performed. Next-generation sequencing (NGS) resolved discordances between MTB/XDR and pDST results. RESULTS: The analysis showed that MTB/XDR has 91.5% and 88.2% sensitivity and 99.5% and 97.7% specificity in detecting respectively isoniazid (INH) and resistance to FQs, demonstrating that MTB/XDR meets the WHO targets for INH resistance detection at the peripheral level. NGS effectively resolved discordances between MTB/XDR and pDST results. CONCLUSIONS: The obtained results allowed designing the proposed diagnostic algorithm for rapid identification of DR-TB, ensuring rapid and equitable access to drug susceptibility testing for TB, ultimately improving TB care and control.

CONTEXTE: La recrudescence de la résistance aux médicaments clés du régime BPaLM (bédaquiline + prétomanide + moxifloxacine) est une préoccupation majeure. Dans les contextes où la résistance aux fluoroquinolones (FQ) est répandue, comme le Pakistan, de nouvelles technologies, telles que Xpert® MTB/XDR, peuvent assurer un dépistage initial de la résistance aux médicaments. Cette étude vise à évaluer la performance de MTB/XDR dans la détection des FQ et de la résistance à l'isoniazide, en proposant un algorithme de diagnostic renouvelé pour la TB pharmacorésistante (DR-TB, pour l'anglais «drug-resistant TB ¼ ). MÉTHODES: Cette étude prospective transversale, approuvée par le comité d'éthique local, a recueilli des échantillons de personnes nouvellement diagnostiquées et précédemment diagnostiquées avec la TB pendant 6 mois. Xpert® MTB/RIF Ultra, MTB/XDR, le GenoType® MTBDRplus, le GenoType® MTBDRsl, la culture et des tests phénotypiques de sensibilité aux médicaments (pDST, pour l'anglais «phenotypic drug susceptibility testing ¼ ) pour les médicaments pertinents (y compris la bédaquiline et la lévofloxacine) ont été effectués. Le séquençage de nouvelle génération (NGS, pour l'anglais «next-generation sequencing ¼ ) a résolu les discordances entre les résultats MTB/XDR et pDST. RÉSULTATS: L'analyse a montré que le MTB/XDR a une sensibilité de 91,5% et 88,2% et une spécificité de 99,5% et 97,7% dans la détection respectivement de l'isoniazide et de la résistance aux FQ, démontrant que le MTB/XDR répond aux objectifs de l'OMS pour la détection de la résistance à l'isoniazide au niveau périphérique. NGS a efficacement résolu les discordances entre les résultats MTB/XDR et pDST. CONCLUSIONS: Les résultats obtenus ont permis de concevoir l'algorithme de diagnostic proposé pour l'identification rapide de la DR-TB, garantissant un accès rapide et équitable aux tests de sensibilité aux médicaments pour la TB, améliorant ainsi la prise en charge et le contrôle de la TB.

Concurrent uper limb and hip fracture in the elderly: experience at our centre. / Fracturas concomitantes de miembro superior y cadera en pacientes mayores de 65 años: experiencia en nuestro centro.

INTRODUCTION: The incidence of hip fracture in the elderly is on the rise, occasionally accompanied by concurrent upper limb fractures. Our investigation aims to determine whether these patients experience poorer functional outcomes, prolonged hospitalization, or higher mortality rates when compared to those with isolated hip fracture. MATERIAL AND METHODS: We retrospectively reviewed 1,088 elderly patients admitted to our centre with hip fracture between January 2017 and March 2020. We recorded the presence of concomitant fractures and their treatment. We analyzed the duration of hospital stay, in-hospital mortality and function. RESULTS: We identified 63 patients with concomitant upper limb fracture (5.6%). Among them, 93.7% were women, and the average age was 86.4 years. 80.9% of the upper limb fractures were distal radius or proximal humerus. Patients with concomitant fracture had increased length of stay (mean, 19.6 vs, 12.8, p=0.002), decreased proportion of patients returning to their own home at discharge (23.6% vs, 26.3%, p=0.042) and increased in-hospital mortality rate (9.5% vs, 5.9%, p=0.003). CONCLUSIONS: Patients with concomitant upper limb fracture require a longer length of stay and exhibit an elevated in-hospital mortality rate. Furthermore, this condition is associated with a reduced short-term functional recovery, thereby decreasing the chances of the patient returning home upon hospital discharge.

Mitochondrial targets in hyperammonemia: Addressing urea cycle function to improve drug therapies.

The urea cycle (UC) is a critically important metabolic process for the disposal of nitrogen (ammonia) produced by amino acids catabolism. The impairment of this liver-specific pathway induced either by primary genetic defects or by secondary causes, namely those associated with hepatic disease or drug administration, may result in serious clinical consequences. Urea cycle disorders (UCD) and certain organic acidurias are the major groups of inherited rare diseases manifested with hyperammonemia (HA) with UC dysregulation. Importantly, several commonly prescribed drugs, including antiepileptics in monotherapy or polytherapy from carbamazepine to valproic acid or specific antineoplastic agents such as asparaginase or 5-fluorouracil may be associated with HA by mechanisms not fully elucidated. HA, disclosing an imbalance between ammoniagenesis and ammonia disposal via the UC, can evolve to encephalopathy which may lead to significant morbidity and central nervous system damage. This review will focus on biochemical mechanisms related with HA emphasizing some poorly understood perspectives behind the disruption of the UC and mitochondrial energy metabolism, namely: i) changes in acetyl-CoA or NAD+ levels in subcellular compartments; ii) post-translational modifications of key UC-related enzymes, namely acetylation, potentially affecting their catalytic activity; iii) the mitochondrial sirtuins-mediated role in ureagenesis. Moreover, the main UCD associated with HA will be summarized to highlight the relevance of investigating possible genetic mutations to account for unexpected HA during certain pharmacological therapies. The ammonia-induced effects should be avoided or overcome as part of safer therapeutic strategies to protect patients under treatment with drugs that may be potentially associated with HA.

A Systematic Review and Meta-Analysis Comparing Surgical and Nonsurgical Treatments for Excessive Gingival Display.

Excessive gingival display (EGD) is defined as more than 2 mm of gingiva display above the maxillary incisors at maximum smile. Various skeletal, dental, and soft tissue etiological factors for EGD have been suggested. This study assessed the effectiveness and stability of surgical (SX) and nonsurgical (NSX) interventions for correction of EGD through a systematic review and meta-analysis following PRISMA 2020 guidelines. An electronic search of Ovid MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science, and LILACS was conducted (2010-2023). Results were expressed as mean change in gingival display using the random-effects model at 1, 3, 6, and 12-month follow-up. At 1 month, SX and NSX treatments yielded a comparable mean reduction of 3.50 mm (2.13-4.86) and 3.43 mm (2.67-4.19) in gingival display, respectively. However, by 6 months, NSX treatments showed a reduction of 0.51 mm compared to 2.86 mm with SX treatments. SX outcomes remained stable past 6 months, while NSX outcomes partially relapsed at 6 months and returned to baseline levels at 12 months. Notably, NSX treatments were more effective in cases with mild initial EGD, while SX treatments showed a better outcome in severe cases. To draw more robust conclusions regarding the treatment outcomes, future primary studies of greater rigor are required.

Integrated behavioural and physiological responses of sand smelt larvae to the effects of warming and hypoxia as combined stressors.

Forecasts indicate that rising temperatures towards the future and the expansion of dead zones will change environmental suitability for fish early stages. Therefore, we assessed the chronic effects of warming (26 °C), hypoxia (<2-2.5 mg L-1) or their combination on mortality rate, growth, behaviour, energy metabolism and oxidative stress using Atherina presbyter larvae as a model species. There were no differences between the treatments in terms of mortality rate. The combination of warming and hypoxia induced faster loss of body mass (+22.7%). Warming, hypoxia or their combination enhanced boldness (+14.7-25.4%), but decreased exploration (-95%-121%), increased the time in frozen state (+60.6-80.5%) and depleted swimming speed (-45.6-50.5%). Moreover, routine metabolic rate was depleted under hypoxia or under the combination of warming and hypoxia (-56.6 and 57.2%, respectively). Under hypoxia, increased catalase activity (+56.3%) indicates some level of antioxidant defence capacity, although increased DNA damage (+25.2%) has also been observed. Larvae also exhibited a great capacity to maintain the anaerobic metabolism stable in all situations, but the aerobic metabolism is enhanced (+19.3%) when exposed to the combination of both stressors. The integrative approach showed that changes in most target responses can be explained physiologically by oxidative stress responses. Increased oxidative damages (lipid peroxidation and DNA damage) and increased interaction between antioxidant enzymes (superoxide dismutase and catalase) are associated to increased time in frozen state and decreased swimming activity, growth rates and boldness. Under all stressful situations, larvae reduced energy-consuming behaviours (e.g. depleted exploration and swimming activity) likely to stabilize or compensate for the aerobic and anaerobic metabolisms. Despite being an active small pelagic fish, we concluded that the sensitive larval phase exhibited complex coping strategies to physiologically acclimate under thermal and hypoxic stress via behavioural responses.

Synthesis of Soluble High Molar Mass Poly(Phenylene Methylene)-Based Polymers.

Poly(phenylene methylene) (PPM) is a multifunctional polymer that is also active as an anticorrosion fluorescent coating material. Although this polymer was synthesized already more than 100 years ago, a versatile synthetic route to obtain soluble high molar mass polymers based on PPM has yet to be achieved. In this article, the influence of bifunctional bis-chloromethyl durene (BCMD) as a branching agent in the synthesis of PPM is reported. The progress of the reaction was followed by gel permeation chromatography (GPC) and NMR analysis. PPM-based copolymers with the highest molar mass reported so far for this class of materials (up to Mn of 205,300 g mol-1) were isolated. The versatile approach of using BCMD was confirmed by employing different catalysts. Interestingly, thermal and optical characterization established that the branching process does not affect the thermoplastic behavior and the fluorescence of the material, thus opening up PPM-based compounds with high molar mass for applications.

Robustness analysis of dynamic trajectory radiotherapy and volumetric modulated arc therapy plans for head and neck cancer.

Background and purpose: Dynamic trajectory radiotherapy (DTRT) has been shown to improve healthy tissue sparing compared to volumetric arc therapy (VMAT). This study aimed to assess and compare the robustness of DTRT and VMAT treatment-plans for head and neck (H&N) cancer to patient-setup (PS) and machine-positioning uncertainties. Materials and methods: The robustness of DTRT and VMAT plans previously created for 46 H&N cases, prescribed 50-70 Gy to 95 % of the planning-target-volume, was assessed. For this purpose, dose distributions were recalculated using Monte Carlo, including uncertainties in PS (translation and rotation) and machine-positioning (gantry-, table-, collimator-rotation and multi-leaf collimator (MLC)). Plan robustness was evaluated by the uncertainties' impact on normal tissue complication probabilities (NTCP) for xerostomia and dysphagia and on dose-volume endpoints. Differences between DTRT and VMAT plan robustness were compared using Wilcoxon matched-pair signed-rank test (α = 5 %). Results: Average NTCP for moderate-to-severe xerostomia and grade ≥ II dysphagia was lower for DTRT than VMAT in the nominal scenario (0.5 %, p = 0.01; 2.1 %, p < 0.01) and for all investigated uncertainties, except MLC positioning, where the difference was not significant. Average differences compared to the nominal scenario were ≤ 3.5 Gy for rotational PS (≤ 3°) and machine-positioning (≤ 2°) uncertainties, <7 Gy for translational PS uncertainties (≤ 5 mm) and < 20 Gy for MLC-positioning uncertainties (≤ 5 mm). Conclusions: DTRT and VMAT plan robustness to the investigated uncertainties depended on uncertainty direction and location of the structure-of-interest to the target. NTCP remained on average lower for DTRT than VMAT even when considering uncertainties.

Metal accumulation in female green sea turtles (Chelonia mydas) from Eastern Atlantic affects their egg quality with potential implications for embryonic development.

Sea turtles, with their global distribution and complex life cycle, often accumulate pollutants such as metals and metalloids due to their extended lifespan and feeding habits. However, there are limited studies exploring the impact of metal pollution on the reproductive health of female sea turtles, specifically focusing on the quality of their eggs, which has significant implications for the future generations of these charismatic animals. São Tomé Island, a crucial nesting and feeding habitat for green sea turtles, underscores the urgent need for comprehensive research in this ecologically significant area. This study aimed to investigate whether metals and metalloids in the blood of nesting female green sea turtles induce genotoxic effects in their erythrocytes and affect their egg morphometric characteristics and the composition of related compartments. Additionally, this study aimed to evaluate whether the quality of energetic reserves for embryo development (fatty acids in yolk's polar and neutral lipids) is influenced by the contamination status of their predecessors. Results revealed correlations between Cu and Hg levels and increased "lobed" erythrocytes, while As and Cu negatively influenced shell thickness. In terms of energy reserves, both polar and neutral lipid fractions contained primarily saturated and monounsaturated fatty acids, with prevalent 18:1n-9, 18:0, 16:0, 14:0, and 12:0 fatty acids in yolk samples. The yolk polar fraction was more susceptible to contaminant levels in female sea turtles, showing consistent negative correlations between pollution load index and essential n3 fatty acids, including linolenic, eicosatrienoic, eicosapentaenoic, and docosapentaenoic acids, crucial for embryonic development. These metals accumulation, coupled with the reduced availability of these key fatty acids, may disrupt the eicosanoid and other important pathways, affecting reproductive development. This study reveals a negative correlation between metal contamination in female sea turtles' blood and egg lipid reserves, raising concerns about embryonic development and the species' future generations.

Dosimetrically motivated beam-angle optimization for non-coplanar arc radiotherapy with and without dynamic collimator rotation.

BACKGROUND: Non-coplanar techniques have shown to improve the achievable dose distribution compared to standard coplanar techniques for multiple treatment sites but finding optimal beam directions is challenging. Dynamic collimator trajectory radiotherapy (colli-DTRT) is a new intensity modulated radiotherapy technique that uses non-coplanar partial arcs and dynamic collimator rotation. PURPOSE: To solve the beam angle optimization (BAO) problem for colli-DTRT and non-coplanar VMAT (NC-VMAT) by determining the table-angle and the gantry-angle ranges of the partial arcs through iterative 4π fluence map optimization (FMO) and beam direction elimination. METHODS: BAO considers all available beam directions sampled on a gantry-table map with the collimator angle aligned to the superior-inferior axis (colli-DTRT) or static (NC-VMAT). First, FMO is performed, and beam directions are scored based on their contributions to the objective function. The map is thresholded to remove the least contributing beam directions, and arc candidates are formed by adjacent beam directions with the same table angle. Next, FMO and arc candidate trimming, based on objective function penalty score, is performed iteratively until a desired total gantry angle range is reached. Direct aperture optimization on the final set of colli-DTRT or NC-VMAT arcs generates deliverable plans. colli-DTRT and NC-VMAT plans were created for seven clinically-motivated cases with targets in the head and neck (two cases), brain, esophagus, lung, breast, and prostate. colli-DTRT and NC-VMAT were compared to coplanar VMAT plans as well as to class-solution non-coplanar VMAT plans for the brain and head and neck cases. Dosimetric validation was performed for one colli-DTRT (head and neck) and one NC-VMAT (breast) plan using film measurements. RESULTS: Target coverage and conformity was similar for all techniques. colli-DTRT and NC-VMAT plans had improved dosimetric performance compared to coplanar VMAT for all treatment sites except prostate where all techniques were equivalent. For the head and neck and brain cases, mean dose reduction-in percentage of the prescription dose-to parallel organs was on average 0.7% (colli-DTRT), 0.8% (NC-VMAT) and 0.4% (class-solution) compared to VMAT. The reduction in D2% for the serial organs was on average 1.7% (colli-DTRT), 2.0% (NC-VMAT) and 0.9% (class-solution). For the esophagus, lung, and breast cases, mean dose reduction to parallel organs was on average 0.2% (colli-DTRT) and 0.3% (NC-VMAT) compared to VMAT. The reduction in D2% for the serial organs was on average 1.3% (colli-DTRT) and 0.9% (NC-VMAT). Estimated delivery times for colli-DTRT and NC-VMAT were below 4 min for a full gantry angle range of 720°, including transitions between arcs, except for the brain case where multiple arcs covered the whole table angle range. These times are in the same order as the class-solution for the head and neck and brain cases. Total optimization times were 25%-107% longer for colli-DTRT, including BAO, compared to VMAT. CONCLUSIONS: We successfully developed dosimetrically motivated BAO for colli-DTRT and NC-VMAT treatment planning. colli-DTRT and NC-VMAT are applicable to multiple treatment sites, including body sites, with beneficial or equivalent dosimetric performances compared to coplanar VMAT and reasonable delivery times.

Effect of Secukinumab Versus Adalimumab Biosimilar on Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: Results From a Head-to-Head Randomized Phase IIIb Study.

OBJECTIVE: Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was to compare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin-17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ-ADL]; tumor necrosis factor inhibitor). METHODS: Biologic-naive patients with active radiographic axial SpA, at high risk of radiographic progression (high-sensitivity C-reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ-ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ-ADL at week 104 (primary endpoint), mean CFB-mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated. RESULTS: Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ-ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB-mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings. CONCLUSION: Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ-ADL arms. The safety of both treatments was consistent with previous reports.

Targeting Longevity Gene SLC13A5: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis.

Reduced expression of the plasma membrane citrate transporter SLC13A5, also known as INDY, has been linked to increased longevity and mitigated age-related cardiovascular and metabolic diseases. Citrate, a vital component of the tricarboxylic acid cycle, constitutes 1-5% of bone weight, binding to mineral apatite surfaces. Our previous research highlighted osteoblasts' specialized metabolic pathway facilitated by SLC13A5 regulating citrate uptake, production, and deposition within bones. Disrupting this pathway impairs bone mineralization in young mice. New Mendelian randomization analysis using UK Biobank data indicated that SNPs linked to reduced SLC13A5 function lowered osteoporosis risk. Comparative studies of young (10 weeks) and middle-aged (52 weeks) osteocalcin-cre-driven osteoblast-specific Slc13a5 knockout mice (Slc13a5cKO) showed a sexual dimorphism: while middle-aged females exhibited improved elasticity, middle-aged males demonstrated enhanced bone strength due to reduced SLC13A5 function. These findings suggest reduced SLC13A5 function could attenuate age-related bone fragility, advocating for SLC13A5 inhibition as a potential osteoporosis treatment.

Eficacia del trasplante de células madre mesenquimales de lipoaspirado en el tratamiento de lesiones crónicas del manguito rotador. Modelo experimental en ratas / Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats

Antecedentes y objetivo: Las roturas del manguito rotador afectan aproximadamente al 30% de la población mayor de 60 años. El tratamiento quirúrgico por vía artroscópica de estas lesiones es el tratamiento de elección, sin embargo, a pesar de las mejoras técnicas de reparación el índice de rerroturas oscila entre el 11 y el 94%. Por ello, los investigadores buscan mejorar el proceso de curación biológica mediante el uso de diferentes alternativas como las células madre mesenquimales (MSC). Nuestro objetivo es evaluar la eficacia de un medicamento de terapia celular elaborado a partir de células madre alogénicas derivadas del tejido adiposo en un modelo de lesión crónica del manguito rotador en ratas. Material y método: Se creó la lesión del supraespinoso en 48 ratas para su posterior sutura a las 4 semanas. A 24 animales se les añadió las MSC en suspensión tras la sutura, y a 24 animales HypoThermosol-FRS® (HTS) como grupo control. En ambos grupos se analizó la histología (escala Åström y Rausing) y la carga máxima, desplazamiento y constante elástica del tendón supraespinoso a los 4 meses de la reparación. Resultados: No se encontraron diferencias estadísticamente significativas en la puntuación histológica comparando los tendones tratados con MSC con respecto a los tendones tratados con HTS (p=0,811) ni tampoco en los resultados de carga máxima (p=0,770), desplazamiento (p=0,852) ni constante elástica (p=0,669) del tendón en ambos grupos. Conclusiones: La adición en suspensión de células derivadas de tejido adiposo a la reparación de una lesión crónica de manguito no mejora las características histológicas ni biomecánicas del tendón suturado.(AU)

Background and aim: Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs). Our objective is to evaluate the efficacy of a Cellular Therapy Drug made from allogeneic stem cells derived from adipose tissue in a rat model of chronic rotator cuff injury. Material and methods: The supraspinatus lesion was created in 48 rats for subsequent suturing at 4 weeks. MSCs in suspension were added to 24 animals after suturing, and HypoThermosol-FRS® (HTS) to 24 animals as a control group. Histology (Åström and Rausing scale) and the maximum load, displacement and elastic constant of the supraspinatus tendon were analyzed in both groups 4 months after the repair. Results: No statistically significant differences were found in the histological score comparing the tendons treated with MSCs with respect to the tendons treated with HTS (P=.811) nor in the results of maximum load (P=.770), displacement (P=.852) or elastic constant (P=.669) of the tendon in both groups. Conclusions: The addition of adipose-derived cells in suspension to the repair of a chronic cuff injury does not improve the histology or biomechanics of the sutured tendon.(AU)

[Translated article] Efficacy of transplantation of lipoaspired mesenchymal stem cells in the treatment of chronic rotator cuff tears. Experimental model in rats / Eficacia del trasplante de células madre mesenquimales de lipoaspirado en el tratamiento de lesiones crónicas del manguito rotador. Modelo experimental en ratas

Antecedentes y objetivo: Las roturas del manguito rotador afectan aproximadamente al 30% de la población mayor de 60 años. El tratamiento quirúrgico por vía artroscópica de estas lesiones es el tratamiento de elección, sin embargo, a pesar de las mejoras técnicas de reparación el índice de rerroturas oscila entre el 11 y el 94%. Por ello, los investigadores buscan mejorar el proceso de curación biológica mediante el uso de diferentes alternativas como las células madre mesenquimales (MSC). Nuestro objetivo es evaluar la eficacia de un medicamento de terapia celular elaborado a partir de células madre alogénicas derivadas del tejido adiposo en un modelo de lesión crónica del manguito rotador en ratas. Material y método: Se creó la lesión del supraespinoso en 48 ratas para su posterior sutura a las 4 semanas. A 24 animales se les añadió las MSC en suspensión tras la sutura, y a 24 animales HypoThermosol-FRS® (HTS) como grupo control. En ambos grupos se analizó la histología (escala Åström y Rausing) y la carga máxima, desplazamiento y constante elástica del tendón supraespinoso a los 4 meses de la reparación. Resultados: No se encontraron diferencias estadísticamente significativas en la puntuación histológica comparando los tendones tratados con MSC con respecto a los tendones tratados con HTS (p=0,811) ni tampoco en los resultados de carga máxima (p=0,770), desplazamiento (p=0,852) ni constante elástica (p=0,669) del tendón en ambos grupos. Conclusiones: La adición en suspensión de células derivadas de tejido adiposo a la reparación de una lesión crónica de manguito no mejora las características histológicas ni biomecánicas del tendón suturado.(AU)

Background and aim: Rotator cuff tears emerge in approximately 30% of the population over 60 years of age. Arthroscopic surgical treatment of these lesions is the treatment of choice, however, despite the improved repair techniques, the rate of re-tears ranges between 11 and 94%. Therefore, researchers seek to improve the biological healing process through the use of different alternatives such as mesenchymal stem cells (MSCs). Our objective is to evaluate the efficacy of a Cellular Therapy Drug made from allogeneic stem cells derived from adipose tissue in a rat model of chronic rotator cuff injury. Material and methods: The supraspinatus lesion was created in 48 rats for subsequent suturing at 4 weeks. MSCs in suspension were added to 24 animals after suturing, and HypoThermosol-FRS® (HTS) to 24 animals as a control group. Histology (Åström and Rausing scale) and the maximum load, displacement and elastic constant of the supraspinatus tendon were analyzed in both groups 4 months after the repair. Results: No statistically significant differences were found in the histological score comparing the tendons treated with MSCs with respect to the tendons treated with HTS (P=.811) nor in the results of maximum load (P=.770), displacement (P=.852) or elastic constant (P=.669) of the tendon in both groups. Conclusions: The addition of adipose-derived cells in suspension to the repair of a chronic cuff injury does not improve the histology or biomechanics of the sutured tendon.(AU)

Artroplastia total de cadera primaria en pacientes con secuelas de poliomielitis / Primary total hip arthroplasty in patients with sequelae of poliomyelitis

Introducción: La prótesis total de cadera (PTC) en pacientes con secuelas de poliomielitis (SP) supone un reto quirúrgico. La morfología displásica, la osteoporosis y la debilidad glútea dificultan la orientación, incrementan el riesgo de fractura y reducen la estabilidad del implante. El objetivo de este estudio es describir una serie de pacientes con SP tratados mediante PTC. Material y métodos: Estudio descriptivo retrospectivo de pacientes con SP intervenidos mediante PTC entre 1999 y 2021 en un hospital de tercer nivel, con seguimiento clínico y radiológico y evaluación funcional y de las complicaciones hasta el presente o hasta el fallecimiento, con un mínimo de 12meses. Resultados: Se intervinieron 16 pacientes, implantándose 13PTC en el miembro parético, 6 por fractura y 7 por coxartrosis, mientras que las otras 3PTC se implantaron en el miembro contralateral. Se implantaron 4 cotilos de doble movilidad como medida antiluxante. Al año postoperatorio, 11 presentaban un balance articular completo sin aumentar los casos de Trendelenburg. El Harris Hip Score (HHS) mejoró 32,1puntos, la escala visual analógica (EVA), 5,25puntos, y la escala de Merlé-d’Augbiné-Poste, 6puntos. La corrección de la discrepancia de longitud fue de 13,77mm. La mediana del seguimiento fue de 3,5años (1-24). Dos casos se revisaron por usura del polietileno y 2 por inestabilidad, sin registrarse infecciones, fracturas periprotésicas o aflojamiento del cotilo o vástago. Conclusiones: La PTC en pacientes con SP permite mejorar la situación clínico-funcional con una tasa de complicaciones aceptable. El riesgo de luxación podría minimizarse con cotilos de doble movilidad.(AU)

Introduction: Total hip arthroplasty (THA) in patients with residual poliomyelitis (RP) is a surgical challenge. Dysplastic morphology, osteoporosis and gluteal weakness hinder orientation, increase fracture risk and reduce implant stability. The aim of this study is to describe a series of patients with RP treated by THA. Material and methods: Retrospective descriptive study of patients with RP treated with THA between 1999 and 2021 in a tertiary hospital, with clinical and radiological follow-up and functional and complication evaluation until present or death, with a minimum of 12months. Results: Sixteen patients underwent surgery, with 13THA implanted in the paretic limb, 6 for fracture and 7 for osteoarthritis, while the remaining 3 were implanted in the contralateral limb. Four dual mobility cups were implanted as an antiluxation measure. At 1year postoperatively, 11 had complete range of motion with no increase in Trendelenburg cases. The Harris hip score (HHS) improved 32.1points, the visual analog scale (VAS) 5.25 points, and the Merlé-d’Augbiné-Poste scale 6 points. The length discrepancy correction was 13.77mm. Median follow-up was 3.5years (1-24). Two cases were revised for polyethylene wear and two for instability, with no infections, periprosthetic fractures, or cup or stem loosening. Conclusions: THA in patients with RP allows improvement of the clinico-functional situation with an acceptable complication rate. The risk of dislocation could be minimized with dual mobility cups.(AU)

[Translated article] Primary total hip arthroplasty in patients with sequelae of poliomyelitis / Artroplastia total de cadera primaria en pacientes con secuelas de poliomielitis

Introducción: La prótesis total de cadera (PTC) en pacientes con secuelas de poliomielitis (SP) supone un reto quirúrgico. La morfología displásica, la osteoporosis y la debilidad glútea dificultan la orientación, incrementan el riesgo de fractura y reducen la estabilidad del implante. El objetivo de este estudio es describir una serie de pacientes con SP tratados mediante PTC. Material y métodos: Estudio descriptivo retrospectivo de pacientes con SP intervenidos mediante PTC entre 1999 y 2021 en un hospital de tercer nivel, con seguimiento clínico y radiológico y evaluación funcional y de las complicaciones hasta el presente o hasta el fallecimiento, con un mínimo de 12meses. Resultados: Se intervinieron 16 pacientes, implantándose 13PTC en el miembro parético, 6 por fractura y 7 por coxartrosis, mientras que las otras 3PTC se implantaron en el miembro contralateral. Se implantaron 4 cotilos de doble movilidad como medida antiluxante. Al año postoperatorio, 11 presentaban un balance articular completo sin aumentar los casos de Trendelenburg. El Harris Hip Score (HHS) mejoró 32,1puntos, la escala visual analógica (EVA), 5,25puntos, y la escala de Merlé-d’Augbiné-Poste, 6puntos. La corrección de la discrepancia de longitud fue de 13,77mm. La mediana del seguimiento fue de 3,5años (1-24). Dos casos se revisaron por usura del polietileno y 2 por inestabilidad, sin registrarse infecciones, fracturas periprotésicas o aflojamiento del cotilo o vástago. Conclusiones: La PTC en pacientes con SP permite mejorar la situación clínico-funcional con una tasa de complicaciones aceptable. El riesgo de luxación podría minimizarse con cotilos de doble movilidad.(AU)

Introduction: Total hip arthroplasty (THA) in patients with residual poliomyelitis (RP) is a surgical challenge. Dysplastic morphology, osteoporosis and gluteal weakness hinder orientation, increase fracture risk and reduce implant stability. The aim of this study is to describe a series of patients with RP treated by THA. Material and methods: Retrospective descriptive study of patients with RP treated with THA between 1999 and 2021 in a tertiary hospital, with clinical and radiological follow-up and functional and complication evaluation until present or death, with a minimum of 12months. Results: Sixteen patients underwent surgery, with 13THA implanted in the paretic limb, 6 for fracture and 7 for osteoarthritis, while the remaining 3 were implanted in the contralateral limb. Four dual mobility cups were implanted as an antiluxation measure. At 1year postoperatively, 11 had complete range of motion with no increase in Trendelenburg cases. The Harris hip score (HHS) improved 32.1points, the visual analog scale (VAS) 5.25 points, and the Merlé-d’Augbiné-Poste scale 6 points. The length discrepancy correction was 13.77mm. Median follow-up was 3.5years (1-24). Two cases were revised for polyethylene wear and two for instability, with no infections, periprosthetic fractures, or cup or stem loosening. Conclusions: THA in patients with RP allows improvement of the clinico-functional situation with an acceptable complication rate. The risk of dislocation could be minimized with dual mobility cups.(AU)

El papel de la cirugía mínimamente invasiva de columna en el tratamiento de las metástasis vertebrales: una revisión narrativa / The role of minimally invasive spine surgery in the treatment of vertebral metastasis: A narrative review

Introducción: Las metástasis vertebrales son un problema muy frecuente y asocian un deterioro importante de la calidad de vida en los pacientes oncológicos. El objetivo de esta revisión es determinar el encaje de las técnicas quirúrgicas mínimamente invasivas dentro del manejo de esta entidad. Métodos: Se realizó una revisión bibliográfica en las bases de datos Google Scholar, PubMed, Scopus y Cochrane. Se revisaron los artículos publicados en los últimos 10 años que fueran de una relevancia y calidad adecuadas. Resultados: Tras el cribado de los 2.184 trabajos identificados inicialmente en las distintas bases de datos, se incluyeron un total de 24 artículos en esta revisión. Conclusión: La cirugía mínimamente invasiva de columna es especialmente útil en pacientes oncológicos frágiles con metástasis vertebrales por la reducida comorbilidad que presentan las técnicas que se engloban en ella en comparación con la de la cirugía abierta convencional. Los avances en tecnología aplicada a la cirugía, como la navegación y la robótica, mejoran la precisión y reducen las complicaciones de esta técnica.(AU)

Background: Spinal metastases are a very common problem which dramatically affects the quality of life of cancer patients. The objective of this review is to address the issue of how minimally invasive surgery can play an important role in treating this pathology. Methods: A literature review was performed, searching in the Google Scholar, PubMed, Scopus and Cochrane databases. Relevant and quality papers published within the last 10 years were included in the review. Results: After screening the 2184 initially identified registers, a total of 24 articles were included for review. Conclusion: Minimally invasive spine surgery is specially convenient for fragile cancer patients with spinal metastases, because of its reduced comorbidity compared to conventional open surgery. Technological advances in surgery, such as navigation and robotics, improve accuracy and safety in this technique.(AU)