Frailty, Sarcopenia and Osteoporosis. / Fragilidad, sarcopenia y osteoporosis.

Frailty, sarcopenia and osteoporosis are entities specific to the elderly, who share some risk factors. For this reason, their relationship has been studied in different works, which have provided disparate results, probably because these studies have not always focused on the same aspects. This article reviews the relationship of frailty and sarcopenia with osteoporosis.

Maresin 1 repletion improves muscle regeneration after volumetric muscle loss.

The acute traumatic or surgical loss of skeletal muscle, known as volumetric muscle loss (VML), is a devastating type of injury that results in exacerbated and persistent inflammation followed by fibrosis. The mechanisms that mediate the magnitude and duration of the inflammatory response and ensuing fibrosis after VML remain understudied, and as such, the development of regenerative therapies has been limited. To address this need, we profiled how lipid mediators, which are potent regulators of the immune response after injury, varied with VML injuries that heal or result in fibrosis. We observed that non-healing VML injuries displayed increased pro-inflammatory eicosanoids and a lack of pro-resolving lipid mediators. Treatment of VML with a pro-resolving lipid mediator synthesized from docosahexaenoic acid, called Maresin 1, ameliorated fibrosis through reduction of neutrophils and macrophages and enhanced recovery of muscle strength. These results expand our knowledge of the dysregulated immune response that develops after VML and identify a novel immuno-regenerative therapeutic modality in Maresin 1.

Romosozumab: confusión respecto a sus indicaciones / Romosozumab: confusion regarding its indications

El romosozumab es, sin duda, un excelente fármaco para el tratamiento de la osteoporosis. No obstante, su elevadoprecio, muy superior al de los fármacos antirresortivos, hizo que inicialmente se aceptara sin dificultad que su indicaciónse limitase a pacientes con un riesgo de fractura particularmente elevado. Sin embargo, la aplicación de esta idea en lapráctica se ha encontrado con algunos problemas. En primer lugar, para describir tal indicación se han utilizado términosdistintos (“riesgo muy alto”, “riesgo alto”, “osteoporosis grave”), el significado concreto de cada uno de los cuales,además, es diferente para unos y otros autores. Por otra parte, y sin un fundamento científico suficiente, se han idointroduciendo conceptos que pretenden ampliar las indicaciones del fármaco hasta prácticamente proponer la genera-lización de su uso (“riesgo inminente”, comienzo del tratamiento de la osteoporosis con anabólicos de forma universalo cuasi-universal). Todo ello ha generado confusión en el médico prescriptor, y ha dado lugar a que las autoridadessanitarias hayan impuesto para su uso normas que han resultado demasiado restrictivas. En el artículo se desarrollanestas ideas -y algunas otras- con detalle.(AU)

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial.

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Aminobisfosfonatos: reconsideración a los 25 años de su aprobación para el tratamiento de la osteoporosis / Aminobisphosphonates: Reconsideration 25 years after their approval for the treatment of osteoporosis

Aminobisphosphonates are widely used in the treatment of osteoporosis. They have a high affinity for hydroxyapatite, binding primarily to resorbing surfaces, but also to forming surfaces and to some extent to resting surfaces. They inhibit osteoclasts, thereby decreasing remodelling units. Consequently, they increase bone mass and reduce stress risers. This decreases the risk of fractures. If this decrease is sufficient, they can be temporarily withdrawn (drug holidays), which prevents serious complications (atypical femoral fracture). They probably reduce mortality. Virtually all patients with osteoporosis can benefit from them at some point in the course of their disease (at the beginning of treatment or after the administration of anabolics, selective estrogen receptor modulators or denosumab). If well tolerated orally, alendronate and risedronate are preferable. Otherwise, zoledronate is preferred. Their efficacy vs. cost-safety-convenience ratio makes aminobisphosphonates reference drugs in the field of osteoporosis. (AU)

Los aminobisfosfonatos se utilizan ampliamente en el tratamiento de la osteoporosis. Tienen gran afinidad por la hidroxiapatita, uniéndose fundamentalmente a las superficies en resorción, pero también a las superficies en formación y, en cierta medida, a las superficies en reposo. Inhiben a los osteoclastos, con lo que disminuyen las unidades de remodelación. En consecuencia, aumentan la masa ósea y reducen los concentradores de tensión. Ello disminuye el riesgo de fracturas. Si esta disminución es suficiente, pueden retirarse transitoriamente (vacaciones terapéuticas), lo que previene complicaciones graves (fractura atípica de fémur). Probablemente disminuyen la mortalidad. Pueden beneficiarse de ellos prácticamente todos los enfermos con osteoporosis en algún momento de su evolución (al comienzo del tratamiento o tras la administración de anabólicos, moduladores selectivos de los receptores estrogénicos o denosumab). Con buena tolerancia oral son preferibles el alendronato y el risedronato. En caso contrario, lo es el zoledronato. Su relación eficacia frente a coste-seguridad-comodidad los convierte en fármacos de referencia en el campo de la osteoporosis. (AU)

Sarcopenic osteoporosis, sarcopenic obesity, and sarcopenic osteoporotic obesity in the Camargo cohort (Cantabria, Spain).

The associations of sarcopenia with osteoporosis or obesity have a very low prevalence. No trend towards an association between osteoporosis and sarcopenia is observed. Sarcopenia and obesity tend not to coincide, as if they were antagonistic disorders. PURPOSE: To know (a) the prevalence in our region of sarcopenic osteoporosis (association of sarcopenia and osteoporosis (T-score < - 2.5)), sarcopenic obesity, and the association of osteoporosis, sarcopenia, and obesity; (b) the tendency of osteoporosis, sarcopenia, and obesity to associate with each other; and (c) the bone mineral density (BMD), the components of sarcopenia, and the prevalence of fragility fractures in these associations. METHODS: The study was performed in the Camargo cohort. Osteoporosis was diagnosed by DXA, sarcopenia by the EWGSOP-1 criteria, and obesity by body mass index (BMI) and fat percentage. Fractures were verified radiographically or by consulting the medical records. RESULTS: The prevalence of sarcopenic osteoporosis was 2.8% and the OR for this association 1.03 (p = 0.89). The prevalence of sarcopenic obesity by BMI was 1.4% and by fat percentage 5.9% (corresponding ORs: 0.18 (p < 0.0001) and 0.58 (p < 0.003) respectively). The prevalence of the association of osteoporosis, sarcopenia, and obesity was 0.0% when assessed by BMI and 0.8% when assessed by fat percentage. Patients with sarcopenic osteoporosis have less muscle mass and more fragility fractures than sarcopenic patients overall. In patients with sarcopenic obesity by fat percentage, muscle mass and strength, as well as physical performance, were similar to those of sarcopenic patients overall. Neither BMD nor fracture prevalence showed differences between patients with sarcopenic obesity and patients with sarcopenia or obesity in general. CONCLUSION: Our study supports the idea that the prevalence of the mixed disorders studied is low. No significant association between osteoporosis and sarcopenia was found. Sarcopenia and obesity seem to tend to occur in different people, as if suffering from one of them hinders suffering from the other.

Aminobisphosphonates: Reconsideration 25 years after their approval for the treatment of osteoporosis. / Aminobisfosfonatos: reconsideración a los 25 años de su aprobación para el tratamiento de la osteoporosis.

Aminobisphosphonates are widely used in the treatment of osteoporosis. They have a high affinity for hydroxyapatite, binding primarily to resorbing surfaces, but also to forming surfaces and to some extent to resting surfaces. They inhibit osteoclasts, thereby decreasing remodelling units. Consequently, they increase bone mass and reduce stress risers. This decreases the risk of fractures. If this decrease is sufficient, they can be temporarily withdrawn (drug holidays), which prevents serious complications (atypical femoral fracture). They probably reduce mortality. Virtually all patients with osteoporosis can benefit from them at some point in the course of their disease (at the beginning of treatment or after the administration of anabolics, selective estrogen receptor modulators or denosumab). If well tolerated orally, alendronate and risedronate are preferable. Otherwise, zoledronate is preferred. Their efficacy vs. cost-safety-convenience ratio makes aminobisphosphonates reference drugs in the field of osteoporosis.

Neutrophil and natural killer cell imbalances prevent muscle stem cell-mediated regeneration following murine volumetric muscle loss.

Volumetric muscle loss (VML) overwhelms the innate regenerative capacity of mammalian skeletal muscle (SkM), leading to numerous disabilities and reduced quality of life. Immune cells are critical responders to muscle injury and guide tissue resident stem cell­ and progenitor-mediated myogenic repair. However, how immune cell infiltration and intercellular communication networks with muscle stem cells are altered following VML and drive pathological outcomes remains underexplored. Herein, we contrast the cellular and molecular mechanisms of VML injuries that result in the fibrotic degeneration or regeneration of SkM. Following degenerative VML injuries, we observed the heightened infiltration of natural killer (NK) cells as well as the persistence of neutrophils beyond 2 wk postinjury. Functional validation of NK cells revealed an antagonistic role in neutrophil accumulation in part via inducing apoptosis and CCR1-mediated chemotaxis. The persistent infiltration of neutrophils in degenerative VML injuries was found to contribute to impairments in muscle stem cell regenerative function, which was also attenuated by transforming growth factor beta 1 (TGFß1). Blocking TGFß signaling reduced neutrophil accumulation and fibrosis and improved muscle-specific force. Collectively, these results enhance our understanding of immune cell­stem cell cross talk that drives regenerative dysfunction and provide further insight into possible avenues for fibrotic therapy exploration.

Sestrins regulate muscle stem cell metabolic homeostasis.

The health and homeostasis of skeletal muscle are preserved by a population of tissue-resident muscle stem cells (MuSCs) that maintain a state of mitotic and metabolic quiescence in adult tissues. The capacity of MuSCs to preserve the quiescent state declines with aging and metabolic insults, promoting premature activation and stem cell exhaustion. Sestrins are a class of stress-inducible proteins that act as antioxidants and inhibit the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling complex. Despite these pivotal roles, the role of Sestrins has not been explored in adult stem cells. We show that SESTRIN1,2 loss results in hyperactivation of the mTORC1 complex, increased propensity to enter the cell cycle, and shifts in metabolic flux. Aged SESTRIN1,2 knockout mice exhibited loss of MuSCs and a reduced ability to regenerate injured muscle. These findings demonstrate that Sestrins help maintain metabolic pathways in MuSCs that protect quiescence against aging.

Acute abdominal dehiscence following laparotomy: A multicentre, international retrospective study.

BACKGROUND: Incisional complications are a common cause of morbidity following laparotomy. Although uncommon, acute abdominal dehiscence (AAD) is a potentially fatal post-operative complication. However, few AAD cases are described in the literature. OBJECTIVES: To describe common features of cases of AAD following ventral midline laparotomy, management and outcomes. STUDY DESIGN: Retrospective case series. METHODS: Hospital records of horses that underwent a ventral midline laparotomy at nine hospitals in the UK, Ireland and USA over a 10-year period (2009-2019) were reviewed. Data were collected for pre-, intra- and post-operative factors that were considered relevant. Descriptive statistical analysis was performed. RESULTS: A total of 63 cases of AAD were identified. AAD occurred due to tearing of sutures through the linea alba or rupture of the body wall adjacent to the suture line in 46 horses (73%). AAD occurred at a median of 5 days (0.5-70 days) post-operatively and broodmares accounted for 25% of the cases (n = 16). Surgical site infection developed prior to AAD in 28 horses (44%); leakage of peritoneal fluid occurred in 5% of horses prior to AAD being identified. Surgical repair was performed in 27 horses (43%), 10 (16%) were treated conservatively and 26 (41%) were euthanised immediately. Repair was most frequently performed using suture (n = 14), wire (n = 5) or a combination (n = 5). Overall survival to hospital discharge was 39% (24/63). Where surgical repair was performed, 15 horses (56%) survived to hospital discharge; 9 horses (90%) managed conservatively survived to hospital discharge. MAIN LIMITATIONS: Follow-up was not performed for all cases following hospital discharge and some data were incompletely recorded in hospital files. CONCLUSIONS: Previously stated causative factors for AAD were not consistent features in the present study. Surgical site infection following laparotomy and pregnant or early post-partum mares may be important risk factors for AAD and warrant further investigation.

Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging.

During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function impacting mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs); however, the relationship between MuSCs and innervation has not been established. Herein, we administered severe neuromuscular trauma to a transgenic murine model that permits MuSC lineage tracing. We show that a subset of MuSCs specifically engraft in a position proximal to the neuromuscular junction (NMJ), the synapse between myofibers and motor neurons, in healthy young adult muscles. In aging and in a mouse model of neuromuscular degeneration (Cu/Zn superoxide dismutase knockout - Sod1-/-), this localized engraftment behavior was reduced. Genetic rescue of motor neurons in Sod1-/- mice reestablished integrity of the NMJ in a manner akin to young muscle and partially restored MuSC ability to engraft into positions proximal to the NMJ. Using single cell RNA-sequencing of MuSCs isolated from aged muscle, we demonstrate that a subset of MuSCs are molecularly distinguishable from MuSCs responding to myofiber injury and share similarity to synaptic myonuclei. Collectively, these data reveal unique features of MuSCs that respond to synaptic perturbations caused by aging and other stressors.

Metabolipidomic profiling reveals an age-related deficiency of skeletal muscle pro-resolving mediators that contributes to maladaptive tissue remodeling.

Specialized pro-resolving mediators actively limit inflammation and support tissue regeneration, but their role in age-related muscle dysfunction has not been explored. We profiled the mediator lipidome of aging muscle via liquid chromatography-tandem mass spectrometry and tested whether treatment with the pro-resolving mediator resolvin D1 (RvD1) could rejuvenate the regenerative ability of aged muscle. Aged mice displayed chronic muscle inflammation and this was associated with a basal deficiency of pro-resolving mediators 8-oxo-RvD1, resolvin E3, and maresin 1, as well as many anti-inflammatory cytochrome P450-derived lipid epoxides. Following muscle injury, young and aged mice produced similar amounts of most pro-inflammatory eicosanoid metabolites of cyclooxygenase (e.g., prostaglandin E2 ) and 12-lipoxygenase (e.g., 12-hydroxy-eicosatetraenoic acid), but aged mice produced fewer markers of pro-resolving mediators including the lipoxins (15-hydroxy-eicosatetraenoic acid), D-resolvins/protectins (17-hydroxy-docosahexaenoic acid), E-resolvins (18-hydroxy-eicosapentaenoic acid), and maresins (14-hydroxy-docosahexaenoic acid). Similar absences of downstream pro-resolving mediators including lipoxin A4 , resolvin D6, protectin D1/DX, and maresin 1 in aged muscle were associated with greater inflammation, impaired myofiber regeneration, and delayed recovery of strength. Daily intraperitoneal injection of RvD1 had minimal impact on intramuscular leukocyte infiltration and myofiber regeneration but suppressed inflammatory cytokine expression, limited fibrosis, and improved recovery of muscle function. We conclude that aging results in deficient local biosynthesis of specialized pro-resolving mediators in muscle and that immunoresolvents may be attractive novel therapeutics for the treatment of muscular injuries and associated pain in the elderly, due to positive effects on recovery of muscle function without the negative side effects on tissue regeneration of non-steroidal anti-inflammatory drugs.

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

3D analysis of bone mineral density in a cohort: age- and sex-related differences.

Women have lower areal BMD (g/cm2) than men; however, the women have smaller-size bones. Our study showed that women ≤ 59 years have a hip volumetric BMD by DXA 3D similar to that of men of the same age. This makes us think about the importance of taking into account bone size at the time of analyzing the sex-related differences in bone mass. PURPOSE: Women have lower areal BMD (g/cm2) than men; however, these studies do not take into account that women have smaller-size bones. Recently, three-dimensional (3D) modeling methods were proposed to analyze volumetric BMD (vBMD). We want to determine the values of vBMD at the hip by DXA-based 3D modeling in a cohort of people in order to know the age- and sex-related differences. METHODS: A total of 2647 people of both sexes (65% women) were recruited from a large cohort (Camargo cohort, Santander, Spain). 3D-SHAPER® software (version 2.8, Galgo Medical, Barcelona, Spain) was used to derive 3D analysis from the hip DXA scans at baseline RESULTS: The differences were less pronounced for vBMD (cortical sBMD 9.3%, trabecular vBMD 6.4%, integral vBMD 2.2%) compared to aBMD (FN aBMD 11.4% and TH aBMD 13.3%). After stratifying by age (≤ 59 years, 60-69 years, 70-79 years, and ≥ 80 years), we observed in ≤ 59 years that aBMD was lower in women compared to men, at FN (0.758 [0.114] g/cm2 vs. 0.833 [0.117] g/cm2; p = 1.4 × 10-20) and TH (0.878 [0.117] g/cm2 vs. 0.990 [0.119] g/cm2; p = 4.1 × 10-40). Nevertheless, no statistically significant difference was observed for integral vBMD (331 [58] mg/cm3 in women and 326 [51] mg/cm3 in men; p = 0.19) and trabecular vBMD (190 [41] mg/cm3 in women and 195 [39] mg/cm3 in men; p = 0.20). CONCLUSION: Our results make us think about the importance of taking into account bone size at the time of analyzing the sex-related differences in bone mass.

Combined Bacterial and Herpes Simplex Virus Keratitis following Small-Incision Lenticule Extraction for the Correction of Myopia.

A 28-year-old male presented unilateral visual loss, intense ocular pain, redness and intraocular hypertension in his right eye 2 days after undergoing small-incision lenticule extraction (SMILE) in both eyes. Initial examination of the affected eye revealed the presence of white infiltrates within the corneal interface, as well as a central epithelial defect. The patient was diagnosed with infectious keratitis, posteriorly the eye was irrigated with balanced saline solution and treatment was initiated with hourly moxifloxacin 0.5%. Since this approach failed to resolve symptoms, a sample from the interface was obtained for PCR assay, which revealed the presence of herpes simplex virus DNA, confirming the cause of the infection. The patient was prescribed a regimen of oral acyclovir, topical ganciclovir and prednisolone. Clinical improvement following resolution of the epithelial defect was observed. Although rare, herpetic keratitis following SMILE is best managed via early diagnosis and initiation of appropriate anti-herpetic treatment.

Effectiveness and safety of a glutaraldehyde-modified, L-tyrosine-adsorbed and monophosphoryl lipid A-Adjuvanted allergen immunotherapy in patients with allergic asthma sensitized to olive pollen: A retrospective, controlled real-world study.

BACKGROUND: Allergy to olive pollen is one of the primary causes of allergic asthma in Spain. Even though allergen immunotherapy (AIT) has shown clinical benefits in patients sensitized to different allergens, studies in asthmatic patients sensitized to olive pollen are insufficient. OBJECTIVE: To assess the effectiveness and safety of an ultra-short course of AIT with an L-tyrosine-adsorbed and monophosphoryl lipid A-adjuvanted olive pollen and olive/grass pollen extract (Pollinex Quattro®) in patients with allergic asthma in the real-world setting. METHODS: Retrospective, controlled study including patients with asthma, with and without allergic rhinitis, caused by sensitization to olive pollen from 11 centers in Spain. Patients received out-of-season (October-March) treatment with AIT in addition to their pharmacological treatment (active group) or pharmacological treatment (control group). Effectiveness variables, including unscheduled visits to the healthcare center, emergency room admissions, symptoms of asthma and rhinitis (following GEMA and ARIA classifications, respectively), and use of medication to treat asthma and rhinitis during the subsequent pollen season were compared between treatment groups. RESULTS: Of 131 study patients, 42 were treated with their usual asthma medication (control group) and 89 were treated with AIT (active group), either Pollinex Quattro® 100% olive pollen (n = 43, 48.3%) or 50% olive pollen/50% grass pollen (n = 46, 51.7%). Patients' demographic and clinical characteristics were similar between groups. The mean (SD) number of unscheduled visits to a healthcare center and emergency room admissions due to allergy symptoms was 2.19 (1.40) and 0.43 (0.63) in the control group, and 1.09 (1.25) and 0.11 (0.51) in the active group (P = 0.001 and P = 0.006, respectively). Severity and control of asthma symptoms remained unchanged (P = 0.347 and P = 0.179, respectively), rhinitis type improved (P = 0.025), and severity remained unchanged in the active compared to the control group. The use of short-acting beta-agonists and inhaled corticosteroids to treat asthma symptoms decreased in the active vs. the control group (P = 0.001 and P = 0.031, respectively). Twelve (13.5%) and two (2.2%) patients in the active group experienced local adverse reactions (edema, swelling, erythema, hives, pruritus, and heat), and systemic adverse reactions (hypertensive crisis and low-grade fever) to AIT, respectively; none was serious. CONCLUSION: AIT with Pollinex Quattro® specific for olive pollen and olive/grass pollens resulted in reduced visits to the healthcare center and emergency room and the use of asthma medication during the pollen season, indicating that this treatment was safe and effective in treating asthma in patients sensitized to these pollens.

COVID-19 y fractura por fragilidad de la cadera. Recomendaciones conjuntas de la Sociedad Española de Fracturas Osteoporóticas y la Sociedad Española de Geriatría y Gerontología / COVID-19 and fragility hip fracture. Joint recommendations of the Spanish Society of Osteoporotic Fractures and the Spanish Society of Geriatrics and Gerontology

No disponible

Resolvin D1 supports skeletal myofiber regeneration via actions on myeloid and muscle stem cells.

Specialized proresolving mediators (SPMs) actively limit inflammation and expedite its resolution by modulating leukocyte recruitment and function. Here we profiled intramuscular lipid mediators via liquid chromatography-tandem mass spectrometry-based metabolipidomics following myofiber injury and investigated the potential role of SPMs in skeletal muscle inflammation and repair. Both proinflammatory eicosanoids and SPMs increased following myofiber damage induced by either intramuscular injection of barium chloride or synergist ablation-induced functional muscle overload. Daily systemic administration of the SPM resolvin D1 (RvD1) as an immunoresolvent limited the degree and duration of inflammation, enhanced regenerating myofiber growth, and improved recovery of muscle strength. RvD1 suppressed inflammatory cytokine expression, enhanced polymorphonuclear cell clearance, modulated the local muscle stem cell response, and polarized intramuscular macrophages to a more proregenerative subset. RvD1 had minimal direct impact on in vitro myogenesis but directly suppressed myokine production and stimulated macrophage phagocytosis, showing that SPMs can modulate both infiltrating myeloid and resident muscle cell populations. These data reveal the efficacy of immunoresolvents as a novel alternative to classical antiinflammatory interventions in the management of muscle injuries to modulate inflammation while stimulating tissue repair.