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Ultrasound-guided (US-guided) loco-regional anesthesia can provide significant analgesia and anesthetic-sparing effects when used in rabbits. The aims of this study were to investigate the thoraco-lumbar anatomy of the rabbits, particularly the quadratus lumborum (QL) muscle, to design an appropriate US-guided quadratus lumborum block (QLB) specific for rabbits, and to define the most adequate volume of injectate required to consistently cover the ventral branches of T11 to L3 without affecting the pelvic limb innervation (L4, L5 and L6). Sixteen adult rabbit cadavers were included in the study. After randomization, four different volumes of injectate (0.1 mL/kg, 0.2 mL/kg, 0.3 mL/kg and 0.4 mL/kg) were tested, with these volumes additionally randomized to two sites of injection (right or left QL fascia). An ultrasound-guided QLB was performed with a solution of lidocaine, iodinated contrast and tissue dye (in a proportion of 3:1:1 volume, respectively), with subsequent computed tomography (CT) and anatomical dissection, to evaluate the spread of the injectate. In all but one case, the US-guided QLB performed with a dorsolateral approach using 0.3 mL/kg was adequate, while a dose of 0.4 mL/kg consistently reached the targeted nerves but also extended to L4 and caudally. This may suggest that an injectate volume of 0.3 mL/kg may be the most appropriate to produce adequate spread while not affecting pelvic limb innervation.
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The objective of this research was to evaluate the efficacy of diclofenac sodium solutions, with or without cetrimide (CTR) added, against polymicrobial root canal biofilms grown in dentin specimens. The study groups were: (1) 5% diclofenac sodium (DCS); (2) 2.5% DCS; (3) 2.5% DCS + 0. 2% CTR; (4) 2.5% DCS + 0.4% CTR and (5) 0.9% saline solution (SS) as the control. After 5 min of solution contact with the biofilms, the antimicrobial activity was evaluated by means of the adenosine triphosphate (ATP) assay as well as confocal laser scanning microscopy (CLSM). Microbial quantification was indicated as the percentage reduction of relative light units (RLUs) for the ATP assay, the Log10 total biovolume and the viability percentage (green cells) for CLSM. Solutions of 2.5% DCS + 0.4% CTR and 5% DCS showed the highest antimicrobial efficacy. Cetrimide increased the antibiofilm activity of diclofenac sodium against endodontic biofilms.
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Antiinfecciosos , Diclofenaco , Diclofenaco/farmacología , Cavidad Pulpar , Hipoclorito de Sodio/farmacología , Irrigantes del Conducto Radicular/farmacología , Cetrimonio , Compuestos de Cetrimonio , Biopelículas , Adenosina Trifosfato , Enterococcus faecalis , Microscopía Confocal , DentinaRESUMEN
Introduction: COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Methods: This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. Results: The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 - 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. Discussion: Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.
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COVID-19 , Enfermedades Transmisibles , Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Humanos , Persona de Mediana Edad , Médula Ósea , Trasplante Homólogo , COVID-19/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedades Transmisibles/complicaciones , Infecciones por Citomegalovirus/complicaciones , Sistema de RegistrosRESUMEN
Persistent infections have become a challenge in dentistry because of growing antibiotic resistance. Nonsteroidal anti-inflammatory drugs (NSAIDs) appear to be a therapeutic alternative to control biofilm infection. The objective of this work is to evaluate the antimicrobial activity and cytotoxicity of sodium diclofenac (DCS), ibuprofen (IBP) and ibuprofen arginine (IBP-arginine) solutions against endodontic polymicrobial biofilms. Sterile radicular dentin blocks of 4 mm × 4 mm × 0.7 mm were used as substrate to grow biofilm. The dentin blocks were submerged into solutions for 5 min. The antimicrobial activity was evaluated by means of the adenosine triphosphate (ATP) assay and confocal laser scanning microscopy (CLSM). Fibroblasts 3T3-L1 (ECACC 86052701) were used to test the cytotoxicity of irrigating solutions. The antibiofilm effects determined by the ATP assay showed that 4% IBP-arginine solution exerted the highest antibiofilm activity, followed by 4% DCS and 4% IBP, with statistical differences among groups (p < 0.001). As for CLSM, 4% DCS and 4% IBP-arginine solutions gave the lowest viable cell percentages, without significant differences between them. Cytotoxicity results at 1/10 dilution were similar for all solutions. At 1/100 dilution, a 4% DCS solution obtained the lowest cell viability for both time periods assayed, 1 h and 24 h. The IBP-arginine group showed the highest cell viability at 24 h. In this preliminary study, in terms of antibiofilm activity and cytotoxicity, a mixed 4% IBP-arginine solution gave the most promising results. NSAID solutions could be recommendable drugs for endodontic disinfection procedures.
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The outcomes of patients with acute lymphoblastic leukaemia (ALL) presenting relapse after allogeneic stem cell transplant (allo-SCT) are poor, with few data available in this setting. OBJECTIVE AND METHODS: To evaluate the outcomes of patients with ALL presenting relapsed after allo-SCT, we performed a retrospective study including 132 from 11 centres in Spain. RESULTS: Therapeutic strategies consisted of palliative treatment (n = 22), chemotherapy (n = 82), tyrosine kinase inhibitors (n = 26), immunotherapy with inotuzumab and/or blinatumumab (n = 19), donor lymphocyte infusions (n = 29 pts), second allo-SCT (n = 37) and CAR T therapy (n = 14). The probability of overall survival (OS) at 1 and 5 years after relapse was 44% (95% confidence interval [CI]: 36%; 52%) and 19% (95% CI: 11%; 27%). In the 37 patients undergoing a second allo-SCT, the 5-year estimated OS probability was 40% [22%; 58%]. Younger age, recent allo-SCT, late relapse, 1st complete remission at 1st allo-SCT and chronic graft-versus-host disease confirmed their positive impact on survival in the multivariable analysis. CONCLUSION: Despite the poor prognosis of patients with ALL presenting relapse after a first allo-SCT, some can be satisfactorily rescued and a second allo-SCT still remains a valid option for selected patients. Moreover, emerging therapies really might improve ALL patients outcome when relapsing after an allo-SCT.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Estudios Retrospectivos , Trasplante Homólogo , Recurrencia Local de Neoplasia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre , Pronóstico , Enfermedad Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , RecurrenciaRESUMEN
INTRODUCTION: Belantamab mafodotin (BM) is a new anti-BCMA antibody-drug conjugate, recently approved for triple-class relapsed and refractory multiple myeloma (RRMM). We assessed real-world outcomes with BM in patients under the Spanish Expanded Access Program (EAP). METHODS: We conducted an observational, retrospective, multicenter study including RRMM patients who received ≥ 1 dose of BM (Nov 2019 to Jun 2021). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs). RESULTS: Thirty-three patients were included with a median of 70 years of age (range, 46-79 years). Median time from diagnosis was 71 months (range, 10-858 months). Median prior lines was 5 (range, 3-8 lines); 90% of patients were triple-/quad-/penta-refractory; 48% showed high-risk cytogenetics. Median BM doses was 3 (range 1-16 doses), with a median follow-up of 11 months (6-15 months). ORR was 42.2% (≥ VGPR, 18.2%). Median PFS was 3 months (95% CI 0.92-5.08) in the overall population, and 11 months (HR 0.26; 95% CI 0.10-0.68) for patients who achieved ≥ PR. PFS was not significantly different according to age, cytogenetic risk, and prior therapy lines. OS was 424 days (95% CI 107-740). Non-hematological TEAEs (57.6% of patients; 30.3% ≥ G3) included keratopathy (51.5%; 21.2% ≥ G3) and patient-reported vision-related symptoms (45.5%). Keratopathy was resolved in 70.6% of patients. G3 hematological TEAEs was 18.2%, thrombocytopenia (21.2%). Dose reductions due to TEAEs: 30.3%; delays: 36.4%. Treatment discontinuation causes: progression (54.5%), toxicity (non-ocular; 6%/ocular; 6% /ocular + non-ocular toxicity; 3%), death (6%), and patient's decision (3%). CONCLUSIONS: BM showed relevant anti-myeloma activity in RRMM with a manageable safety profile. These results corroborate those observed in the BM pivotal trial.
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AIM: There is a need to explore new alternatives for root canal disinfection in regenerative endodontics, since the current strategies are far from ideal. Currently, the potential use of diclofenac (DC) is being investigated for controlling root canal infections. The objective was to evaluate the antimicrobial efficacy of novel DC-based hydrogels (DCHs) against polymicrobial biofilms grown in radicular dentine and root canals and to compare results with triantibiotic (TAH) and diantibiotic (DAH) hydrogels, and calcium hydroxide (Ca[OH]2 ). METHODOLOGY: The in vitro antimicrobial activity of intracanal medicaments was evaluated against 3-week-old polymicrobial root canal biofilms grown on human radicular dentine. Dentine samples were obtained and randomly divided into the study groups (n = 4/group): (1) 1 mg/ml TAH; (2) 1 mg/ml DAH; (3) 5% diclofenac (DCH); (4) 2.5% DCH; (5) 1.25% DCH; (6) 1 mg/ml DAH + 5% DCH; (7) Ca(OH)2 paste; (8) positive control. The microbial viability, in terms of percentage of intact cell membranes, was assessed after 7 days by confocal scanning laser microscopy (CSLM). The ex vivo efficacy of intracanal medications was evaluated in root canals infected with a polymicrobial suspension. Intracanal microbiological samples at baseline (S1) and 7 days post-treatment (S2) were taken; microbial quantification and cell viability were assessed by quantitative polymerase chain reaction (qPCR) and flow cytometry (FC). The mean Log10 of bacterial DNA copies in root canal samples before (S1) and the Log10 reduction of DNA copies S1-S2 in qPCR were recorded. The absolute value of total cells stained, and the percentage reduction of intact membrane cells after treatment (S1-S2), were analysed by FC. Global comparison was done using the Kruskal-Wallis test, whilst the Mann-Whitney U test was used for pair-by-pair comparison. RESULTS: Confocal scanning laser microscopy analysis indicated that the greatest effectiveness was obtained with 5% DCH, showing significant differences with respect to the other groups (p < .001). In root canals, the highest Log10 DNA reduction S1-S2 was obtained with 5% DCH and TAH, with no differences between them. The results of FC showed that only 5% DCH proved significantly superior to the other treatments. CONCLUSIONS: Sodium DC hydrogels demonstrate antimicrobial efficacy against endodontic biofilms.
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Antiinfecciosos , Hidrogeles , Humanos , Diclofenaco/farmacología , Antiinfecciosos/farmacología , ADNRESUMEN
This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0-80.3) for allogeneic, and 60.6 years (7.7-81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2-292.7) in allogeneic and 24.6 months (-0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.
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COVID-19/complicaciones , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , SARS-CoV-2/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/virología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/virología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Trasplante Homólogo , Adulto JovenRESUMEN
We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-ß (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).
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COVID-19/epidemiología , Trasplante de Células Madre Hematopoyéticas , Trasplante de Órganos , Receptores de Trasplantes , COVID-19/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , España/epidemiologíaRESUMEN
B-cell precursor acute lymphoblastic leukaemia (B-ALL) is a malignancy of lymphoid progenitor cells with altered genes including the Janus kinase (JAK) gene family. Among them, tyrosine kinase 2 (TYK2) is involved in signal transduction of cytokines such as interferon (IFN) α/ß through IFN-α/ß receptor alpha chain (IFNAR1). To search for disease-associated TYK2 variants, bone marrow samples from 62 B-ALL patients at diagnosis were analysed by next-generation sequencing. TYK2 variants were found in 16 patients (25.8%): one patient had a novel mutation at the four-point-one, ezrin, radixin, moesin (FERM) domain (S431G) and two patients had the rare variants rs150601734 or rs55882956 (R425H or R832W). To functionally characterise them, they were generated by direct mutagenesis, cloned in expression vectors, and transfected in TYK2-deficient cells. Under high-IFNα doses, the three variants were competent to phosphorylate STAT1/2. While R425H and R832W induced STAT1/2-target genes measured by qPCR, S431G behaved as the kinase-dead form of the protein. None of these variants phosphorylated STAT3 in in vitro kinase assays. Molecular dynamics simulation showed that TYK2/IFNAR1 interaction is not affected by these variants. Finally, qPCR analysis revealed diminished expression of TYK2 in B-ALL patients at diagnosis compared to that in healthy donors, further stressing the tumour immune surveillance role of TYK2.
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Simulación de Dinámica Molecular , Mutación , Proteínas de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras B , TYK2 Quinasa , Adolescente , Adulto , Línea Celular Tumoral , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Proteínas de Neoplasias/química , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/enzimología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , TYK2 Quinasa/química , TYK2 Quinasa/genética , TYK2 Quinasa/metabolismoRESUMEN
This is the first case of acquired severe neutropenia in the context of COVID-19 reported to date. This could illustrate another less frequent hematological disorder related to this novel viral infection.
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The diagnosis and treatment of nasal foreign bodies usually includes a combination of rhinoscopy and imaging techniques, such as CT. The purpose of this retrospective, multicenter study was to describe the CT characteristics of nasal foreign bodies in dogs and cats and to determine if different nasal CT features exist between acute and chronic cases. Twenty dogs and six cats met the inclusion criteria. Eleven nasal foreign bodies (42%) were detected confidently with CT. The foreign body had a linear shape in 81% of cases and displayed a "tubular-like appearance" in 54% of cases. In five cases (19%), a foreign body was suspected but not clearly visible. Additional CT changes were present in the nasal passages in 96% of the cases. The presence of turbinate destruction (P = .021) and mucosal thickening (P = .014) on CT were associated with the presence of a chronic nasal foreign body. In this sample, the nature of the foreign body did not influence its visibility and was not associated with specific CT characteristics. Computed tomography may be useful in the investigation of nasal foreign bodies, however, a negative CT examination does not exclude their presence.
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Enfermedades de los Gatos/diagnóstico por imagen , Enfermedades de los Perros/diagnóstico por imagen , Cuerpos Extraños/veterinaria , Enfermedades Nasales/veterinaria , Animales , Gatos , Perros , Femenino , Cuerpos Extraños/diagnóstico por imagen , Masculino , Cavidad Nasal/diagnóstico por imagen , Cavidad Nasal/patología , Nariz/diagnóstico por imagen , Nariz/patología , Enfermedades Nasales/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/veterinariaRESUMEN
Three cases of gallbladder agenesis (GA) have been previously reported in the English-speaking veterinary literature. Affected dogs can be either asymptomatic or symptomatic with vomiting, retching, and anorexia previously reported. The previously reported cases and the dog in this report had marked elevations in alanine aminotransferase concentrations, and liver histopathology consistently showed bridging fibrosis and biliary hyperplasia. The condition is most often diagnosed in humans during exploratory surgery, which was also the case in the previous three dogs reported with GA. Computed tomography (CT) or MRI is now recommended for diagnosis of the condition in humans, and this is the first report of CT findings in an affected dog diagnosed without surgery. Bile stasis and cholangiohepatits have been proposed as secondary pathologies in both humans and dogs with GA, and histopathology and CT findings in this case support those theories.
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Anomalías Congénitas/veterinaria , Enfermedades de los Perros/congénito , Vesícula Biliar/anomalías , Tomografía Computarizada por Rayos X/veterinaria , Animales , Anomalías Congénitas/diagnóstico por imagen , Anomalías Congénitas/patología , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/patología , Perros , Vesícula Biliar/diagnóstico por imagen , Vesícula Biliar/patología , MasculinoRESUMEN
Lymphoblastic lymphomas (LBLs) are uncommon malignant neoplasms derived from immature T- or B-lymphoid progenitor cells. Although cutaneous involvement may reach 33% in B-LBL, only 12 cutaneous cases of T-LBL have been published. We report the case of a 49-year-old woman with 2-month history of erythematous-violaceous plaques in the sternal region and breasts. Histopathologic examination showed a dense monomorphus infiltrate in dermis and positive immunostainings for CD3, CD99 and terminal deoxynucleotidyl transferase, thus indicating T-LBL. Staging work-up only revealed a mediastinal mass at diagnosis. After a 51-month follow-up and different treatment regimens, the patient remains alive although she has presented four relapses, all of them extramedullary.
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Antígeno 12E7/metabolismo , Neoplasias de la Mama , Complejo CD3/metabolismo , Dermis , Proteínas de Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras , Neoplasias Cutáneas , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Dermis/metabolismo , Dermis/patología , Femenino , Humanos , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapiaRESUMEN
This report describes, for the first time in small animal literature, the spontaneous resorption of herniated Hansen type I intervertebral disc material in the cervical spine of a chondrodystrophic dog over a 4-month period, documented by magnetic resonance imaging. Clinical signs (cervical hyperpathia) responded to conservative treatment during the same period.
Résorption spontanée d'une hernie discale chez un chien détectée par imagerie par résonance magnétique. Cet article décrit, pour la première fois dans la littérature des petits animaux, la résorption spontanée d'une hernie Hansen de type I du matériel du disque intervertébral dans la colonne cervicale d'un chien chondrodystrophique pendant une période de 4 mois et documentée par imagerie par résonance magnétique (IRM). Les signes cliniques (hyperpathie cervicale) ont répondu à un traitement conservateur durant la même période.(Traduit par Isabelle Vallières).
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Enfermedades de los Perros/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/veterinaria , Imagen por Resonancia Magnética/veterinaria , Animales , Vértebras Cervicales , Perros , Disco Intervertebral , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Remisión EspontáneaRESUMEN
BACKGROUND: The use of antimicrobial solutions has been recommended to disinfect demineralized dentin prior to placing the filling material. The aim of this study was to evaluate the ability of several antimicrobials in controlling Streptococcus mutans (SM) biofilm formed in dentin. METHODS: Antimicrobial activity of 0.2% and 2% chlorhexidine (CHX), 0.2% cetrimide (CTR) and 0.2%, 0.5%, 1% and 2% alexidine (ALX) was assayed on 1-week SM biofilm formed on standardized coronal dentin blocks. Results of SM biofilm antimicrobial activity by different protocols were expressed as the kill percentage of biofilm and the term "eradication" was used to denote the kill of 100% of the bacterial population. To compare the efficacies of the different protocols the Student t test was used, previously subjecting data to the Anscombe transformation. RESULTS: All ALX concentrations tested and 0.2% CTR achieved a kill percentage higher than 99%, followed by 2% CHX with percentages above 96% (no statistically significant difference among them). Whereas 2% ALX and 0.2% CTR respectively showed eradication in 10 and 9 of the twelve specimens, 0.2% CHX did not produce eradication in any case. CONCLUSIONS: The present study shows that, when used for one minute, 2% and 1% alexidine, and 0.2% cetrimide, achieve eradication of Streptococcus mutans biofilm in most specimens when applied to a dentin-volumetric model.
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Antibacterianos/farmacología , Biguanidas/farmacología , Biopelículas/efectos de los fármacos , Compuestos de Cetrimonio/farmacología , Clorhexidina/farmacología , Streptococcus mutans/efectos de los fármacos , Streptococcus mutans/fisiología , Cetrimonio , Dentina/microbiología , Relación Dosis-Respuesta a Droga , Humanos , Viabilidad Microbiana/efectos de los fármacos , Factores de TiempoRESUMEN
Here we report the efficacy, safety and health-related quality-of-life (HRQoL) associated with long-term lenalidomide and dexamethasone (Len + Dex) treatment in patients with relapsed or refractory multiple myeloma (RRMM) enrolled in the Spanish cohort of the MM-018 study. In this open-label, multicenter, single-arm expanded access study, 63 patients received Len + Dex until disease progression. The overall response rate was 78%, with 21% of the patients achieving a complete response. The quality of response improved with continuous treatment. The median duration of response was 18.4 months. Median time-to-progression and progression-free survival was 13.3 months for both; median overall survival was not reached. Len + Dex had a manageable safety profile consistent with previously reported phase III studies. HRQoL assessments (n = 42) at baseline and 6 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ MY-20 questionnaires revealed that patients with RRMM treated with long-term lenalidomide reported clinically relevant improvements in certain QoL and symptoms scores regardless of treatment response (ClinicalTrials.gov: NCT00420849).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Neutropenia/inducido químicamente , Recurrencia , España , Encuestas y Cuestionarios , Talidomida/administración & dosificación , Talidomida/efectos adversos , Talidomida/análogos & derivados , Trombocitopenia/inducido químicamente , Factores de Tiempo , Resultado del TratamientoRESUMEN
Lenalidomide is an oral immunomodulatory drug that has helped improve outcomes in multiple myeloma (MM) patients. Combination lenalidomide and dexamethasone (Len+Dex) has been shown to increase response rates and prolong survival compared with dexamethasone alone in patients with relapsed or refractory MM (RRMM). Clinical benefit may be greatest when Len+Dex is given at first relapse, and continued treatment appears to provide greater depth of response and improved survival outcomes. The most common adverse events associated with Len+Dex are cytopenias, which are predictable and manageable. Len+Dex is associated with an increased risk of venous thromboembolism, which necessitates adequate prophylaxis. The risk of second primary malignancies does not appear to be increased in patients with RRMM treated with lenalidomide-based therapy. Here we review the safety and efficacy of Len+Dex in RRMM, and provide an overview of data from Spain on the use of Len+Dex in RRMM.
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Plasmacytoma is a frequent complication of multiple myeloma, either at diagnosis or within disease progression. The extramedullary disease confers a poorer prognosis and is biologically distinct with high-risk molecular and histological features, being resistant to conventional treatments. Radiation therapy remains the most effective treatment for extramedullary lesions to achieve local control. There are very limited data from randomized trials regarding the most appropriate systemic treatment. Case reports such as those presented here, as well as retrospective analysis of series, suggest that lenalidomide is an effective agent, in combination with dexamethasone, in this setting. Additional studies are needed to define the proper management of this condition.
Asunto(s)
Antineoplásicos/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Plasmacitoma/tratamiento farmacológico , Anciano , Terapia Combinada , Femenino , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Mieloma Múltiple/radioterapia , Plasmacitoma/patología , Plasmacitoma/radioterapiaRESUMEN
We evaluated the clinical results of lenalidomide (Len) as a compassionate salvage therapy in refractory/relapsed multiple myeloma (MM) patients. A nationwide multi-centre, retrospective research study was performed to evaluate clinical data from patients with advanced MM for which compassionate use of lenalidomide was requested. The primary endpoints were the overall response rate (ORR) and the time to progression (TTP). Secondary objectives included safety and overall survival (OS) since starting of lenalidomide therapy. Data collected from the Spanish Compassionate Use Registry included 111 patients treated in 2006-2008. The median (range) number of previous treatment lines was 3 (1-8). The median duration of lenalidomide treatment while on study was of 4.9 months (1-18). Dexamethasone was given concomitantly with Len in 89% of patients. The ORR was 66% (4% of patients had stringent complete, 11% complete and 11% very good partial responses). Median TTP and OS were 13.0 and 17.4 months, respectively. The depth of response was significantly associated with a longer OS. Toxicity, mainly myelosuppression, was predictable and manageable with Len dose adjustments and cytokine support. Lenalidomide as salvage compassionate therapy in refractory/relapsed MM showed, in this series of heavily pre-treated patients, similar efficacy to that reported in pivotal clinical trials with acceptable tolerance.