[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.

Dolor lumbar somático tratado con terapia neural y ozono paravertebral / Somatic low back pain treated with neural therapy and paravertebral ozone

La presente investigación tuvo como objetivo general evaluar el efecto de la terapia neural e infiltración paravertebral segmentaria con ozono en el dolor lumbar somático de los pacientes que asistieron a la consulta de terapia del dolor en el Hospital Dr. Pedro García Clara, Ciudad Ojeda Estado Zulia-Venezuela, en el periodo comprendido del 01 de abril al 31 de mayo del 2016. Fue un estudio prospectivo, explicativo-comparativo y el diseño fue cuasi-experimental. Se seleccionaron 60 pacientes de ambos sexos entre edades comprendidas de 18 a 60 años, se dividieron en dos grupos de 30 pacientes, al primer grupo denominado A, se le realizó terapia neural segmentaria lumbar utilizando procaína al 1% y consecutivamente se le aplicó infiltración paravertebral con ozono a una concentración de 15ug; y al grupo B, se le realizó terapia neural con lidocaína al 1% y posteriormente se le aplicó la infiltración paravertebral con ozono a una concentración de 15ug, ambos grupos con un volumen de 10mL. Para el análisis de los datos se utilizó estadística descriptiva e inferencial, específicamente la prueba t de Student para las muestras relacionadas. Resultados: indicaron que en ambas terapias, al evaluar el dolor con la escala visual análoga, se encontraron diferencias estadísticamente significativas (p<0,05), en ambos grupos. Conclusiones: no hubo diferencias estadísticamente significativas con respecto a los cambios hemodinámicos y la disminución del dolor fue significativa en ambos grupos, pero más notable en el grupo A(AU)

The present study was aimed at evaluating the overall effect of neural therapy and segmental paravertebral ozone infiltration in lumbar somatic pain patients attending the consultation of pain therapy Dr. Pedro Garcia Clara Hospital of Ciudad Ojeda Estado Zulia-Venezuela, in the period from 01 April to 31 May 2016. It was a comparative-explanatory, prospective study design was quasi-experimental, 60 patients of either sex between aged from 18 to 60 years were selected, they were divided into two groups of 30 patients, the first group called A, underwent neural therapy lumbar segmental using procaine 1% and consecutively was applied paravertebral infiltration with ozone at a concentration of 15ug; and group B, underwent neural therapy with lidocaine 1% and was subsequently applied the paravertebral infiltration with ozone at a concentration of 15ug, both groups with a volume of 10mL. For data analysis the mean, standard deviation, and inferential statistics, specifically the Student t test for related samples was used. Results: indicated that both therapies, to assess pain with visual analogue scale, statistically significant differences (p<0.05) in both groups. Conclusions: There were no statistically significant differences with respect to hemodynamic changes and pain reduction was significant in both groups, but more remarkable in group A(AU)

Spanish consensus on the use of natalizumab (Tysabri®)-2013.

INTRODUCTION: Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in patients with relapsing-remitting multiple sclerosis, by reducing relapses, slowing disease progression, and improving magnetic resonance imaging patterns. However, the drug has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The first consensus statement on natalizumab use, published in 2011, has been updated to include new data on diagnostic procedures, monitoring for patients undergoing treatment, PML management, and other topics of interest including the management of patients discontinuing natalizumab. MATERIAL AND METHODS: This updated version followed the method used in the first consensus. A group of Spanish experts in multiple sclerosis (the authors of the present document) reviewed all currently available literature on natalizumab and identified the relevant topics would need updating based on their clinical experience. The initial draft passed through review cycles until the final version was completed. RESULTS AND CONCLUSIONS: Studies in clinical practice have demonstrated that changing to natalizumab is more effective than switching between immunomodulators. They favour early treatment with natalizumab rather than using natalizumab in a later stage as a rescue therapy. Although the drug is very effective, its potential adverse effects need to be considered, with particular attention to the patient's likelihood of developing PML. The neurologist should carefully explain the risks and benefits of the treatment, comparing them to the risks of multiple sclerosis in terms the patient can understand. Before treatment is started, laboratory tests and magnetic resonance images should be available to permit proper follow-up. The risk of PML should be stratified as high, medium, or low according to presence or absence of anti-JC virus antibodies, history of immunosuppressive therapy, and treatment duration. Although the presence of anti-JC virus antibodies is a significant finding, it should not be considered an absolute contraindication for natalizumab. This update provides general recommendations, but neurologists must use their clinical expertise to provide personalised follow-up for each patient.

Effect of glatiramer acetate (Copaxone) on the immunophenotypic and cytokine profile and BDNF production in multiple sclerosis: a longitudinal study.

We assessed the effect of glatiramer acetate (GA) on the immunophenotypic and cytokine profile and the BDNF production by peripheral blood mononuclear cells, and their association with the clinical response in 19 naïve-treated MS patients prospectively followed-up after GA therapy. Two patients withdrew the therapy. After a median follow-up of 21 months, twelve were considered responders and five as non-responders. Non-responder patients had significant longer disease duration and a higher EDSS score at baseline. In the responder group, a significant decrease in the percentage of INF-gamma producing total lymphocytes, CD4+ and CD8+ T cells, and reduced percentage of IL-2 producing CD4+ and CD8+ T cells were observed at 12, 18 and 24 months. These changes were associated with a significant increase in the percentage of CD3+, CD4+ and CD4(+) CD45RA(+) T cells, and BDNF production from month 6 that remained significant throughout the study. We did not observe significant changes in the nonresponder group for any of the parameters studied. Our data suggest that GA treatment induces a downmodulation of proinflammatory cytokines associated with the regulation of the peripheral T cell compartment and with increased production of BDNF that might be related to the clinical response.

Interaction between smoking and the Sstl polymorphism of the apo C-III gene determines plasma lipid response to diet.

BACKGROUND: It has recently been demonstrated that the lipid profile of smokers improves if they follow a Mediterranean diet. AIM: To establish whether the Sstl polymorphism of the apo C-III gene interacts with smoking and determines the lipid response to diet in healthy subjects. METHODS AND RESULTS: Fifty-nine volunteers (18 smokers: 8 with the S1S1 genotype, and 10 with the S2 allele; 41 non-smokers: 29 with the S1S1 genotype and 12 with the S1S2 genotype) consecutively followed three different diets: a diet enriched in saturated fatty acids (SFA) (38% fat, 20% SFA) followed by a randomised, cross-over period during which they ate a diet enriched in carbohydrates (NCEP-1) (30% fat, 10% SFA, 55% carbohydrates) and a diet enriched in monounsaturated fatty acids (MUFA) (8% fat, 22% MUFA). Cholesterol, triacylglycerol, LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) levels were measured at the end of each dietary period. The smokers carrying the S1S1 genotype were not influenced by any of the diets, but the atherogenic ratio decreased in the carriers of the S2 allele when they changed from the diet rich in SFA to a diet rich in olive oil or carbohydrates (p < 0.039). No significant difference was observed when the non-smoking carriers of the S2 allele changed from one diet to another, but there was a decrease in the LDL-C/HDL-C ratio when the subjects with the S1S1 genotype changed from the saturated diet to either of the other diets (p < 0.001). CONCLUSIONS: Smoking interacts with the apo CM polymorphism and determines the level of lipid response to dietary changes.

Plasma methadone concentrations as an indicator of opioid withdrawal symptoms and heroin use in a methadone maintenance program.

Plasma methadone concentrations and its main metabolite D,L-2-ethylidiene-1,5-dimethyl-3,5-diphenylpyrrolidine (EDDP) were determined in 93 patients under methadone maintenance treatment to assess their relationship with heroin use and opioid withdrawal symptoms. Neither plasma concentrations of methadone nor EDDP were significantly different when patients that used heroin in last 3 months were compared with those testing negative for this drug (methadone, 355 +/- 217 versus 369 +/- 216 ng/ml, t = 0.29, P = NS; EDDP, 49 +/- 28 versus 54 +/- 40 ng/ml, t = 0.51, P = NS). No correlation between opioid withdrawal scale scores and plasma concentrations of methadone (r = 0.02, P = NS) and EDDP (r = -0.14, P = NS) was found. Therapeutic drug monitoring during methadone maintenance seems to be useful for assessing compliance with treatment but not for predicting heroin use and subjective withdrawal symptoms.

[Liposome amphotericin in the treatment of deep mycoses in patients not severely immunosuppressed. An efficient alternative with low toxicity]. / Anfotericina liposómica en el tratamiento de micosis profundas en pacientes no gravemente inmunodeprimidos. Una alternativa eficaz y poco tóxica.

Amphotericin is a powerful antifungal agent of high toxicity. Encapsulation in liposomes has led to new perspectives although clinical experience is still slight. Four patients, who were neither carriers of antibodies against the human immunodeficiency virus nor neutropenic, diagnosed of meningeal cryptococcosis, pleural aspergillosis, cerebral aspergillosis and ophthalmic candidiasis, respectively and treated with liposomal amphotericin are reported. The treatment was effective and well tolerated. Clinical improvement was observed in the patient with cerebral aspergillosis but magnetic resonance demonstrated persistence of the lesions. Only slight deterioration in renal function was observed in one case and in the other two renal failure improved upon substitution of conventional amphotericin by liposomal amphotericin. The slight systemic toxicity and the absence of local intolerance allowed the administration of high doses and shortening of the therapeutic schedule.

Immature endodermal teratoma of the ovary: embryologic correlations and immunohistochemistry.

Two grade 2 ovarian immature, predominantly endodermal teratomas are reported. The teratomas were in stage I and occurred in two girls, 9 and 10 years of age, who were treated with triple chemotherapy. These neoplasms differed from the usual immature ovarian teratoma as they contained no neuroectodermal components and had high alpha-fetoprotein and low human chorionic gonadotropin levels as their serum markers despite the absence of other concomitant germ cell tumors. The epithelia of the teratomas demonstrated exclusively the embryologic development of endoderm, ranging from early endoderm to tissues similar to esophagus, liver, and intestinal structures. All epithelial derivatives were positive for alpha-fetoprotein and alpha 1-antitrypsin. Liver and esophagus expressed fibrinogen, while intestine and esophagus were positive not only for carcinoembryonic antigen and chromogranins but also for thyroglobulin, thus reflecting yet another type of endodermal differentiation into thyroid. Focal human chorionic gonadotropin positivity associated with primitive intestinal and esophageal epithelia may reflect the early embryologic relationships between endoderm and trophoblast. These cases demonstrate that simultaneous alpha-fetoprotein and human chorionic gonadotropin secretion may occur in immature teratoma. The mesenchymal component also showed a wide range of differentiation, from primitive mesoblastic cells to differentiated cells, such as hemopoietic foci, smooth muscle, bone, and cartilage. Both the primitive endoderm and the mesenchyme co-expressed vimentin and keratin, reflecting their intimate developmental relationships and possibly supporting the hypothesis of mesenchyme originating from endoderm, as suggested by previous embryologic studies. Since endodermal and mesenchymal areas similar to those described here are found in association with yolk sac tumors and embryonal carcinoma, it is possible that the present cases may represent an endodermal differentiation accomplished by either of these developmentally related germ cell tumors.