Biological relapse in multiple myeloma: Outcome and treatment strategies in a Spanish real-world setting.

Recommendations regarding the best time to start treatment in patients with relapsed/refractory multiple myeloma (RRMM) after biological relapse/progression (BR) are unclear. This observational, prospective, multicenter registry aimed to evaluate the impact on time to progression (TTP) of treatment initiation at BR versus at symptomatic clinical relapse (ClinR) based on the Spanish routine practice in adult patients with RRMM. Patients had two or less previous treatment lines and at least one previous partial response. Baseline characteristics and treatment outcomes were recorded, and survival was analyzed. Of 225 patients, 110 were treated at BR (TxBR group) and 115 at ClinR (TxClinR group) according to the investigators' criteria. The proportion of patients with higher ECOG, previous noncomplete remission (CR), and second relapse were significantly higher in the TxBR group compared to the TxClinR group. TheTxClinR group showed improved outcomes, including TTP, compared to the TxBR group. Progression-free survival increased in the TxClinR group (56.2 months) compared to the TxBR group (32.5 months) (p = 0.0137), and median overall survival also increased (p = 0.0897). Median TTP was significantly longer in patients relapsing from a CR (50.4 months) and in their first relapse (38.7 months) compared to those relapsing from a non-CR response (32.9 months) and in their second relapse (25.2 months). Physicians seemed to start treatment earlier in RRMM patients with poor prognosis features. Previous responses to anti-MM treatment and the number of prior treatment lines were identified as prognosis factors, whereby relapse from CR and first relapse were associated with a longer time to progression.

Outlining cardiac ion channel protein interactors and their signature in the human electrocardiogram.

Protein-protein interactions are essential for normal cellular processes and signaling events. Defining these interaction networks is therefore crucial for understanding complex cellular functions and interpretation of disease-associated gene variants. We need to build a comprehensive picture of the interactions, their affinities and interdependencies in the specific organ to decipher hitherto poorly understood signaling mechanisms through ion channels. Here we report the experimental identification of the ensemble of protein interactors for 13 types of ion channels in murine cardiac tissue. Of these, we validated the functional importance of ten interactors on cardiac electrophysiology through genetic knockouts in zebrafish, gene silencing in mice, super-resolution microscopy and patch clamp experiments. Furthermore, we establish a computational framework to reconstruct human cardiomyocyte ion channel networks from deep proteome mapping of human heart tissue and human heart single-cell gene expression data. Finally, we integrate the ion channel interactome with human population genetics data to identify proteins that influence the electrocardiogram (ECG). We demonstrate that the combined channel network is enriched for proteins influencing the ECG, with 44% of the network proteins significantly associated with an ECG phenotype. Altogether, we define interactomes of 13 major cardiac ion channels, contextualize their relevance to human electrophysiology and validate functional roles of ten interactors, including two regulators of the sodium current (epsin-2 and gelsolin). Overall, our data provide a roadmap for our understanding of the molecular machinery that regulates cardiac electrophysiology.

New Cable Delay Measurement System for VGOS Stations.

This paper presents the new cable delay measurement system (CDMS) designed at Yebes Observatory (IGN, Spain), which is required for the VLBI Global Observing System (VGOS) stations. This system measures the phase difference between the 5 MHz reference signal from the hydrogen maser and the 5 MHz signal that reaches the broadband receiver through a coaxial cable, for the generation of calibration tones. As a result, the system detects the changes in the length of that coaxial cable due to temperature variations along the cable run and flexures caused by VGOS radio telescope movements. This CDMS outperforms the previous versions: firstly, it does not require a frequency counter for phase/delay measurements; secondly, it largely reduces the use of digital circuits; hence, reducing digital noise; and thirdly, it has a remotely controlled automatic calibration subsystem. The system was tested in the laboratory and in the radio telescope, and the measurements of both set-ups are shown. These measurements include the total noise, accuracy, hysteresis, and stability. The results in the radio telescope can be correlated with the different factors that affect the cable, such as temperature and flexures. The system allows to achieve an RMS noise of less than 0.5 ps, significantly improving the requirements established in VGOS. The system is currently installed in the Red Atlántica de Estaciones Geodinámicas y Espaciales (RAEGE)Yebes VGOS 13.2 m radio telescope, and will be installed in the Norwegian Mapping Authority (NMA) twin VGOS radio telescopes, in the Finnish Geospatial Research Institute (FGI) VGOS station and in the RAEGE Santa María VGOS radio telescope (Açores, Portugal).

Terminal Crossbreeding of Murciano-Granadina Goats to Boer Bucks: Effects on Reproductive Performance of Goats and Growth of Kids in Artificial Rearing.

The aim of this work was to improve the growth characteristics of Murciano-Granadina (MG) kids through terminal crossbreeding of MG goats to Boer bucks. Four experiments were carried out, using a total of 354 MG goats, half of which were mated with MG bucks (n = 12) and the other half with Boer bucks (n = 12). The kids were raised in artificial rearing until slaughter weight (9 kg). The birth weight and average daily gain were recorded in crossed kids (n = 197 and 145, respectively) and purebred kids (n = 257 and 169, respectively). Crossed kids presented significant differences (p < 0.001) compared to MG purebred kids in birth weight (+ 24%), mortality in artificial rearing (-37%), average daily gain (+32%) and milk powder conversion rate (-16%). However, the reproductive performance rates of MG goats mated with Boer bucks were slightly worse (pregnancy rate: 78.5% vs. 86.6%, p < 0.05; kidding rate: 62.0% vs. 75.7%; p < 0.01; prolificacy: 1.9 vs. 2.1 kids/parturition), especially when the matings took place in non-breeding season (experiments conducted at latitude 38-39° N). It is concluded that the terminal crossbreeding of MG goats to Boer bucks (those not used to produce replacement kids) could be an interesting option for ethical goat production.

La cirugía en el tratamiento de la crisis tirotóxica / Surgery for the Treatment of Thyrotoxic Crisis

RESUMEN La crisis tirotóxica es una complicación de la tirotoxicosis mal tratada y se asocia con una elevada mortalidad. Requiere tratamiento médico urgente en unidades de cuidados intensivos. Mujer de 42 años, con antecedentes personales de hipertensión arterial y nódulo tiroideo hiperfuncionante desde hace 18 años, con abandono del tratamiento médico hace dos años, que acude a urgencias con disnea paroxística nocturna, taquicardia, hipertensión arterial, gran bocio y anasarca. Ingresa en la unidad de cuidados intensivos con diagnóstico de crisis tirotóxica e inicia el tratamiento médico con medidas de soporte precisas, la que incluye intubación orotraqueal. Debido a la dificultad de manejo clínico y respiratorio de la paciente, se decide realizar tratamiento quirúrgico urgente. Se practica una tiroidectomía total de bocio multinodular parcialmente intratorácico y una traqueostomía preventiva. El resultado de anatomía patológica fue: bocio multinodular tóxico. La paciente fue dada de alta con función tiroidea normal, cierre de traqueostomía y buena fonación, tras mes y medio de hospitalización. A pesar de que un tratamiento médico conservador es el adecuado de la tirotoxicosis, los síntomas y signos sistémicos de la crisis tirotóxica y sus manifestaciones órgano-específicas, asociados a una persistente dificultad respiratoria por síntomas compresivos derivados del gran bocio, se consideró que la tiroidectomía urgente en este caso estaba indicada, dato que se corroboró ante la buena evolución posoperatoria. El tratamiento de la tirotoxicosis es fundamentalmente clínico, sin embargo, la cirugía puede ser útil ante la dificultad en el manejo clínico(AU)

Abstract The thyrotoxic crisis is a complication of poorly treated thyrotoxicosis and is associated with high mortality. This condition requires urgent medical treatment in intensive care units. A 42-year-old woman, with a personal history of high blood pressure, hyperfunctioning thyroid nodule for 18 years, and abandonment of medical treatment since two years ago, presented to the emergency department with paroxysmal nocturnal dyspnea, tachycardia, high blood pressure, large goiter, and anasarca. She was admitted into the intensive care unit with a diagnosis of thyrotoxic crisis and started to receive medical treatment under precise support measures, including orotracheal intubation. Due to the patient's difficult clinical and respiratory management, it was decided to perform urgent surgical treatment. She was performed a total thyroidectomy of partial intrathoracic multinodular goiter and a preventive tracheostomy. The result of pathological anatomy was toxic multinodular goiter. The patient was discharged with normal thyroid function, tracheostomy closure, and good phonation, after a month and a half of hospitalization. Despite the fact that conservative medical treatment is the adequate one for thyrotoxicosis, the systemic symptoms and signs of the thyrotoxic crisis, and its organ-specific manifestations, associated with persistent respiratory distress due to compression symptoms derived from large goiter, urgent thyroidectomy needed to be indicated in this case, a fact corroborated after good postoperative evolution. The treatment of thyrotoxicosis is fundamentally clinical; however, surgery can be useful given the difficulty in clinical management(AU)

Ending open defecation in Guinea-Bissau: It all starts under a mango tree

Using toilets and washing hands with soap is essential to keep children and families in good health. But in Guinea-Bissau, open defecation remains a deeply rooted practice. Going out in open spaces rather than using a toilet is a dangerous challenge: human waste near waterways and homes spreads diseases quickly, putting children and their families at risk. Diarrhoea, which is related to poor sanitation and hygiene, is one of the top killers of children in the country ─ accounting for 9 per cent of children who die before their fifth birthday. However, getting rid of open defecation is possible. Take Quinara, a region in the south of Guinea-Bissau. In 2018, Quinara was recognized as the first region to become 'open defecation free' (ODF) in Guinea-Bissau. This is a remarkable achievement in a country where nearly one in six people still go out in the open. So, how did Quinara do it? Ask families in a community to identify areas around the home they use as toilets. Use a combination of shock, shame, pride and disgust ─ instead of abstract health messages ─ to trigger behaviour change. And watch the community transform. This approach is called Community-Led Total Sanitation (CLTS). It typically takes three to six months for a whole community to give up defecating in the open. And this contributes to a healthier environment for everyone.

Cannabis use in patients with fibromyalgia: effect on symptoms relief and health-related quality of life.

BACKGROUND: The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users. METHODS: Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36). RESULTS: Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI. CONCLUSIONS: The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted.

Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting.

AIMS: Despite progress in anti-emetic treatment, many patients still suffer from chemotherapy-induced nausea and vomiting (CINV). This is a pilot, randomized, double-blind, placebo-controlled phase II clinical trial designed to evaluate the tolerability, preliminary efficacy, and pharmacokinetics of an acute dose titration of a whole-plant cannabis-based medicine (CBM) containing delta-9-tetrahydrocannabinol and cannabidiol, taken in conjunction with standard therapies in the control of CINV. METHODS: Patients suffering from CINV despite prophylaxis with standard anti-emetic treatment were randomized to CBM or placebo, during the 120 h post-chemotherapy period, added to standard anti-emetic treatment. Tolerability was measured as the number of withdrawals from the study during the titration period because of adverse events (AEs). The endpoint for the preliminary efficacy analysis was the proportion of patients showing complete or partial response. RESULTS: Seven patients were randomized to CBM and nine to placebo. Only one patient in the CBM arm was withdrawn due to AEs. A higher proportion of patients in the CBM group experienced a complete response during the overall observation period [5/7 (71.4%) with CMB vs. 2/9 (22.2%) with placebo, the difference being 49.2% (95% CI 1%, 75%)], due to the delayed period. The incidence of AEs was higher in the CBM group (86% vs. 67%). No serious AEs were reported. The mean daily dose was 4.8 sprays in both groups. CONCLUSION: Compared with placebo, CBM added to standard antiemetic therapy was well tolerated and provided better protection against delayed CINV. These results should be confirmed in a phase III clinical trial.

Cannabinoides y emesis: nuevas evidencias, nuevas preguntas / Cannabinoids and emesis: new evidences, new questions

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Scientific drug information in newspapers: sensationalism and low quality. The example of therapeutic use of cannabinoids.

OBJECTIVE: We aimed to analyse the quality of newspaper articles (NAs) concerning the therapeutic use of cannabis published in Spanish newspapers. METHODS: A preliminary questionnaire of the Index of Scientific Quality was used [scores ranged from 0 (no misleading) to 14 (misinformation in each item)]. RESULTS: Of the 29 NAs analysed, 16 (55.2%) were scored as 4 or lower, and 6 (20.7%) scored 7 or higher. Up to 23 NAs (79.3%) did not manage the knowledge related to cannabinoids; 20 (69%) gave a sensationalist message; 11 (37.9%) were able to wrongly influence clinical decision taking; and 8 (27.6%) misled medical concepts. CONCLUSION: The leading medical journals could play an especially relevant role while preparing their press releases if they specify study limitations and context.

Uso terapéutico del cannabis: resultados de una entrevista prospectiva en Cataluña / Therapeutic use of cannabis: results of a prospective survey in Catalonia (Spain)

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[News about therapeutic use of Cannabis and endocannabinoid system]. / Novedades sobre las potencialidades terapéuticas del Cannabis y el sistema cannabinoide.

Growing basic research in recent years led to the discovery of the endocannabinoid system with a central role in neurobiology. New evidence suggests a therapeutic potential of cannabinoids in cancer chemotherapy-induced nausea and vomiting as well as in pain, spasticity and other symptoms in multiple sclerosis and movement disorders. Results of large randomized clinical trials of oral and sublingual Cannabis extracts will be known soon and there will be definitive answers to whether Cannabis has any therapeutic potential. Although the immediate future may lie in plant-based medicines, new targets for cannabinoid therapy focuses on the development of endocannabinoid degradation inhibitors which may offer site selectivity not afforded by cannabinoid receptor agonists.

Síndrome de hipersensibilidad por antiepilépticos / Syndrome of hypersensitivity by antiepileptic drugs

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Sospecha clinica de la broncoaspiración del lactante su relación con el asma infantil / Clinical susception of bronchoaspiration of infant its relation with child asthma

La microaspiración reiterada de alimento (leche) es el mecanismo más probable de obstrucción bronquial recidivante (O.B.R.) vinculada al reflujo gastroesofágico (R.G.E.) del lactante. Esta sospecha clínica de broncoaspiración del lactante es difícil de poner en evidencia con los métodos tradicionales usados para el diagnóstico de la aspiración por reflujo. (Radiografía contrastada esofagogástrica y/o Centellografía gastroisotópica). Desde 1984 venimos aplicando en nuestro medio una técnica citológica fácil y económica que permite el diagnóstico de la Microaspiración Alimentaria (M.A.A.) por medio del hallazgo de vacuolas grasas (fracción no absorvible en el pulmón de glóbulo graso de la leche) en macrófagos alveolados (L.M.M.). Ser realizó el presente trabajo para verificar la asociación de reflujo y microaspiración en lactantes con O.B.R. Tambiém se observó el comportamiento de las inmunoglobulinas circulantes y de sereción. El estudio se realizó en 30 lactantes menores de 1 añi de edad diagnosticados como M.A.A. +, que concurrieron a nuestro centro divididos en 2 grupos según antecedentes alérgicos familiares (A.A.F.). Se constató en ambos casos una alta incidencia de asociación entre O.B.R. y/o N.aR. y R.G.E. así como se observaron alteraciones en las respuestas inmune humoral basadas estas fundamentalmente en el hallazgo de valores elevados de IgG e IgAs en ambos grupos así como valores muy por encima de 2DS de IgE en la masa poblacional estudiadas sin antecedentes elérgicos