Quality of life following transobturator sling surgery for female stress urinary incontinence.

OBJECTIVE: This descriptive study examines quality of life in women undergoing placement of a midurethral sling for stress urinary incontinence. MATERIALS AND METHODS: This was a retrospective cohort study based on data from 51 women consecutively undergoing this procedure at a tertiary hospital in the years 2014 and 2015. The main outcome variable was quality of life assessed through the Sandvick severity test and International Consultation on Incontinence Short Quality of Life Questionnaire (ICIQ-IU-SF) at the time points baseline or presurgery, and 6 months and 5 years postsurgery. Factors associated with treatment failure were determined through binary logistic regression. RESULTS: At 5-year follow up we obtained an absolute reduction of 8.78 points (95% CI 6.43-11.14; p < 0.001) in the ICIQ-IU-SF questionnaire and 4.54 (95% CI 3.25-5.83; p < 0.001) in the Sandvick severity test score, compared to baseline, in the 35 patients that completed follow-up. Out of the 51 patients that were followed, the rate of success in incontinence correction was 86.3% (44/50) with a failure rate of 12% (6/50). Multiparity and previous gynaecological surgery were identified as predisposing factors for treatment failure. Obesity was associated with a worse treatment outcome. CONCLUSION: Sling treatment for incontinence was successful in 86.3% (44/50) of participants and remained effective 5 years after surgery in terms of quality of life.

[Resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogenic addictions: BRAF and ALK]. / Résistance aux anti-EGFR via l'acquisition successive et cumulée de deux nouvelles addictions oncogénique BRAF et ALK.

Targeted therapies are the standard first-line treatment for metastatic lung adenocarcinoma with certain molecular abnormalities. These abnormalities are particularly common in Southeast Asia and French Polynesia. A 51-year-old Tahitian female non-smoker was diagnosed in 2018 with stage IV lung adenocarcinoma harboring a p.L858R EGFR mutation. She received gefitinib as first-line treatment. Due to locoregional progression and the presence of a resistance mutation (p.T790M of EFGR), she received osimertinib as second-line treatment, after which chemotherapy was proposed as 3rd-line treatment. An additional biopsy detected not only the previously known EGFR mutation, but also a BRAF p.V600E mutation. Following disease progression during chemotherapy, the patient received targeted therapies combining dabrafenib, trametinib and osimertinib. Due to a dissociated response after four months of treatment, a 5th line of paclitaxel bevacizumab was initiated. Subsequent to additional progression and given the ALK rearrangement shown on the re-biopsy, 6th-line treatment with alectinib was proposed. As the response was once again dissociated, a final line was proposed before stopping active treatments due to their toxicity and overall deterioration in the patient's state of health. This exceptional case is characterized by resistance to anti-EGFR through the successive and cumulative acquisition of two new oncogene addictions. The authors underline the importance of re-biopsy at each progression, leading (if at all feasible) to yet around round of targeted therapy.

Open vs. robot-assisted preperitoneal inguinal hernia repair. Are they truly clinically different?

INTRODUCTION: Inguinal hernia repair lacks a standard repair technique, with laparo-endoscopic and open preperitoneal methods showing similar outcomes. Despite higher costs, the popularity of robotic surgery is on the rise, driven by technological advantages. Controversies persist in comparing open repair techniques with the robotic approach, given contradictory results. The objective of this study was to compare postoperative outcomes, including complications, chronic pain, and recurrence, between open and robotic-assisted preperitoneal inguinal hernia repair. METHODS: This single-center retrospective study encompassed patients undergoing elective inguinal hernia repair in a specialized unit, employing both open preperitoneal and robotic-assisted laparoscopic approaches from September 2018 to May 2023. Comparative analysis of short- and long-term outcomes between these techniques was conducted. Additionally, multivariate logistic regression was employed to explore predictors of postoperative complications. RESULTS: A total of 308 patients met the inclusion criteria. 198 (64%) patients underwent surgery using an open preperitoneal approach and 110 (36%) using robot-assisted laparoscopy. Patients in the robot-assisted group were younger (P = 0.006) and had fewer comorbidities (P < 0.001). There were no differences between the groups in terms of postoperative complications (P = 0.133), chronic pain (P = 0.463) or recurrence (P = 0.192). Multivariate analysis identified ASA ≥ III (OR, 1.763; 95%CI, 1.068-3.994; P = 0.027) and inguinoscrotal hernias (OR, 2.371, 95%CI, 1.407-3.944; P = 0.001) as risk factors of postoperative complications. CONCLUSIONS: Both open preperitoneal and robotic-assisted laparoscopic approaches show similar outcomes for complications, chronic pain, and recurrence when performed by experienced surgeons. The open preperitoneal approach, with its quicker operative time, may be advantageous for high-comorbidity cases. Treatment choice should consider patient factors, surgeon experience, and healthcare resources.

Lateral incisional hernia. EVEREG registry analysis.

BACKGROUND: The aim of this study is to analyze the data collected on lateral incisional hernias (LIH) in the National Incisional Hernia Registry (EVEREG) and assess current practices and outcomes in LIH repair. METHODS: A retrospective cohort study was conducted using LIH data recorded over 10 years (2012-2022). Comorbidities, hernia characteristics, short-term complications, and recurrences were studied, along with their association with the type of approach used, either open or laparoscopic, in elective surgery. RESULTS: 1742 LIH cases were studied. According to the EHS classification, these included L1 409 (23.5%), L2 388 (22.3%), L3 565 (32.4%), L4 150 (8.6%) and combined 230 (13.2%). An open approach was performed in 1528 (87.7%) cases and laparoscopic in 214 (12.3%). The median age was 66 ± 12.45 years, with a majority of males, 934 (53.6%). The median body mass index was 29 ± 5.18 kg/m2. The most observed comorbidity was arterial hypertension (957 patients, 55%). A specialist was present in 638 interventions (56%). The 24-month follow-up was 17.9%, and recurrence in those cases was 27.2%, with a higher incidence when there was no specialist present during the intervention, onlay mesh position, and larger defect size. CONCLUSIONS: Surgery for LIH is common, although laparoscopic approach remains infrequent. Furthermore, it is associated with a high percentage of recurrences that increases when there is no specialist in abdominal wall surgery present.

TET enzymes and 5hmC epigenetic mark: new key players in carcinogenesis and progression in gynecological cancers.

DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine (5mC). In general, DNA methylation in cancer is associated with the repression of the expression of tumor suppressor genes (TSG) and the demethylation with the overexpression of oncogenes. DNA methylation was considered a stable modification for a long time, but in 2009, it was reported that DNA methylation is a dynamic modification. The Ten-Eleven-Translocations (TET) enzymes include TET1, TET2, and TET3 and participate in DNA demethylation through the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC). The 5hmC oxidates to 5-formylcytosine (5fC) and 5-carboxylcitosine (5caC), which are replaced by unmodified cytosines via Thymine-DNA Glycosylase (TDG). Several studies have shown that the expression of TET proteins and 5hmC levels are deregulated in gynecological cancers, such as cervical (CC), endometrial (EC), and ovarian (OC) cancers. In addition, the molecular mechanisms involved in this deregulation have been reported, as well as their potential role as biomarkers in these types of cancers. This review shows the state-of-art TET enzymes and the 5hmC epigenetic mark in CC, EC, and OC.

[Translated article] Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study. / Condicionantes de acceso a nuevos medicamentos dermatológicos en España: resultados del proyecto EQUIDAD.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Classification of light Yorkshire pigs at different production stages using ordinary least squares and machine learning methods.

Pig homogeneity and growth are major concerns for the pig industry today. Variability in pigs' size has a strong impact on profitability as uniformity plays a key role in the overall economic value of pigs produced. This research focused on statistical methods to identify pigs at risk of growth retardation at different stages of production. Data from 125 083 Yorkshire pigs at weaning (18-28 d), 59 533 pigs at the end of the nursery period (70-82 d) and 48 862 pigs at slaughter (155-170 d) were analyzed under three different cut-points (lowest 10, 20 and 30%) to characterize light animals. Records were randomly split into 2:1 training:testing sets, and each training data set was analyzed through an ordinary least squares approach and four machine learning algorithms (decision tree, random forest, and two alternative boosting approaches). A wide range of weighting functions were applied to give increased relevance to lighter pigs. Each resulting classification norm was used to classify light pigs in the testing data set. Both sensitivity and specificity were retained to construct the receiver operating characteristic curve, and the statistical performance of each analytical approach was evaluated by the area under the curve (AUC). In all production stages and cut-points, the random forest machine learning algorithm provided the highest AUC, closely followed by boosting procedures. For weaning BW (WW), factors related to birth BW and litter size accounted for more than 75% of the important prediction factors for light pigs. BW at the end of the nursery period and slaughter BW analyses revealed a similar pattern where WW and BW at the end of the nursery period accounted for more than 40 and 50% of statistical importance among the prediction factors, respectively. Machine learning algorithms are useful tools to easily evaluate the risk factors affecting the efficiency and homogeneity in swine. Since the BW at birth and weaning are key factors, sow nutrition and feeding management during gestation and lactation, along with piglet management during lactation, are identified as important influences on pig weight variability.

Esofagitis eosinofílica de tórpida evolución / Eosinophilic esophagitis with torpid evolution

Introducción: La esofagitis eosinofílica es una enfermedad inmunomediada, crónica y progresiva, combinando disfunción esofágica e infiltrado eosinofílico exclusivo del esófago. Tanto su diagnóstico como su respuesta a los tratamientos requieren de evaluación histológica mediante endoscopias repetidas. Caso clínico. Varón de 11 años con disfagia para sólidos de años de evolución con empeoramiento en los últimos meses; angustia ante las ingestas con estancamiento ponderal; vómitos en impactaciones alimentarias; pirosis postprandial. Antecedentes patológicos: broncoespasmos de repetición y sensibilización a Alternaria. Exploración física: signos de hipotrofia pondero-estatural (somatometría: alrededor de –2 desviaciones estándares; Carrascosa 2017). Pruebas complementarias: analítica general sin alteraciones significativas incluyendo inmunoglobulinas E específicas alimentarias; prick test sensibilización a neumoalérgenos; gastroscopia mucosa esofágica edematosa, estrías longitudinales y exudados blanquecinos, mucosa gástrica signos de gastritis, mucosa duodenal normal; histología con un máximo 35 eosinófilos por campos de gran aumento y gastritis crónica leve-moderada con infección por Helicobacter pylori. Tratamiento y evolución: inducción a la remisión con inhibidores bomba de protones a dosis altas con buena respuesta clínica y macroscópica (parcial histológica), reduciendo a dosis de mantenimiento; ante recaída macroscópica (no histológica) se cambia a dieta exenta de leche y gluten sin respuesta; segundo intento de remisión con inhibidores sin éxito; finalmente se pautan corticoides deglutidos con buena respuesta tanto macroscópica como histológica; pendiente control con dosis de mantenimiento, asintomático. Comentarios. Como se aprecia en nuestro caso, esta enfermedad conlleva un difícil manejo ante la afectación parcheada de la mucosa y la discordancia clínico-histológica, lo que complica la interpretación de sus resultados.(AU)

Introduction: Eosinophilic esophagitis is an immunemediated, chronic and progressive disease, combining esophageal dysfunction and eosinophilic infiltrate exclusive to the esophagus. Both its diagnosis and its response to treatments require histological evaluation through repeated endoscopies. Case report. 11-year-old male with dysphagia for solids of years of evolution with worsening in recent months; anxiety before eating with weight stagnation; vomiting in food impactions; postprandial heartburn. Pathological history: repeated bronchospasms and sensitization to Alternaria. Physical examination: signs of weight-height hypotrophy (somatometry: around –2 standard deviations; Carrascosa 2017). Complementary tests: general blood test without significant alterations including food-specific immunoglobulins E; prick test sensitization to pneumoallergens; gastroscopy edematous esophageal mucosa, longitudinal furrows and whitish exudates, gastric mucosa signs of gastritis, normal duodenal mucosa; histology with a maximum of 35 eosinophils per high-power fields and mild-moderate chronic gastritis with Helicobacter pylori infection. Treatment and evolution: induction of remission with high-dose proton pump inhibitors with good clinical and macroscopic response (partial histological), reducing to maintenance doses; In the event of a macroscopic (non-histological) relapse, a diet free of milk and gluten is started without response; second attempt at remission with inhibitors without success; finally, swallowed corticosteroids are prescribed with good macroscopic and histological response; pending control with maintenance dose, asymptomatic. Discussion. Like our case shows, this disease has a difficult management due to patchy involvement of the mucosa and clinical-histological discordance, which complicates the interpretation of its results.(AU)

Efectividad y seguridad de los nuevos anticuerpos monoclonales en la profilaxis de la migraña / Effectiveness and safety of new monoclonal antibodies in migraine prophylaxis

Objetivos: Analizar la efectividad y seguridad en vida real de los nuevos anticuerpos monoclonales subcutáneos para la profilaxis de la migraña. Métodos: Estudio observacional retrospectivo llevado a cabo desde enero de 2020 hasta abril de 2021 con pacientes diagnosticados de migraña crónica o episódica. Las variables de interés se analizaron por el personal facultativo farmacéutico en una base de datos anonimizada. Esta base se completa como práctica clínica habitual durante la entrevista clínica en la consulta de pacientes externos. Resultados: Se analizaron 53 pacientes. Se observó una reducción del número de crisis respecto al valor basal a los 3, a los 6 y a los 12 meses de tratamiento, así como de otros fármacos para el tratamiento de la migraña. La mayoría de reacciones adversas descritas fueron de tipo leve, obligando a la suspensión del tratamiento de solo uno de los pacientes. Se describió un aumento de la tensión arterial en varios pacientes, así como una incidencia de estreñimiento superior a los ensayos pivotales. Conclusiones: Este estudio muestra una disminución del número de crisis de migraña y del uso de otros fármacos antimigrañosos tras el uso de anticuerpos monoclonales. Los tratamientos se pueden considerar seguros, observándose una baja incidencia de reacciones adversas graves. La mayoría de pacientes fueron tratados con erenumab. Se dispone de menos datos a medida que avanza del tiempo de estudio, por lo que resulta necesario recopilar más información para conocer el perfil de efectividad y seguridad de estos fármacos a largo plazo.(AU)

Objectives: To analyse the effectiveness and safety in real life of new subcutaneous monoclonal antibodies for the prophylaxis of migraine. Methods: Retrospective observational study conducted from January 2020 to April 2021 with patients diagnosed with chronic or episodic migraine. The variables of interest were collected by the pharmacist in an anonymised database during the clinical interview in the outpatient clinic. This databased is completed as standard clinical practice during the clinical interview in the outpatient clinic. Results: 53 patients were analysed. A reduction in the number of attacks from baseline was observed at 3, 6 and 12 months of treatment, as well as for other migraine treatment drugs. Most of the adverse reactions described were mild, leading to discontinuation of treatment in only one patient. An increase in blood pressure was reported in several patients, as well as a higher incidence of constipation than in pivotal trials. Conclusions: This study shows a decrease in the number of migraine attacks and in the use of other anti-migraine drugs after the use of monoclonal antibodies. The treatments can be considered safe, with a low incidence of serious adverse reactions. Most patients were treated with erenumab. Less information is available as the study time progresses, so more information needs to be collected to understand the long-term effectiveness and safety profile of these drugs.(AU)

Multiphase diets may improve feed efficiency in fattening crossbreed Holstein bulls: a retrospective simulation of the economic and environmental impact.

Beef industry needs alternative feeding strategies to enhance both economic and environmental sustainability. Among these strategies, adjusting the diet dynamically according to the change of nutritional requirements (multiphase diet) has demonstrated its economic and environmental benefits in pig production systems. Therefore, this retrospective study aims to assess, through simulation, the theoretical economic and environmental benefits of introducing a multiphase diet for crossbreed bulls feeding (one or more diet changes). For this, individual data of BW, BW gain, and daily intake were recorded from 342 bulls during the last fattening period (112 days). These data were used to estimate individual trajectory of energy and protein requirements, which were subsequently divided by individual intake to calculate the required dietary energy and protein concentrations. The area between two functions (i.e., ƒ1: constant protein concentration in the original diet during fattening and ƒ2: estimated protein concentration requirements) was minimised to identify the optimal moments to adjust the dietary concentration of energy and protein. The results indicated that both energy and protein intake exceeded requirements on average (+16% and +28% respectively, P < 0.001), justifying the adoption of a multiphase diet. Modelling the individual trajectories of required metabolisable protein (MP, g/kg DM) during the fattening period resulted in exponential decay model in relation to BW [32120 × exp(-0.026 × BW) + 59.9], while the dietary net energy concentration followed a slightly quadratic model [2.26-0.0026 × BW + 0.000003 × BW2]. Minimisation of the area between curves showed two optimal moments to adjust the diet: at 312 kg and 385 kg of BW, indicating three diet phases: (a) <312 kg, (b) 312-385 kg, and (c) 385-600 kg. For the second and third phases, the dietary energy and protein concentration should be 70 g MP/kg DM and 1.70 Mcal/kg DM and 61 g MP/kg DM and 1.65 Mcal/kg DM, respectively. These diet adjustments might improve economic profitability by 29 €/animal, reduce estimated nitrogen excretions by 16% (P < 0.001), and maintain similar weight gain (P > 0.16) compared to the commercial diet. However, the decrease in dietary energy concentration led to increased fibre concentration, which in turn increased the estimated CH4 emissions of animals with the multiphase diet (+44%, P < 0.001). Hence, multiphase diet could theoretically reduce feeding cost and nitrogen excretion from fattening cattle. Further in vivo studies should confirm these results and find optimal nutritional strategies to improve economic profitability and environmental impact.

Parálisis de sueño durante la siesta como síntoma inicial de narcolepsia / Sleep paralysis during naptime as initial symptom of narcolepsy

Introducción: La narcolepsia es una enfermedad de etiología desconocida, de prevalencia muy baja (el 0,02-0,16% en adultos, aunque debe ser mayor, dado el infradiagnóstico), caracterizada por la presencia de somnolencia diurna excesiva, alucinaciones hipnagógicas y/o hipnopómpicas, parálisis de sueño y/o cataplejía (si está presente, se habla de narcolepsia de tipo 1 y, si no, de narcolepsia de tipo 2), cuya media de retraso diagnóstico se sitúa entre los 10 y los 15 años. Caso clínico: Varón de 16 años que consulta tras visitar a distintos especialistas por presentar parálisis de sueño durante las siestas, que le producen miedo y ocasional caída de objetos de las manos (diagnosticadas como posibles mioclonías). En la anamnesis nos sorprendió la presencia de parálisis de sueño inmediatamente tras el inicio de las siestas y, en la anamnesis dirigida, esos movimientos bruscos provocados por emociones eran compatibles con cataplejías, por lo que realizamos un estudio polisomnográfico nocturno y un test de latencias múltiples del sueño. Con la evolución aparecieron alucinaciones hipnopómpicas y sueño fragmentado nocturno, así como ocasional somnolencia diurna (se completó así la tétrada sintomatológica típica de la narcolepsia con cataplejía de tipo 1). Conclusión: Es importante el conocimiento de esta enfermedad, plantearla como diagnóstico diferencial en pacientes con episodios de somnolencia incoercible, realizar la derivación a consultas especializadas en trastornos de sueño y una buena anamnesis dirigida, e indicar las pruebas complementarias necesarias para el diagnóstico de esta enfermedad infradiagnosticada para su correcto manejo, tan determinante para la mejora de la calidad de vida de estos pacientes.(AU)

Introduction: Narcolepsy is a disease of unknown etiology, with a very low prevalence (0.02-0.16% in adults, although it must be higher, given the underdiagnosis), characterized by the presence of excessive daytime sleepiness, hypnagogic and/or hypnopompic hallucinations, sleep paralysis and/or cataplexy (if present, we speak of type 1 narcolepsy and, if not, type 2 narcolepsy), whose average diagnostic delay is between 10 and 15 years. Case report: A 16-year-old male who consulted after visiting different specialists for presenting sleep paralysis during naps, which cause him fear and occasional objects falling from his hands (diagnosed as possible myoclonus). In the anamnesis we were surprised by the presence of sleep paralysis immediately after the start of the naps and, in the directed anamnesis, these sudden movements caused by emotions were compatible with cataplexies, so we performed a nocturnal polysomnographic study and a multiple sleep latency test. With evolution came hypnopompic hallucinations and fragmented nocturnal sleep, as well as occasional daytime sleepiness (thus completing the typical symptomatic tetrad of type 1 narcolepsy with cataplexy). Conclusion: Knowledge of this disease is important, considering it as a differential diagnosis in patients with episodes of intractable sleepiness, send these patients to expert doctors in sleep disorders and doing a good anamnesis, performing the necessary complementary tests for the diagnosis of this underdiagnosed disease for its correct management, which is decisive for improving the quality of life of these patients.(AU)

Comparative analysis of signalling pathways in tissue protein metabolism in efficient and non-efficient beef cattle: acute response to an identical single meal size.

Protein turnover has been associated to residual feed intake (RFI) in beef cattle. However, this relationship may be confounded by feeding level and affected by the composition of the diet being fed. Our aim was to assess postmortem the protein metabolism signalling pathways in skeletal muscle and liver of 32 Charolais young bulls with extreme RFI phenotypes. Bulls were fed two contrasting diets during the whole fattening period but were subjected to a similar and single nutritional stimulus, induced by their respective concentrate, just prior to slaughter. The key targets were protein degradation (autophagy and ubiquitin) and synthesis signalling pathways through western-blot analysis, as well as hepatic transaminase activity. To ensure a precise assessment of all animals at the same postprandial time, they were provided with a test meal (2.5 kg of either a high-starch and high-protein concentrate or high-fibre and low-protein concentrate) 3 hours prior to slaughter, irrespective of their RFI grouping. Blood and tissues were sampled at the slaughterhouse (3 h and 3 h30 postprandially, respectively). In response to an identical single meal size, efficient RFI animals showed higher (P < 0.05) postprandial plasma ß-hydroxybutyrate concentrations and insulinemia (only with the high-starch concentrate) than non-efficient animals. Moreover, efficient RFI bulls had lower muscle (P = 0.04) and liver (P = 0.08) ubiquitin protein abundance (degradation pathway) and tended to have lower alanine transaminase activity in the liver (P = 0.06) compared to non-efficient bulls, regardless of diet. A positive correlation between protein degradation potential and amino acid catabolism was identified in this study (r = 0.52, P = 0.004), which was interpreted as being biologically linked to the RFI phenotype. Efficient RFI bulls also had a faster potential for protein synthesis in the muscle, as indicated by their greater ratio of phosphorylated to total form of ribosomal protein S6 kinase (P = 0.05), regardless of diet. Results on protein synthesis pathway in muscle and plasma metabolite concentrations suggested that efficient RFI cattle may have a faster nutrient absorption and insulin responsiveness after feeding than inefficient cattle. We did not find significant differences in hepatic protein synthesis pathways between the two RFI groups (P > 0.05). Our findings suggest that, in response to an identical single meal size, efficient RFI animals exhibited lower activation of tissue protein degradation pathways and faster muscle protein synthesis activation compared to their inefficient counterparts. This pattern was observed regardless of the composition of the tested meals.

Isavuconazole-tacrolimus drug-drug interactions in HSCT patients.

OBJECTIVES: Because tacrolimus has a narrow therapeutic window and exhibits both intraindividual and interindividual variability, we attempted to establish the percentage of calcineurin inhibitor (CNI) dose reduction to prevent toxicity and ensure stem cell engraftment when using this immunosuppressant with the antifungal isavuconazole (ISA). By calculating the tacrolimus concentration/dose (C/D) ratio, we expected to demonstrate the magnitude of change in the C/D ratio from baseline after ISA administration. METHODS: We evaluated the interaction between ISA, a new triazole antifungal used in prophylaxis for invasive fungal infections, and the CNI class of immunosuppressive drugs, specifically tacrolimus, in 11 blood samples from HSCT recipients. RESULTS: The mean tacrolimus C/D ratio increased 1.44-fold from baseline 48 h after ISA administration (P = 0.001). CONCLUSIONS: Although further investigation is needed, the results of this study suggest that a reduction of 18% in tacrolimus may be recommended.

Androgen deprivation therapy in localized prostate cancer. Current status and future trends.

INTRODUCTION: Prostate cancer (PCa) has been recognized as an androgen-sensitive disease since the investigations from Huggins and Hodges in 1941. Thanks to these findings, they received the Nobel Prize in 1966. This was the beginning of the development of androgen deprivation therapy (ADT) as treatment for patients with PCa. OBJECTIVE: To summarize the current indications of ADT in localized PCa. EVIDENCE ACQUISITION: We conducted a comprehensive English and Spanish language literature research, focused on the main indications for ADT in localized PCa. EVIDENCE SYNTHESIS: Nowadays, the indications for ADT as monotherapy in localized PCa have been limited to specific situations, to patients unwilling or unable to receive any form of local treatment if they have a PSA-DT < 12 months, and either a PSA > 50 ng/mL, a poorly differentiated tumor, or troublesome local disease-related symptoms. ADT can be used in combination with local treatment in different scenarios. Although neoadjuvant treatment with ADT prior to surgery with curative intent has no clear oncological impact, as a future sight, PCa is a heterogeneous disease, and there could be a group of patients with high-risk localized disease that could benefit. CONCLUSIONS: We need to optimize the treatment with ADT in localized PCa, selecting the patients accordingly to their disease characteristics. Given that the therapeutic armamentarium evolves day by day, there is a need for the development of new clinical trials, as well as a molecular studies of patients to identify those who might benefit from an early multimodal treatment.