Cirugía citorreductora en pacientes con cáncer de próstata oligometastásico. Revisión sistemática de la literatura científica / Cytoreductive surgery in patients with oligometastatic prostate cancer. systematic review of the scientific literature

Introducción La aparición de pruebas de imagen más específicas y sensibles, junto con el empleo cada vez más extendido de técnicas mínimamente invasivas, ha centrado el interés urológico sobre el cáncer de próstata oligometastásico. A pesar de esto, aún queda por determinar el manejo óptimo de esta patología. Objetivo Evaluar la eficacia y seguridad de la cirugía citorreductora en pacientes con cáncer de próstata oligometastásico. Adquisición de la evidencia Revisión sistemática de la literatura científica (01/01/2010-31/12/2021) en las bases de datos Medline, Embase, Cochrane Library, CINAHL, Scopus, Agencias de Evaluación de Tecnologías Sanitarias y ClinicalTrials.gov. Los descriptores utilizados han sido prostatectomy, prostatic neoplasm, radical prostatectomy, y los términos de búsqueda libre prostatectomy y oligomestastasicprostate. Los criterios de inclusión fueron estudios con pacientes con cáncer de próstata oligometastásico e intervenidos mediante prostatectomía radical citorreductora (CRP). Síntesis de la evidencia La revisión sistemática incluyó cuatro estudios observacionales, dos ensayos clínicos y dos series de casos, de calidad moderada. Los resultados observados sugieren un beneficio en cuanto a eficacia en aquellos pacientes oligometastásico sometidos a una cirugía de próstata citorreductora. Por otro lado, la mayoría de estos estudios revelan una reducción en el número de las complicaciones locales cuando se compara con los mejores tratamientos sistémicos. Conclusiones La cirugía citorreductora en este grupo de pacientes, es un procedimiento seguro que reduce las complicaciones locales, que ofrece resultados prometedores en cuanto a supervivencia. Hasta la fecha, la falta de ensayos prospectivos limita el papel de esta opción terapéutica a entornos experimentales (AU)

Introduction Interest in oligometastatic prostate cancer has spiked due to the emergence of new evidence regarding more specific and accurate imaging, and the wider use of minimally invasive techniques. Nevertheless, the optimal management of this pathology is yet to be determined. Objective Assess the efficacy and safety of cytoreductive surgery in patients suffering from oligometastatic prostate cancer. Evidence gathering Systematic review of the scientific literature (01/01/2010-31/12/2021) within the MedLine, Embase, Cochrane Library, Cinahl, Scopus, Spanish Healthcare Technology Assessment Agencies (AETS, Agencias de Evaluación de Tecnologías Sanitarias) and ClinicalTrials.gov databases. The keywords used were prostatectomy, prostatic neoplasm, radical prostatectomy; the free search terms were prostatectomy and oligometastaticprostate. The inclusion criteria comprised studies on patients with oligometastatic prostate cancer who had been operated on using radical cytoreductive prostatectomy. Evidence synthesis The systematic review included 4 observational studies, 2 clinical trials, and 2 case series, of moderate quality. The results observed suggest that oligometastatic prostate cancer patients who had undergone cytoreductive prostate surgery obtained a benefit in terms of efficacy. Conversely, the majority of these studies showed a reduction in the number of localized complications, when compared to the best systemic treatments. Conclusions Cytoreductive surgery in this group of patients is a safe procedure that reduces the incidence of localized complications and that presents promising results with regard to survival rates. To date, the lack of prospective trials limits the use of this therapeutic option to experimental environments (AU)

[Efficacy, effectiveness and safety of the adjuvanted influenza vaccine in the population aged 65 or over]. / Eficacia, efectividad y seguridad de la vacuna antigripal adyuvada en población de 65 o más años de edad.

Most of the complications and deaths related to seasonal flu occur in the elderly population (≥65 years) with comorbidities, and the influenza vaccine is the most effective way to prevent them. Immunization is less effective in older adults due to immunosenescence. MF59-adjuvanted vaccines, designed to improve the magnitude, persistence and amplitude of the immune response in elderly people, have been used in clinical practice since 1997 in their trivalent formulation and, since 2020, in their tetravalent formulation. Data from various studies show that these vaccines are not only safe for all age groups, with a reactogenicity profile similar to that of the conventional vaccine, but also that they are especially effective in boosting the immune response in the population aged 65 or over by increasing antibody titers after vaccination and significantly reducing the risk of hospital admission. Adjuvanted vaccines have been shown to provide cross-protection against heterologous strains and to be as effective as the high-dose vaccine in the population aged 65 or over. In this review, the scientific evidence on the efficacy and effectiveness of the MF59-adjuvanted vaccine in real clinical practice in people ≥65 years of age is analyzed through a narrative and descriptive review of the literature with data from clinical trials, observational studies and systematic reviews or meta-analysis.

Cytoreductive surgery in patients with oligometastatic prostate cancer. Systematic review of the scientific literature.

INTRODUCTION: Interest in oligometastatic prostate cancer has spiked due to the emergence of new evidence regarding more specific and accurate imaging, and the wider use of minimally invasive techniques. Nevertheless, the optimal management of this pathology is yet to be determined. OBJECTIVE: Assess the efficacy and safety of cytoreductive surgery in patients suffering from oligometastatic prostate cancer. EVIDENCE GATHERING: Systematic review of the scientific literature (01/01/2010-31/12/2021) within the MedLine, Embase, Cochrane Library, Cinahl, Scopus, Spanish Healthcare Technology Assessment Agencies (AETS, Agencias de Evaluación de Tecnologías Sanitarias) and ClinicalTrials.gov databases. The keywords used were prostatectomy, prostatic neoplasm, radical prostatectomy; the free search terms were prostatectomy and oligometastatic prostate. The inclusion criteria comprised studies on patients with oligometastatic prostate cancer who had been operated on using radical cytoreductive prostatectomy. EVIDENCE SYNTHESIS: The systematic review included 4 observational studies, 2 clinical trials, and 2 case series, of moderate quality. The results observed suggest that oligometastatic prostate cancer patients who had undergone cytoreductive prostate surgery obtained a benefit in terms of efficacy. Conversely, the majority of these studies showed a reduction in the number of localized complications, when compared to the best systemic treatments. CONCLUSIONS: Cytoreductive surgery in this group of patients is a safe procedure that reduces the incidence of localized complications and that presents promising results with regard to survival rates. To date, the lack of prospective trials limits the use of this therapeutic option to experimental environments.

Eckhaus selection: The mechanism of pattern persistence in a reaction-diffusion system.

In this work, we show theoretically and numerically that a one-dimensional reaction-diffusion system, near the Turing bifurcation, produces different number of stripes when, in addition to random noise, the Fourier mode of a prepattern used to initialize the system changes. We also show that the Fourier modes that persist are inside the Eckhaus stability regions, while those outside this region follow a wave number selection process not predicted by the linear analysis. To test our results, we use the Brusselator reaction-diffusion system obtaining an excellent agreement between the weakly nonlinear predictions of the real Ginzburg-Landau equations and the numerical solutions near the bifurcation. Although the persistence of patterns is not relevant as a simple generating mechanism of self-organization, it is crucial to understand the formation of patterns that occurs in multiple stages. In this work, we discuss the relevance of our results on the robustness and diversity of solutions in multiple-steps mechanisms of biological pattern formation and auto-organization in growing domains.

Generation of ECG signals from a reaction-diffusion model spatially discretized.

We propose a model to generate electrocardiogram signals based on a discretized reaction-diffusion system to produce a set of three nonlinear oscillators that simulate the main pacemakers in the heart. The model reproduces electrocardiograms from healthy hearts and from patients suffering various well-known rhythm disorders. In particular, it is shown that under ventricular fibrillation, the electrocardiogram signal is chaotic and the transition from sinus rhythm to chaos is consistent with the Ruelle-Takens-Newhouse route to chaos, as experimental studies indicate. The proposed model constitutes a useful tool for research, medical education, and clinical testing purposes. An electronic device based on the model was built for these purposes.

Expanding the clinical features of autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation by description of a novel patient.

BACKGROUND: Autoinflammation and phospholipase Cγ2-associated antibody deficiency and immune dysregulation (APLAID) is an exceedingly rare monogenic autoinflammatory disease. To date, only five cases have been reported with four distinct pathogenic mutations. OBJECTIVES: We present a novel case of APLAID, corroborated by molecular analysis, with newly described clinical findings including central nervous system vasculitis (CNSV); and distinctive histopathological characteristics that may expand our knowledge of this rare disease's phenotype. METHODS: This is a case report presentation of a 3-year-old boy, seen at a reference paediatric hospital in Mexico. His parents authorized the use of his clinical information and photographs. RESULTS: A 3-day-old boy presented to the emergency department with a vesiculo-pustular rash that resolved within 1 week. Two months later, he developed widespread papules and pseudovesicles that evolved into infiltrated plaques. He also had periodical flares of conjunctivitis, diarrhoea and erythematous blistering acral plaques triggered by upper respiratory infections. By the age of 10 months, he experienced seizures and CNSV. Laboratory work-up showed mild neutropenia, decreased serum levels of immunoglobulins and B-cell lymphopenia. A skin biopsy revealed a dense, perivascular and interstitial histiocytic and granulomatous infiltrate, with palisading granulomas, and leucocytoclastic vasculitis with karyorrhexis. APLAID syndrome was confirmed by Sanger sequencing of PLCG2 gene [heterozygous genotype LRG_376t1:c.2543T>C or p.(Leu848Pro)]. CONCLUSIONS: Presence of CNSV has not been previously described in APLAID, however as the number of reported patients with APLAID is very small, it is possible that the overall spectrum of clinical manifestations has not been completely elucidated. The herein identified p.(Leu848Pro) variant was also documented in a Portuguese patient, suggesting that it could be a PLCG2 gene 'hot-spot'.

Mushroom productivity trends in relation to tree growth and climate across different European forest biomes.

Although it is logical to think that mycorrhizal mushroom production should be somehow related to the growth of the trees from which the fungi obtain carbohydrates, little is known about how mushroom yield patterns are related to tree performance. In this study, we delved into the understanding of the relationships between aboveground fungal productivity, tree radial growth patterns and climatic conditions across three latitudinally different bioclimatic regions encompassing Mediterranean, temperate and boreal forest ecosystems in Europe. For this purpose, we used a large assemblage of long-term data of weekly or biweekly mushroom yield monitoring in Spain, Switzerland and Finland. We analysed the relationships between annual mushroom yield (considering both biomass and number of sporocarps per unit area), tree ring features (tree ring, earlywood and latewood widths), and meteorological conditions (i.e. precipitation and temperature of summer and autumn) from different study sites and forest ecosystems, using both standard and partial correlations. Moreover, we fitted predictive models to estimate mushroom yield from mycorrhizal and saprotrophic fungal guilds based on climatic and dendrochronological variables. Significant synchronies between mushroom yield and climatic and dendrochronological variables were mostly found in drier Mediterranean sites, while few or no significant correlations were found in the boreal and temperate regions. We observed positive correlations between latewood growth and mycorrhizal mushroom biomass only in some Mediterranean sites, this relationship being mainly mediated by summer and autumn precipitation. Under more water-limited conditions, both the seasonal wood production and the mushroom yield are more sensitive to precipitation events, resulting in higher synchrony between both variables. This comparative study across diverse European forest biomes and types provides new insights into the relationship between mushroom productivity, tree growth and weather conditions.

Periodically kicked network of RLC oscillators to produce ECG signals.

We propose a simple model of the electrical activity of the heart that reproduces realistic healthy electrocardiogram (ECG) signals. The model consists of two RLC linear oscillators periodically kicked by impulses of the main pacemaker with the frequency rate of a real heart. In the proposed model, one oscillator represents the atria, another represents the ventricles, and an electrical cardiac conduction system is included using a coupling capacitor, which can be either unidirectional or bidirectional. The network of the two capacitively coupled oscillators is periodically kicked by the main pacemaker to introduce the periodic forcing of limit cycles into the system; a time delay is introduced to represent the electrical transport delay from atria to ventricles. In this manner, healthy synthetic ECG signals are obtained by combining the signals of the currents of the oscillators. We show that an analytical solution of the model can be obtained when a single impulse is applied. From this, by the superposition principle, a solution with an impulse train is obtained. Note that analytical treatment is a feature not available in current cardiac oscillator models.

Long-term deterioration after one-stage unicompartmental knee arthroplasty and anterior cruciate ligament reconstruction.

PURPOSE: Treatment for unicompartmental knee osteoarthritis (OA) is controversial in young patients with concomitant anterior cruciate ligament (ACL) deficiency. The aim of the current study is to report long-term results after the combination of unicompartmental knee arthroplasty (UKA) and ACL reconstruction. METHODS: Retrospective study of one-stage medial UKA and ACL reconstruction was performed on eight patients at a mean age of 52 years (42-60). Clinical and radiological results were assessed and analyzed after a mean follow-up of 14.6 years. RESULTS: Patients were satisfied and mean personal satisfaction rate was 8.8 (4-10). At the last follow-up, mean WOMAC score was 26 (1-52) and mean global KSS was 154 (102-200). One revision surgery to total knee arthroplasty was performed 9 years after the combined procedure due to aseptic loosening. One more case of clinical deterioration was observed 13 years after index surgery. CONCLUSIONS: Combined UKA and ACL reconstruction can be a therapeutic option for young and active patients with concomitant knee instability and unicompartmental OA. The procedure is highly demanding and reliable only in hands of experienced surgeons. Overall, satisfactory outcome can be achieved at a minimum follow-up of 10 years. However, clinical deterioration can be observed in the long term.

Papaverine-sensitive phosphodiesterase activity is measured in bovine spermatozoa.

Cyclic adenosine monophosphate (cAMP) plays a crucial role as a signaling molecule for capacitation, motility, and acrosome reaction in mammalian spermatozoa. It is well-known that cAMP degradation by phosphodiesterase (PDE) enzyme has a major impact on sperm functions. This study was undertaken to characterize cAMP-PDE activity in bovine spermatozoa. Total cAMP-PDE activity in cauda epididymal and ejaculated spermatozoa was 543.2 ± 49.5 and 1252.6 ± 86.5 fmoles/min/106 spermatozoa, respectively. Using different family-specific PDE inhibitors, we showed that in cauda epididymal and ejaculated spermatozoa, the major cAMP-PDE activity was papaverine-sensitive (44.5% and 57.5%, respectively, at 400 nm, papaverine is a specific inhibitor of the PDE10 family). These data are supporting the functional presence of PDE10 in bovine spermatozoa and were further confirmed by western blot to be PDE10A. Using immunocytochemistry, we showed immunoreactive signal for PDE10A present on the post-acrosomal region of the head and on the flagella of ejaculated spermatozoa. Using papaverine, we showed that it promotes tyrosine phosphorylation of sperm proteins, phosphorylation of Erk1 and Erk2, and Ca2+ release from Ca2+ store. These results suggest that PDE10 is functionally present in bovine spermatozoa and is affecting different molecular events involved in capacitation, most probably by cAMP local regulation.

Characterization of cAMP-phosphodiesterase activity in bovine seminal plasma.

The second messenger cyclic adenosine monophosphate (cAMP) has a central role in sperm physiology. Extracellular cAMP can be sequentially degraded into 5'AMP and adenosine by ecto-phosphodiesterases (ecto-PDE) and ecto-nucleotidases, a phenomenon called extracellular cAMP-adenosine pathway. As cAMP-adenosine pathway is involved in sperm capacitation, we hypothesize that extracellular PDEs are functionally present in seminal plasma. Exclusively measuring cAMP-PDE activity, total activity in bovine seminal plasma was 10.1 ± 1.5 fmoles/min/µg. Using different family-specific PDE inhibitors, we showed that in seminal plasma, the major cAMP-PDE activity was papaverine sensitive (47.5%). These data support the presence of PDE10 in bovine seminal plasma and was further confirmed by western blot. In epididymal fluid, total cAMP-PDE activity was 48.2 ± 14.8 fmoles/min/µg and we showed that the major cAMP-PDE activity was 3-isobutyl-methylxanthine insensitive and thus ascribed to PDE8 family. PDE10A mRNAs were found in the testis, epididymis, and seminal vesicles. cAMP-PDE activity is present in bovine seminal plasma and epididymal fluid. The results suggest a role for ecto-PDEs present in those fluids in the signaling pathways involved in sperm functions.

Planar modes free piezoelectric resonators using a phononic crystal with holes.

By using the principles behind phononic crystals, a periodic array of circular holes made along the polarization thickness direction of piezoceramic resonators are used to stop the planar resonances around the thickness mode band. In this way, a piezoceramic resonator adequate for operation in the thickness mode with an in phase vibration surface is obtained, independently of its lateral shape. Laser vibrometry, electric impedance tests and finite element models are used to corroborate the performances of different resonators made with this procedure. This method can be useful in power ultrasonic devices, physiotherapy and other external medical power ultrasound applications where piston-like vibration in a narrow band is required.

Gene Interactions Provide Evidence for Signaling Pathways Involved in Cleft Lip/Palate in Humans.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common craniofacial birth defect that has a complex etiology. Genome-wide association studies have recently identified new loci associated with NSCL/P, but these loci have not been analyzed in a Mexican Mestizo population. A complex etiology implies the presence of genetic interactions, but there is little available information regarding this in NSCL/P, and no signaling pathway has been clearly implicated in humans. Here, we analyzed the associations of 24 single nucleotide polymorphisms (SNPs) with NSCL/P in a Mexican Mestizo population (133 cases, 263 controls). The multifactorial dimensionality reduction method was used to examine gene-gene and gene-folic acid consumption interactions for the 24 SNPs analyzed in this study and for 2 additional SNPs that had previously been genotyped in the same study population. Six SNPs located in paired box 7, ventral anterior homeobox 1, sprouty RTK signaling antagonist 2, bone morphogenetic protein 4, and tropomyosin 1 genes were associated with higher risks of NSCL/P (P = 0.0001 to 0.04); 2 SNPs, 1 each in netrin 1 and V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B, were associated with a lower risk of NSCL/P (P = 0.013 to 0.03); and 2 SNPs, 1 each in ATP binding cassette subfamily A member 4 (ABCA4) and noggin, showed associations with NSCL/P that approached the threshold of significance (P = 0.056 to 0.07). In addition, 6 gene-gene interactions (P = 0.0001 to 0.001) and an ABCA4-folic acid consumption interaction (P < 0.0001) were identified. On the basis of these results, combined with those of previous association studies in the literature and biological characterizations of murine models, we propose an interaction network in which interferon regulatory factor 6 plays a central role in the etiology of NSCL/P.

Evaluación de la vacuna pandémica antigripal A/H1N1 adyuvada MF59. Revisión sistemática de la literatura / Assessment of the MF59-adjuvanted pandemic influenza A/H1N1 vaccine. Systematic review of literature

Objetivo: Evaluar la eficacia y la seguridad de la vacuna adyuvada MF59 en la gripe pandémica en población infantil. Métodos: Se ha elaborado una revisión sistemática de la literatura médica (2005-2012). Para ello se realizó una búsqueda bibliográfica en fuentes de datos electrónicas como MedLine o Embase y búsqueda manual en revistas especializadas, utilizando descriptores MeSH y términos de búsqueda libre. Los criterios de inclusión fueron ensayos clínicos que incluyeran a niños vacunados frente a la gripe A/H1N1 con la vacuna adyuvada MF59 y se comparaba frente a otras dosis vacunales con o sin adyuvante MF59, registrando resultados de seguridad e inmunogenicidad. La calidad de los ensayos clínicos se evaluó utilizando los criterios del cuestionario CASPe. Resultados: Se seleccionaron 4 ensayos clínicos de calidad moderada. Los efectos adversos locales y sistémicos fueron de carácter leve o moderado, sin diferencias entre los grupos vacunados. Los porcentajes de seroconversión y seroprotección alcanzados fueron superiores con las vacunas que utilizaron el adyuvante MF59. Los títulos de anticuerpos alcanzados también fueron mayores en las vacunas adyuvadas. Conclusiones: La vacuna pandémica antigripal adyuvada con MF59 presenta un buen perfil de eficacia y seguridad. Los efectos adversos que puede ocasionar son comunes y se presentan de manera similar a los que acontecen al utilizar vacunas no adyuvadas (AU)

Objective: To assess the efficacy and safety of MF59-adjuvanted pandemic influenza A/H1N1vaccine in children. Methods: A systematic review of the literature was performed after searching the MedLine and Embase electronic databases, and manual search in specialties journals, with MeSH terms and free terms. Inclusion criteria were clinical trials with children vaccinated with MF59-adjuvanted influenza A/H1N1 vaccine, compared with other vaccines doses with/without MF59-adjuvanted. The immunogenicity and safety of the vaccine was recorded. The quality of the studies included was assessed by CASPe checklist. Results: Four clinical trials with moderate quality were selected. The local and systemic adverse effects were rare and mild, with no differences between groups. Seroconversion and seroprotection levels were higher with MF59-adjuvanted vaccines. Antibody titres were also higher with the adjuvant vaccines. Conclusions: The adjuvant vaccine has a good efficacy and safety profile. The adverse effects that may occur are common and appear similarly in both vaccination groups (AU)

Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine in infants: a meta-analysis.

Pneumococcal infections are a major cause of morbidity and mortality worldwide. Pneumococcal conjugate vaccines represent major progress in the prevention of invasive pneumococcal disease in the paediatric population. We performed a meta-analysis, in accordance with the PRISMA statement, in order to assess the immunogenicity and safety of 13-valent pneumococcal conjugate vaccines in infants. A literary search was conducted using electronic databases and specialized journals were searched manually. Inclusion criteria were: clinical trials with infants vaccinated with 13-valent pneumococcal conjugate, compared to 7-valent vaccine. We recorded the results in terms of the immunogenicity and safety of the vaccines. The quality of the studies included was assessed using the CASP and Jadad checklists. We included nine randomized clinical trials of 258 potentially relevant references in the meta-analysis. The studies included had high-moderate quality. Both vaccines were well tolerated in all groups of infants, and most local reactions and systemic events were of mild or medium intensity and typical of any injected vaccine. All studies included in the meta-analysis showed high immunogenicity for both pneumococcal vaccines in all tested serotypes. An anti-polysaccharide antibody concentration of ≥0.35 µg/mL was achieved in at least 89% of the infants. Our results suggest that the 13-valent pneumococcal conjugate vaccine has a similar safety profile, and is as effective as, the 7-valent vaccine in the prevention of invasive pneumococcal disease caused by the seven common serotypes, and could provide expanded protection against the six additional serotypes.

Riesgo radiológico y radiación del paciente en la nefrolitotomía percutánea / Radiological risk and radiation of the percutaneous nephrolithotomy patient

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[Assessment of the MF59-adjuvanted pandemic influenza A/H1N1 vaccine. Systematic review of literature]. / Evaluación de la vacuna pandémica antigripal A/H1N1 adyuvada MF59. Revisión sistemática de la literatura.

OBJECTIVE: To assess the efficacy and safety of MF59-adjuvanted pandemic influenza A/H1N1 vaccine in children. METHODS: A systematic review of the literature was performed after searching the MedLine and Embase electronic databases, and manual search in specialties journals, with MeSH terms and and free terms. Inclusion criteria were clinical trials with children vaccinated with MF59-adjuvanted influenza A/H1N1 vaccine, compared with other vaccines doses with/without MF59-adjuvanted. The immunogenicity and safety of the vaccine was recorded. The quality of the studies included was assessed by CASPe checklist. RESULTS: Four clinical trials with moderate quality were selected. The local and systemic adverse effects were rare and mild, with no differences between groups. Seroconversion and seroprotection levels were higher with MF59-adjuvanted vaccines. Antibody titres were also higher with the adjuvant vaccines. CONCLUSIONS: The adjuvant vaccine has a good efficacy and safety profile. The adverse effects that may occur are common and appear similarly in both vaccination groups.

Nonlinear effects on Turing patterns: time oscillations and chaos.

We show that a model reaction-diffusion system with two species in a monostable regime and over a large region of parameter space produces Turing patterns coexisting with a limit cycle which cannot be discerned from the linear analysis. As a consequence, the patterns oscillate in time. When varying a single parameter, a series of bifurcations leads to period doubling, quasiperiodic, and chaotic oscillations without modifying the underlying Turing pattern. A Ruelle-Takens-Newhouse route to chaos is identified. We also examine the Turing conditions for obtaining a diffusion-driven instability and show that the patterns obtained are not necessarily stationary for certain values of the diffusion coefficients. These results demonstrate the limitations of the linear analysis for reaction-diffusion systems.