Ensaios clínicos de pacientes únicos em homeopatia: aspectos técnicos, educacionais e éticos / Single-case studies in homeopathy: technical, educational and ethical aspects

ensaio clínico de pacientes únicos (ECPU/ensaio n-de-1) consiste na observação sistemática de condutas terapêuticas adotadas para otimizar o restabelecimento da saúde em um único paciente, com múltiplos cruzamentos ao longo do tratamento, podendo ter adicionalmente propósito de pesquisa clínica. Foi proposto há décadas e tem sido mais utilizado nas áreas de psicologia clínica, recebendo maior atenção em estudos médicos nos últimos anos. Embora seja considerado como o tipo de estudo com maior força para tomada de decisões terapêuticas, ainda são escassas as publicações sobre o seu emprego em medicina. Este artigo aborda as possibilidades dos ECPUs na avaliação dos resultados clínicos da homeopatia, explorando seus aspectos metodológicos, éticos e educacionais característicos em comparação aos ensaios clínicos randomizados tradicionais. Em pesquisa clínica, diferentemente dos ensaios convencionais, os ECPUs permitem a participação mais direta do paciente na escolha dos procedimentos e acompanhamento dos resultados, com possibilidade de alterações imediatas e sem que seja necessária sua exclusão do estudo, além de implicações de ordem econômica, política e ética. Podem ser utilizados no teste de medicamentos usados de modo off label, sem as restrições impostas à inclusão de pacientes vulneráveis nos estudos clínicos habituais, com excessiva artificialização no delineamento experimental. Poderiam ser ainda adotados nas diversas fases de teste clínico dos medicamentos, reduzindo a exposição de grande número de participantes aos riscos da pesquisa e baixa margem de extrapolação clínica dos resultados ao conjunto da população. Em homeopatia, podem ajudar a aprimorar o conhecimento dos medicamentos já em uso ou a melhor detectar os efeitos de novas substâncias testadas em ensaios patogenéticos homeopáticos. Em função do seu propósito principal de otimização do tratamento individual ­ e do alinhamento com os princípios éticos da autonomia e beneficência associados à prática da medicina centrada-no-paciente ou de precisão - podem ser desenvolvidos em conjunto com o paciente e familiares, sem a obrigatoriedade de aprovação prévia por Comissões de Ética Médica ou Comitês de Ética em Pesquisa.

The single-patient clinical trial (n-of-1 trial) is primarily designed to systematically observe outcomes from different therapeutic options to optimize the restoration of health in a single patient, with multiple crossovers throughout the treatment. They may additionally have a clinical research purpose. They have been proposed for decades and were mostly used in clinical psychology, receiving greater attention in medical studies in recent years. Although it is considered the type of study with the greatest strength for therapeutic decision-making, there are still few publications with its application in medicine. This article discusses the possibilities of single-patient clinical trials in assessing homeopathy outcomes, exploring their characteristic methodological, educational and ethical aspects compared to traditional randomized clinical trials. In clinical research, unlike conventional trials, single-patient clinical trials allow for more direct patient participation in choosing procedures and monitoring results, with the possibility of immediate changes without the need for their exclusion from the study, in addition to economic, political and ethical implications. They can be used in testing off-label drugs without the restrictions imposed on the inclusion of vulnerable patients in usual clinical studies, with excessive artificiality in the experimental design. They could also be adopted in the various clinical trial phases of drugs, reducing the exposure of many participants to the risks of research and low margin of clinical extrapolation of the results to the entire population. In homeopathy, they can help refine the knowledge of medications already in use or better detect the effects of new substances tested in homeopathic pathogenetic trials. Due to their purpose of optimizing individual treatment ­ and alignment with the principles of patient-centered or precision medicine ­ they can be developed jointly with the patient and her family without the mandatory prior approval by Medical Ethics Committees or Research Ethics Committees.

Precision diagnosis of hepatocellular carcinoma / 中华医学杂志(英文版)

Hepatocellular carcinoma (HCC) is the most common type of primary hepatocellular carcinoma (PHC). Early diagnosis of HCC remains the key to improve the prognosis. In recent years, with the promotion of the concept of precision medicine and more in-depth analysis of the biological mechanism underlying HCC, new diagnostic methods, including emerging serum markers, liquid biopsies, molecular diagnosis, and advances in imaging (novel contrast agents and radiomics), have emerged one after another. Herein, we reviewed and analyzed scientific advances in the early diagnosis of HCC and discussed their application and shortcomings. This review aimed to provide a reference for scientific research and clinical practice of HCC.

Precision medicine in gestational trophoblastic disease / Philippine Journal of Obstetrics and Gynecology

@#Precision medicine is a form of medicine that utilizes information about a person’s own genes to prevent, diagnose, or treat disease. In trophoblastic disease, precision medicine is important for accurate diagnosis, risk stratification, prognostication, and management. Immunohistochemistry, particularly p57kip2, has become an important ancillary procedure for the accurate identification of complete hydatidiform mole (HM). Molecular genotyping, on the other hand, is now considered the gold standard for the accurate classification of HM. Both tests are important for prognostication and the determination of the appropriate follow‑up plan. For gestational trophoblastic neoplasia, immunohistochemical markers can confirm the histologic diagnosis of its various types. Molecular genotyping differentiates gestational from nongestational tumors with overlapping histology and allows for precise identification of the index or causative pregnancy of a choriocarcinoma.

Research advances of various omics analyses in chronic refractory wounds on body surface / 中华烧伤杂志

The diagnosis and treatment of chronic refractory wounds on body surface has always been full of challenges, and it also poses a huge burden on medical care and society. High-throughput sequencing combined with omics analysis can reveal potential mechanisms of chronic wound formation, and identify potential biomarkers related to diagnosis, prognosis, and screening of chronic wound. Combined with multiple levels of omics analysis, the detailed molecular mechanism of chronic wound development can be further explored and understood, so as to provide clues for the formulation of personalized treatment methods and lay a solid foundation for the precision medicine of chronic wounds. Therefore, this review addresses the recent progress of various omics analyses in chronic refractory wounds on body surface.

Research progress on genome-guided precision oncology and development ideas of antitumor Chinese medicine / 中国中药杂志

Genome-guided oncology refers to a new treatment concept that transcends histological classification and pathological ty-ping and uses drugs according to the genetic characteristics of tumors. New drug development technology and clinical trial design based on this concept provide new ideas for the clinical application of precision oncology. The multi-component and multi-target characteristics of Chinese medicine provide rich resources for the development of tumor-targeting drugs from natural products, and the design of the master protocol trial aiming at the characteristics of precision oncology supports the rapid clinical screening of effective tumor-targeting drugs. The emergence of the synthetic lethality strategy breaks through the bottleneck that the drug can only target the oncogene but cannot do anything to the tumor suppressor gene with the loss-of-function mutation in the past. With the rapid development of high-throughput sequencing technology, the cost of sequencing is also decreasing. For the development of tumor-targeting drugs, how to keep up with the update speed of target information is a difficult problem of concern. Based on the integration of innovative ideas and me-thods of precision oncology, network pharmacology, and synthetic lethality strategy on synthetic lethal interaction network of antitumor Chinese medicine compatibility formula design, and the combination of improvement of innovative clinical trial methods, such as master protocol trial, basket trial, and umbrella trial, unique advantages of Chinese medicine are expected to be exerted beyond the antibody-based drugs and small molecule-based drugs and corresponding targeted drugs are potentially developed for clinical application.

Tensor decomposition: new strategy for deciphering mechanism of precision medicine for same treatment of different diseases / 中国中药杂志

The aging society has led to a substantial increase in the number of clinical comorbidities. To meet the needs of comorbidity treatment, polypharmacy is widely used in clinical practice. However, polypharmacy has drawbacks such as treatment conflict. Same treatment of different diseases refers to treating different diseases with same treatment. Therefore, the principle of same treatment of different diseases can alleviate the problems caused by polypharmacy. Under the research background of precision medicine, it becomes possible to explore the mechanism of same treatment of different diseases and achieve its clinical application. However, drugs successfully developed in the past have revealed shortcomings in clinical use. To better interpret the mechanism of precision medicine for same treatment of different diseases, under the multi-dimensional attributes including dynamic space and time, omics was performed, and a new strategy of tensor decomposition was proposed. With the characteristics of complete data, tensor decomposition is advantageous in data mining and can fully grasp the connotation of precision treatment of different diseases with same treatment under dynamic spatiotemporal changes. This method is used for drug repositioning in some biocomputations. By taking advantage of the dimensionality reduction of tensor decomposition and integrating the dual influences of time and space, this study achieved accurate target prediction of same treatment of different diseases at each stage, and discovered the mechanism of precision medicine of same treatment for different diseases, providing scientific support for precision prescription and treatment of different diseases with same treatment in clinical practice. This study thus conducted preliminary exploration of the pharmacological mechanism of precision Chinese medicine treatment.

A new target of precision medicine in sepsis: gut microbiome modified tryptophan metabolism / 中华危重病急救医学

Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Despite significant advances in anti-infective, immunomodulatory, and organ function support technologies, the precise and targeted management of sepsis remains a challenge due to its high heterogeneity. Studies have identified disturbed tryptophan (TRP) metabolism as a common mechanism in multiple diseases, which is involved in both immune regulation and the development of multi-organ damages. The rise of research on intestinal microflora has further highlighted the critical role of microflora-regulated TRP metabolism in pathogen-host interactions and the "cross-talk" among multi-organs, making it a potential key target for precision medicine in sepsis. This article reviews TRP metabolism, the regulation of TRP metabolism by the intestinal microflora, and the characteristics of TRP metabolism in sepsis, providing clues for further clinical targeting of TRP metabolism for precision medicine in sepsis.

Estado actual y retos futuros en el tratamiento de las enfermedades reumáticas / Current status and future challenges in the treatment of rheumatic diseases

Las nuevas estrategias, que incluyen el diagnóstico y el tratamiento tempranos, el enfoque de tratamiento dirigido a un objetivo, la remisión como ese objetivo principal del tratamiento, la participación de los pacientes en las decisiones terapéuticas, junto con el desarrollo de nuevos tratamientos efectivos, han cambiado las expectativas de los reumatólogos y de los pacientes con enfermedades reumáticas. Todavía existen, sin embargo, importantes desafíos tales como la seguridad a largo plazo de los tratamientos actuales y poder escoger tratamientos más individualizados y eficaces, de forma tal de elegir el mejor tratamiento para cada paciente. El futuro, como en el resto de la medicina, probablemente sea la prevención del desarrollo de enfermedades reumáticas. Discutiremos estos temas en esta revisión. (AU)

New strategies, including early diagnosis and treatment, targeted therapy, remission as the main objective of treatment, patient involvement in therapeutic decision-making, and the development of new effective therapies, have changed the expectations of rheumatologists and patients with rheumatic diseases.There are still serious challenges, such as the long-term safety of current treatments and the ability to make more individualized and effective treatments to choose the best treatment for each patient. The future, as that of the whole of medical science, will probably lie in preventing the development of rheumatic diseases. We will discuss these issues in this review. (AU)

Medicina personalizada en urología: Perspectiva desde un sistema de salud con escasez / Personalized Medicine in Urology: Perspective from a Sparse Health System

La medicina personalizada (MP) trae la promesa del cuidado individual a través de la identificación de variaciones genéticas que permitan determinar la predisposición ante una enfermedad, ofreciendo una prevención oportuna y específica, o adaptando las estrategias terapéuticas de manera particular.[1] [2] Su esencia es la integración de la investigación biomédica y la información clínica,[3] [4] con la esperanza de reducir el gasto en salud y la garantía de acceso equitativo a los ciudadanos.[4] La rapidez y bajo costo en la secuenciación del genoma ha permitido su implementación en la práctica clínica.[1] En urología estos avances han facilitado una mejor comprensión de los subtipos histológicos de las neoplasias del tracto genitourinario, facilitando el uso de tratamientos específicos y un seguimiento más oportuno.[2] [5] [6] Sin embargo, su aplicación en la identificación de biomarcadores no ha sido completamente determinada

Personalized medicine (PM) brings the promise of individualized care through the identification of genetic variations that allow determining the predisposition to a disease, offering timely and specific prevention, or adapting therapeutic strategies in a particular way.[1] [2] Its essence is the integration of biomedical research and clinical information,[3] [4] with the hope of reducing health spending and guaranteeing equitable access to citizens.[4] The speed and low cost of genome sequencing has allowed its implementation in clinical practice.[1] In urology, these advances have facilitated a better understanding of the histological subtypes of histological subtypes of neoplasms in urology. The speed and low cost of genome sequencing has allowed its implementation in clinical practice.[1] In urology these advances have facilitated a better understanding of the histological subtypes of neoplasms of the genitourinary tract, facilitating the use of specific treatments and more timely follow-up.[2] [5] [6] However, its application in the identification of biomarkers has not been fully determined.

Biobancos en otorrinolaringología / Biobanks in otolaryngology

Resumen Los biobancos son una innovadora herramienta biotecnológica y un recurso fundamental para el continuo avance en la investigación científica biomédica, y para el advenimiento de la medicina de precisión. Se han desarrollado de forma exponencial durante los últimos 20 años en el mundo, como también a nivel de nuestro país, con la creación de 10 biobancos desde el año 2004. En ellos se almacenan y organizan distintos tipos de muestras biológicas, asociadas a datos epidemiológicos y genéticos de donantes voluntarios. Todos los especímenes almacenados deben ser preservados con estándares de calidad garantizados, a modo de asegurar trazabilidad, integridad y calidad de las muestras. A pesar de que la mantención de un biobanco puede significar altos costos, a fin de cuentas, abaratan costos de los estudios clínicos, dado que es precisamente el biobanco quien se encarga de la obtención de datos y muestras clínicas confiables, permitiendo realizar múltiples estudios a partir de las mismas muestras. A través de este proceso, los biobancos permiten mantener una fuente confiable de recur-sos para la investigación en diversas áreas de la medicina, dentro de ellas la otorrinolaringología. En otorrinolaringología, los biobancos han significado un gran avance, facilitando la investigación en relación con hipoacusia, presbiacusia y tinnitus, así como en el área oncológica. En un futuro, se espera que la comunidad científica haga uso de este recurso, pudiendo expandir su utilidad no solo en el área médica, sino también en otras profesiones de la salud, maximizando así su gigantesco potencial.

Abstract Biobanks are novel biotechnological tools and a fundamental resource for the constant development of biomedical research, as much as for the growing practice of precision medicine. They have proliferated worldwide over the past 20 years and Chile has not been left behind with the creation of 10 bio-banks since 2004. Biobanks store and organize different types of biological samples associated with epidemiological and genetic data from volunteer donors. These samples are stored and preserved under guaranteed quality standards to ensure their traceability, integrity, and quality. Even though the price of maintaining a biobank may seem high, after all, they reduce the costs of research, since biobanks are responsible of the acquisition and storage of data and samples, allowing the performance of multiple studies from the same collection of specimens. In this direction, biobanks grant a constant source of well-founded scientific material for investigation in a wide range of medical fields, such as otolaryngology among them. In otolaryngology, the biobanks have meant a great improvement, facilitating investigations related to deafness, presbycusis, tinnitus and oncology. In the future we hope the scientific community will expand the use this innovative tool over a broader medical field and towards other health-related professions, making the most of its enormous potential.

Facteurs prédictifs de la surdité professionnelle induite par le bruit chez les travailleurs des centrales électriques / Predictive factors of occupational noise-induced hearing loss in power plant workers

Analyser le lien entre la surdité professionnelle induite par le bruit et les caractéristiques socioprofessionnelles des travailleurs. Méthodes: C'était une étude prospective et analytique, par enquête avec évaluation audiométrique du 1er août au 30 septembre 2020, concernant 92 travailleurs des deux centrales de la Société Nationale d'Electricité de N'Djamena.Les tests de khi2et de corrélation de Pearson étaient utilisés à la recherche d'un lien entre la surdité due au bruit et les facteurs socioprofessionnels; une différence était dite statistiquement significative si p <0,05. Résultats: L'échantillon était constitué de 96% d'hommes. L'âge variait de 23 à 64 ans avec une moyenne de 38,7 ± 9,0 ans. Quarante-sept (51%) employés étaient formés sur la sécurité en milieu professionnel. Les agents de quarts représentaient 45% des cas (n=41). La durée d'exposition moyenne au bruit était de 10,8 ± 8,5 ans. Le port des équipements de protection individuelle était régulier dans 86% des cas (n =79). La surdité professionnelle a été observée dans 55% des cas (n=51). L'âge (p <10-3) et la durée d'exposition au bruit (p=0,002) étaient les facteurs associés significativement à la surdité. Conclusion: L'âge et l'ancienneté sont les facteurs prédictifs de la surdité chez les travailleurs exposés aux bruits des centrales électriques de N'Djamena.

Progress in Precision Medicine of Radiomics in Abdominal Tumors Practice / 中国医疗器械杂志

With the advent of the era of artificial intelligence, as an emerging technology, radiomics can extract a large amount of quantitative information describing the physiological condition and phenotypic characteristics of tumors with high throughput from the massive data of CT, MRI and other imaging tomography, and analyze these high-dimensional imaging omics features containing disease pathophysiological information can be used to accurately determine tumor differentiation, staging, and predict tumor behavior, which has broad application prospects. This article aims to introduce the technical principles of radiomics and its abdominal tumor application status, and to prospect its application prospects in pediatric abdominal neuroblastoma.

Research progress of micronucleus visualization analysis and artificial intelligence detection strategy / 中华预防医学杂志

The micronucleomics test can comprehensively display a variety of harmful endpoints, such as DNA damage and repair, chromosome breakage or loss and cell growth inhibition, with fast, simple and economical feature. Micronucleomics is not only widely used in the comprehensive assessment of the types and modes of genetic action of exogenous chemicals (such as drugs, food additives, cosmetics, environmental pollutants, etc.), but also plays an important role in the screening and risk assessment of cancer population at high risk. However, the traditional micronucleomics image counting method has the characteristics of time-consuming, low accuracy, and high cost, which cannot meet the current analysis requirements of large-scale, multi-index, rapidity, high precision and visualization. In recent years, with the rapid development of the era of precision medicine based on big data, visualized analysis of new micronucleomics based on machine learning and detection strategies based on deep learning have shown a good application prospect. This review, based on the application value of micronucleomics, systematically compares the traditional and new artificial intelligence counting of micronucleus images, and discusses the future direction of micronucleus image detection.

Development and optimization of cosolvent-based blended Sertraline orodispersible films - A step to personalized medicine

Abstract Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.

Impact of different scan strategies and implant angulation on impression accuracy of full arch multiple implant: an in vitro study / Impacto de diferentes estratégias de escaneamento e angulação dos implantes na acurácia da moldagem de implantes múltiplos em arco completo: um estudo in vitro

Objective: to evaluate the impact of three different scan strategies and implant angulation on impression accuracy of an intraoral scanner for full-arch multiple implant scan. Material and Method: A maxillary edentulous model with six implant analogs served as a reference model. The four anterior analogs were positioned parallel to each other, the distal right and the distal left was placed with an angulation of 15o and 20o, respectively. Thirty impression were performed using an intraoral scanner (CEREC Primescan). The master cast was digitalized with an industrial reference scanner (ATOS Core 80). All scans were converted to standard tessellation language (STL), superimposed on the reference scan with a 3d inspection software (GOM Inspect Professional 2019) and then analyzed. Results: All linear distances presented equivalence [p<0.01] to those found on the reference scan for all scan strategies. All scan strategies presented a tendency of negative means for linear distances except for d4 in strategy C. All angular distances did not present equivalence [p=0.05] to those found on the reference scan. Significant 3D deviations [p<0.05] were found between strategy B (0.02 ± 0.01) and C (0.05 ± 0.04) for d1. In all others linear and angular distances no statistically significant difference was found between strategies A, B and C. Conclusions: There was no statistically significant difference between strategies A, B and C except for d1 in strategy B and C; Implant angulation did not affect the accuracy of the CEREC Primescan IOS (AU)

Objetivo: avaliar o impacto de três diferentes estratégias de escaneamento e angulação do implante na acurácia da moldagem de um scanner intraoral na moldagem de múltiplos implantes em arco completo. Material e Métodos: Um modelo edêntulo de maxila contendo seis análogos de implante serviu como modelo de referência. Os quatro análogos anteriores foram posicionados paralelos entre si, o distal direito e o distal esquerdo foram posicionados com angulação de 15o e 20o, respectivamente. Trinta moldagens foram realizadas usando um scanner intraoral (CEREC Primescan). O modelo mestre foi digitalizado com um scanner de referência industrial (ATOS Core 80). Todas as escaneamentos foram convertidas para a linguagem de mosaico padrão (STL), sobrepostas ao escaneamento de referência com um software de inspeção 3D (GOM Inspect Professional 2019) e, em seguida, analisadas. Resultados: Todas as distâncias lineares apresentaram equivalência [p <0,01] àquelas encontradas na escaneamento de referência para todas as estratégias. Todas as estratégias de escaneamento apresentaram tendência de médias negativas para distâncias lineares, exceto para d4 na estratégia C. Todas as distâncias angulares não apresentaram equivalência [p = 0,05] às encontradas no escaneamento de referência. Desvios 3D significativos [p <0,05] foram encontrados entre a estratégia B (0,02 ± 0,01) e C (0,05 ± 0,04) para d1. Em todas as outras distâncias lineares e angulares, nenhuma diferença estatisticamente significativa foi encontrada entre as estratégias A, B e C. Conclusões: Não houve diferença estatisticamente significante entre as estratégias A, B e C, exceto para d1 na estratégia B e C; A angulação do implante não afetou a precisão do CEREC Primescan. (AU)