A Cluster of Diutina catenulata Funguria in Patients with Coronavirus Disease 2019 (COVID-19) Hospitalized in a Tertiary Reference Hospital from Rio de Janeiro, Brazil.

During the COVID-19 pandemic, fungal infections, especially pulmonary aspergillosis, mucormycosis, and invasive candidiasis, have emerged as a significant health concern. Beyond Candida albicans, the most common cause of invasive candidiasis, other rare ascomycetous yeast species have been described in tertiary care units, potentially posing a broader health threat. We have isolated, from September 2020 to June 2021, nine Diutina catenulata strains from urine samples of six patients. This was intriguing as this fungus had not been previously identified in our institution, nor after June 2021. Therefore, we decided to outline the clinical features of the patients with this rare pathogen, to describe phenotypic characteristics, including antifungal susceptibility profiles, of this yeast species and to identify the genetic makeup through whole-genome sequencing analysis to evaluate if this was a cluster of genetically similar D. catenulata isolates in our institution. The strains were identified through MALDI-TOF MS analyses and Sanger sequencing of two rDNA regions. All patients yielding D. catenulata from urine samples needed ventilator support and used urinary catheters during hospitalization for treatment of COVID-19. None of them had received COVID-19 vaccines. Morphological and biochemical profiles of the nine strains were largely consistent, although fluconazole susceptibility varied, ranging from 4 to 32 µg/mL. Phylogenomic analysis revealed minimal genetic variation among the isolates, with low intrapopulation variation, supported by the identification of only 84 SNPs across all strains. Therefore, we propose that the yeast strains isolated were part of a cluster of D. catenulata funguria in the context of COVID-19.

Loop-Mediated Isothermal Amplification for the Diagnosis of Sporotrichosis by Sporothrix brasiliensis.

We aimed to develop and validate a Loop-mediated Isothermal Amplification (LAMP) assay to Sporothrix brasiliensis. LAMP reaction was developed using six primers designed based on calmodulin gene. In the LAMP reaction, we tested twenty isolates of S. brasiliensis from animals and humans, along with ten tissue samples extracted from the left footpad of mice that had been experimentally infected with S. brasiliensis. In addition, it included DNA samples from various other fungal species for specificity evaluation. All S. brasiliensis isolates yielded positive results in the LAMP, and the limit of DNA detection was 1 ng/µL. All murine samples were positive in the test while DNA from other fungal species were all negative, resulting in 100% of sensitivity and specificity of primers. LAMP diagnosis technique is a promising alternative to sporotrichosis diagnosis, in a simple and cost-effective way. Further studies are warranted to validate this technique using animal model samples obtained from both humans and animals.

Fecal microbiota transplantation ameliorates high-fat diet-induced memory impairment in mice.

Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high-fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3-day fecal microbiota transplantation (FMT) regimen from low-fat (control) diet-fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD-induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD-induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns.

Proceedings of the second international meeting on endemic mycoses of the Americas (IMEMA) and first international symposium on implantation mycoses (ISIM).

The second international meeting on endemic mycoses of the Americas (IMEMA) and the first international symposium on implantation mycoses (ISIM) took place in Santiago del Estero, Argentina, on September 25-27, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors on the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges.

IMEMA/ISIM, held in Santiago del Estero, Argentina, convened experts to discuss endemic and implantation mycoses, covering topics such as epidemiology, diagnostics, treatment, and advocacy. The event highlighted ongoing efforts in combating these diseases.

Genomic and morphological characterization of Knufia obscura isolated from the Mars 2020 spacecraft assembly facility.

Members of the family Trichomeriaceae, belonging to the Chaetothyriales order and the Ascomycota phylum, are known for their capability to inhabit hostile environments characterized by extreme temperatures, oligotrophic conditions, drought, or presence of toxic compounds. The genus Knufia encompasses many polyextremophilic species. In this report, the genomic and morphological features of the strain FJI-L2-BK-P2 presented, which was isolated from the Mars 2020 mission spacecraft assembly facility located at the Jet Propulsion Laboratory in Pasadena, California. The identification is based on sequence alignment for marker genes, multi-locus sequence analysis, and whole genome sequence phylogeny. The morphological features were studied using a diverse range of microscopic techniques (bright field, phase contrast, differential interference contrast and scanning electron microscopy). The phylogenetic marker genes of the strain FJI-L2-BK-P2 exhibited highest similarities with type strain of Knufia obscura (CBS 148926T) that was isolated from the gas tank of a car in Italy. To validate the species identity, whole genomes of both strains (FJI-L2-BK-P2 and CBS 148926T) were sequenced, annotated, and strain FJI-L2-BK-P2 was confirmed as K. obscura. The morphological analysis and description of the genomic characteristics of K. obscura FJI-L2-BK-P2 may contribute to refining the taxonomy of Knufia species. Key morphological features are reported in this K. obscura strain, resembling microsclerotia and chlamydospore-like propagules. These features known to be characteristic features in black fungi which could potentially facilitate their adaptation to harsh environments.

Brain wave oscillations as an objective neurophysiological biomarker of homeopathic subjective well-being [Pré-print]

Homeopathy uses the "similitude principle" to arouse a therapeutic reaction in the body against its own disorders. For this to occur optimally, the medicinal pathogenetic effects must present similarity with the totality of the individual's symptoms. To assess if this similarity has been successfully achieved, Hahnemann states that "improvement in the disposition and mind"­i.e., subjective well-being­is the most important parameter to consider. Aim Our aim was to perform a narrative review of the literature, exploring what is known about subjective well-being as a marker of therapeutic action, and to formulate ways in which subjective well-being might be quantifiable and applied in future homeopathy research. The concept of subjective well-being has been extensively studied in the complementary and conventional medical literature. Improved well-being has been observed in clinical trials, including those in the fields of positive psychology and meditation. Positive subjective outcomes of this nature are supported by objective evidence through associated changes in brain oscillatory activity using electroencephalography and/or "brain mapping" by functional magnetic resonance imaging. Neurophysiological responses in the brain have been identified in subjects after they ingested a homeopathic medicine. The concept of subjective well-being is supported by a body of literature and is a measurable entity. When viewed from the perspective of electrophysiological changes, brain activity is an objective neurophysiological biomarker with a potential to quantify individual well-being in the context of homeopathy research.

Brain Wave Oscillations as an Objective Neurophysiological Biomarker of Homeopathic Subjective Well-Being.

BACKGROUND: Homeopathy uses the "similitude principle" to arouse a therapeutic reaction in the body against its own disorders. For this to occur optimally, the medicinal pathogenetic effects must present similarity with the totality of the individual's symptoms. To assess if this similarity has been successfully achieved, Hahnemann states that "improvement in the disposition and mind"-i.e., subjective well-being-is the most important parameter to consider. AIM: Our aim was to perform a narrative review of the literature, exploring what is known about subjective well-being as a marker of therapeutic action, and to formulate ways in which subjective well-being might be quantifiable and applied in future homeopathy research. RESULTS: The concept of subjective well-being has been extensively studied in the complementary and conventional medical literature. Improved well-being has been observed in clinical trials, including those in the fields of positive psychology and meditation. Positive subjective outcomes of this nature are supported by objective evidence through associated changes in brain oscillatory activity using electroencephalography and/or "brain mapping" by functional magnetic resonance imaging. Neurophysiological responses in the brain have been identified in subjects after they ingested a homeopathic medicine. CONCLUSIONS: The concept of subjective well-being is supported by a body of literature and is a measurable entity. When viewed from the perspective of electrophysiological changes, brain activity is an objective neurophysiological biomarker with a potential to quantify individual well-being in the context of homeopathy research.

Epidemiological, clinical, and genomic landscape of coccidioidomycosis in northeastern Brazil.

Coccidioidomycosis, listed as a priority mycosis by the WHO, is endemic in the United States but often overlooked in Central and South America. Employing a multi-institutional approach, we investigate how disease characteristics, pathogen genetic variation, and environmental factors impact coccidioidomycosis epidemiology and outcomes in South America. We identified 292 cases (1978-2021) and 42 outbreaks in Piauí and Maranhão states, Brazil, the largest series outside the US/Mexico epidemic zone. The male-to-female ratio was 57.4:1 and the most common activity was armadillo hunting (91.1%) 4 to 30 days before symptom onset. Most patients (92.8%) exhibited typical acute pulmonary disease, with cough (93%), fever (90%), and chest pain (77%) as predominant symptoms. The case fatality rate was 8%. Our negative binomial regression model indicates that reduced precipitation levels in the current (p = 0.015) and preceding year (p = 0.001) predict heightened incidence. Unlike other hotspots, acidic soil characterizes this region. Brazilian strains differ genomically from other C. posadasii lineages. Northeastern Brazil presents a distinctive coccidioidomycosis profile, with armadillo hunters facing elevated risks. Low annual rainfall emerges as a key factor in increasing cases. A unique C. posadasii lineage in Brazil suggests potential differences in environmental, virulence, and/or pathogenesis traits compared to other Coccidioides genotypes.

B cells and the coordination of immune checkpoint inhibitor response in patients with solid tumors.

Immunotherapy profoundly changed the landscape of cancer therapy by providing long-lasting responses in subsets of patients and is now the standard of care in several solid tumor types. However, immunotherapy activity beyond conventional immune checkpoint inhibition is plateauing, and biomarkers are overall lacking to guide treatment selection. Most studies have focused on T cell engagement and response, but there is a growing evidence that B cells may be key players in the establishment of an organized immune response, notably through tertiary lymphoid structures. Mechanisms of B cell response include antibody-dependent cellular cytotoxicity and phagocytosis, promotion of CD4+ and CD8+ T cell activation, maintenance of antitumor immune memory. In several solid tumor types, higher levels of B cells, specific B cell subpopulations, or the presence of tertiary lymphoid structures have been associated with improved outcomes on immune checkpoint inhibitors. The fate of B cell subpopulations may be widely influenced by the cytokine milieu, with versatile roles for B-specific cytokines B cell activating factor and B cell attracting chemokine-1/CXCL13, and a master regulatory role for IL-10. Roles of B cell-specific immune checkpoints such as TIM-1 are emerging and could represent potential therapeutic targets. Overall, the expanding field of B cells in solid tumors of holds promise for the improvement of current immunotherapy strategies and patient selection.

Tracing histoplasmosis genomic epidemiology and species occurrence across the USA.

ABSTRACTHistoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of Histoplasma capsulatum sensu lato, Histoplasma mississippiense (Nam1) and H. ohiense (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 Histoplasma isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, H. ohiense and H. mississippiense; with sporadic cases caused by H. suramericanum in California and Texas. While H. ohiense is prevalent in eastern states, H. mississipiense was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that H. ohiense thrives in places with warmer and drier conditions, while H. mississippiense is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.

Safety and efficacy of nivolumab in elderly patients with metastatic clear cell renal cell carcinoma: Analysis of the NIVOREN GETUG-AFU 26 study.

INTRODUCTION: Immune checkpoint inhibitors are standard of care in metastatic renal cell carcinoma but their activity and safety in elderly patients is insufficiently explored. We evaluated outcomes of elderly patients with mRCC treated with nivolumab in the GETUG-AFU 26 NIVOREN phase 2 trial (NCT03013335) and conducted exploratory circulating biomarker analyses. METHODS: Patients with mRCC were treated with nivolumab after at least one antiangiogenic therapy. The main endpoint of this analysis was safety in patients ≥ 70 years old (y.o), as per the rate of treatment-related grade 3-5 events (TRAE). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival. Exploration of candidate biomarkers associated with aging included baseline circulating cytokines involved in inflammation, adhesion, immune checkpoints, angiogenesis (IL6, IL7, IL8, BAFF, CXCL13, VCAM-1, 4-1BB, VEGF). RESULTS: Of 720 patients, 515 were < 70 y.o and 205 ≥ 70 y.o. Patients ≥ 70 y.o exhibited numerically less IMDC poor risk disease (21.0% vs 26.9%), sarcomatoid component (4.9% vs 9.8%) or brain metastases (5.9% vs. 14.7%), but more previous treatment lines (≥ 2 in 54.1% vs 48.5%). TRAE were higher in patients ≥ 70 y.o (24.9% vs. 17.9%, p = 0.033). Respective ORR (19.2% vs. 22.1%) and median PFS (4.5 versus 3.0 months, HR 0.97 [95%CI 0.81-1.15]) were similar. Overall survival was shorter in patients ≥ 70 y.o (19.3 versus 26.9 months, HR 1.26 [95%CI 1.04-1.51]), but not significantly in a competitive risk model. Only V-CAM1 and 4-1BB were found to be increased in patients ≥ 70 y.o. CONCLUSIONS: Nivolumab displayed higher grade 3/4 TRAE but manageable toxicity in elderly patients, with sustained activity. Elderly patients did not display specific inflammatory or angiogenic circulating profiles.

Molecular detection of Paracoccidioides spp. in environmental samples from the Southwestern Amazon.

Paracoccidioidomycosis is an infection with the potential for environmental dissemination, especially in regions of hot and humid climate, where human cases have been recorded in the Southwestern Amazon of Brazil, specifically in the state of Acre. Despite studies providing information about the presence of these fungi in soil and animal samples, such as armadillos, further investigations are still needed to determine the epidemiological distribution of the genus Paracoccidioides. The aim of this study was to detect the occurrence of Paracoccidioides fungi in the Southwestern Amazon. To achieve this, 60 soil samples were collected from armadillo burrows on rural properties in the in the municipalities of Acrelândia, Bujari, Plácido de Castro, Rio Branco, Sena Madureira, and Senador Guiomard, located in the state of Acre, Brazil. Fungal DNA was extracted from these samples using the DNEASY® PowerSoil kit-Quiagen, followed by Nested PCR technique with ITS4 and ITS5 as external primers, and PBITS-E and PBITS-R as internal primers. DNA amplification products of about 380 bp compatible with Paracoccidioides spp. were detected in six samples (10%), being sequenced and identified as P. brasiliensis. These findings indicate that the soils of the Acre state could be considered a potential source for Paracoccidioides spp., suggesting that local infections are likely.

Exposure-response relationship of cabozantinib in patients with metastatic renal cell carcinoma treated in routine care.

BACKGROUND: Interindividual pharmacokinetic variability may influence the clinical benefit or toxicity of cabozantinib in metastatic renal cell carcinoma (mRCC). We aimed to investigate the exposure-toxicity and exposure-response relationship of cabozantinib in unselected mRCC patients treated in routine care. METHODS: This ambispective multicenter study enrolled consecutive patients receiving cabozantinib in monotherapy. Steady-state trough concentration (Cmin,ss) within the first 3 months after treatment initiation was used for the PK/PD analysis with dose-limiting toxicity (DLT) and survival outcomes. Logistic regression and Cox proportional-hazards models were used to identify the risk factors of DLT and inefficacy in patients, respectively. RESULTS: Seventy-eight mRCC patients were eligible for the statistical analysis. Fifty-two patients (67%) experienced DLT with a median onset of 2.1 months (95%CI 0.7-8.2). In multivariate analysis, Cmin,ss was identified as an independent risk factor of DLT (OR 1.46, 95%CI [1.04-2.04]; p = 0.029). PFS and OS were not statistically associated with the starting dose (p = 0.81 and p = 0.98, respectively). In the multivariate analysis of PFS, Cmin, ss > 336 ng/mL resulted in a hazard ratio of 0.28 (95%CI, 0.10-0.77, p = 0.014). By contrast, Cmin, ss > 336 ng/mL was not statistically associated with longer OS. CONCLUSION: Early plasma drug monitoring may be useful to optimise cabozantinib treatment in mRCC patients treated in monotherapy, especially in frail patients starting at a lower than standard dose.

Multi-locus sequencing typing reveals geographically related intraspecies variability of Sporothrix brasiliensis.

Sporotrichosis is a subcutaneous mycosis caused by pathogenic Sporothrix species. Among them, Sporothrix brasiliensis is the main species associated with endemic regions in South America, especially Brazil. It is highly virulent and can be spread through zoonotic transmission. Molecular epidemiological surveys are needed to determine the extent of genetic variation, to investigate outbreaks, and to identify genotypes associated with antifungal resistance and susceptibility. This study investigated the sequence variation of different constitutive genes and established a novel multilocus sequence typing (MLST) scheme for S. brasiliensis. Specific primers were designed for 16 genes using Primer-BLAST software based on the genome sequences of three S. brasiliensis strains (ATCC MYA-4823, A001 and A005). Ninety-one human, animal, and environmental S. brasiliensis isolates from different Brazilian geographic regions (South, Southeast, Midwest and Northeast) andtwo isolates from Paraguay were sequenced. The loci that presented the highest nucleotide diversity (π) were selected for the MLST scheme. Among the 16 studied genetic loci, four presented increased π value and were able to distinguish all S. brasiliensis isolates into seven distinct haplotypes. The PCR conditions were standardized for four loci. Some of the obtained haplotypes were associated with the geographic origin of the strains. This study presents an important advance in the understanding of this important agent of sporotrichosis in Brazil. It significantly increased the discriminatory power for genotyping of S. brasiliensis isolates, and enabled new contributions to the epidemiological studies of this human and animal pathogen in Brazil and in other countries.

"Homeopathy is not placebo effect": proof of the scientific evidence for homeopathy [Editorial]

Homeopathy has been a medical practice recognized worldwide for more than two centuries, providing care, teaching, and research activities in several health institutions and medical schools. It employs a clinical approach based on non-conventional and complementary scientific principles (principle of therapeutic similitude, homeopathic pathogenetic experimentation, and use of dynamized doses and individualized medicines), with the aim of awakening a curative response from the body against its own disorders or diseases1. Homeopathy proposes to understand and treat the sick-disease binomial according to a vitalist, globalizing, and humanist anthropological approach, valuing the different aspects of the sick individuality (mental, general, and physical) and contributes to maintain health and organic homeostasis, acting as a therapeutic alternative for various health disorders2,3. However, to achieve this objective, homeopathic therapy must be well conducted and follow the epistemological premises of the homeopathic model1, among which include applying therapeutic similitude/similarity between the set of signs and symptoms of the sick individual (characteristic symptomatic totality of the sick-disease binomial) and the set of pathogenetic signs and symptoms caused by the medicine in the healthy individual (homeopathic pathogenetic experimentation), meaning individualized homeopathic treatment.

Homeopathy is not placebo effect: proof of scientific evidence for homeopathy

Homeopathy has been a medical practice recognized worldwide for more than two centuries, performing care, teaching and research activities in several health institutions and medical schools. It employs a clinical approach based on heterodox and complementary scientific principles (principle of therapeutic similitude, homeopathic pathogenetic experimentation, use of individualized medicines and dynamized or potentiated doses), with the aim of awakening a curative response in the body against its own disorders and/or diseases. Based on different premises from those used by conventional medical practice, homeopathy is often the target of unfounded and widespread criticism from individuals who systematically deny homeopathic assumptions and any scientific evidence that proves them due to their pseudoskeptical and pseudoscientific stance, which prevents a correct and bias-free analysis. In order to enlighten doctors, researchers, health professionals and the general public, demystifying culturally rooted dogmatic positions and the pseudoskeptical fallacies that "there is no scientific evidence for homeopathy" and "homeopathy is placebo effect", the Technical Chamber of Homeopathy of the Regional Council of Medicine of the State of São Paulo (TC-Homeopathy, Cremesp) prepared the "Special Dossier: Scientific Evidence for Homeopathy" in 2017, made available in three independent editions (online in Portuguese and English; printed in Portuguese) in the Revista de Homeopatia (São Paulo). Then, the dossier was published in Spanish in the La Homeopatía de México journal in 2023 in an edition commemorating the journal's 90th anniversary. Encompassing nine narrative reviews on the various lines of homeopathy research and containing hundreds of scientific articles describing experimental and clinical studies, the Dossier highlighted the state of the art of homeopathic science. Proving and expanding this scientific evidence in 13 chapters, the current work aims to update and clarify knowledge in the area. In addition to elucidating the epistemological premises of the homeopathic model in detail, the work describes the various aspects of basic and clinical research which endorse homeopathic practice and treatment in a continuum of information, data and bibliographic references. The work discusses various topics related to research in homeopathy, covering everything from "homeopathic clinical epidemiology" to "pseudoskeptic and pseudoscientific strategies used in attacks on homeopathy", including "pharmacological basis of the principle of similitude", "experimental studies in biological models", "randomized controlled clinical trials", "systematic reviews, meta-analyses and global reports" and "observational studies", among others. In view of the fact that it becomes fruitless and tiring to describe and analyze all the studies and experiments from the different research lines, we suggest and systematize in the different chapters for those who want to delve deeper into the areas of interest, bibliographical surveys of existing literature through the different databases. As we reiterate throughout the work, despite the difficulties and limitations that exist in developing research in homeopathy due to both methodological aspects and the lack of institutional and financial support, the set of experimental and clinical studies described is indisputable proof that "there is scientific evidence for homeopathy" and "homeopathy is not placebo effect", contrary to falsely disseminated prejudice. However, new studies must continue to be developed to improve clinical practice and elucidate peculiar aspects of the homeopathic paradigm. Acting as an integrative and complementary therapy to other specialties, homeopathy can add efficacy, effectiveness, efficiency and safety to medical practice, acting in a curative and preventive manner, reducing symptomatic manifestations and the predisposition to falling ill, with low cost and minimal adverse events, helping doctors to fulfill their "highest and only mission, which is to make sick people healthy, which is called healing" (Samuel Hahnemann, Organon of Medicine, § 1).

La homeopatía no es efecto placebo: comprobación de las evidencias científicas en homeopatía / Homeopathy is not Placebo Effect: Proof of Scientific Evidence for Homeopathy

La Homeopatía ha sido una práctica médica de renombre mundial durante más de dos siglos, desarrollando actividades asistenciales, docentes y de investigación en varias instituciones de salud y escuelas de medicina. Emplea un enfoque clínico basado en principios científicos heterodoxos y complementarios (principio de similitud terapéutica, experimentación patogénica homeopática, uso de medicamentos individualizados y dosis dinamizadas), con el objetivo de despertar una respuesta curativa del organismo frente a sus propios trastornos o enfermedades. Partiendo de premisas diferentes a las empleadas por la práctica médica convencional, la Homeopatía suele ser objeto de críticas infundadas y generalizadas por parte de individuos que niegan sistemáticamente los supuestos homeopáticos y cualquier evidencia científica que los demuestre porque tienen una postura pseudoescéptica y pseudocientífica que impide un análisis correcto y desprejuiciado. Son "pseudoescépticos" disfrazados de "pseudocientíficos". Ilustrar a médicos, investigadores, profesionales de la salud y al público en general, desmitificando las posturas dogmáticas culturalmente arraigadas y las falacias pseudoescépticas de que "no hay evidencia científica en la Homeopatía" y "la Homeopatía es un efecto placebo", en 2017, la Cámara Técnica de Homeopatía del Consejo Regional de Medicina del Estado de São Paulo (CT-Homeopatía, Cremesp) elaboró el "Dossier Especial: Evidencia Científica en Homeopatía", disponible en tres ediciones independientes (en línea en portugués e inglés; impresa en portugués) en la Revista de Homeopatía (São Paulo). En 2023, el dossier fue publicado en español en la revista La Homeopatía de México, en una edición conmemorativa del 90 aniversario de la revista. Abarcando nueve revisiones narrativas sobre las diversas líneas de investigación en Homeopatía, que contienen cientos de artículos científicos que describen estudios experimentales y clínicos, el dossier destacó el estado del arte de la ciencia homeopática. Demostrando y ampliando esta evidencia científica, el presente trabajo ("La Homeopatía no es Efecto Placebo": Comprobación de las Evidencias Científicas en Homeopatía) pretende esclarecer los conocimientos en el área en trece capítulos. Además de dilucidar en detalle las premisas epistemológicas del modelo homeopático, el trabajo describe, en un continuo de información, datos y referencias bibliográficas, los diversos aspectos de la investigación básica y clínica que avalan la práctica y el tratamiento homeopático. Discutiendo diversos temas relacionados con la investigación en Homeopatía, el libro aborda desde la "epidemiología clínica homeopática" hasta las "estrategias pseudoescépticas y pseudocientíficas utilizadas en los ataques a la Homeopatía", pasando por el "fundamento farmacológico del principio de similitud", "estudios experimentales en modelos biológicos", "ensayos clínicos controlados aleatorizados", "revisiones sistemáticas, metaanálisis e informes globales" y "estudios observacionales", entre otros. Como hemos reiterado a lo largo del libro, a pesar de las dificultades y limitaciones en el desarrollo de la investigación en Homeopatía, tanto por aspectos metodológicos como por la ausencia de apoyo institucional y financiero, el conjunto de estudios experimentales y clínicos descritos es una prueba irrefutable de que "existen evidencias científicas en Homeopatía" y "la Homeopatía no es efecto placebo", contrariamente al prejuicio falsamente difundido. Actuando como terapia integradora y complementaria a otras especialidades, la Homeopatía puede agregar eficacia, efectividad, eficiencia y seguridad a la práctica médica, reduciendo las manifestaciones sintomáticas y la predisposición a la enfermedad, con bajo costo y mínimos eventos adversos.