Effect of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide in combination with antibacterial drugs against Klebsiella pneumoniae.

Klebsiella pneumoniae is a species of Gram-negative bacteria related to a wide range of infections and high rates of drug resistance. The combined use of antibacterial agents is one of the strategies that has been analyzed in recent years as part of the alternatives in the treatment of drug-resistant infections. Recently, the antibacterial activity of of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide has been demonstrated against K. pneumoniae, also indicating that this acetamide did not show significant cytotoxic potential in preliminary tests. Thus, it becomes an interesting substance for future studies that explore its antimicrobial capacity, including investigating its association with antibacterial drugs. Based on this, this research aimed to analyze the effects of the association of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide (CFA) with ciprofloxacin, cefepime, ceftazidime, meropenem and imipenem against K. pneumoniae strains. The results showed additivity when the substance was combined with ciprofloxacin and cefepime, indifference when associated with ceftazidime and synergistic effect when combined with meropenem and imipenem. Thus, the acetamide was able to optimize the effects of antibacterial drugs, reducing the concentrations necessary to cause bacterial death. These data indicate a potential future clinical use of these combinations, and further studies are needed to analyze this viability.

Oral paracoccidioidomycosis: a retrospective study of 95 cases from a single center and literature review.

BACKGROUND: The ecoepidemiological panorama of paracoccidioidomycosis (PCM) is dynamic and still ongoing in Brazil. In particular, data about the oral lesions of PCM are barely explored. The aim of this study was to report the clinicopathological features of individuals diagnosed with oral PCM lesions at an oral and maxillofacial pathology service in Rio de Janeiro, Brazil, in the light of a literature review. MATERIAL AND METHODS: A retrospective study was conducted on oral biopsies obtained from 1958 to 2021. Additionally, electronic searches were conducted in PubMed, Embase, Scopus, Web of Science, Latin American and Caribbean Center on Health Sciences Information, and Brazilian Library of Dentistry to gather information from large case series of oral PCM. RESULTS: Ninety-five cases of oral PCM were surveyed. The manifestations were more frequent among males (n=86/90.5%), middle-aged/older adults (n=54/58.7%), and white individuals (n=40/51.9%). The most commonly affected sites were the gingiva/alveolar ridge (n=40/23.4%) and lip/labial commissure (n=33/19.3%); however, one (n=40/42.1%) or multiple sites (n=55/57.9%) could also be affected. In 90 (94.7%) patients, "mulberry-like" ulcerations/moriform appearance were observed. Data from 21 studies (1,333 cases), mostly Brazilian (90.5%), revealed that men (92.4%; male/female: 11.8:1) and individuals in the fifth and sixth decades of life were the most affected (range: 7-89 years), with the gingiva/alveolar ridge, palate, and lips/labial commissure being the sites most frequently affected. CONCLUSIONS: The features of oral PCM lesions are similar to those reported in previous studies from Latin America. Clinicians should be aware of the oral manifestations of PCM, with emphasis on the clinicodemographic aspects and differential diagnoses, especially considering the phenomenon of the emergence of reported cases in rural and/or urban areas of Brazil.

Gingival neoplasms: a multicenter collaborative study of 888 patients in Brazil.

BACKGROUND: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. MATERIAL AND METHODS:  All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. RESULTS:  From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). CONCLUSIONS:  Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers.

Morita-Baylis-Hillman adducts derived from thymol: synthesis, in silico studies and biological activity against Giardia lamblia.

Giardiasis is a neglected disease, and there is a need for new molecules with less side effects and better activity against resistant strains. This work describes the evaluation of the giardicidal activity of thymol derivatives produced from the Morita-Baylis-Hillman reaction. Thymol acrylate was reacted with different aromatic aldehydes, using 1,4-diazabicyclo[2.2.2]octane (DABCO) as a catalyst. Eleven adducts (8 of them unpublished) with yields between 58 and 80% were obtained from this reaction, which were adequately characterized. The in silico prediction showed theoretical bioavailability after oral administration as well as antiparasitic activity against Giardia lamblia. Compound 4 showed better biological activity against G. lamblia. In addition to presenting antigiardial activity 24 times better than thymol, this MBHA was obtained in a short reaction time (3 h) with a yield (80%) superior to the other investigated molecules. The molecule was more active than the precursors (thymol and MBHA 12) and did not show cytotoxicity against HEK-293 or HT-29 cells. In conclusion, this study presents a new class of drugs with better antigiardial activity in relation to thymol, acting as a basis for the synthesis of new bioactive molecules. Molecular hybridization technique combined with the Morita-Baylis-Hillman reaction provided new thymol derivatives with giardicidal activity superior to the precursor molecules.

Primary melanoma of the oral cavity: A multi-institutional retrospective analysis in Brazil.

BACKGROUND: Melanoma is an aggressive malignant tumor, rarely observed in the oral cavity. The aim of this study was to describe the clinicopathologic features of a series of oral melanomas. MATERIAL AND METHODS: A retrospective descriptive study was performed. A total of 15,482 biopsy records from two oral and maxillofacial pathology services in Brazil were analyzed. All cases of oral melanomas were reviewed, and clinical, demographic, histopathological data, treatment, and follow-up status were collected. In addition, immunohistochemistry stains (pan-cytokeratin AE1/AE3, vimentin, α-SMA, CD45, S-100 protein, HMB-45, Melan A, and Ki-67) were performed. RESULTS: The series comprised of 5 males (71.4%) and 2 females (28.6%), with a mean age of 58.0 ± 9.2 years (range: 45-69 years) and a 2.5:1 male-to-female ratio. The gingiva (n = 3, 42.8%) and hard palate (n = 2, 28.6%) were the most common affected sites, presenting clinically as ulcerated swellings with a brown to black color. Cervical lymph node metastasis was detected in three patients during the first examination. Microscopically, 6 cases (85.7%) were melanotic, and one (14.3%) was amelanotic. Most cases (n = 4, 57.1%) presented a predominance of epithelioid cells. S-100 and HMB-45 were positive in all cases (n = 7, 100.0%). In contrast, only 4 cases (57.1%) were positive for Melan-A. The proliferative index with Ki-67 was high, with labeling index ranging from 70.0% to more than 90% of positive cells. Five patients died from complications of the tumors after a mean follow-up period of 7.8 months. CONCLUSIONS: Melanoma is an aggressive malignant tumor that rarely occurs in the oral cavity. It occurs mainly in adult and elderly patients and often is diagnosed in advanced stages. The current findings were similar to previous studies and reflected the characteristics of the services from where lesions were retrieved.

Oral pigmented lesions: a retrospective analysis from Brazil.

BACKGROUND: Pigmented lesions are uncommon in the oral mucosa, and studies investigating the incidence and types of these lesions are desired to improve the diagnostic knowledge of clinicians. The aim of this study was to analyze the distribution of oral pigmented lesions in a Brazilian population. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. Oral pigmented lesions were retrieved from the files of two oral and maxillofacial pathology services from Brazil over a 45-year period (1974-2019). The clinical data and the diagnoses of each case were retrieved and included in a Microsoft Excel® database. RESULTS: From 77.074 lesions diagnosed in this period, 761 (0.99%) represented pigmented lesions of the oral mucosa, including 351 (46.1%) melanocytic and 410 (53.9%) non-melanocytic lesions, with a higher incidence in females (73.2%) between the fourth and seventh decades of life. Amalgam tattoo (53.6%) represented the most common lesion, followed by melanotic macule (18.3%) and racial pigmentation (10.8%). Other pigmented lesions included nevus (9.9%), post-inflammatory pigmentation (3%), melanoma (2.1%), melanoacanthoma (1.4%), smoker's melanosis (0.4%), drug-induced pigmentation (0.3%), and melanotic neuroectodermal tumor of infancy (0.1%). The buccal mucosa was the most commonly affected site (25.2%), followed by the alveolar ridge (14.5%), and gingiva (11.8%). CONCLUSIONS: The current findings were similar to previous studies with minor differences due methodology and characteristics of the services from where lesions were retrieved. The knowledge of these data may contribute to a better understanding of oral pigmented lesions and assist clinicians to better recognize and manage them.

Development of an annual drought classification system based on drought severity indexes.

In order to characterize the occurrence and intensity of droughts in the Doce River Basin, as well as to develop a system for its classification, four different drought indexes were evaluated: Percent of Normal Precipitation (PNP), Deciles Method (DM), Rainfall Anomaly Index (RAI) and Standardized Precipitation Index (SPI). The indices were calculated annually, based on precipitation data from 89 rainfall stations of the Brazilian National Water Agency (ANA). Nine analysis units (AUs) were determined in the basin and the Thiessen Polygons method was used to obtain the average precipitation in the respective drainage areas. The indices were calculated for each AU and then related to the drought intensity classes. An overall classification of the indices was proposed for the drought classification system for a 30-year base period, from 1985 to 2015. The most critical hydrological years of the Doce River Basin in relation to the drought were 1994/1995, 2000/2001 and 2014/2015, the latter being the most critical of the last 30 years. The results show that the annual drought classification system proved to be efficient in the identification of events, allowing to verify that the Doce River Basin presents a severe climatic drought condition, on average, every seven years.

The predictive effect of primary tumour location in the treatment of metastatic colorectal cancer: a Canadian consensus statement.

In recently published data, the predictive value of primary tumour location for the treatment of metastatic colorectal cancer with available biologic therapies has been explored. Recognizing the potential effect of those data on clinical practice, we convened a meeting of Canadian experts who treat metastatic colorectal cancer to develop a set of national, evidence-based treatment guidelines based on primary tumour location. This report summarizes the relevant evidence and presents the consensus recommendations of those experts.

Ecohydrological modeling and environmental flow regime in the Formoso River, Minas Gerais State, Brazil.

This paper aimed at determining the environmental flow regime in a 1 km stretch of the Formoso River, MG, using River2D model. To carry out the ecohydrological modeling, the following information was used: bathymetry, physical and hydraulic features, and the Habitat Suitability Index for species of the Hypostomus auroguttatus. In the River2D, the Weighted Usable Areas were determined from the average long-term streamflows with percentage from 10% to 100%. Those streamflows were simulated for the later construction of optimization matrices that maximize the habitat area throughout the year. For H. auroguttatus Juvenile, higher values of Weighted Usable Area were associated with the percentage of 60% and 70% of the average long-term streamflows in October and September, respectively. For H. auroguttatus Adult, the highest value of Weighted Usable Area was associated with the percentage of 100% of the average long-term streamflow in September. The environmental flows found for this stretch of the Formoso River varied over the year. The lowest environmental flow was observed in December (2.85 m3 s-1), while the highest was observed in May (4.13 m3 s-1). This paper shows the importance of ecohydrological studies in forming a basis for water resources management actions.

Prosthetic Oral Rehabilitation of a Child With S-ECC: A Case Report with Histopathologic Analysis.

The aim of this case report is to describe the treatment planning of a young child with severe early childhood caries (S-ECC) as well as the prosthetic rehabilitation technique. A 3-year-old female child was referred to the pediatric dentistry clinic with the chief complaint of tooth pain, difficulty in eating and recurrent hospitalizations caused by dental infections. The mother reported intermittent episodes of fever and recurrent swelling of child's face. The girl presented angular cheilitis and was referred to a dietitian. The treatment plain consisted on a behavior changes in oral hygiene habits, exodontias of all primary teeth and oral rehabilitation with a prosthesis. The extracted teeth with periapical lesions were submitted to histopathologic analysis (hematoxilin and eosin staining) and revealed an inflammatory infiltrate. The aesthetic requirement of children with S-ECC has been a challenge to pediatric dentists. In the present case, the oral rehabilitation provided for the children better aesthetic, nutrition, phonation, and functional conditions.

Convergence of a specialized root trait in plants from nutrient-impoverished soils: phosphorus-acquisition strategy in a nonmycorrhizal cactus.

In old, phosphorus (P)-impoverished habitats, root specializations such as cluster roots efficiently mobilize and acquire P by releasing large amounts of carboxylates in the rhizosphere. These specialized roots are rarely mycorrhizal. We investigated whether Discocactus placentiformis (Cactaceae), a common species in nutrient-poor campos rupestres over white sands, operates in the same way as other root specializations. Discocactus placentiformis showed no mycorrhizal colonization, but exhibited a sand-binding root specialization with rhizosheath formation. We first provide circumstantial evidence for carboxylate exudation in field material, based on its very high shoot manganese (Mn) concentrations, and then firm evidence, based on exudate analysis. We identified predominantly oxalic acid, but also malic, citric, lactic, succinic, fumaric, and malonic acids. When grown in nutrient solution with P concentrations ranging from 0 to 100 µM, we observed an increase in total carboxylate exudation with decreasing P supply, showing that P deficiency stimulated carboxylate release. Additionally, we tested P solubilization by citric, malic and oxalic acids, and found that they solubilized P from the strongly P-sorbing soil in its native habitat, when the acids were added in combination and in relatively low concentrations. We conclude that the sand-binding root specialization in this nonmycorrhizal cactus functions similar to that of cluster roots, which efficiently enhance P acquisition in other habitats with very low P availability.

Cyclin D1-induced proliferation is independent of beta-catenin in head and neck cancer.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) progression and metastasis have previously been associated with the activation of phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) and Wnt signalling pathways, which lead to the activation of pro-proliferative genes, such as cyclin D1. The current study aims to investigate whether there is a crosstalk between these pathways in HNSCC and which pathway is more likely to regulate cyclin D1. MATERIAL AND METHODS: Two HNSCC and a control keratinocyte cell lines were treated with EGF and wortmannin to respectively activate and block the PI3K-Akt and Wnt pathways. Partial and total levels of cyclin D1, beta-catenin and Akt were evaluated by Western blotting and immunofluorescence. Twenty-four paraffin-embedded samples of human HNSCC, as well as normal oral mucosa biopsies, were also immunohistochemically evaluated for beta-catenin and cyclin D1 expression. RESULTS: Following both treatments, change in cyclin D1 protein was correlated with Akt levels only. Cytoplasmic staining for beta-catenin and loss of its membranous expression in the HNSCC invasive areas were found in 92% of the HNSCC biopsies. CONCLUSION: Taken together, we show that the change in cyclin D1 levels is more likely to be due to the EGFR-Akt pathway activation than due to beta-catenin nuclear translocation.

Estimating motor unit numbers from a CMAP scan: Repeatability study on three muscles at 15 centres.

OBJECTIVE: To assess the repeatability and suitability for multicentre studies of MScanFit motor unit number estimation (MUNE), which involves modelling compound muscle action potential (CMAP) scans. METHODS: Fifteen groups in 9 countries recorded CMAP scans twice, 1-2 weeks apart in healthy subjects from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. The original MScanFit program (MScanFit-1) was compared with a revised version (MScanFit-2), designed to accommodate different muscles and recording conditions by setting the minimal motor unit size as a function of maximum CMAP. RESULTS: Complete sets of 6 recordings were obtained from 148 subjects. CMAP amplitudes differed significantly between centres for all muscles, and the same was true for MScanFit-1 MUNE. With MScanFit-2, MUNE differed less between centres but remained significantly different for APB. Coefficients of variation between repeats were 18.0% for ADM, 16.8% for APB, and 12.1% for TA. CONCLUSIONS: It is recommended for multicentre studies to use MScanFit-2 for analysis. TA provided the least variable MUNE values between subjects and the most repeatable within subjects. SIGNIFICANCE: MScanFit was primarily devised to model the discontinuities in CMAP scans in patients and is less suitable for healthy subjects with smooth scans.

Patient-centered Outcomes in Breast Cancer: Description of EQ-5D-5L and EORTC-QLQ-BR23 Measurements in Real-world Data and Their Association With Survival.

AIMS: In recent years, major improvements in breast cancer treatments have led to a significant increase in survival. Despite that, this population's quality of life (QoL) information is lacking, especially real-world data. MATERIALS AND METHODS: This was a prospective, multicentre, observational study of female breast cancer patients, without prior systemic treatment, treated between 2012 and 2019 in private health care in Brazil. QoL was assessed by two questionnaires, the EQ-5D-5L and the EORTC-QLQ-BR23. Additional data were retrospectively collected. RESULTS: The study comprised 1372 patients, most with early-stage disease (80.2% stages 0-II). At a median follow-up of 25.6 months, the estimated 3-year overall survival was 93.6%. Patients with locally advanced and metastatic breast cancer had the lowest visual analogue scale scores and the highest symptom burden in all dimensions of EQ-5D-5L, but with the most significant improvement after treatment. With the EORTC-QLQ-BR23 questionnaire, patients undergoing lumpectomy had a better perception of body image. Axillary dissection led to greater arm symptoms after 12 months, radiotherapy enhanced breast symptoms and patients treated with chemotherapy had significant worsening in the effects of systemic therapy compared with endocrine or HER2 therapy. Staging and immunohistochemical subtype correlated with survival and with several QoL parameters, but overall survival was not independently affected by patient-reported outcomes in this cohort. CONCLUSION: Our results show that early diagnosis and access to treatments with fewer side-effects, such as endocrine or targeted therapy, and less aggressive surgeries are the best strategies to achieve a better QoL for breast cancer patients.

First complete NMR data and theoretical study of an antimicrobial formylated dihydrochalcone from Psidium guineense Sw.

Chalcones are a widespread group of natural compounds characterized by the basic structure 1,3-diaryl-2-propen-1-one. In this study, we focused on the uncommon formylated chalcone 3'-formyl-2',4',6'-trihydroxy-5'-methyldihydrochalcone that possess interesting antimicrobial and anticancer potential. Considering the pharmacological relevance of this compound, we report its isolation and the first complete and unequivocal NMR data for this substance, corroborated by in silico theoretical study. In addition to that, its antibacterial potential was evaluated and the compound presented strong activity against Pseudomonas aeruginosa.[Formula: see text].

Vasorelaxation, induced by Dictyota pulchella (Dictyotaceae), a brown alga, is mediated via inhibition of calcium influx in rats.

This study aimed to investigate the cardiovascular effects elicited by Dictyota pulchella, a brown alga, using in vivo and in vitro approaches. In normotensive conscious rats, CH(2)Cl(2)/MeOH Extract (CME, 5, 10, 20 and 40 mg/kg) from Dictyota pulchella produced dose-dependent hypotension (-4 ± 1; -8 ± 2; -53 ± 8 and -63 ± 3 mmHg) and bradycardia (-8 ± 6; -17 ± 11; -257 ± 36 and -285 ± 27 b.p.m.). In addition, CME and Hexane/EtOAc Phase (HEP) (0.01-300 µg/mL) from Dictyota pulchella induced a concentration-dependent relaxation in phenylephrine (Phe, 1 µM)-pre-contracted mesenteric artery rings. The vasorelaxant effect was not modified by the removal of the vascular endothelium or pre-incubation with KCl (20 mM), tetraethylammonium (TEA, 3 mM) or tromboxane A(2) agonist U-46619 (100 nM). Furthermore, CME and HEP reversed CaCl(2)-induced vascular contractions. These results suggest that both CME and HEP act on the voltage-operated calcium channel in order to produce vasorelaxation. In addition, CME induced vasodilatation after the vessels have been pre-contracted with L-type Ca(2+) channel agonist (Bay K 8644, 200 nM). Taken together, our data show that CME induces hypotension and bradycardia in vivo and that both CME and HEP induce endothelium-independent vasodilatation in vitro that seems to involve the inhibition of the Ca(2+) influx through blockade of voltage-operated calcium channels.

Immunohistochemical analysis of BRCA1 and acetyl-histone H3 in squamous cell carcinoma of the mobile tongue.

OBJECTIVE: The objective of this study was to evaluate the immunoexpression profiles of breast cancer 1 (BRCA1) and acetyl-histone H3 (AcH3) in squamous cell carcinoma of the mobile tongue (SCC-MT) and their correlation with epidemiologic data and the histopathological grade of tumors. STUDY DESIGN: Incisional biopsies of 43 SCC-MT were submitted to immunohistochemistry for AcH3 and BRCA1. Samples were microscopically graded as well differentiated (n = 21) or poorly differentiated (n = 22). Both groups were submitted to statistical analysis (P < .05) regarding the percentage of positive cells. RESULTS: Thirty-nine cases were positive for AcH3 (91%), but no difference was observed for the histologic grading (P = .27). Positivity for BRCA1 was observed in all samples regardless of their cellular locations. Most cases in the poorly differentiated group presented with less than 10% nuclear staining (P < .01) and a predominance of cytoplasmic staining (P = .034). The well-differentiated group showed nuclear staining in most of the cases, with more than 50% of cells staining positive (P < .01). CONCLUSION: AcH3 and BRCA1 were expressed in all samples. There was a significant decrease in cytoplasmic BRCA1 expression in the poorly differentiated group, suggesting BRCA1 as a possible prognostic marker for SCC-MT.

Araçain, a tyrosol derivative and other phytochemicals from Psidium guineense Sw.

Psidium guineense Sw. (Myrtaceae) is a shrub distributed all over South America and Brazil. Its leaves are traditionally used to treat digestive problems and infections. Several biological activities have been reported for P. guineense extracts, however phytochemical studies are scarce. The present study is on the isolation of compounds from P. guineense leaf extracts using chromatographic and spectroscopic techniques and evaluation of their antibacterial activity. Araçain, a tyrosol derivative was isolated as a natural product for the first time. Other compounds isolated were ursolic acid, a phaeophorbide and three flavonoids. The extracts were tested for their antimicrobial activity against Klebsiella pneumoniae strains and they showed moderate to high antibacterial activity.

The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.

A twelve-week, four-arm, randomized, double-blind, placebo-controlled, phase 2 prospective clinical trial to evaluate the efficacy and safety of an anthroposophic multimodal treatment on chronic pain in outpatients with postpolio syndrome.

INTRODUCTION: Chronic pain and fatigue are the main symptoms of postpoliomyelitis syndrome (PPS). This study aimed to evaluate the efficacy and safety of an anthroposophic multimodal treatment for chronic pain in PPS outpatients. METHODS: A twelve-week, four-arm, randomized, double-blind, placebo-controlled, phase 2 prospective clinical trial was designed to compare four groups (n = 48): groups A and B received daily active experimental transdermal gel (ETG) or placebo gel (PTG), respectively; groups C and D received weekly external therapies, art therapies, and neurofunctional reorganization, plus either daily ETG or PTG, respectively. The pain symptoms were evaluated through a visual analogue scale (VAS), the McGill questionnaire, and thermography. Quality of life and resilience were evaluated by the WHOQOL-BREF and Antonovsky sense of coherence questionnaires applied at baseline and after the interventions. RESULTS: No related adverse events occurred, and 10% of the patients reports dysphagia improvement. In the groups C and D, pain reduction was statistically significant in both the placebo group (p = .02, d = 1.315) and in the ETG (p = .005, d = 2.035). However, following the week-to-week evolution of pain with the concomitant use of the ETG, this significant pain reduction occurred earlier from the 4th week and continued to decrease (p = .016, d = 1.369). In the group that received the complete multimodal treatment, the greatest significant benefit in increasing quality of life occurred in the physical domain and elevation in resilience with an emphasis on meaning and comprehension domains. CONCLUSIONS: The anthroposophic multimodal treatment group presented both safety and efficacy as an analgesic in the groups that received the nonpharmacological therapies, much earlier when associated with the ETG. The multimodal approach corresponded to the pattern of better efficacy for both pain reduction and improvement in quality of life and resilience.