[Onco'sport testing by patients: Lived experience of patients with cancer practicing adapted physical activity as part of the Onco'sport program, a qualitative study]. / Onco'sport à l'épreuve des patients : expérience vecue des patients atteints d'un cancer pratiquant de l'activité physique adaptée dans le cadre du programme Onco'sport, une étude qualitative.

INTRODUCTION: Physical activity is a major determinant in the prevention of chronic diseases, equally on the side effects of treatments and the consequences of the disease. It improves quality of life, but also reduces morbidity and mortality, and therefore health expenses. A sedentary lifestyle is the fourth cause of premature death in the world, in the context of chronic non-communicable diseases. In France, the prescription for adapted physical activity (APA) has been included in the law since 2016. With the development of "Maisons Sport santé", the Onco'sport program was developed to enable people affected by cancer to participate in adapted physical activity. The objective of our work is to explore the lived experience of cancer patients practicing adapted physical activity as part of the Onco'sport program. METHODS: This is a qualitative study of 10 semi-directed individual interviews with patients participating in the Onco'sport program, recruited from the "Maison Sport Santé" from Nîmes and the association "Les Roses du Gard". A phenomenological analysis was carried out with a semiopragmatic approach. RESULTS: For all participants, the APA through a program provides professional supervision of Physical Activity, influences adherence and builds confidence. This program is at the origin of changes in lifestyle habits and improves the relationship with illness and their cancer thanks to the physical and psychological benefits felt. Thus, APA appears as a full-fledged supportive care which requires informing patients and promoting it so that access is facilitated and becomes a standard. Health professionals including general practitioners do not currently have an important place in the promotion of APA, and patients most often obtain documentation on their own or through associations of patient. CONCLUSION: An APA program like Onco'sport is often the cause of a return to physical activity in patients, brings overall well-being and changes lifestyle habits. It seems important to promote physical activity to patients but also to the general population, given the benefits. This promotion involves easier access to this type of supervised program, financial support and better training of health professionals.

Steroid Premedication Might Protect From Postoperative Erythema Nodosum Leprosum in Leprosy: A Case Report.

Leprosy is known for its diverse pathophysiologic involvement and resulting multisystemic manifestation and morbidities. Despite global efforts to eliminate this public health illness, it is still prevalent in some Asian and European countries. Perioperative management of a leprosy patient is challenging owing to the indirect and direct involvement of the airway, respiratory, and cardiac systems; treatment-related side-effects involving the hepato-renal systems affecting the anesthesia techniques and drugs pharmacokinetic and pharmacodynamics. While anaesthesiologists are aware of such happenings and often tailor the anesthesia management for the concerning issues, immunological aspects of the disease and drug-related adverse events are less enquired about, such as type-2 lepra reaction, i.e., erythema nodosum leprosum (ENL), etc. Further, data on perioperative ENL management and prevention are still being determined. We report one case of a 52-year-old female who underwent gynecology surgery and developed ENL on the third postoperative day, which was managed using Steroids. Unfortunately, the patient had a surgical site infection, which required another surgery within the month, while the patient was still under the steroid successfully without any adverse events. Although a single case cannot provide causation or association, the case is presented to highlight the probable preventive action of steroids on the occurrence of postoperative ENL, where surgical stress is considered a risk factor.

Autologous human preclinical modeling of melanoma interpatient clinical responses to immunotherapeutics.

BACKGROUND: Despite recent advances in immunotherapy, a substantial population of late-stage melanoma patients still fail to achieve sustained clinical benefit. Lack of translational preclinical models continues to be a major challenge in the field of immunotherapy; thus, more optimized translational models could strongly influence clinical trial development. To address this unmet need, we designed a preclinical model reflecting the heterogeneity in melanoma patients' clinical responses that can be used to evaluate novel immunotherapies and synergistic combinatorial treatment strategies. Using our all-autologous humanized melanoma mouse model, we examined the efficacy of a novel engineered interleukin 2 (IL-2)-based cytokine variant immunotherapy. METHODS: To study immune responses and antitumor efficacy for human melanoma tumors, we developed an all-autologous humanized melanoma mouse model using clinically annotated, matched patient tumor cells and peripheral blood mononuclear cells (PBMCs). After inoculating immunodeficient NSG mice with patient tumors and an adoptive cell transfer of autologous PBMCs, mice were treated with anti-PD-1, a novel investigational engineered IL-2-based cytokine (nemvaleukin), or recombinant human IL-2 (rhIL-2). The pharmacodynamic effects and antitumor efficacy of these treatments were then evaluated. We used tumor cells and autologous PBMCs from patients with varying immunotherapy responses to both model the diversity of immunotherapy efficacy observed in the clinical setting and to recapitulate the heterogeneous nature of melanoma. RESULTS: Our model exhibited long-term survival of engrafted human PBMCs without developing graft-versus-host disease. Administration of an anti-PD-1 or nemvaleukin elicited antitumor responses in our model that were patient-specific and were found to parallel clinical responsiveness to checkpoint inhibitors. An evaluation of nemvaleukin-treated mice demonstrated increased tumor-infiltrating CD4+ and CD8+ T cells, preferential expansion of non-regulatory T cell subsets in the spleen, and significant delays in tumor growth compared with vehicle-treated controls or mice treated with rhIL-2. CONCLUSIONS: Our model reproduces differential effects of immunotherapy in melanoma patients, capturing the inherent heterogeneity in clinical responses. Taken together, these data demonstrate our model's translatability for novel immunotherapies in melanoma patients. The data are also supportive for the continued clinical investigation of nemvaleukin as a novel immunotherapeutic for the treatment of melanoma.

[Mechanism of Kuntai Capsules in treatment of polycystic ovary syndrome rat models based on AGE-RAGE signal pathway].

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.

A retrospective study of dose-dense paclitaxel and carboplatin plus bevacizumab as first-line treatment of advanced epithelial ovarian cancer.

OBJECTIVE: This study compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer. METHODS: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III-IV ovarian cancer. Progression-free survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ² test. RESULTS: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017. No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32-0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41-1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable. CONCLUSION: This study could not demonstrate that adding Bev to ddTC improves prognosis. Further studies with more cases are warranted.

Geriatric assessment-identified impairments and frailty in adults with cancer younger than 65: An opportunity to optimize oncology care.

INTRODUCTION: Frailty, a state of increased vulnerability to stressors due to aging or treatment-related accelerated aging, is associated with declines in physical, cognitive and/or social functioning, and quality of life for cancer survivors. For survivors aged <65 years, little is known about frailty status and associated impairments to inform intervention. We aimed to evaluate the prevalence of frailty and contributing geriatric assessment (GA)-identified impairments in adults aged <65 versus ≥65 years with cancer. MATERIALS AND METHODS: This study is a secondary analysis of clinical trial data (NCT04852575). Participants were starting a new line of systemic therapy at a community-based oncology private practice. Before starting treatment, participants completed an online patient-reported GA and the Physical Activity (PA) Vital Sign questionnaire. Frailty score and category were derived from GA using a validated deficit accumulation model: frail (>0.35), pre-frail (0.2-0.35), or robust (0-0.2). PA mins/week were calculated, and participants were coded as either meeting/not-meeting guidelines (≥90 min/week). We used Spearman (ρ) correlation to examine the association between age and frailty score and chi-squared/Fisher's-exact or ANOVA/Kruskal-Wallis statistic to compare frailty and PA outcomes between age groups. RESULTS: Participants (n = 96) were predominantly female (62%), Caucasian (68%), beginning first-line systemic therapy (69%), and 1.75 months post-diagnosis (median). Most had stage III to IV disease (66%). Common cancer types included breast (34%), gastrointestinal (23%), and hematologic (15%). Among participants <65, 46.8% were frail or pre-frail compared to 38.7% of those ≥65. There was no association between age and frailty score (ρ = 0.01, p = 0.91). Between age groups, there was no significant difference in frailty score (p = 0.95), the prevalence of frailty (p = 0.68), number of GA impairments (p = 0.33), or the proportion meeting PA guidelines (p = 0.72). However, older adults had more comorbid conditions (p = 0.03) and younger adults had non-significant but clinically relevant differences in functional ability, falls, and PA level. DISCUSSION: In our cohort, the prevalence of frailty was similar among adults with cancer <65 when compared to those older than 65, however, types of GA impairments differed. These results suggest GA and the associated frailty index could be useful to identify needs for intervention and inform clinical decisions during cancer treatment regardless of age. Additional research is needed to confirm our findings.

Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice.

Purpose: Alcohol consumption increases the risk of breast cancer and promotes cancer progression. Alcohol exposure could affect both processes of the mammary carcinogenesis, namely, the cell transformation and onset of tumorigenesis as well as cancer aggressiveness including metastasis and drug resistance/recurrence. However, the cellular and molecular mechanisms underlying alcohol tumor promotion remain unclear. There are four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38ß, p38γ and p38δ. We have previously demonstrated alcohol exposure selectively activated p38γ MAPK in breast cancer cells in vitro and in vivo. Pirfenidone (PFD), an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis, is also a pharmacological inhibitor of p38γ MAPK. This study aimed to determine whether PFD is useful to inhibit alcohol-induced promotion of breast cancer. Methods: Female adolescent (5 weeks) MMTV-Wnt1 mice were exposed to alcohol with a liquid diet containing 6.7% ethanol. Some mice received intraperitoneal (IP) injection of PFD (100 mg/kg) every other day. After that, the effects of alcohol and PFD on mammary tumorigenesis and metastasis were examined. Results: Alcohol promoted the progression of mammary tumors in adolescent MMTV-Wnt1 mice. Treatment of PFD blocked tumor growth and alcohol-promoted metastasis. It also significantly inhibited alcohol-induced tumorsphere formation and cancer stem cell (CSC) population. Conclusion: PFD inhibited mammary tumor growth and alcohol-promoted metastasis. Since PFD is an FDA-approved drug, the current findings may be helpful to re-purpose its application in treating aggressive breast cancer and alcohol-promoted mammary tumor progression.

Cefadroxil and cephalexin pharmacokinetics and pharmacodynamics in children with musculoskeletal infections.

Cephalexin, a first-generation cephalosporin, is the first-line oral therapy for children with musculoskeletal infections due to methicillin-susceptible Staphylococcus aureus (MSSA). Cefadroxil, a similar first-generation cephalosporin, is an attractive alternative to cephalexin given its longer half-life. In this study, we describe the comparative pharmacokinetics (PK) and pharmacodynamics (PD) of cephalexin and cefadroxil in children with musculoskeletal infections. Children aged 6 months to 18 years with a musculoskeletal infection were enrolled in a prospective, open-label, crossover PK study and given single oral doses of cefadroxil (50-75 mg/kg up to 2,000 mg) and cephalexin (50 mg/kg up to 1,375 mg). Population PK models were developed and used for dosing simulations. Our primary PD target was the achievement of free antibiotic concentrations above the minimum inhibitory concentration (fT >MIC) for 40% of the day for MICs ≤ 4 mg/L. PK of cephalexin (n = 15) and cefadroxil (n = 14) were best described using a one-compartment, first-order absorption model, with a lag time component for cefadroxil. PK parameters were notable for cefadroxil's longer half-life (1.61 h) than cephalexin's (1.10 h). For pediatric weight bands, our primary PD target was achieved by cephalexin 25 mg/kg/dose, maximum 750 mg/dose, administered three times daily and cefadroxil 40 mg/kg/dose, maximum 1,500 mg/dose, administered twice daily. More aggressive dosing was required to achieve higher PD targets. Among children with musculoskeletal infections, oral cephalexin and cefadroxil achieved PD targets for efficacy against MSSA. Given less frequent dosing, twice-daily cefadroxil should be further considered as an alternative to cephalexin for oral step-down therapy for serious infections due to MSSA.

A blinded, randomized and controlled multicenter field study investigating the safety and efficacy of long-term use of enflicoxib in the treatment of naturally occurring osteoarthritis in client-owned dogs.

Background: Enflicoxib is a COX-2 selective NSAID shown to be efficacious and safe in the treatment of pain and inflammation associated with canine osteoarthritis (OA) in clinical studies of 6 weeks duration. Objective: This prospective, multisite, blinded, randomized, placebo-controlled, parallel-group field study aimed to confirm the safety and efficacy of enflicoxib in long-term canine OA treatments. Animals: A total of 109 client owned dogs with clinical and radiographic signs of OA for at least 3 weeks were enrolled with 78 dogs completing all study visits. Methods: Dogs were randomized at a 3:1 ratio to receive enflicoxib (n = 83) or placebo (n = 26) once weekly during 6 months. Dogs underwent veterinary assessments from Day 0 to Day 189 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). Safety was assessed clinically and by repeated blood and urine sample analysis. The efficacy outcome measure was the treatment response according to the CSS and secondarily the treatment response according to the CBPI. The primary safety outcome was the incidence of adverse events (AEs) and secondarily the evolution of the clinical pathology parameters. Results: Percentages of CSS responders for enflicoxib were 71.6; 74.6 and 71.6% on Days 44, 135 and 189 respectively, always showing statistically significant differences (p < 0.05) vs. placebo (41.7, 33.3, and 20.8% respectively). Treatment response according to owner assessments followed the same pattern, achieving significant differences compared to placebo after 2 weeks of treatment. The incidence and type of AEs were as described in previous enflicoxib studies of shorter duration and as for other NSAIDs, with no tendency to increase over time. No relevant changes in hematology, biochemistry or urine parameters were observed. Conclusions and clinical relevance: Enflicoxib safety and efficacy profile is maintained after a long-term treatment, which together with its weekly administration, makes it a good alternative for the chronic treatment of dogs with naturally occurring OA.

Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron.

BACKGROUNDAs Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection in the respiratory tract. Thus, elucidating the prophylactic efficacy of NAbs via nasal spray addresses an important clinical need.METHODSThe applicable potential of a nasal spray cocktail containing 2 NAbs was characterized by testing its neutralizing potency, synergetic neutralizing mechanism, emergency protective and therapeutic efficacy in a hamster model, and pharmacokinetics/pharmacodynamic (PK/PD) in human nasal cavity.RESULTSThe 2 NAbs displayed broad neutralizing efficacy against Omicron, and they could structurally compensate each other in blocking the Spike-ACE2 interaction. When administrated through the intranasal mucosal route, this cocktail demonstrated profound efficacy in the emergency prevention in hamsters challenged with authentic Omicron BA.1. The investigator-initiated trial in healthy volunteers confirmed the safety and the PK/PD of the NAb cocktail delivered via nasal spray. Nasal samples from the participants receiving 4 administrations over a course of 16 hours demonstrated potent neutralization against Omicron BA.5 in an ex vivo pseudovirus neutralization assay.CONCLUSIONThese results demonstrate that the NAb cocktail nasal spray provides a good basis for clinical prophylactic efficacy against Omicron infections.TRIAL REGISTRATIONwww.chictr.org.cn, ChiCTR2200066525.FUNDINGThe National Science and Technology Major Project (2017ZX10202203), the National Key Research and Development Program of China (2018YFA0507100), Guangzhou National Laboratory (SRPG22-015), Lingang Laboratory (LG202101-01-07), Science and Technology Commission of Shanghai Municipality (YDZX20213100001556), and the Emergency Project from the Science & Technology Commission of Chongqing (cstc2021jscx-fyzxX0001).

EXECUTIVE FUNCTIONS IN YOUNG ADULTS AGED 19 TO 24 YEARS WITH BREAST CANCER: AN EXPLORATORY REVIEW OF THE LITERATURE BETWEEN 2015 AND 2020 / FUNCIONES EJECUTIVAS EN ADULTOS JÓVENES DE 19 A 24 AÑOS CON CÁNCER DE MAMA: REVISIÓN EXPLORATORIA DE LITERATURA ENTRE 2015 Y 2020

With the growth and aging of the population, along with economic growth and changes in lifestyles associated with increased quality of life, the main burden of disease shifted from infectious diseases to noncommunicable and complex diseases. However, it is cancer that has increased its incidence in the world population, especially in low- and middle-income countries, where 70% of cancer deaths occur.  The research is articulated to sustainable development goal three, in particular on the effect of cancer on cognitive functioning, because cancer pain impairs cognitive functioning. A simple review for executive functions and breast cancer in PROSPERO indicated an absence of reviews on this topic. Reason why, our aim is to describe executive functions and treatment effect by chemotherapy/radiotherapy in young adult breast cancer patients between 2015 and 2020 in the scientific literature. Materials and methods: exploratory literature review according to PRISMA protocol for exploratory reviews. Articles published in Scopus, PubMed, ScienceDirect, scielo, google academic, in Spanish, English, French. With the keywords: ("Executive Function") AND ("Neoplasms") OR "breast cancer" OR "Drug Therapy," AND ("Young Adult"), searches were performed until February 4, 2020. Results: 16 articles included in the review. Clinical and methodological heterogeneity was found on patients' executive functions and treatment. However, we did find executive function impairment among patients assessed by both treatment and cancer. Conclusions: A systematic review on the subject and meta-analysis are suggested to identify the effect size, accompanied by the statistical evidence identified in the studies. Colombia could investigate this topic because there is no Colombian research.

Con el crecimiento y envejecimiento de la población, junto al crecimiento económico y los cambios en los estilos de vida asociados al incremento en la calidad de vida, la principal carga de morbilidad pasó de las enfermedades infecciosas a las no transmisibles y complejas. Sin embargo, es el cáncer incrementó su incidencia en la población mundial, especialmente en países de ingresos bajos y medios, dónde el 70% de las muertes por cáncer se presentan.  La investigación se articula al objetivo de desarrollo sostenible tres, en particular sobre el efecto del cáncer sobre el funcionamiento cognitivo, debido a que el dolor por cáncer deteriora el funcionamiento cognitivo. Una revisión sencilla por funciones ejecutivas y cáncer de mama en PROSPERO indicó una ausencia de revisiones en este tema. Razón por la cual, nuestro objetivo es describir las funciones ejecutivas y el efecto del tratamiento por quimioterapia/radioterapia en pacientes con cáncer de mama en adultos jóvenes entre 2015 y 2020 en la literatura científica. Materiales y métodos: Revisión exploratoria de literatura según protocolo PRISMA para revisiones exploratorias. Artículos publicados en Scopus, PubMed, ScienceDirect, scielo, google académico, en idioma español, inglés, francés. Con las palabras clave: ("Executive Function") AND ("Neoplasms") OR "breast cancer" OR "Drug Therapy," AND ("Young Adult"), las búsquedas se realizaron hasta el 4 de febrero de 2020. Resultados: 16 artículos incluidos en la revisión. Se encontró heterogeneidad clínica y metodológica sobre las funciones ejecutivas de los pacientes y el tratamiento. Sin embargo, sí se encontró afectación de funciones ejecutivas entre los pacientes evaluados tanto por el tratamiento cómo por el cáncer. Conclusiones: Se sugiere una revisión sistemática sobre el tema y meta-análisis para identificar el tamaño del efecto, acompañado de la evidencia estadística identificada en los estudios. Colombia podría investigar sobre esta temática debido a que no hay investigaciones colombianas.

Com o crescimento e o envelhecimento da população, juntamente com o desenvolvimento económico e as mudanças nos estilos de vida associadas ao aumento da qualidade de vida, o principal fardo da doença mudou de doenças infecciosas para doenças não transmissíveis e complexas. No entanto, é o câncer que aumentou a sua incidência na população mundial, especialmente nos países de baixa e média renda, onde 70% das mortes por câncer ocorrem. A pesquisa está articulada com o Objectivo de Desenvolvimento Sustentável 3, em particular sobre o efeito do câncer sobre o funcionamento cognitivo, porque a dor do cancro prejudica a função cognitiva. Uma simples revisão para funções executivas e câncer de mama em PROSPERO indicou uma ausência de comentários sobre este tópico. A razão pela qual, nosso objetivo é descrever as funções executivas e o efeito do tratamento por quimioterapia/radioterapia em pacientes jovens adultos com câncer de mama entre 2015 e 2020 na literatura científica. Materiais e métodos: revisão da literatura exploratória de acordo com o protocolo PRISMA para revisões exploratórias. Artigos publicados em Scopus, PubMed, ScienceDirect, scielo, google academic, em espanhol, inglês, francês. Com as palavras-chave: ("Função Executiva") E ("Neoplasmas") OU "câncer de mama" OU" Terapia de drogas," E ("Jovem Adulto"), as pesquisas foram realizadas até 4 de fevereiro de 2020. Resultados: 16 artigos incluídos na revisão. Foi encontrada heterogeneidade clínica e metodológica nas funções executivas e no tratamento dos pacientes. No entanto, descobrimos que a função executiva foi prejudicada entre os pacientes avaliados tanto pelo tratamento como pelo câncer. Conclusões: Sugere-se uma revisão sistemática do assunto e meta-análise para identificar o tamanho do efeito, acompanhada das provas estatísticas identificadas nos estudos. A Colômbia poderia investigar este assunto porque não há pesquisa colombiana.

Assessing the Effectiveness of Stabilized Cysteamine 5% Cream Compared to Hydroquinone 4%/Ascorbic Acid 3% Combination Cream in Treating Acne-induced Post-inflammatory Hyperpigmentation: A Randomized, Controlled Study.

Objective: Postinflammatory hyperpigmentation (PIH) is a common sequela of acne vulgaris. Topical treatment with hydroquinone is the standard treatment, but may be associated with complications. Cysteamine is a relatively safe depigmenting agent with an observed depigmenting effect. We designed this study to assess the efficacy of a cysteamine 5% cream in treating acne-induced PIH. Methods: Twenty-eight out of 32 participants finalized this investigator-blind, randomized, and controlled trial (registered in Iranian Registry of Clinical Trials [IRCTID: IRCT20140212016557N5]). We randomized the patients to apply either cysteamine 5% or hydroquinone 4%/ascorbic acid 3% (HC) cream. Postacne hyperpigmentation index (PAHPI) and melanin index were the assessment measures after four months of treatment. We evaluated the quality of life by the Dermatology Life Quality Index (DLQI) questionnaire. Results: Both cysteamine and HC cream significantly decreased the PAHPI score and melanin index of acne-induced PIH patients (p<0.05). The decrease in PAHPI score and melanin index were not significantly different in treatment groups after four months (p>0.05). Quality of life ameliorated significantly only with cysteamine treatment. However, no significant change in quality of life was observed between groups. Limitations: Limitations of our study include the relatively small sample size and absence of follow-up. Conclusion: Cysteamine cream is an effective treatment of post-acne PIH, with similar efficacy to the accepted treatment of PIH, i.e., hydroquinone cream.

Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial.

Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 µg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. Clinical Trial Registration: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

Preclinical evaluation of two phylogenetically distant arenavirus vectors for the development of novel immunotherapeutic combination strategies for cancer treatment.

BACKGROUND: Engineered arenavirus vectors have recently been developed to leverage the body's immune system in the fight against chronic viral infections and cancer. Vectors based on Pichinde virus (artPICV) and lymphocytic choriomeningitis virus (artLCMV) encoding a non-oncogenic fusion protein of human papillomavirus (HPV)16 E6 and E7 are currently being tested in patients with HPV16+ cancer, showing a favorable safety and tolerability profile and unprecedented expansion of tumor-specific CD8+ T cells. Although the strong antigen-specific immune response elicited by artLCMV vectors has been demonstrated in several preclinical models, PICV-based vectors are much less characterized. METHODS: To advance our understanding of the immunobiology of these two vectors, we analyzed and compared their individual properties in preclinical in vivo and in vitro systems. Immunogenicity and antitumor effect of intratumoral or intravenous administration of both vectors, as well as combination with NKG2A blockade, were evaluated in naïve or TC-1 mouse tumor models. Flow cytometry, Nanostring, and histology analysis were performed to characterize the tumor microenvironment (TME) and T-cell infiltrate following treatment. RESULTS: Despite being phylogenetically distant, both vectors shared many properties, including preferential infection and activation of professional antigen-presenting cells, and induction of potent tumor-specific CD8+ T-cell responses. Systemic as well as localized treatment induced a proinflammatory shift in the TME, promoting the infiltration of inducible T cell costimulator (ICOS)+CD8+ T cells capable of mediating tumor regression and prolonging survival in a TC-1 mouse tumor model. Still, there was evidence of immunosuppression built-up over time, and increased expression of H2-T23 (ligand for NKG2A T cell inhibitory receptor) following treatment was identified as a potential contributing factor. NKG2A blockade improved the antitumor efficacy of artARENA vectors, suggesting a promising new combination approach. This demonstrates how detailed characterization of arenavirus vector-induced immune responses and TME modulation can inform novel combination therapies. CONCLUSIONS: The artARENA platform represents a strong therapeutic vaccine approach for the treatment of cancer. The induced antitumor immune response builds the backbone for novel combination therapies, which warrant further investigation.

Relationship between hand-foot skin reaction and external force on patients with hepatocellular carcinoma: A cohort study.

PURPOSE: Hand-foot skin reaction (HFSR), a side effect of tyrosine kinase inhibitor (TKI) treatment, makes it difficult to walk and perform daily activities because of pain in the limbs. HFSR occurs predominantly in the sites where external forces (pressure and shear stress) are applied. This study aimed to determine whether pressure or shear stress induces the occurrence of HFSR. METHODS: This cohort study was conducted in patients who received TKI treatment for hepatocellular carcinoma. The external forces applied to the sole of the patients' foot while walking was measured, and its association with the occurrence of HFSR was examined. The degree of HFSR was assessed by the patient's response during the examination and by photographs of their feet. The patients' feet were divided into low (grade <2) or high (grade ≥2) HFSR foot group, and the differences in external forces between the groups were analyzed using t-test and Cox hazard analysis. RESULTS: Analysis of the feet of 55 study participants (n = 110) showed no significant difference between the groups on t-test (p ≥ 0.05), however, Cox hazard analysis showed an increased risk of HFSR with higher peak shear stress values at the fifth metatarsal head (hazard ratio = 1.01, p = 0.047; 95% confidence interval = 1.00-1.02). CONCLUSION: Shear stress is possibly related to HFSR occurrence. Nurses should assess whether patients' shoes fit their feet before initiating TKI treatment. They should instruct patients to wear shoes that are fit of both diameter and width for their feet.

D3/Penta 21 clinical trial design: A randomised non-inferiority trial with nested drug licensing substudy to assess dolutegravir and lamivudine fixed dose formulations for the maintenance of virological suppression in children with HIV-1 infection, aged 2 to 15 years.

BACKGROUND: There is increasing interest in utilising two-drug regimens for HIV treatment with the goal of reducing toxicity and improve acceptability. The D3 trial evaluates the efficacy and safety of DTG/3TC in children and adolescents and includes a nested pharmacokinetics(PK) substudy for paediatric drug licensing. METHODS: D3 is an ongoing open-label, phase III, 96-week non-inferiority randomised controlled trial(RCT) conducted in South Africa, Spain, Thailand, Uganda and the United Kingdom. D3 has enrolled 386 children aged 2- < 15 years, virologically suppressed for ≥6 months, with no prior treatment failure. Participants were randomised 1:1 to receive DTG/3TC or DTG plus two nucleoside reverse transcriptase inhibitors(NRTIs), stratified by region, age (2- < 6, 6- < 12, 12- < 15 years) and DTG use at enrolment (participants permitted to start DTG at enrolment). The primary outcome is confirmed HIV-1 RNA viral rebound ≥50 copies/mL by 96-weeks. The trial employs the Smooth Away From Expected(SAFE) non-inferiority frontier, which specifies the non-inferiority margin and significance level based on the observed event risk in the control arm. The nested PK substudy evaluates WHO weight-band-aligned dosing in the DTG/3TC arm. DISCUSSION: D3 is the first comparative trial evaluating DTG/3TC in children and adolescents. Implications of integrating a PK substudy and supplying data for prompt regulatory submission, were carefully considered to ensure the integrity of the ongoing trial. The trial uses an innovative non-inferiority frontier for the primary analysis to allow for a lower-than-expected confirmed viral rebound risk in the control arm, while ensuring interpretability of results and maintaining the planned sample size in an already funded trial. TRIAL REGISTRATION: International Standard Randomised Clinical Trial Number Register: ISRCTN17157458. European Clinical Trials Database: 2020-001426-57. CLINICALTRIALS: gov: NCT04337450.

Methotrexate treatment strategies for rheumatoid arthritis: a scoping review on doses and administration routes.

BACKGROUND: To describe the evidence of methotrexate (MTX) initiation strategies in patients with rheumatoid arthritis (RA) and, in the case of non-responders, analyse the efficacy and safety of route and dose optimisation. METHODS: We conducted a comprehensive scoping review of randomised controlled trials according to PRISMA Scoping Reviews Checklist and the framework proposed by Arksey and O'Malley. PubMed, EMBASE, and Cochrane were searched without language restriction, and hand searches of relevant articles were examined. RESULTS: We identified 1,367 potentially eligible studies, of which 12 were selected based on the titles and abstracts and then on the full-length articles. In naïve-MTX patients, a linear dose-response relationship for starting dose was found between 5 mg/m2/week (7.5-10 mg/week) and 10 mg/m2/week (15-22 mg/week), without toxicity correlation. A higher initial dose of MTX (25 mg vs. 15 mg) was more effective, resulting in fewer dose increases due to ineffectiveness and more dose reductions due to higher remission rates. There was also a trend towards increased gastrointestinal toxicity. Comparing different routes of administration of MTX, subcutaneous MTX showed a statistically higher ACR20 response (85%) in comparison with oral MTX (77%) (p < 0.05). The clinical efficacy and safety of accelerated and conventional start MTX regimens were comparable between 7.5 and 15 mg with a 2,5 mg dose increase every two weeks. In RA patients who have failed the initial treatment with MTX, the stepwise increase in MTX doses is associated with a higher ACR20 response and sustained remission rate than other strategies. In MTX non-responders, optimisation to SC MTX was associated with improvements in ACR20 and ACR50 rates with similar toxicity between groups. In the early RA patients subgroup, SC MTX showed higher ACR20 response rates than oral MTX, and intensive oral methods have a much higher sustained remission rate, shorter mean time to remission, and better clinical disease activity measures than conventional treatments. CONCLUSIONS: Higher starting doses of MTX and initial subcutaneous MTX made better performance in improving the ACR20 response, although the clinical effectiveness and safety of other MTX start regimens are comparable. This scoping review provides evidence in support of optimising MTX treatment in terms of route and dose prior to concluding that MTX treatment in RA patients has failed.

High-Resolution Ultrasound in Evaluation of Peripheral Neuropathy in Patients of Hansen's Disease.

Introduction: Hansen's disease (HD) is a major public health problem in developing countries. It causes peripheral neuropathy, and if left untreated, it leads to deformities. It is important to diagnose such cases early, and prompt treatment should be given to patients to preserve nerve function. Materials and Methods: A total of 40 patients with HD who were already on multi-drug therapy (MDT) or treatment-naive were included in this study. These were clinically diagnosed cases of HD as per the Ridley-Jopling classification, and these patients were subjected to high-resolution ultrasonography (HRUS). A total of 19 controls were also included. The patients were clinically evaluated, and HRUS of bilateral ulnar nerves (UNs) was performed in all cases and controls. The other peripheral nerves, if clinically thickened, were evaluated using HRUS. Results: The cross-sectional area (CSA) of the UN in cases was significantly thickened as compared to controls. There was no difference in the CSA of patients on MDT as compared to treatment naïve patients. In two patients with pure neuritic HD, the clinical examination missed the bilateral nerve enlargement, and only unilateral nerve thickening was clinically appreciated. However, bilateral thickening was detected on HRUS. Conclusion: HRUS is a non-invasive and sensitive diagnostic tool that gives significant information on nerve structure and morphology. HRUS adds a new dimension to diagnosing HD, particularly the pure neuritic type, with the assessment of early nerve damage, which can prevent disabilities. HRUS is an objective diagnostic tool that can complement the clinical examination.