High-Dose versus Low-Dose Oxytocin for Labor Augmentation: A Meta-Analysis of Randomized Controlled Trials.

Background/Objectives: Although oxytocin administration is recommended for delayed labor progress, there is no consensus over the preferred optimal dose of oxytocin. We aimed to perform a meta-analysis of pregnancy outcomes comparing high-dose versus low-dose oxytocin regimens for augmentation of delayed labor. Methods: PubMed, Embase, and Cochrane databases were systematically searched for studies comparing high-dose with low-dose oxytocin for labor augmentation from inception up to May 2023. The outcomes assessed were cesarean rate, instrumental delivery rate, postpartum hemorrhage, neonatal death, and uterine tachysystole. Subgroup analysis was performed with randomized controlled trials (RCTs) and propensity-matched studies. Statistical analysis was performed using Rstudio. Heterogeneity was assessed with I2 statistics, and a random-risk effect was used if I2 > 50%. Results: Twenty-one studies met inclusion criteria, and eighteen were RCTs. A total of 14.834 patients were included, of whom 7.921 (53.3%) received high-dose and 6.913 (46.6%) received low-dose oxytocin during labor augmentation. No statistical differences were found in cesarean delivery, neonatal mortality, postpartum hemorrhage and vaginal instrumentation rate. However, uterine tachysystole incidence was significantly higher with high-dose oxytocin (95% Cl, 1.30-1.94, p = 0.3; 0.6; I2 = 9%). Conclusions: Labor augmentation with a low-dose oxytocin regimen is effective as with a high-dose regimen, but with significantly less uterine tachysystole events, which can lead to intrauterine and neonatal complications. Our findings suggest that a low-dose regimen may be safe and effective for labor augmentation in medical practice.

Anti-steatotic effects of PPAR-alpha and gamma involve gut-liver axis modulation in high-fat diet-fed mice.

AIM: To evaluate the effects of PPARα and PPARγ activation (alone or in combination) on the gut-liver axis, emphasizing the integrity of the intestinal barrier and hepatic steatosis in mice fed a high saturated fat diet. METHODS: Male C57BL/6J were fed a control diet (C) or a high-fat diet (HF) for ten weeks. Then, a four-week treatment started: HF-α (WY14643), HF-γ (low-dose pioglitazone), and HF-αγ (combination). RESULTS: The HF caused overweight, insulin resistance, impaired gut-liver axis, and marked hepatic steatosis. Treatments reduced body mass, improved glucose homeostasis, and restored the gut microbiota diversity and intestinal barrier gene expression. Treatments also lowered the plasma lipopolysaccharide concentrations and favored beta-oxidation genes, reducing macrophage infiltration and steatosis in the liver. CONCLUSION: Treatment with PPAR agonists modulated the gut microbiota and rescued the integrity of the intestinal barrier, alleviating hepatic steatosis. These results show that these agonists can contribute to metabolic-associated fatty liver disease treatment.

Worldwide risk assessment of phthalates and bisphenol A in humans: The need for updating guidelines.

Phthalates and bisphenol A (BPA) are compounds widely used as raw materials in the production of plastics, making them ubiquitous in our daily lives. This results in widespread human exposure and human health hazards. Although efforts have been conducted to evaluate the risk of these compounds in diverse regions around the world, data scattering may mask important trends that could be useful for updating current guidelines and regulations. This study offers a comprehensive global assessment of human exposure levels to these chemicals, considering dietary and nondietary ingestion, and evaluates the associated risk. Overall, the exposure daily intake (EDI) values of phthalates and BPA reported worldwide ranged from 1.11 × 10-7 to 3 700 µg kg bw-1 d-1 and from 3.00 × 10-5 to 6.56 µg kg bw-1 d-1, respectively. Nevertheless, the dose-additive effect of phthalates has been shown to increase the EDI up to 5 100 µg kg bw-1 d-1, representing a high risk in terms of noncarcinogenic (HQ) and carcinogenic (CR) effects. The worldwide HQ values of phthalates and BPA ranged from 2.25 × 10-7 to 3.66 and from 2.74 × 10-7 to 9.72 × 10-2, respectively. Meanwhile, a significant number of studies exhibit high CR values for benzyl butyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP). Moreover, DEHP has shown the highest maximum mean CR values for humans in numerous studies, up to 179-fold higher than BBP. Despite mounting evidence of the harmful effects of these chemicals at low-dose exposure on animals and humans, most regulations have not been updated. Thus, this article emphasizes the need for updating guidelines and public policies considering compelling evidence for the adverse effects of low-dose exposure, and it cautions against the use of alternative plasticizers as substitutes for phthalates and BPA because of the significant gaps in their safety.

Outcomes and survival predictors of Latin American older adults with acute myeloid leukemia: Data from a single center

ABSTRACT Introduction: Acute myeloid leukemia (AML) is most commonly presented in older adults; however, it appears 10 years earlier in Latin American countries. Clinical evolution in older adults from this populations has not been characterized. We analyzed outcomes and survival predictors. Methods: Patients ≥ 55 years old diagnosed with AML at a hematology referral center from 2005 to 2020 receiving intensive chemotherapy (IC), low-dose cytarabine (LDAC) and best supportive care (BSC) were included. Survival analysis included the Kaplan-Meier and Cox models and the cumulative incidence of relapse (CIR). Results: Seventy-five adults were included and the overall survival (OS) was 4.87, 1.67 and 1.16 months, using IC, LDAC and BSC, respectively. The IC led to a higher OS (p < 0.001) and was a protective factor for early death, at a cost of more days spent hospitalized and more non-fatal treatment complications; non-significant differences were found between the LDAC and BSC. Eight (10.7%) patients underwent hematopoietic cell transplantation, with a higher OS (p = 0.013). Twenty (26.7%) patients achieved complete remission; 12 (60%) relapsed with a 6-month CIR of 57.9% in those < 70 years old vs. 86.5% in those ≥ 70 years old, p = 0.034. Multivariate analysis showed the white blood cell count (WBC) and IC had a significant impact on the patient survival, whereas chronological age and the Charlson comorbidity index (CCI) did not. Conclusion: AML in low-middle income countries demands a different approach; the IC improves survival, even with a high incidence of relapse, and should be offered as first-line treatment. Eligibility criteria should include WBC and a multidimensional evaluation. The age per se and the CCI should not be exclusion criteria to consider IC.

Low-Dose Naltrexone in Rheumatological Diseases.

Background: Naltrexone has been approved for alcohol and opioid abuse by the FDA. At low-dose naltrexone (LDN) has been used in several diseases including chronic pain and autoimmune conditions, including rheumatic disorders. Aim: To review the use of LDN in rheumatic diseases: systemic sclerosis (SSc), dermatomyositis (DM), Sjögren's syndrome (SS), rheumatoid arthritis (RA), and fibromyalgia (FM). Methods: PubMed and Embase databases were searched for articles on LDN and rheumatic diseases between 1966 and August 2022. Results: Seven studies in FM have been identified: in this disease LDN has showed beneficial effects on pain and well-being. In SS, two articles with 3 cases description showed that LDN may be of help in the pain treatment. LDN relieved pruritus in scleroderma (a case description with a series of 3 patients) and dermatomyositis (description of 3 patients in two articles). In RA a study using Norwegian Prescription Database showed that LDN was associated to reduction in the use of analgesic and DMARDs. No serious side effects were detected. Conclusion: This review shows that LDN is a promising and safe therapy to be used in some rheumatic disease. However, the data is limited and needs to be reproduced in larger studies.

Efficacy and safety of ultra-low-dose estradiol and norethisterone in postmenopausal Brazilian women.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of oral ultra-low-dose continuous combination of 17ß-estradiol (17ß-E2) and norethisterone acetate (NETA) in postmenopausal Brazilian women. METHODS: Postmenopausal women (age 45-60 years) with amenorrhea >12 months and intact uterus, with moderate to severe vasomotor symptoms, were included. The vasomotor symptoms and endometrial bleeding were evaluated by a daily diary for 24 weeks, and the women were assessed at baseline and endpoint. RESULTS: A total of 118 women were included. The group treated with 0.5 mg 17ß-E2/0.1 mg NETA (n = 58) showed a percentage reduction of 77.1% in the frequency of vasomotor symptoms versus 49.9% in the placebo group (n = 60) (p = 0.0001). The severity score showed a reduction in the treatment group when compared to the placebo (p < 0.0001). The adverse events were comparable between the groups; however, in the 0.5 mg 17ß-E2/0.1 mg NETA group there were more complaints of vaginal bleeding; despite that, in most cycles in both treatment groups, more than 80% of women experienced amenorrhea. CONCLUSIONS: The combination of 0.5 mg 17ß-E2/0.1 mg NETA in a continuous combination regimen was shown to be effective in reducing the frequency and severity of vasomotor symptoms in Brazilian postmenopausal women.

Outcomes and survival predictors of Latin American older adults with acute myeloid leukemia: Data from a single center.

INTRODUCTION: Acute myeloid leukemia (AML) is most commonly presented in older adults; however, it appears 10 years earlier in Latin American countries. Clinical evolution in older adults from this populations has not been characterized. We analyzed outcomes and survival predictors. METHODS: Patients ≥ 55 years old diagnosed with AML at a hematology referral center from 2005 to 2020 receiving intensive chemotherapy (IC), low-dose cytarabine (LDAC) and best supportive care (BSC) were included. Survival analysis included the Kaplan-Meier and Cox models and the cumulative incidence of relapse (CIR). RESULTS: Seventy-five adults were included and the overall survival (OS) was 4.87, 1.67 and 1.16 months, using IC, LDAC and BSC, respectively. The IC led to a higher OS (p < 0.001) and was a protective factor for early death, at a cost of more days spent hospitalized and more non-fatal treatment complications; non-significant differences were found between the LDAC and BSC. Eight (10.7%) patients underwent hematopoietic cell transplantation, with a higher OS (p = 0.013). Twenty (26.7%) patients achieved complete remission; 12 (60%) relapsed with a 6-month CIR of 57.9% in those < 70 years old vs. 86.5% in those ≥ 70 years old, p = 0.034. Multivariate analysis showed the white blood cell count (WBC) and IC had a significant impact on the patient survival, whereas chronological age and the Charlson comorbidity index (CCI) did not. CONCLUSION: AML in low-middle income countries demands a different approach; the IC improves survival, even with a high incidence of relapse, and should be offered as first-line treatment. Eligibility criteria should include WBC and a multidimensional evaluation. The age per se and the CCI should not be exclusion criteria to consider IC.

Evaluation of the Effect of Low-dose Aspirin on the Prevention of Preterm Delivery in Women with a History of Spontaneous Preterm Delivery / Avaliação do efeito da aspirina em baixa dose na prevenção do parto prematuro em mulheres com história de parto prematuro espontâneo

Abstract Objective Currently, uteroplacental vascular disorders are considered one of the main mechanisms of spontaneous preterm delivery (PTD). Low-dose aspirin is used to prevent pre-eclampsia, which has a similar mechanism; hence, the present study aimed to investigate the effect of low-dose aspirin on the prevention of PTD in women with a history of spontaneous PTD. Methods The present pilot randomized clinical trial was conducted on 54 pregnant women in the aspirin group (taking 80 mg daily until the 36th week and classic treatment) and 53 patients in the control group (only receiving classic treatment). Results Forty-three patients (40%) presented before 37 weeks due to symptoms of PTL. Preterm delivery (< 37 weeks) occurred in 28 patients (26%), and there was no significant difference between the aspirin and control groups (10 patients [19%] and 18 patients [34%], respectively; p = 0.069). The time of preterm delivery was early (< 34 weeks) in 6 patients (21%), and its cause was spontaneous labor in 23 patients (82%) which was not significantly different between the two groups (p > 0.05). Out of 40 patients with spontaneous labor, 25 patients (63%) had a PTD, which was significantly lower in the aspirin group than in the control group (9 patients [45%] versus 16 patients [80%], respectively; p = 0.022). Conclusion The findings of the present study demonstrated that despite the reduction in the incidence of PTD using low-dose aspirin, the reduction rate was not statistically significant. On the other hand, in patients with spontaneous labor prone to PTD, aspirin was effective in reducing the incidence of PTD.

Resumo Objetivo Atualmente, os distúrbios vasculares uteroplacentários são considerados um dos principais mecanismos de parto prematuro espontâneo (PTD). A aspirina em baixa dose é usada para prevenir a pré-eclâmpsia, que tem um mecanismo semelhante; portanto, o presente estudo teve como objetivo investigar o efeito da aspirina em baixa dosagem na prevenção de PTD em mulheres com história de PTD espontâneo. Métodos O presente ensaio clínico piloto randomizado foi realizado em 54 gestantes do grupo aspirina (tomando 80 mg diários até a 36ª semana e tratamento clássico) e 53 pacientes do grupo controle (somente tratamento clássico). Resultados Quarenta e três pacientes (40%) apresentaram-se antes de 37 semanas devido a sintomas de PTL. O parto prematuro (< 37 semanas) ocorreu em 28 pacientes (26%) e não houve diferença significativa entre os grupos aspirina e controle (10 pacientes [19%] e 18 pacientes [34%], respectivamente; p = 0,069). O tempo de parto prematuro foi precoce (< 34 semanas) em 6 pacientes (21%) e sua causa foi trabalho de parto espontâneo em 23 pacientes (82%) que não foi significativamente diferente entre os dois grupos (p > 0,05). Das 40 pacientes com trabalho de parto espontâneo, 25 pacientes (63%) tiveram PTD, que foi significativamente menor no grupo aspirina do que no grupo controle (9 pacientes [45%] versus 16 pacientes [80%], respectivamente; p = 0,022). Conclusão Os achados do presente estudo demonstraram que, apesar da redução na incidência de DPT com o uso de aspirina em baixa dosagem, a taxa de redução não foi estatisticamente significativa. Por outro lado, em pacientes com trabalho de parto espontâneo propensas a PTD, a aspirina foi eficaz na redução da incidência de PTD.

Análise de custo-efetividade do rastreamento com tomografia computadorizada de baixa dose para detecção precoce de câncer de pulmão sob a perspectiva do Sistema Único de Saúde / Cost-effectiveness analysis of low-dose computed tomography screening for early detection of lung cancer from the perspective of the Unified Health System

O câncer de pulmão é reconhecidamente um dos mais agressivos dentre os tumores, com alta letalidade. A detecção precoce do câncer de pulmão com tomografia computadorizada de baixa dose tem sido avaliada em diversos países e implementada em alguns. Entretanto, a implementação do rastreamento com uso dessa tecnologia para detecção precoce de novos casos, permanece questionado no mundo, e no Brasil não está recomendado. Por esse motivo, foi elaborada uma avaliação de custo-efetividade do uso da tomografia computadorizada de baixa dose como estratégia de rastreamento para detecção precoce do câncer de pulmão em população de risco sob a perspectiva do Sistema Único de Saúde como órgão financiador. Inicialmente uma revisão sistemática foi elaborada e descrita uma síntese das diferentes abordagens disponíveis nas avaliações econômicas. Os 30 estudos selecionados e incluídos na revisão mostraram qualidade global, com bom padrão metodológico, que atendeu a mais de 80% dos critérios estabelecidos pelo formulário (Consensus Health Economic Criteria list). A análise da eficiência comparativa entre duas alternativas (anual e bianual) para o diagnóstico precoce de câncer de pulmão, considerando a estratégia de rastreamento com tomografia computadorizada de baixa dose e a conduta clínica sem rastreio, como cenário de referência, teve por base uma coorte hipotética de 100.000 indivíduos assintomáticos, e tabagistas de alto risco. O horizonte temporal considerou a expectativa de vida dos indivíduos, e a perspectiva foi o Sistema Único de Saúde como financiador da assistência à saúde. Apenas os custos médicos diretos dos itens relacionados ao processo de diagnóstico e tratamento foram estimados. O desfecho foi medido em anos de vida ganhos. O desconto de 5% foi aplicado aos custos e benefícios. E realizadas análises de sensibilidade determinística univariada e probabilística. A razão de custo-efetividade incremental da estratégia de rastreamento anual com a tomografia computadorizada de baixa dose para a detecção precoce de câncer de pulmão foi estimada em R$ 97.583,52 por cada ano de vida ganho e de R$ 56.642,20 por ano de vida ganho, com o rastreio a cada dois anos. A análise determinística mostrou que o impacto da redução da incidência de câncer de pulmão, em ambas as alternativas (anual e bianual), chega a gerar quase o triplo dos gastos estimados para a razão de custo-efetividade incremental. Para o anual esse aumento chega a R$ 176.834,47, fora do limiar de R$105.000,00, enquanto o rastreamento bianual, mesmo dobrando os gastos, ainda se manteria dentro do limiar de custo-efetividade atualmente definido para o país. Os demais parâmetros de relevância (sensibilidade do rastreamento para detecção de câncer e a proporção de diagnósticos em estadio I/II com o rastreamento) não impactaram nos resultados finais. A análise probabilística das alternativas de rastreamento mostrou para o rastreamento anual 52% das simulações dentro do limiar estabelecido e 94,2% referente ao bianual. O resultado do modelo econômico mostrou resultados favoráveis com a adoção da estratégia de rastreamento de câncer de pulmão com uso de tomografia computadorizada de baixa dose comparada a condução clínica, realizada a cada dois anos em população de alto risco, sob a perspectiva do SUS. (AU)

Lung cancer is one of the most aggressive tumors, with high lethality. Early detection of lung cancer with low-dose computed tomography has been evaluated in several countries and implemented in some. However, the implementation of screening using this technology for early detection of new cases remains questioned worldwide, but in Brazil, it has not been recommended. Thus, a cost-effectiveness assessment of a screening strategy with low-dose computed tomography for early lung cancer detection in a high-risk population under the Unified Health System perspective as a funding body. First, a systematic review was performed and synthesized the different approaches available in economic evaluations. Thirty studies selected and included in the review showed overall quality, with a well-designed methodological standard, which met more than 80% of the criteria established by the Consensus Health Economic Criteria (CHEC) list form. The analysis of the comparative efficiency between two alternatives (annual and biannual) for the early diagnosis of lung cancer, considering the screening strategy with low-dose computed tomography and the clinical management, without screening, as a reference scenario, was based on a cohort hypothetical 100,000 asymptomatic individuals, and high-risk smokers. The time horizon considered the individuals' life expectancy, and the perspective was the Brazilian Unified Health System as the funder of health care. Only the direct medical costs of items related to the diagnosis and treatment process were estimated. The outcome measure was life years gained. A discount of 5% has been applied to costs and benefits. A deterministic and probabilistic sensitivity analysis has been performed. The incremental cost-effectiveness ratio of the annual screening strategy for early lung cancer detection has been estimated at BRL 97,583.52 for each life-year gained and BRL 56,642.20 per year of life gained, with screening every two years. The deterministic analysis showed that the impact of reducing the incidence of lung cancer, in both alternatives (annual and biannual) generated almost three times the estimated expenses for the incremental cost-effectiveness ratio. For the annual survey, this increase reaches BRL 176,834.47, outside the BRL 105,000.00 threshold, while biannual screening, even doubling the expenses, would remain within the cost-effectiveness threshold currently defined for the country. The other relevant parameters (screening sensitivity for cancer detection and the proportion of stage I/II diagnoses with screening) have no impact on the final results. The probabilistic analysis showed that 52% of simulations within the established threshold correspond to the annual screening, and 94.2% to the biannual. The economic model designed to evaluate the cost-effectiveness of lung cancer screening using low-dose computed tomography compared to clinical care showed favorable results from the strategy performed every two years in a high-risk population, under the SUS perspective. (AU)

Effects of ultra-low dose hormone therapy on biochemical bone turnover markers in postmenopausal women: A randomized, placebo-controlled, double-blind trial.

OBJECTIVE: Evaluate the effects of ultra-low-dose hormone therapy (Ultra-LD HT) with 17ß-estradiol 0.5 mg and norethisterone acetate 0.1 mg (E2 0.5/NETA 0.1) versus placebo on bone turnover markers (BTM) in postmenopausal women. STUDY DESIGN: A multicenter, double-blind, randomized, placebo-controlled study was performed with 107 participants who received one tablet daily of E2 0.5/NETA 0.1 or placebo for 24-weeks. Bone formation markers-N-terminal propeptide of type I procollagen (PINP) and Bone-specific alkaline phosphatase (BSAP), and bone resorption markers-C-telopeptide of type I collagen (CTX-I) and N-telopeptide crosslinked of type I collagen (NTX) were assessed before and at 12 and 24-weeks of treatment. RESULTS: Women treated with E2 0.5/NETA 0.1 had a significant reduction in the PINP marker from baseline (58.49 ± 21.12 µg/L) to week 12 (48.31 ± 20.99 µg/L) and week 24 (39.16 ± 16.50 µg/L). Placebo group, the PINP marker did not differ significantly. The analysis of the BSAP indicated a significant increase in the placebo group (13.8 ± 5.09 µg/L and 16.29 ± 4.3 µg/L, at baseline and week 24, respectively), whereas in the treatment group the values did not change. The analysis of the NTX marker showed a significant reduction only in the treatment group (43.21 ± 15.26 nM/mM and 33.89 ± 14.9 nM/mM, at baseline and week 24, respectively). CTX-I had a significant decrease in the treatment group from baseline (0.3 ± 0.16 ng/L) to week 12 (0.21 ± 0.14 ng/L) and week 24 (0.21 ± 0.12 ng/L). CONCLUSION: Women receiving E2 0.5/NETA 0.1 experienced reductions in bone resorption and formation markers, an expected effect during the anti-resorptive therapy, suggesting a protective bone effect with the Ultra-LD HT.

Antibacterial and antifungal capacity of three commercially available mouthwashes with different concentrations of chlorhexidine / Efecto antibacteriano y antifúngico de tres enjuagues bucales comerciales con diferentes concentraciones de clorhexidina

Abstract Chlorhexidine was introduced almost seven decades ago and has a myriad of applications in dentistry. Few studies have evaluated the antimicrobial and antifungal capacity of different concentrations of chlorhexidine mouthwashes. Therefore, the aim of this study, was to evaluate in vitro, the antibacterial and antifungal capacity of three commercially available mouthwashes in Costa Rica, with different concentrations of chlorhexidine, 0.12%, 0.06%, and 0.03%. The experimental method selected was the Kirby-Bauer method to evaluate the antibacterial and antifungal effect of each compound by measuring the inhibitory effect on Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Candida albicans strains, exposed to the antiseptic solutions. All samples showed some degree of antibacterial and antifungal effect. Even though we provide in vitro results, our findings are of relevance since all the species used in our experiment are microorganisms that may be present in dental plaque. Our results further support evidence that oral hygiene regimens may include mouthwashes with low doses of chlorhexidine and maintain reasonable antibacterial and antifungal efficacy.

Resumen La clorhexidina se introdujo hace casi siete décadas y tiene una gran variedad de aplicaciones en odontología. Pocos estudios han evaluado la capacidad antimicrobiana y antifúngica de diferentes concentraciones de enjuagues bucales con clorhexidina. Por lo tanto, el objetivo de este estudio fue evaluar in vitro, la capacidad antibacteriana y antifúngica de tres enjuagues bucales disponibles comercialmente en Costa Rica, con diferentes concentraciones de clorhexidina, 0.12%, 0.06% y 0.03%. El método experimental seleccionado fue el método Kirby-Bauer para evaluar el efecto antibacteriano y antifúngico de cada compuesto midiendo el efecto inhibidor sobre Staphylococcus aureus, Enterococcus faecalis, Escherichia coli y Candida albicans, expuestos a la solución antiséptica. Todas las muestras mostraron algún grado de efecto antibacteriano y antifúngico. Aunque proporcionamos resultados in vitro, nuestros hallazgos son de relevancia, ya que todas las especies utilizadas en nuestro experimento son microorganismos que pueden estar presentes en la placa dental. Nuestros resultados respaldan aún más la evidencia de que los regímenes de higiene bucal pueden incluir enjuagues bucales con dosis bajas de clorhexidina y mantener una eficacia antibacteriana y antifúngica razonable.

Brachytherapy for Central Serous Chorioretinopathy.

Brachytherapy is widely used for the treatment of choroidal melanoma and has recently been explored for the treatment of wet age-related macular degeneration. We propose the use of low dose radiation via episcleral brachytherapy in refractory cases of central serous chorioretinopathy (CSCR). The pathogenesis of CSCR involves dilatation and hyperpermeability of large choroidal vessels. Low dose radiation can induce intimal proliferation in large choroidal vessels and decrease their hyperpermeability. Concerns about the use of brachytherapy in CSCR include damage to the choriocapillaris or the retinal vessels. This can be addressed with the use of a specialized device through which a very precise and appropriate dose can be delivered. The dose of the radiation delivered decreases exponentially at a depth of approximately 0.5-1.5 mm from the devise-sclera interface. Considering an increased choroidal thickness in cases of CSCR, delivery of a safe dose can be assured.

Effect of short-term corticosteroid usage on acute urinary toxicity following Cs-131 prostate brachytherapy.

PURPOSE: To evaluate short-term patient reported urinary quality of life scores in patients with prostate cancer treated at our institution with and without perioperative prednisone following Cesium-131 (131Cs) prostate LDR brachytherapy. METHODS AND MATERIALS: We started routinely using a perioperative 7-day course of prednisone at a dose of 5 mg per day, beginning 1 day prior to 131Cs prostate LDR brachytherapy from 2013 with goal of improving acute urinary symptomatology. One hundred consecutive patients treated with prednisone were selected, with comparison to 100 consecutive patients who were not treated with prednisone. We analyzed for differences in mean change with standard deviation (SD) in EPIC and AUA scores at 0.5-1 month and 3 months with or without prednisone by Mann-Whitney U Test. Binary logistic regression was performed to assess for impact of prednisone on postoperative urinary catheter use. RESULTS: Pretreatment EPIC and AUA scores were available in 197 patients. Less reduction in EPIC US score was noted at 0.5-1.0 month in the group who received prednisone with mean change of -22.9 (SD 15.4) when compared to the group who did not receive prednisone with mean change of -31.7 (SD 19.3), p < 0.01, with significance lost at 3 months. There was no significant difference in acute urinary retention requiring postoperative urinary catheter placement with perioperative prednisone (OR 1.13, p = 0.71). CONCLUSIONS: A short course of perioperative low-dose prednisone was associated with less severe worsening in urinary symptoms by the EPIC questionnaire at the 0.5-1.0-month timepoint suggesting some improvement in acute urinary quality of life, although differences did not remain statistically significant at 3 months.

Disease activity and therapeutic drug monitoring of polyglutamates of methotrexate after daily or weekly administration of low-dose methotrexate in patients recently diagnosed with rheumatoid arthritis.

Low-dose methotrexate can be challenging to treat rheumatoid arthritis due to side effects, lack of adherence and risk of medication errors. The aim of this study was to explore the safety and efficacy of low-dose methotrexate administered daily or weekly in patients with rheumatoid arthritis. Patients were randomized according to a total oral dose of 12.5 mg of methotrexate administered: (A) divided in 5 days/week and (B) once per week. Patients were assessed along 24 weeks after starting treatment. Polyglutamates of methotrexate were quantified by ultrahigh-performance liquid chromatography coupled to tandem mass spectrometer. Patients from groups A and B showed a good response to methotrexate treatment in 29% and 25.5%, respectively, and a global frequency of adverse events of 37%. Methotrexate polyglutamate 3 concentrations were higher in normal weight (body mass index 18.5-24.9 kg/m2 ) than in obese (body mass index 30 kg/m2 ) patients with a median (interquartile range) of 28 (17.95-45.15) and 10.35 (5.22-30.88) nM without differences between dosage groups. Daily dosage regimen represents a therapeutic alternative without compromising the efficacy and safety of methotrexate treatment and with similar adherence patterns than weekly dosage regimen; further, methotrexate polyglutamate 3 concentrations could be a useful tool for therapeutic drug monitoring purposes.

Low-dose radiation therapy for hand osteoarthritis: shaking hands again?

BACKGROUND: Hand osteoarthritis (HOA) is one of the most common causes of pain and functional disability in western countries and there is still no definitive cure. Low-dose radiation therapy (LDRT) has anti-inflammatory properties that have shown to be effective in the symptomatic relief of various degenerative musculoskeletal disorders. We designed a clinical protocol using LDRT for symptomatic HOA and present results and tolerance in the first 100 patients included. MATERIALS AND METHODS: Between April 2015 and March 2021, 100 patients with a median age of 60 were treated. Fifty-seven patients suffering from proximal/distal interphalangeal joint pain, 40 patients with thumb arthritis, 2 patients with radiocarpal joint affection and 1 patient with metacarpophalangeal joint pain were enrolled. LDRT comprised of 6 fractions of 0.5-1 Gy on every other day up to a total dose of 3-6 Gy. Clinical response was evaluated according to the visual analog scale (VAS) for pain level and the von Pannewitz score (VPS) for joint functionality. Any patients not achieving subjective adequate pain relief after 8 weeks of treatment were offered a second identical LDRT course. RESULTS: With a median follow-up of 10.5 months (range 7.55-12.45), 94% reported an improvement in the pain, with a significant reduction in the VAS level after 3, 6 and 12 months (p < 0.001). Sixty-three patients needed a second course of treatment at a median time interval of 12 weeks (range 9-14). The mean VAS score before treatment was 8 (range 3-10). After treatment, it was 5 (range 1-10). After 3, 6 and 12 months, the mean VAS scores were 4 (range 0-9), 3 (range 0-9) and 3.5 (range 0-9), respectively. Seventy patients reported functionality improvements after LDRT according to the von Pannewitz score. No acute or late complications were observed. CONCLUSION: LDRT appears to be safe and useful for HOA and is associated with good rates of pain relief and functionality improvements. However, further studies are necessary to confirm these promising results.

The clinical efficacy of low-dose whole-lung irradiation in moderate-to-severe COVID-19 pneumonia: RTMX-20 trial.

This is a paired prospective comparative cohort study with 58 patients, in order to analyze the clinical LD-WLI in patients with moderate or severe COVID19 pneumonia. The results of this study show that the Radiotherapy could be an option to improve the clinical response for patients with COVID-19.

Effect of low glyphosate doses on flowering and seed germination of glyphosate-resistant and -susceptible Digitaria insularis.

BACKGROUND: Herbicide hormesis is characterized by stimulation of various growth and developmental parameters, such as biomass and height, at low herbicide doses. Other possible hormetic effects are earlier flowering, higher seed weight, more seeds, and a shorter plant life cycle, which could favor the propagation of the species. This study tested the early flowering in glyphosate-resistant and -susceptible Digitaria insularis biotypes under treatment with low glyphosate doses. RESULTS: Hormesis caused by low glyphosate doses occurred in all experiments. The hormetic effects were a decrease in time necessary for the formation of inflorescences and increased seed weight and germination speed. Higher glyphosate doses were required for the hormetic effect in the glyphosate-resistant than the -susceptible D. insularis biotype. CONCLUSIONS: Hormesis caused by low glyphosate doses in D. insularis may provide an advantage for the dissemination of this species, helping to alter the weed flora. As the doses that cause stimulation in glyphosate-resistant biotypes are higher than in glyphosate-susceptible biotypes, the selection of resistant biotypes may be favored in glyphosate-sprayed fields, increasing the rate of infestation of glyphosate-resistant biotypes.

Glyphosate hormesis attenuates water deficit stress in safflower (Carthamus tinctorius L.) by modulating physiological and biochemical mediators.

Changes in photosynthetic machinery can induce physiological and biochemical damage in plants. Low doses of glyphosate have been shown to exert a positive effect in mitigating the deleterious effects of water deficit in plants. Here, the physiological and biochemical mechanisms of safflower plants (Carthamus tinctorius L.) were studied under conditions of water deficit mediated by the attenuating effect of low-dose glyphosate. The plants were divided into two groups of water regimes in soil, without water deficit (-10 kPa) and with water deficit (-70 kPa), and were exposed to different concentrations of glyphosate (0, 1.8, 3.6, 7.2, 18, 36, 72, 180, 360, and 720 g a.e. ha-1). Evident protective responses at the physiological and biochemical levels were obtained after applying low doses of glyphosate to plants under water deficit, with a limiting dose for the occurrence of hormesis (LDS) = 72 g a.e. ha-1. The water deficit in plants resulted in hydrogen peroxide (H2O2) accumulation and consequently lipid peroxidation (LPO) associated with the accumulation of shikimic acid and glyphosate in plants, which triggered an increase in the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) that act by dismuting the levels of reactive oxygen species (ROS), maintaining, and/or increasing the maximum quantum efficiency of photosystem II (Fv/Fm), effective quantum yield of photosystem II (ΦPSII), electron transport rate (ETR), photochemical extinction coefficient (qP), and non-photochemical extinction coefficient (NPQ). APX appears to be the main enzyme involved in eliminating H2O2. Low doses of glyphosate act as water deficit ameliorators, allowing the plant to maintain/increase metabolism at physiological and biochemical levels by activating antioxidant enzymes in the dismutation of ROS in safflower plants.

Analgesic effects of low-dose radiotherapy in greater trochanteric pain syndrome: results in a clinical series of 155 patients with recurrent or refractory symptoms.

PURPOSE: This prospective study assessed the effects of low-dose radiotherapy in patients diagnosed with greater trochanteric pain syndrome (GTPS) with recurrent symptoms or refractory to previous conservative measures. METHODS: We evaluated a total of 155 patients (90.3% women, mean age 69 years). Most patients (n = 136) received 10 Gy (1 Gy/day/3 fractions per week on alternate days), but after recommendations of DEGRO guidelines published in 2015, the remaining 19 patients (12.2%) received 6 Gy (1 Gy/day/3 fractions per week on alternate days). RESULTS: At the pre-treatment visit, the mean (standard deviation, SD) visual analog scale (VAS) score was 8), which decreased to 5 (SD 2.2) after 1 month of the end of treatment and to 4 (SD 2.3) after 4 months. An objective symptom response with increased mobility, better sleep quality, and reduction of analgesic medication was found in 56% of patients at 1 month. In 129 patients (83.2%), there was a decrease of at least 1 point in the VAS score, and in 49 patients (29.0%), the VAS score was lower than 3. The mean length of follow-up was 45 months. The probability of maintaining the analgesic response estimated by the Kaplan-Meier method was 53% at 5 years. CONCLUSION: Low dose radiotherapy effectively improved pain in the trochanteric area in most patients with recurrent or refractory GTPS, allowing a reduction in the need for analgesic medications and, more, importantly, better functioning and mobility. Further randomized studies in selected populations of GTPS are needed to define the treatment position of low-dose radiotherapy in this clinical setting.