A new copper(II) complex containing long-chain aliphatic hydrazide and 1,10-phenanthroline upregulates ADP hydrolysis in triple-negative breast cancer cells.

Copper can be opportunely complexed to modulate oncogenic pathways, being a promising strategy for cancer treatment. Herein, three new copper(II) complexes containing long-chain aliphatic hydrazides and 1,10-phenanthroline (1,10-phen), namely, [Cu(octh)(1,10-phen)(H2O)](NO3)21, [Cu(dech)(1,10-phen)(H2O)](NO3)22 and [Cu(dodh)(1,10-phen)(H2O)](NO3)2.H2O 3 (where octh = octanoic hydrazide, dech = decanoic hydrazide, dodh = dodecanoic hydrazide) were successfully prepared and characterized by several physical-chemical methods. Furthermore, X-ray structural analysis of complex 2 indicated that the geometry around the copper(II) ion is distorted square-pyramidal, in which hydrazide and 1,10-phenanthroline act as bidentate ligands. A water molecule in the apical position completes the coordination sphere of the metal ion. All new copper(II) complexes were cytotoxic to breast cancer cell lines (MCF7, MDA-MB-453, MDA-MB-231, and MDA-MB-157) and selective when compared to the non tumor lineage MCF-10A. In particular, complex 2 showed half-maximal inhibitory concentration (IC50) values ranging between 2.7 and 13.4 µM in MDA-MB231 cells after 24 and 48 h of treatment, respectively. Furthermore, this complex proved to be more selective for tumor cell lines when compared to doxorubicin and docetaxel. Complex 2 inhibited the clonogenicity of MDA-MB231 cells, increasing adenosine diphosphate (ADP) hydrolysis and upregulating ecto-nucleoside triphosphate diphosphohydrolase 1 (ENTPD1) transcriptional levels. In this sense, we suggest that the inhibitory effect on cell proliferation may be related to the modulation of adenosine monophosphate (AMP) levels. Thus, a novel copper(II) complex with increased cytotoxic effects and selectivity against breast cancer cells was obtained, contributing to medicinal chemistry efforts toward the development of new chemotherapeutic agents.

Tailoring Potential Natural Compounds for the Treatment of Luminal Breast Cancer.

Breast cancer (BC) is the most diagnosed cancer worldwide, mainly affecting the epithelial cells from the mammary glands. When it expresses the estrogen receptor (ER), the tumor is called luminal BC, which is eligible for endocrine therapy with hormone signaling blockade. Hormone therapy is essential for the survival of patients, but therapeutic resistance has been shown to be worrying, significantly compromising the prognosis. In this context, the need to explore new compounds emerges, especially compounds of plant origin, since they are biologically active and particularly promising. Natural products are being continuously screened for treating cancer due to their chemical diversity, reduced toxicity, lower side effects, and low price. This review summarizes natural compounds for the treatment of luminal BC, emphasizing the activities of these compounds in ER-positive cells. Moreover, their potential as an alternative to endocrine resistance is explored, opening new opportunities for the design of optimized therapies.

Urgent-Start Peritoneal Dialysis: Brazilian Experience.

INTRODUCTION: Unplanned peritoneal dialysis (PD) is an important option for chronic kidney disease (CKD) patients requiring kidney replacement therapy urgently as it offers the convenience of home-based therapy. The objective of this study was to assess the Brazilian urgent-start PD program in three different dialysis centers where there is shortage of hemodialysis (HD) beds. METHODS: This prospective, multicentric cohort study included incident patients with stage 5 CKD and no permanent vascular access established who started urgent PD between July 2014 and July 2020 in three different hospitals. Urgent-start PD was defined as initiation of treatment up to 72 h after catheter placement. Patients were followed up from catheter insertion and assessed according to mechanical and infectious complications related to PD, patients, and technique survival. RESULTS: Over 6 years, 370 patients were included in all three study centers. Mean patient age was 57.8 ± 16.32 years. Diabetic kidney disease was the main underlying condition (35.1%) and uremia was the main cause for dialysis indication (81.1%). Concerning complications related to PD, 24.3% had mechanical complications, 27.3% had peritonitis, 28.01% had technique failure, and 17.8% died. On logistic regression, hospitalization (p = 0.003) and exit site infection (p = 0.002) were identified as predictors of peritonitis, while mechanical complications (p = 0.004) and peritonitis (p < 0.001) were identified as predictors of technique failure and switching to HD. Age (p < 0.001), hospitalization (p = 0.012), and bacteremia (p = 0.021) were observed to predict death. The number of patients on PD increased at least 140% in all three participating centers. CONCLUSION: PD is a feasible option for patients starting dialysis in an unplanned manner and may be a useful tool for reducing shortage of HD beds.

Glyphosate and Aminomethylphosphonic Acid (AMPA) Modulate Glutathione S-Transferase in Non-Tumorigenic Prostate Cells.

Glyphosate (GLY) was developed in the early 1970s and has become the most used broad-spectrum herbicide in the world so far. Its main metabolite is aminomethylphosphonic acid (AMPA), and the accumulation of GLY and its derivative compounds raises some concerns regarding possible health outcomes. In this study, we aimed to evaluate the effects of GLY and AMPA on prostate cell lines by evaluating cell viability, proliferation, gene and protein expression, and cellular pathways involved in the response to oxidative stress. Our results indicated that GLY and AMPA reduced the cell viability of tumorigenic and non-tumorigenic prostate cell lines only at higher concentrations (10 mM GLY and 20 mM AMPA). In contrast, both compounds increased the clonogenicity of non-tumorigenic PNT2 cells, mainly at concentrations below the IC50 (5 mM GLY and 10 mM AMPA). Moreover, treatment of non-tumorigenic cells with low concentrations of GLY or AMPA for 48 h increased GSTM3 expression at both mRNA and protein levels. In contrast, the treatments decrease the GST activity and induced an increase in oxidative stress, mainly at lower concentrations. Therefore, both compounds can cause cellular damage even at lower concentrations in non-tumorigenic PNT2 cells, mainly affecting cell proliferation and oxidative stress.

Increase in peritoneal dialysis-related hospitalization rates after telemedicine implementation during the COVID-19 pandemic / Aumento de las tasas de hospitalización relacionadas con la diálisis peritoneal después de la implementación de telemedicina durante la pandemia de la COVID-19

Introduction and objectives: To minimize our peritoneal dialysis (PD) population exposure to coronavirus disease (COVID-19), in April 2020 we developed and implemented a telemedicine program. In this investigation, we aimed to compare the hospitalization rates and metabolic disorders in patients undergoing PD 6 months before and after the COVID-19 pandemic and telemedicine implementation. Materials and methods: This single-center retrospective analysis included all active prevalent patients undergoing PD from April 2020. Dialysis records were reviewed to obtain clinical, demographic, laboratory, appointment, and hospitalization data. We compared hospitalization rates (total, non-PD-related, and PD-related), hospitalization-associated factors, and metabolic disorders (hemoglobin, serum potassium, and serum phosphate) 6 months before and after the pandemic. Results: Our sample comprised 103 participants. During the pre-pandemic and post-pandemic periods, there were 13 and 27 hospital admissions, respectively. The total hospitalization incident rate ratio (IRR) was 2.48 (95% confidence interval [CI], 1.29–4.75). PD-related hospitalizations increased from 3 to 15 episodes (IRR=7.25 [95% CI, 2.11–24.78]). In the pre-pandemic period, the educational level was lower in participants hospitalised due to PD-related issues than in participants not hospitalised. In the post-pandemic period, only sex distribution differed between patients not hospitalised and those hospitalised due to non-PD-related issues. Only serum potassium levels changed significantly in the post-pandemic period (4.79±0.48 vs. 4.93±0.54mg/dL; P<0.01). (AU)

Introducción y objetivos: Para minimizar la exposición de nuestra población de diálisis peritoneal (DP) a la enfermedad por coronavirus (COVID-19), en abril del 2020 desarrollamos e implementamos un programa de telemedicina. En esta investigación, nuestro objetivo fue comparar las tasas de hospitalización y los trastornos metabólicos en pacientes sometidos a DP 6 meses antes y después de la pandemia de COVID-19 y la implementación de la telemedicina. Materiales y métodos: Este análisis retrospectivo de un solo centro incluyó a todos los pacientes prevalentes activos sometidos a DP desde abril del 2020. Se revisaron los registros de diálisis para obtener datos clínicos, demográficos, de laboratorio, de citas y de hospitalización. Comparamos las tasas de hospitalización (total, no relacionada con la DP y relacionada con la DP), los factores asociados a la hospitalización y los trastornos metabólicos (hemoglobina, potasio sérico y fosfato sérico) 6 meses antes y después de la pandemia. Resultados: Nuestra muestra fue compuesta por 103 participantes. Durante los períodos prepandémico y pospandémico, hubo 13 y 27 ingresos hospitalarios, respectivamente. La razón de la tasa de incidentes de hospitalización (TIR) total fue de 2,48 (intervalo de confianza [IC] del 95%, 1,29-4,75). Las hospitalizaciones relacionadas con la DP aumentaron de 3 a 15 episodios (TIR=7,25 [IC del 95%, 2,11-24,78]). En el período prepandémico, el nivel educativo fue más bajo en los participantes hospitalizados debido a problemas relacionados con la DP que en los participantes no hospitalizados. En el período posterior a la pandemia, solo la distribución por sexo difirió entre los pacientes no hospitalizados y los hospitalizados debido a problemas no relacionados con la DP. Solo los niveles de potasio sérico cambiaron significativamente en el período pospandémico (4.79±0.48 frente a 4.93±0.54 mg/dL; P<0.01). (AU)

Increase in peritoneal dialysis-related hospitalization rates after telemedicine implementation during the COVID-19 pandemic.

INTRODUCTION AND OBJECTIVES: To minimize our peritoneal dialysis (PD) population exposure to coronavirus disease (COVID-19), in April 2020 we developed and implemented a telemedicine program. In this investigation, we aimed to compare the hospitalization rates and metabolic disorders in patients undergoing PD 6 months before and after the COVID-19 pandemic and telemedicine implementation. MATERIALS AND METHODS: This single-center retrospective analysis included all active prevalent patients undergoing PD from April 2020. Dialysis records were reviewed to obtain clinical, demographic, laboratory, appointment, and hospitalization data. We compared hospitalization rates (total, non-PD-related, and PD-related), hospitalization-associated factors, and metabolic disorders (hemoglobin, serum potassium, and serum phosphate) 6 months before and after the pandemic. RESULTS: Our sample comprised 103 participants. During the pre-pandemic and post-pandemic periods, there were 13 and 27 hospital admissions, respectively. The total hospitalization incident rate ratio (IRR) was 2.48 (95% confidence interval [CI], 1.29-4.75). PD-related hospitalizations increased from 3 to 15 episodes (IRR=7.25 [95% CI, 2.11-24.78]). In the pre-pandemic period, the educational level was lower in participants hospitalised due to PD-related issues than in participants not hospitalised. In the post-pandemic period, only sex distribution differed between patients not hospitalised and those hospitalised due to non-PD-related issues. Only serum potassium levels changed significantly in the post-pandemic period (4.79±0.48 vs. 4.93±0.54mg/dL; P<0.01). CONCLUSION: This study showed a significant increase in hospitalization rates after the COVID-19 pandemic period and telemedicine implementation, mainly due to PD-related infectious causes. Strategies to improve distance monitoring assistance are needed for the PD population.

Increase in peritoneal dialysis-related hospitalization rates after telemedicine implementation during the COVID-19 pandemic.

Introduction and objectives: To minimize our peritoneal dialysis (PD) population exposure to coronavirus disease (COVID-19), in April 2020 we developed and implemented a telemedicine program. In this investigation, we aimed to compare the hospitalization rates and metabolic disorders in patients undergoing PD 6 months before and after the COVID-19 pandemic and telemedicine implementation. Materials and methods: This single-center retrospective analysis included all active prevalent patients undergoing PD from April 2020. Dialysis records were reviewed to obtain clinical, demographic, laboratory, appointment, and hospitalization data. We compared hospitalization rates (total, non-PD-related, and PD-related), hospitalization-associated factors, and metabolic disorders (hemoglobin, serum potassium, and serum phosphate) 6 months before and after the pandemic. Results: Our sample comprised 103 participants. During the pre-pandemic and post-pandemic periods, there were 13 and 27 hospital admissions, respectively. The total hospitalization incident rate ratio (IRR) was 2.48 (95% confidence interval [CI], 1.29-4.75). PD-related hospitalizations increased from 3 to 15 episodes (IRR = 7.25 [95% CI, 2.11-24.78]). In the pre-pandemic period, the educational level was lower in participants hospitalised due to PD-related issues than in participants not hospitalised. In the post-pandemic period, only sex distribution differed between patients not hospitalised and those hospitalised due to non-PD-related issues. Only serum potassium levels changed significantly in the post-pandemic period (4.79 ± 0.48 vs. 4.93 ± 0.54 mg/dL; P < 0.01). Conclusion: This study showed a significant increase in hospitalization rates after the COVID-19 pandemic period and telemedicine implementation, mainly due to PD-related infectious causes. Strategies to improve distance monitoring assistance are needed for the PD population.

Introducción y objetivos: Para minimizar la exposición de nuestra población de diálisis peritoneal (DP) a la enfermedad por coronavirus (COVID-19), en abril del 2020 desarrollamos e implementamos un programa de telemedicina. En esta investigación, nuestro objetivo fue comparar las tasas de hospitalización y los trastornos metabólicos en pacientes sometidos a DP 6 meses antes y después de la pandemia de COVID-19 y la implementación de la telemedicina. Materiales y métodos: Este análisis retrospectivo de un solo centro incluyó a todos los pacientes prevalentes activos sometidos a DP desde abril del 2020. Se revisaron los registros de diálisis para obtener datos clínicos, demográficos, de laboratorio, de citas y de hospitalización. Comparamos las tasas de hospitalización (total, no relacionada con la DP y relacionada con la DP), los factores asociados a la hospitalización y los trastornos metabólicos (hemoglobina, potasio sérico y fosfato sérico) 6 meses antes y después de la pandemia. Resultados: Nuestra muestra fue compuesta por 103 participantes. Durante los períodos prepandémico y pospandémico, hubo 13 y 27 ingresos hospitalarios, respectivamente. La razón de la tasa de incidentes de hospitalización (TIR) total fue de 2,48 (intervalo de confianza [IC] del 95%, 1,29-4,75). Las hospitalizaciones relacionadas con la DP aumentaron de 3 a 15 episodios (TIR = 7,25 [IC del 95%, 2,11-24,78]). En el período prepandémico, el nivel educativo fue más bajo en los participantes hospitalizados debido a problemas relacionados con la DP que en los participantes no hospitalizados. En el período posterior a la pandemia, solo la distribución por sexo difirió entre los pacientes no hospitalizados y los hospitalizados debido a problemas no relacionados con la DP. Solo los niveles de potasio sérico cambiaron significativamente en el período pospandémico (4.79 ± 0.48 frente a 4.93 ± 0.54 mg/dL; P < 0.01). Conclusión: Este estudio mostró un aumento significativo en las tasas de hospitalización después del período pandémico de COVID-19 y la implementación de la telemedicina, principalmente debido a causas infecciosas relacionadas con la DP. Se necesitan estrategias para mejorar la asistencia de monitoreo a distancia para la población con DP.

Urgent vs. planned peritoneal dialysis initiation: complications and outcomes in the first year of therapy / Diálise peritoneal de início urgente versus planejado: complicações e desfechos no primeiro ano de terapia

Abstract Introduction: Urgent-start peritoneal dialysis (US-PD) has been proposed as a safe modality of renal replacement therapy (RRT) for end-stage renal disease (ESRD) patients with an indication for emergency dialysis initiation. We aimed to compare the characteristics, 30-day complications, and clinical outcomes of US-PD and planned peritoneal dialysis (Plan-PD) patients over the first year of therapy. Methods: This was a single-center retrospective study that included incident adult patients followed for up to one year. US-PD was considered when incident patients started therapy within 7 days after Tenckhoff catheter implantation. Plan-PD group consisted of patients who started therapy after the breaking period (15 days). Mechanical and infectious complications were compared 30 days from PD initiation. Hospitalization and technique failure during the first 12 months on PD were assessed by Kaplan-Meier curves and the determinants were calculated by Cox regression models. Results: All patients starting PD between October/2016 and November/2019 who fulfilled the inclusion criteria were analyzed. We evaluated 137 patients (70 in the US-PD x 67 Plan-PD). The main complications in the first 30 days were catheter tip migration (7.5% Plan-PD x 4.3% US-PD - p= 0.49) and leakage (4.5% Plan-PD x 5.7% US-PD - p=0.74). Most catheters were placed using the Seldinger technique. The main cause of dropout was death in US-PD patients (15.7%) and transfer to HD in Plan-PD patients (13.4%). The occurrence of complications in the first 30 days was the only risk factor for dropout (OR = 2.9; 95% CI 1.1-7.5, p = 0.03). Hospitalization rates and technique survival were similar in both groups. Conclusion: The lack of significant differences in patients' outcomes between groups reinforces that PD is a safe and applicable dialysis method in patients who need immediate dialysis.

Resumo Introdução: A diálise peritoneal de início urgente (US-PD) foi proposta como modalidade segura de terapia renal substitutiva (TRS) para pacientes com doença renal em estágio 5 (DRC-5) com indicação de início de diálise de emergência. Buscamos comparar características, complicações em 30 dias e desfechos clínicos de pacientes em US-PD e diálise peritoneal planejada (DP-plan) no primeiro ano de terapia. Métodos: Estudo retrospectivo de centro único, que incluiu pacientes adultos incidentes em DP acompanhados por até um ano. Considerou-se US-PD quando os pacientes iniciaram terapia até 7 dias após implante do cateter Tenckhoff. O grupo DP-plan consistiu de pacientes iniciando terapia após período break-in (15 dias). Compararam-se complicações mecânicas e infecciosas 30 dias após o início da DP. Hospitalização e falha da técnica durante os primeiros 12 meses em terapia foram avaliados por curvas Kaplan-Meier e os seus determinantes foram analisados por modelos de regressão de Cox. Resultados: Analisaram-se todos os pacientes iniciando DP entre Outubro/2016-Novembro/2019 que preencheram os critérios de inclusão. Avaliamos 137 pacientes (70 US-PD x 67 DP-plan). As principais complicações nos primeiros 30 dias foram migração da ponta do cateter (7,5% DP-plan x 4,3% US-PD - p= 0,49) e extravasamento (4,5% DP-plan x 5,7% US-PD - p=0,74). A maioria dos cateteres foi implantada pela técnica de Seldinger. A principal causa de saída da terapia foi óbito em pacientes em US-PD (15,7%) e transferência para HD em pacientes em DP-plan (13,4%). A ocorrência de complicações nos primeiros 30 dias foi o único fator de risco para saída da terapia (OR = 2,9; IC 95% 1,1-7,5, p = 0,03). Taxas de hospitalização e sobrevida da técnica foram similares em ambos os grupos. Conclusão: A ausência de diferenças significativas nos desfechos dos pacientes entre os grupos reforça que DP é um método de diálise seguro e aplicável em pacientes que necessitam diálise imediata.

Gene expression patterns associated with multidrug therapy in multibacillary leprosy.

Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.

The Type I Interferon Pathway Is Upregulated in the Cutaneous Lesions and Blood of Multibacillary Leprosy Patients With Erythema Nodosum Leprosum.

In leprosy patients, acute inflammatory episodes, known as erythema nodosum leprosum (ENL), are responsible for high morbidity and tissue damage that occur during the course of Mycobacterium leprae infection. In a previous study, we showed evidence implicating DNA-sensing via TLR9 as an important inflammatory pathway in ENL. A likely important consequence of TLR9 pathway activation is the production of type I interferons (IFN-I) by plasmacytoid dendritic cells (pDCs), also implicated in the pathogenesis of several chronic inflammatory diseases. In this study, we investigated whether the IFN-I pathway is activated during ENL. Blood samples and skin lesions from multibacillary patients diagnosed with ENL were collected and the expression of genes of the IFN-I pathway and interferon-stimulated genes were compared with samples collected from non-reactional multibacillary (NR) patients. Whole blood RNAseq analysis suggested higher activation of the IFN-I pathway in ENL patients, confirmed by RT-qPCR. Likewise, significantly higher mRNA levels of IFN-I-related genes were detected in ENL skin biopsies when compared to NR patient lesions. During thalidomide administration, the drug of choice for ENL treatment, a decrease in the mRNA and protein levels of some of these genes both in the skin and blood was observed. Indeed, in vitro assays showed that thalidomide was able to block the secretion of IFN-I by peripheral blood mononuclear cells in response to M. leprae sonicate or CpG-A, a TLR9 ligand. Finally, the decreased frequencies of peripheral pDCs in ENL patients, along with the higher TLR9 expression in ENL pDCs and the enrichment of CD123+ cells in ENL skin lesions, suggest the involvement of these cells as IFN-I producers in this type of reaction. Taken together, our data point to the involvement of the pDC/type I IFN pathway in the pathogenesis of ENL, opening new avenues in identifying biomarkers for early diagnosis and new therapeutic targets for the better management of this reactional episode.

Urgent vs. planned peritoneal dialysis initiation: complications and outcomes in the first year of therapy.

INTRODUCTION: Urgent-start peritoneal dialysis (US-PD) has been proposed as a safe modality of renal replacement therapy (RRT) for end-stage renal disease (ESRD) patients with an indication for emergency dialysis initiation. We aimed to compare the characteristics, 30-day complications, and clinical outcomes of US-PD and planned peritoneal dialysis (Plan-PD) patients over the first year of therapy. METHODS: This was a single-center retrospective study that included incident adult patients followed for up to one year. US-PD was considered when incident patients started therapy within 7 days after Tenckhoff catheter implantation. Plan-PD group consisted of patients who started therapy after the breaking period (15 days). Mechanical and infectious complications were compared 30 days from PD initiation. Hospitalization and technique failure during the first 12 months on PD were assessed by Kaplan-Meier curves and the determinants were calculated by Cox regression models. RESULTS: All patients starting PD between October/2016 and November/2019 who fulfilled the inclusion criteria were analyzed. We evaluated 137 patients (70 in the US-PD x 67 Plan-PD). The main complications in the first 30 days were catheter tip migration (7.5% Plan-PD x 4.3% US-PD - p= 0.49) and leakage (4.5% Plan-PD x 5.7% US-PD - p=0.74). Most catheters were placed using the Seldinger technique. The main cause of dropout was death in US-PD patients (15.7%) and transfer to HD in Plan-PD patients (13.4%). The occurrence of complications in the first 30 days was the only risk factor for dropout (OR = 2.9; 95% CI 1.1-7.5, p = 0.03). Hospitalization rates and technique survival were similar in both groups. CONCLUSION: The lack of significant differences in patients' outcomes between groups reinforces that PD is a safe and applicable dialysis method in patients who need immediate dialysis.

Annexin A1 as a Regulator of Immune Response in Cancer.

Annexin A1 is a 37 kDa phospholipid-binding protein that is expressed in many tissues and cell types, including leukocytes, lymphocytes and epithelial cells. Although Annexin A1 has been extensively studied for its anti-inflammatory activity, it has been shown that, in the cancer context, its activity switches from anti-inflammatory to pro-inflammatory. Remarkably, Annexin A1 shows pro-invasive and pro-tumoral properties in several cancers either by eliciting autocrine signaling in cancer cells or by inducing a favorable tumor microenvironment. Indeed, the signaling of the N-terminal peptide of AnxA1 has been described to promote the switching of macrophages to the pro-tumoral M2 phenotype. Moreover, AnxA1 has been described to prevent the induction of antigen-specific cytotoxic T cell response and to play an essential role in the induction of regulatory T lymphocytes. In this way, Annexin A1 inhibits the anti-tumor immunity and supports the formation of an immunosuppressed tumor microenvironment that promotes tumor growth and metastasis. For these reasons, in this review we aim to describe the role of Annexin A1 in the establishment of the tumor microenvironment, focusing on the immunosuppressive and immunomodulatory activities of Annexin A1 and on its interaction with the epidermal growth factor receptor.

Potential Role of CXCL10 in Monitoring Response to Treatment in Leprosy Patients.

The treatment of multibacillary cases of leprosy with multidrug therapy (MDT) comprises 12 doses of a combination of rifampicin, dapsone and clofazimine. Previous studies have described the immunological phenotypic pattern in skin lesions in multibacillary patients. Here, we evaluated the effect of MDT on skin cell phenotype and on the Mycobacterium leprae-specific immune response. An analysis of skin cell phenotype demonstrated a significant decrease in MRS1 (SR-A), CXCL10 (IP-10) and IFNG (IFN-γ) gene and protein expression after MDT release. Patients were randomized according to whether they experienced a reduction in bacillary load after MDT. A reduction in CXCL10 (IP-10) in sera was associated with the absence of a reduction in the bacillary load at release. Although IFN-γ production in response to M. leprae was not affected by MDT, CXCL10 (IP-10) levels in response to M. leprae increased in cells from patients who experienced a reduction in bacillary load after treatment. Together, our results suggest that CXCL10 (IP-10) may be a good marker for monitoring treatment efficacy in multibacillary patients.

Urgent vs. early-start peritoneal dialysis: patients' profile and outcomes / Diálise peritoneal de urgência vs. início precoce: perfil dos pacientes e resultados

ABSTRACT Introduction: Peritoneal dialysis (PD) has been considered a safe option of therapy in end-stage renal disease patients with urgent need of dialysis. Recently, it was proposed that Urgent-Start-PD (US-PD) be defined when PD starts within 72 hours after catheter placement and "early start" PD (ES-PD) when PD starts between 3 and 14 days after. We aimed to compare demographic and clinical characteristics between patients in US-PD and ES-PD as well as 30-day complications, 6-month hospitalization, and dropout rate. Methods: Adult patients starting PD within 14 days after catheter insertion (October/2016 - February/2019) were included and divided into US-PD group and ES-PD group based on the their PD initiation time. Clinical and demographic data, fill volume for the first PD session, 30-day complications, 6-month hospitalization, and dropout rate were assessed. Results: In our study, 72 patients were analyzed (US-PD=40, ES-PD=32) with mean age of 53.2±15.2 years old. No differences between US-PD and ES-PD regarding demographic characteristics, 30-day complications, 6-month hospitalization, and dropout events were found. The most frequent short-term complication in patients who started PD urgently was leakage. The most common cause of dropout was transfer to HD. Conclusion: Fifty five percent of our sample started PD less than 72 hours after catheter insertion. The lack of difference in the measured outcomes compared to patients that had therapy initiated after this period encourages the use of urgent PD when needed.

RESUMO Introdução: A diálise peritoneal (DP) tem sido considerada uma opção segura de terapia em pacientes com doença renal terminal com necessidade urgente de diálise. Recentemente, foi proposto que a DP de início urgente (US-PD) fosse definida quando a DP iniciar dentro de 72 horas após o implante do cateter, e a DP de "início precoce" (ES-PD) quando a DP iniciar entre 3 e 14 dias após o procedimento. Nosso objetivo foi comparar características demográficas e clínicas entre pacientes em US-PD e ES-PD, bem como complicações em 30 dias, internação por 6 meses e taxa de saída do tratamento. Métodos: Pacientes adultos iniciando DP em até 14 dias após a inserção do cateter (outubro/2016 - fevereiro/2019) foram incluídos e divididos no grupo US-PD ou ES-PD com base no tempo de início da DP. Dados clínicos e demográficos, volume de preenchimento na primeira sessão de DP, complicações em 30 dias, hospitalização por 6 meses e taxa de saída foram avaliados. Resultados: Em nosso estudo, 72 pacientes foram analisados (US-PD = 40, ES-PD = 32) com média de idade de 53,2 ± 15,2 anos. Não foram encontradas diferenças entre US-PD e ES-PD em relação às características demográficas, complicações em 30 dias, hospitalização por 6 meses e saída do tratamento. A complicação de curto prazo mais frequente nos pacientes que iniciaram a DP com urgência foi o extravasamento de líquido peritoneal. A causa mais comum de saída foi a transferência para HD. Conclusão: Mais da metade da nossa amostra iniciou a DP menos de 72 horas após a inserção do cateter. A falta de diferença nos desfechos mensurados em comparação com os pacientes que iniciaram o tratamento após esse período incentiva o uso de US-PD quando necessário.

Assessment of patients referred to urgent start peritoneal dialysis: when does the nurse contraindicate? / Avaliação de pacientes indicados para diálise peritoneal urgent start: quando o enfermeiro contraindica?

Abstract Introduction: Urgent-start peritoneal dialysis (US-PD) has been used worldwide with very positive results. The prior assessment of candidates for this therapy by a nurse can favor the success of the therapy. Objectives: To identify the profile of patients who are candidates for US-PD, the causes of contraindication of the method by the nurse and their permanence in the method after 30 days, as well as the growth of the service after implementing the program. Methods: We retrospectively analyzed the forms used to assess candidates for US-PD applied by nurses between May 2017 and August 2019 in a clinic in Santa Catarina. We analyzed information on demographic profile, reasons for contraindication and permanence in the method after 30 days, as well as service growth after the program was implemented. Results: Of the 215 patients indicated for US-PD, 51% were male, 55% were under 60 years old, 51% had diabetes mellitus and 89% were hypertensive. Of these, 173 (80%) patients had the nurse's approval for PD. The only cause contraindicated was the inability to self-care associated with the lack of family support. In the first 30 days after the assessment, 89% of the patients who started PD remained on it. During the study period, the PD service grew by 91%. Conclusion: During the study period, a fifth of patients referred to US-PD received contraindication by nursing due to self-care inability associated with the lack of family support. After 30 days, 89% of the patients remained on it.

Resumo Introdução: A diálise peritoneal (DP) de início urgente ou urgent start (DP-US) vem sendo utilizada mundialmente e apresenta resultados bastante positivos. A avaliação prévia dos candidatos a essa terapia por um enfermeiro pode favorecer o sucesso do tratamento. Objetivos: Identificar o perfil dos pacientes candidatos à DP-US, as causas de contraindicação do método pelo enfermeiro e sua permanência após 30 dias, bem como o crescimento do serviço com a implementação do programa. Métodos: Foram analisados retrospectivamente formulários de avaliação dos candidatos à DP-US aplicados pelos enfermeiros entre maio de 2017 a agosto de 2019 em uma clínica de diálise localizada na região sul brasileira. Foram analisadas informações referentes a perfil demográfico, motivos para contraindicação e permanência no método após 30 dias, bem como crescimento do serviço após implementação do programa. Resultados: Dos 215 pacientes indicados para DP-US, 51% eram do sexo masculino, 55% tinham menos de 60 anos, 51% apresentavam diabetes mellitus, 89% eram hipertensos. Desses, 173 (80%) pacientes obtiveram parecer positivo do enfermeiro para DP. A única causa para contraindicação foi a incapacidade para autocuidado associado à falta de apoio familiar. Nos primeiros 30 dias após a avaliação, 89% dos pacientes que iniciaram a DP-US permaneceram na técnica. No período do estudo, o serviço de DP teve um crescimento de 91%. Conclusão: Um quinto dos pacientes indicados à DP-US recebeu contraindicação pela enfermagem devido à incapacidade de autocuidado associado à falta de apoio familiar. Após 30 dias, 89% dos pacientes haviam permanecido na técnica.

Assessment of patients referred to urgent start peritoneal dialysis: when does the nurse contraindicate?

INTRODUCTION: Urgent-start peritoneal dialysis (US-PD) has been used worldwide with very positive results. The prior assessment of candidates for this therapy by a nurse can favor the success of the therapy. OBJECTIVES: To identify the profile of patients who are candidates for US-PD, the causes of contraindication of the method by the nurse and their permanence in the method after 30 days, as well as the growth of the service after implementing the program. METHODS: We retrospectively analyzed the forms used to assess candidates for US-PD applied by nurses between May 2017 and August 2019 in a clinic in Santa Catarina. We analyzed information on demographic profile, reasons for contraindication and permanence in the method after 30 days, as well as service growth after the program was implemented. RESULTS: Of the 215 patients indicated for US-PD, 51% were male, 55% were under 60 years old, 51% had diabetes mellitus and 89% were hypertensive. Of these, 173 (80%) patients had the nurse's approval for PD. The only cause contraindicated was the inability to self-care associated with the lack of family support. In the first 30 days after the assessment, 89% of the patients who started PD remained on it. During the study period, the PD service grew by 91%. CONCLUSION: During the study period, a fifth of patients referred to US-PD received contraindication by nursing due to self-care inability associated with the lack of family support. After 30 days, 89% of the patients remained on it.

Urgent vs. early-start peritoneal dialysis: patients' profile and outcomes.

INTRODUCTION: Peritoneal dialysis (PD) has been considered a safe option of therapy in end-stage renal disease patients with urgent need of dialysis. Recently, it was proposed that Urgent-Start-PD (US-PD) be defined when PD starts within 72 hours after catheter placement and "early start" PD (ES-PD) when PD starts between 3 and 14 days after. We aimed to compare demographic and clinical characteristics between patients in US-PD and ES-PD as well as 30-day complications, 6-month hospitalization, and dropout rate. METHODS: Adult patients starting PD within 14 days after catheter insertion (October/2016 - February/2019) were included and divided into US-PD group and ES-PD group based on the their PD initiation time. Clinical and demographic data, fill volume for the first PD session, 30-day complications, 6-month hospitalization, and dropout rate were assessed. RESULTS: In our study, 72 patients were analyzed (US-PD=40, ES-PD=32) with mean age of 53.2±15.2 years old. No differences between US-PD and ES-PD regarding demographic characteristics, 30-day complications, 6-month hospitalization, and dropout events were found. The most frequent short-term complication in patients who started PD urgently was leakage. The most common cause of dropout was transfer to HD. CONCLUSION: Fifty five percent of our sample started PD less than 72 hours after catheter insertion. The lack of difference in the measured outcomes compared to patients that had therapy initiated after this period encourages the use of urgent PD when needed.