[Chilean consensus on diagnosis and management of pancreatic cystic neoplasms]. / Consenso chileno de diagnóstico y manejo de neoplasias quísticas pancreáticas. Club de páncreas Chile-SCHGE.

Pancreatic cystic neoplasms (PCN) are frequently detected on abdominal images performed for non-pancreatic indications. Their prevalence in asymptomatic population ranges from 2.7 to 24.8%, and increases with age. There are several types of pancreatic cysts. Some may contain cancer or have malignant potential, such as mucinous cystic neoplasms, including mucinous cystadenoma (MCN) and intraductal papillary mucinous neoplasms (IPMN). In contrast, others are benign, such as serous cystadenoma (SCA). However, even those cysts with malignant potential rarely progress to cancer. Currently, the only treatment for pancreatic cysts is surgery, which is associated with high morbidity and occasional mortality. The Board of the Chilean Pancreas Club of the Chilean Gastroenterology Society developed the first Chilean multidisciplinary consensus for diagnosis, management, and surveillance of PCN. Thirty experts were invited and answered 21 statements with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree. A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. The consensus was approved by the Board of Directors of the Chilean Pancreas Club for publication.

Arthralgia and myalgia associated with aromatase inhibitors: frequency and characterization in real-life patients.

Introduction: Adjuvant treatment with aromatase inhibitors (AI) in oestrogen receptor-positive and/or progesterone receptor-positive breast cancer (BC) has been shown to increase overall survival. However, arthralgias and myalgias are common adverse effects in patients treated with AI. Objective: To evaluate the frequency and characteristics of arthralgias and myalgias in patients with early BC-treated adjuvantly with AI in the Mastology Unit of the Oncology Service of the Hospital de Clínicas and the Departmental Hospital of Soriano. Materials and methods: A prospective, cross-sectional and descriptive study was performed. A questionnaire was administered to patients to assess the presence and characteristics of arthralgias and myalgias associated with AI. Statistical analysis: 'Age' was described with measures of central tendency and dispersion. Qualitative variables were presented in absolute and relative frequencies. Logistic models were used to evaluate the association between patient characteristics, tumour characteristics, treatment characteristics and the presence of pain. Results were presented by odds ratio and p-value, using R software (version 4.1.2) with a significance threshold of 5%. Results: 83 patients were included, with a median age of 69 years. 75.9% presented arthralgias and/or myalgias related to treatment, with an average intensity of 5-7. 80.9% received non-steroidal anti-inflammatory drugs (NSAIDs), achieving satisfactory analgesia. The presence of arthralgias and myalgias was significantly associated with age and time since the last menstrual period (LMP), being more frequent in patients older than 50 years and those with more than 5 years since the LMP. Conclusion: Approximately 70% of the patients presented arthralgias or myalgias. These findings suggest a possible role of oestrogen withdrawal in its mechanism of development. Multidisciplinary and translational research is crucial to evaluate the ethology and therapeutic options for patients with AI-related arthralgia.

Efficacy of First-Line Treatment With Pertuzumab and Trastuzumab in Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in Routine Clinical Practice.

Background: The first-line treatment for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) involves a combination of trastuzumab, pertuzumab, and a taxane (TPH). This study assessed the efficacy of trastuzumab and pertuzumab (PH) in routine practice, following the treatment protocols of Uruguay's National Resources Fund (FNR), akin to clinical trials. Methods: Patients with advanced MBC treated with PH between 2008 and 2022 per FNR protocols were evaluated. The Kaplan-Meyer method and log-rank test were utilized for analyzing overall survival (OS). Demographic and clinical variables, including age, menopausal status, and hormone receptors (HR), were analyzed. Results: The study included 318 PH-treated patients. The median age was 56 years, with 63.2% being postmenopausal and 60.4% HR and HER-2 positive. With a median follow-up of 17.2 months, the median OS was 29 months. OS varied based on HR status and the presence of metastases at different sites, significantly lower in patients with brain, cutaneous/subcutaneous, and pulmonary metastases. Additionally, OS was higher in patients treated at private institutions compared to public ones. Conclusions: This study demonstrates the disparity in oncological treatment efficacy between clinical trials and clinical reality in Uruguay, emphasizing the importance of authentic environment research for more representative and effective medicine in Latin America.

[Pharmacokinetics of vancomycin in children hospitalized in a critical care unit]. / Farmacocinética de vancomicina en niños hospitalizados en una unidad de paciente crítico.

INTRODUCTION: Monitoring PK/PD of vancomycin with basal and peak serum levels and the area under the curve of drug exposure 24 h/MIC (ABC 24 h/MIC) could optimize the management of children. OBJECTIVE: To study the PK of vancomycin in children hospitalized in the Pediatric Intensive Care Unit (PICU), assessing PK/PD parameters withABC24 h/MIC. METHODS: Retrospective, descriptive study in the PICU (Hospital Luis Calvo Mackenna) between January 2008-March 2010. We included children < 18 years who required antimicrobial treatment with vancomycin for suspected/confirmed staphylococcal infection using a dose of 40 mg/k/day. Plasmatic levels were performed one hour postinfusion and 30 min prior to the next dose. The following PK/PD parameters were calculated: vancomycin clearance, elimination rate constant, volume of distribution, half-life (T1/2) and ABC 24 h/ MIC. RESULTS: We enrolled eighty-four children. According to ABC 24 h/MIC obtained, 54% (45/84) of children reached an optimal level (> 400 mg*hr/L). Based on the traditional PK/PD parameters, 49% of cases (41/84) presented a basal level of vancomycin in the therapeutic range (5-15 µg/mL) and of those, only 39% (16/41) had a ABC 24 h/MIC over 400 mg*h/L. DISCUSSION: Based on our results, children admitted to PICU could be exposed to sub therapeutic doses of vancomycin. We recommend to implement tailored antimicrobial treatment monitoring vancomycin PK/PD parameters.

Assessing Adherence to Adjuvant Hormone Therapy in Breast Cancer Patients in Routine Clinical Practice.

Background: Adjuvant hormone therapy (HT) in patients with hormone receptor-positive breast cancer (BC) increases overall survival (OS). A lack of adherence to adjuvant endocrine therapy is common, 31.0-73.0% of women discontinue endocrine treatment before 5 years. The aim of the study was to assess adherence to HT in routine clinical practice in patients assisted at the Clinical Oncology Department of the Hospital de Clinicas - Universidad de la Republica, Uruguay. Methods: Patients treated with HT for stage 0-III BC between 2017 and 2019 were included. The medication possession (MPR) rate was calculated using pharmacy records, and the Morisky-Green Scale was applied to assess adherence. Adherent patients were those with MPR ≥ 0.80 and who correctly answered the Morisky-Green treatment adherence questionnaire. The association of adherence with polypharmacy, treatment, and patient characteristics was assessed using simple logistic models. The associations between qualitative variables and adherence were assessed using simple logistic regression model or Fisher's exact test. The association between quantitative variables and adherence was assessed using the Student's t-test. The odds ratio (OR) for non-adherence to treatment and its 95% confidence interval were estimated. Results: Totally, 118 patients were included; 65.2% were treated with aromatase inhibitors (AIs), 36.0% presenting polypharmacy. The adherence rate at the end of 2 years was 81.0 %; and it was associated with age (P = 0.03, OR = 0.96 for non-adherence), with adherent and non-adherent patients having a mean age of 65.0 and 60.3 years, respectively; however, adherence was not associated with polypharmacy, territory of origin, marital status, living alone, level of education, occupation, or stage. The adherence profile was similar for both drugs, but homemakers and retired women showed greater adherence to AI. Conclusions: Adherence to HT was assessed in real life, with 19.0% of the patients not adhering to the treatment, despite the known benefit for OS, being a well-tolerated treatment, and being provided free of charge. Older patients were associated with being more adherent. The results show the need of the Pharmacy Service and Department of Clinical Oncology Medical Oncology combining efforts to develop coordinated strategies and interventions to increase adherence, given the impact that this may have on patients' OS.

Inclusion of information technology-based assessments of health-related quality of life in routine oncology practice in Uruguay.

BACKGROUND: Previous research has shown that the inclusion of patient-reported outcomes measures in the patient's visit to the oncologists might improve the quality of global health care. The aim of the study was to assess the feasibility, acceptance, and utility perceived by patients and oncologists of health-related quality of life (HRQL) assessments obtained prior to clinical visits, and to evaluate if this has an impact on patient's well-being in a sample of Spanish-speaking patients from Uruguay. METHODS: Patients assisted regularly in the Oncology Clinic were randomized into two groups: an intervention group that completed a set of questionnaires (European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-C30 (EORTC QLQ-C30) and Hospital Anxiety and Depression Scale using a touch screen device and a control group that did not respond to these questionnaires. At 2 months, the responses of all the participants to the Functional Assessment of Cancer Therapy-General (FACT-G) were collected over a telephone to determine whether there were differences in the HRQL between the intervention and control groups. The graphed scores of the intervention group were included in the clinical history of the patient during consultation. Patients and physicians completed the questionnaires on the usefulness of these measurements. RESULTS: In total, 58 patients participated in this study: 36 in the intervention group and 22 in the control group; 65% of the participants were female, and median age was 59 years (18-79). Regarding patients, 97% found the questionnaires easy to complete and thought that they included important questions. As for oncologists, 68.8% used the information and 87.5% found it useful for the consultation. There were no significant differences in the FACT-G scores between the intervention and control groups. CONCLUSIONS: The routine HRQL assessments using an electronic device prior to the consultations were positively valued by almost all patients and physicians. This could significantly contribute to a better understanding of the patient's overall problems during consultation. These results confirm the benefits of integrating the patient's self-reported quality of life outcomes into consultations.

Population-based screening of Uruguayan Ashkenazi Jews for recurrent BRCA1 and BRCA2 pathogenic sequence variants.

In Ashkenazi Jews (AJ) three recurring pathogenic sequence variants (PSVs) are detected in ~2.5% of the general population in the BRCA1 (c.68_69del = 185delAG, c.5266dup = 5382insC), and BRCA2 (c.5946del = 6174delT). Population-based screening for these PSVs in AJ women is part of the health basket in Israel. To assess the feasibility and outcome of BRCA genotyping in the Jewish population of Uruguay, AJ in the greater Montevideo area were recruited using ethically approved protocol and without pretest counseling were genotyped for the three predominant AJ PSVs in the BRCA genes. Independently confirmed PSV carriers were counseled, and genetic testing was offered to additional family members. Overall, 327 participants were enrolled: 312 (95%) female, 261 (80%) had all four grandparents AJ, and 14 (4%) women were breast cancer survivors with a mean age ± standard deviation (SD) 50 ± 11.5 years. The BRCA1 c.68_69del PSV was detected in three cancer free participants (0.92%, CI 95% 0.31-2.6), all with a suggestive family history. No carriers of the other two recurrent PSVs were detected. Online oncogenetic counseling was provided for all carriers. In conclusion, the rate of the BRCA1 c.68_69del PSV was similar with the rate in other AJ communities. AJ population BRCA genotyping screens in Uruguay seem feasible and should be promoted.

Trastuzumab-induced cardiotoxicity in early breast cancer over a 10-year period in Uruguay.

This srudy aimed to estimate the prevalence of trastuzumab-induced cardiotoxicity in Uruguayan women diagnosed with human epidermal growth factor receptor 2 (HER2)-positive breast cancer over a 10-year period, who were treated under the financial coverage of the National Resources Fund (Fondo Nacional de Recursos). This was an observational, descriptive study based on the analysis of an anonymized database of Uruguayan women diagnosed with HER2-positive breast cancer who received adjuvant trastuzumab treatment from to 2006 to 2016, provided by the Fondo Nacional de Recursos. Statistical analysis was performed using SPSS Statistics version 25, and variables were assessed using measures of central tendency, dispersion, contingency tables, and proportions. The chi-square test was used to analyze the association between the different variables. The study included 1401 patients diagnosed with stage I to III HER2-positive breast cancer. The mean age at diagnosis was 52 years. The prevalence of cardiotoxicity was 20.3%. Most patients who discontinued treatment owing to cardiotoxicity eventually resumed treatment (92.6%). Moreover, the prevalence of cardiotoxicity was similar among patients who received regimens with and without anthracyclines. No association was observed between prior cardiovascular events or trastuzumab administration (concurrent vs sequential) and the development of cardiotoxicity. In the present study, the prevalence of cardiotoxicity was similar to that reported nationally and internationally. Most patients did not develop cardiotoxicity, while the ones who developed it remained asymptomatic and cardiotoxicity was reversible.

Functional hypervariability and gene diversity of cardioactive neuropeptides.

Crustacean cardioactive peptide (CCAP) and related peptides are multifunctional regulatory neurohormones found in invertebrates. We isolated a CCAP-related peptide (conoCAP-a, for cone snail CardioActive Peptide) and cloned the cDNA of its precursor from venom of Conus villepinii. The precursor of conoCAP-a encodes for two additional CCAP-like peptides: conoCAP-b and conoCAP-c. This multi-peptide precursor organization is analogous to recently predicted molluscan CCAP-like preprohormones, and suggests a mechanism for the generation of biological diversification without gene amplification. While arthropod CCAP is a cardio-accelerator, we found that conoCAP-a decreases the heart frequency in Drosophila larvae, demonstrating that conoCAP-a and CCAP have opposite effects. Intravenous injection of conoCAP-a in rats caused decreased heart frequency and blood pressure in contrast to the injection of CCAP, which did not elicit any cardiac effect. Perfusion of rat ventricular cardiac myocytes with conoCAP-a decreased systolic calcium, indicating that conoCAP-a cardiac negative inotropic effects might be mediated via impairment of intracellular calcium trafficking. The contrasting cardiac effects of conoCAP-a and CCAP indicate that molluscan CCAP-like peptides have functions that differ from those of their arthropod counterparts. Molluscan CCAP-like peptides sequences, while homologous, differ between taxa and have unique sequences within a species. This relates to the functional hypervariability of these peptides as structure activity relationship studies demonstrate that single amino acids variations strongly affect cardiac activity. The discovery of conoCAPs in cone snail venom emphasizes the significance of their gene plasticity to have mutations as an adaptive evolution in terms of structure, cellular site of expression, and physiological functions.

Impact of the COVID-19 pandemic on health care activities at a Uruguayan mastology unit.

PURPOSE: Health emergency due to COVID-19 started in Uruguay on March 13, 2020; our mastology unit tried to ensure adequate oncological care, and protect patients from the virus infection and complications. OBJECTIVE: To assess the health care activities in the "peak" of the pandemic during 3 months. MATERIALS AND METHODS: we collected data from the electronic health record. RESULTS: There were a total of 293 medical appointments from 131 patients (221 face-to-face), that decreased by 16.7% compared to the same period in 2019 (352 appointments). The medical appointments were scheduled to evaluate the continuity of systemic treatment or modifications (95 patients; 72.5%), follow-up (17; 12.9%), first-time consultation (12; 9.1%), and assess paraclinical studies (7; 5.3%). The patients were on hormone therapy (81 patients; 74%), chemotherapy (CT) (21; 19%), and anti-HER2 therapies (9; 8%). New twenty treatments were initiated. Of the 14 patients that were on adjuvant/neoadjuvant CT, 9 (64.3%) continued with the same regimen with the addition of prophylactic granulocyte-colony-stimulating factors (G-CSF), and 5 (35.7%), who were receiving weekly paclitaxel, continued the treatment with no changes. Of the seven patients that were on palliative CT, 2 (28.5%) continued the treatment with the addition of G-CSF, 3 (42.8%) continued with weekly capecitabine or paclitaxel with no treatment changes, and 2 (28.5%) changed their treatment regimen (a less myelosuppressive regimen was selected for one and due to progression of the disease in the other patient). The ninety patients who were receiving adjuvant, neoadjuvant, or palliative criteria hormone therapy and/or anti-HER2 therapies, continued the treatment with no changes. CONCLUSIONS: The evidence suggests that, although medical appointments decreased by approximately 17%, we could maintain healthcare activities, continued most of the treatments while the most modified was CT with G-CSF to avoid myelosuppression.

Survival and Time to Initiation of Adjuvant Chemotherapy Among Breast Cancer Patients in Uruguay.

INTRODUCTION: Increases in disease-free survival and overall survival (OS) with the use of adjuvant chemotherapy in early breast cancer (BC) are widely known; however, the optimal time to initiate treatment with adjuvant chemotherapy remains controversial. OBJECTIVE: To evaluate the time elapsed between surgery and the initiation of adjuvant chemotherapy and its possible impact on OS in patients diagnosed with BC stages I-III. MATERIALS AND METHODS: This retrospective study included 112 patients diagnosed with BC stages I-III who received adjuvant chemotherapy at the Mastology Unit of the Hospital de Clínicas in Uruguay from 2009 to 2019. OS was estimated using the Kaplan-Meier method, and a Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals. RESULTS: No statistically significant association was found between the time from surgery to the initiation of chemotherapy and the described variables. OS was worse for patients initiating chemotherapy more than 90 days after breast surgery (n = 19) (HR 7.63; p = 0.004) and between 61 and 90 days after surgery (n = 46) (HR 4.58; p = 0.040) compared to those who started before 30 days (n = 23). Controlling by type of surgery and stage, the prognosis of patients who started chemotherapy between 61 and 90 days after surgery was similar to that of patients who underwent chemotherapy within the first 30 days, controlling for surgery (HR 4.10; p = 0.056) and controlling for stage (HR 3.76; p = 0.075). Prognosis was worse for patients with stage III disease (p = 0.022) who underwent a mastectomy and/or axillary lymph node dissection (p = 0.025). CONCLUSION: Patients who started chemotherapy more than 90 days following surgery and those with stage III disease or underwent mastectomy and/or axillary lymph node dissection who initiated it between 61 and 90 days had a worse OS. Multiple factors are involved in the time between surgery and the initiation of chemotherapy, and further studies are needed to evaluate which of these factors influence the delay of chemotherapy in order to design strategies to avoid such delays and their negative impact on survival.

Prevalence of Known Risk Factors in Uruguayan Women Treated for Breast Cancer at a University Hospital.

INTRODUCTION: In Uruguay, breast cancer has the highest incidence and mortality of all cancer in women. Knowledge of the distribution of risk factors related to disease development supports the implementation of prevention strategies in routine clinical practice. This study aimed to determine the epidemiological profile for breast cancer and the frequency of mammographic surveillance in the surveyed population. MATERIALS AND METHODS: A survey was conducted among Uruguayan women diagnosed with breast cancer who were assisted in the mastology unit of the oncology service of the Hospital de Clínicas in Montevideo, Uruguay, from September 1, 2018, to March 1, 2020. RESULTS: This study included 398 respondents, with a median (SD) age at diagnosis of 61 (34-86) years. A total of 310 respondents (78.0%) had 1 or more risk factors. Most women aged over 50 years (264 out of a total of 338 [78.1%]) underwent mammographic surveillance at least biennially. CONCLUSIONS: Consistent with international reports, most respondents had a risk factor. Among the group of respondents aged over 50 years, most underwent mammographic and clinical surveillance at least biennially. Although it is only possible to formulate conclusions about the surveyed women because of the study design, the obtained data further our understanding of the epidemiological profile of the Uruguayan population, which can contribute to prevention practices.

Effectiveness of a Gamification Strategy to Prevent Childhood Obesity in Schools: A Cluster Controlled Trial.

OBJECTIVE: The aim of this study was to examine the effectiveness of a school-based gamification strategy to prevent childhood obesity. METHODS: Schools were randomized in Santiago, Chile, between March and May 2018 to control or to receive a nutrition and physical activity intervention using a gamification strategy (i.e., the use of points, levels, and rewards) to achieve healthy challenges. The intervention was delivered for 7 months and participants were assessed at 4 and 7 months. Primary outcomes were mean difference in BMI z score and waist circumference (WC) between trial arms at 7 months. Secondary outcomes were mean difference in BMI and systolic and diastolic blood pressure between trial arms at 7 months.  RESULTS: A total of 24 schools (5 controls) and 2,197 students (653 controls) were analyzed. Mean BMI z score was lower in the intervention arm compared with control (adjusted mean difference -0.133, 95% CI: -0.25 to -0.01), whereas no evidence of reduction in WC was found. Mean BMI and systolic blood pressure were lower in the intervention arm compared with control. No evidence of reduction in diastolic blood pressure was found. CONCLUSIONS: The multicomponent intervention was effective in preventing obesity but not in reducing WC. Gamification is a potentially powerful tool to increase the effectiveness of school-based interventions to prevent obesity.

Effectiveness of Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in a Real-Life Setting: One Decade of Experience Under National Treatment Coverage Regulations.

PURPOSE: Trastuzumab has shown an overall survival (OS) benefit in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), in both the adjuvant and the metastatic setting. We assessed the effectiveness of trastuzumab in patients treated in daily practice according to national treatment coverage protocols and compared our results with those reported by randomized clinical trials. These coverage protocols included patient selection criteria similar to those of those clinical trials and were developed by the Uruguayan National Resource Fund (FNR), the agency that has funded these prescriptions for more than a decade. PATIENTS AND METHODS: We included all patients with HER2-positive BC treated with trastuzumab under FNR coverage approved between January 1, 2006, and December 31, 2016. The source of data was the FNR database, and primary outcome was OS, analyzed through Cox proportional hazards regression analysis. RESULTS: A total of 1,944 women were included: 1,085 women (55.8%) were postmenopausal and 1,240 (63.7%) had HER2 and hormone receptor-positive BC. Trastuzumab was administered as adjuvant therapy to 1,233 patients (63.5%), of whom 154 also received it as a neoadjuvant treatment. Three hundred nineteen patients (16.4%) received trastuzumab for advanced disease. Five-year OS in the adjuvant setting was 86.4% (95% CI, 84.0% to 88.7%). The median survival of patients with advanced BC was 25.1 months (95% CI, 10.1 to 42.5 months). CONCLUSION: Our survival results are not inferior to those reported in clinical trials, in both adjuvant and advanced settings. Importantly, these results support the relevance and the feasibility of treating patients in routine practice, following coverage protocols based on patient selection criteria and methods supported by positive clinical trials. In addition, these results favor quality and appropriate access to BC treatment in our country.

[Endoscopic argon plasma coagulation in recurrent tracheoesophageal fistula. Clinical series and review of the literature]. / Tratamiento endoscópico con argón plasma en fístula traqueoesofágica recurrente. Serie clínica y revisión de la literatura médica.

INTRODUCTION: Recurrent tracheoesophageal fistula (RTEF) is a complication that occurs in up to 15% of patients after esophageal atresia repair. The clinical features include coughing, aspiration, recurrent pneumonia and failure to thrive. Surgical treatment is recommended. However, since 1980, the endoscopic route has been used as a therapeutic alternative. Distinct techniques have been employed with an overall success rate of 63%. PURPOSE: To evaluate a new endoscopic treatment for RTEF with argon plasma coagulation (APC). METHODS: Six patients with RTEF treated with endoscopic APC between 2003 and 2007 at a single institution (Clinica Alemana, Santiago, Chile) were included. We also performed a systematic literature search. Nineteen articles were selected, with a total of 77 patients treated through the endoscopic route. RESULTS: Treatment was successful in 66% of the patients with a follow-up of more than 12 months. On average, the patients required two applications of APC. This success rate was similar to that reported in published series. CONCLUSION: Endoscopic treatment with APC in RTEF seems to be useful and easily applied. Because of the complexity of surgical treatment, we recommend endoscopic treatment as the first approach in patients with RTEF.

Identification and electrophysiological properties of a sphingosine-dependent plasma membrane Ca2+ channel in Trypanosoma cruzi.

Trypanosoma cruzi is the causative agent of Chagas disease. The only two drugs accepted for the treatment of this infection are benznidazole and nifurtimox, which are of limited use in the predominant chronic phase. On the search for new drugs, the intracellular Ca2+ regulation has been postulated as a possible target, due to differences found between host cells and the parasite. The mechanisms involved in the intracellular Ca2+ regulation of T. cruzi have been partially elucidated. However, nothing is known about a putative channel responsible for the Ca2+ entry into this parasite. In contrast, in Leishmania spp., a closely related hemoflagelate, a sphingosine-activated plasma membrane Ca2+ channel has been recently described. The latter resembles the L-type voltage-gated Ca2+ channel present in humans, but with distinct characteristics. This channel is one of the main targets concerning the mechanism of action of miltefosine, the unique oral drug approved against leishmaniasis. In the present work, we describe for the first time, the electrophysiological characterization of a sphingosine-activated Ca2+ channel of T. cruzi by reconstituting plasma membrane vesicles into giant liposomes and patch clamp. This channel shares some characteristic as activation by Bay K8644 and inhibition by channel blockers such as nifedipine. However, the T. cruzi channel differs from the L-type VGCC in its activation by sphingosine and/or miltefosine. Albeit the conductance for each, Ba2+ , Ca2+ and Sr2+ was similar, the parasite channel appears not to be voltage dependent. A gene that presents homology in critical amino acids with its human ortholog Ca2+ channel was identified.

Bactridine 2 effect in DRG neurons. Identification of NHE as a second target.

Bactridine 2 (Bact-2) is an antibacterial toxin from Tityus discrepans venom which modifies isoforms 1.2, 1.4 and 1.6 voltage-dependent sodium (Nav) channels. Bactridine-induced Na+ outflow in Yersinia enterocolitica was blocked by amiloride, suggesting that Bact-2 effect was mediated by an amiloride sensitive sodium channel. In this study we show that Bact-2 increases also an outward rectifying current in rat dorsal root ganglia (DRG) sensory neurons; therefore, the nature of the outward rectifying currents was characterized and then the effect of Bact-2 on these currents was studied. These currents are enhanced by amiloride, are decreased by Na+ when an outward pH gradient is present and its reversal potential coincides with that of a Cl-/H+ exchanger, suggesting that rectifying currents are produced by the electrogenic Cl-/H+ exchanger modulated by the Na+/H+ antiporter. Bact-2 also leads to an increase of the outward currents in a similar way to the produced by the inhibition of the Na+/H+ exchanger. Additionally, the subsequent application of Bact-2 after blocking the Na+/H+ exchanger does not produce any further effect, suggesting that Bact-2 modifies the outward current by modulating the activity of the Na+/H+ exchanger. The effect of Bact-2 on pHi regulation was determined using the pH indicator BCECF. The results show that the Na+/H+ exchanger is blocked by amiloride and Na+ free solutions and is modulated by Bact-2 in a similar way as cariporide. This study validates that besides Nav channels, Bact-2 modulates the activity of the Na+/H+ exchanger.

Características clínico- patológicas y evolución del cáncer de mama en pacientes asistidas en la Unidad de Mastología del Hospital de Clínicas

Introducción: En Uruguay el cáncer de mama (CM) ocupa el primer lugar en incidencia y mortalidad por cáncer en la mujer, se trata de una enfermedad multifactorial que guarda relación con la herencia genética, historial hormonal estrogénico, estilo de vida, factores ambientales y culturales. Objetivos: investigar las características clínico-patológicas de pacientes con CM diagnosticadas en el Hospital de Clínicas y evaluar la sobrevida global total (SVG) y de acuerdo al subtipo biológico. Metodología: se recolectaron datos relacionados con las características clínico-patológicas y la evolución de pacientes tratadas por CM en el período comprendido entre el 1º de enero del 2011 y 31 de diciembre de 2020 asistidas en la Unidad de Mastología del Hospital de Clínicas. Se calculó la SVG para todas las pacientes, globalmente, y según el subtipo biológico. Resultados: se incluyeron 390 pacientes. Las características clínico-patológicas fueron: carcinoma ductal: 83%, estadio: in situ (1.8 %), I (27.7 %), II (29.7 %), III (23.6%), IV (12.6 %). Con respecto al perfil biológico: 235 tumores (60.3%) fueron RRHH+ HER 2−, 88 tumores (22.6%) fueron HER2 +, mientras que otros 41 tumores (10.5%) fueron clasificados como triple negativos (TN). La SVG para la totalidad de las pacientes tuvo una mediana de 92 meses. Las tasas de SVG a 2 y 5 años fueron para las luminales de 92% y 64%; en las TN la tasa de SVG a 24 meses fue de 69%, siendo a 5 años de 53.3% y en las HER2 + 76.6% y 67.3% respectivamente. Conclusiones: La mayoría de los tumores fueron diagnosticados en estadios precoces, siendo estos datos son concordantes con los reportados en estudios realizados a nivel nacional. La frecuencia de tumores RE/RP+ algo inferior a la reportada en estudios previos (70%) a nivel nacional, mientras que la de tumores HER 2 + TN fue similar a la reportada en estudios europeos, norteamericanos y en Latinoamérica donde se la prevalencia encontrada es del 20%

Introduction: In Uruguay, breast cancer (BC) ranks first in incidence and mortality from cancer in women. It is a multifactorial disease that is related to genetic inheritance, estrogenic hormonal history, lifestyle, environmental and cultural factors. Objectives: to investigate the clinicopathological characteristics of patients with BC diagnosed at the Hospital de Clínicas and to evaluate the overall overall survival (SVG) and according to the biological subtype. Metodology: data related to the clinicopathological characteristics and the evolution of patients treated for BC in the period between January 1, 2011 and December 31, 2020 assisted in the Mastology Unit of the Hospital de Clínicas were collected. Overall survival (SVG) was calculated for all patients, globally, and according to biological subtype. Results: 390 patients were included. The clinicopathological characteristics were: ductal carcinoma: 83%, stage: in situ (1.8%), I (27.7%), II (29.7%), III (23.6%), IV (12.6%). Regarding the biological profile: 235 tumors (60.3%) were HR+ HER 2−, 88 tumors (22.6%) were HER2 +, while another 41 tumors (10.5%) were classified as triple negative (TN). The SVG for all the patients had a median of 92 months. SVG rates at 2 and 5 years were 92% and 64% for luminals; in TN the 24-month survival rate was 69%, being 53.3% at 5 years and in HER2 + 76.6% and 67.3% respectively. Conclusions: Most of the tumors were diagnosed in early stages, these data being consistent with those reported in studies carried out at the national level. The frequency of ER/RP+ tumors was somewhat lower than that reported in previous studies (70%) at the national level, while that of HER 2 + TN tumors was similar to that reported in European, North American and Latin American studies where the prevalence found is 20%

Introdução: No Uruguai, o câncer de mama (CM) ocupa o primeiro lugar em incidência e mortalidade por câncer em mulheres. É uma doença multifatorial que está relacionada à herança genética, história hormonal estrogênica, estilo de vida, fatores ambientais e culturais. Objetivos: investigar as características clinicopatológicas dos pacientes com CM diagnosticados no Hospital de Clínicas e avaliar a sobrevida global (OSV) e segundo o subtipo biológico. Material e método: foram coletados dados referentes às características clínico-patológicas e à evolução dos pacientes atendidos por CM no período de 1º de janeiro de 2011 a 31 de dezembro de 2020 atendidos na Unidade de Mastologia do Hospital de Clínicas. A sobrevida global (SVG) foi calculada para todos os pacientes, globalmente e de acordo com o subtipo biológico. Resultados: 390 pacientes foram incluídos. As características clínico-patológicas foram: carcinoma ductal: 83%, estádio: in situ (1,8%), I (27,7%), II (29,7%), III (23,6%), IV (12,6%). Quanto ao perfil biológico: 235 tumores (60,3%) eram HR+ HER 2−, 88 tumores (22,6%) eram HER2+, enquanto outros 41 tumores (10,5%) foram classificados como triplo negativo (TN). O SVG para todos os pacientes teve uma mediana de 92 meses. As taxas de SVG aos 2 e 5 anos foram de 92% e 64% para luminais; em TN a sobrevida em 24 meses foi de 69%, sendo 53,3% em 5 anos e em HER2 + 76,6% e 67,3%, respectivamente. Conclusões: A maioria dos tumores foi diagnosticada em estágios iniciais, sendo esses dados consistentes com os relatados em estudos realizados em nível nacional. A frequência de tumores ER/RP+ foi um pouco menor do que a relatada em estudos anteriores (70%) em nível nacional, enquanto a de tumores HER 2 + TN foi semelhante à relatada em estudos europeus, norte-americanos e latino-americanos, onde a prevalência encontrado é 20%

Repercusión de la pandemia COVID-19 en el diagnóstico y tratamiento del cáncer de mama en pacientes asistidas en la Unidad de Mastología del Hospital de Clínicas

Introducción: la crisis sanitaria por COVID-19 impactó en la atención de diversas patologías, entre ellas, el cáncer. Con el fin de disminuir el riesgo de contraer SARS-CoV-2 se redujo el número de consultas, lo que determinó un aumento en la tasa de morbilidad y mortalidad para otras patologías, lo que se ha denominado la "segunda pandemia". Objetivo: describir la actividad asistencial de la Unidad de Mastología (UM) en el período marzo 2020 - marzo 2022 y compararla con la del período marzo 2019 - marzo 2021. Objetivo: describir la actividad asistencial de la Unidad de Mastología (UM) en el período marzo 2020 - marzo 2022 y compararla con la del período marzo 2019 - marzo 2021. Material y método: estudio observacional retrospectivo que incluyó a pacientes asistidas por cáncer de mama (CM) en el período marzo 2019 - marzo 2022. Resultados: durante el año previo a la pandemia se asistieron 30 nuevas pacientes. En cuanto al tiempo entre el diagnóstico anatomopatológico y el primer tratamiento, en 73,3% fue ≤ 2 meses, 16,6% > 2 meses y ≤ 4 meses y en 10% fue > 4 meses. Durante la pandemia se asistieron 50 pacientes nuevas, lo que se traduce en un descenso de 16,6%. En cuanto al tiempo entre el diagnóstico anatomopatológico y el primer tratamiento: en 41% fue ≤ 2 meses, 33% > 2 meses y ≤ 4 meses y en 25% fue > 4 meses. Conclusiones: si bien se logró mantener la actividad asistencial y dar continuidad a la mayoría de los tratamientos, durante la pandemia COVID-19 se redujo el número de pacientes derivadas al servicio en aproximadamente 16,6% y se produjo un aumento en el tiempo transcurrido entre el diagnóstico y el primer tratamiento.

Introduction: the COVID-19 health crisis had a significant impact on the management of various pathologies, including cancer. To reduce the risk of contracting SARS-CoV-2, the number of consultations was reduced, leading to increased morbidity and mortality rates for other pathologies, which has been referred to as the "second pandemic." Objective: The aim of this study is to describe the clinical activity of the Breast Unit (BU) during the period March 2020-2022 and compare it with the activity during the period March 2019-2021. Objective: the aim of this study is to describe the clinical activity of the Breast Unit (BU) during the period March 2020-2022 and compare it with the activity during the period March 2019-2021. Method: retrospective observational study including patients attending the BU during the period March 2019-2022. Results: in the year before the pandemic, 30 new patients were assisted. Regarding the time between anatomopathological diagnosis and the initiation of the first treatment: in 73.3% of cases, it was ≤ 2 months, 16.6% > 2 months and ≤ 4 months, and in 10%, it was > 4 months. During the pandemic, 50 new patients were assisted, representing a decrease of approximately 16.6% in the number of new patients attended. Regarding the time between anatomopathological diagnosis and the initiation of the first treatment: in 41% of cases, it was ≤ 2 months, 33% > 2 months and ≤ 4 months, and in 25%, it was > 4 months. Conclusion: although the BU managed to maintain its clinical activity and continuity of most treatments during the COVID pandemic, there was a reduction in the number of patients referred to the service by approximately 16.6% and an increase in the time elapsed between diagnosis and the initiation of the first treatment.

Introdução: a crise sanitária causada pela COVID-19 impactou o atendimento de diversas patologias, inclusive o câncer. Para diminuir o risco de contrair SARS-CoV-2, reduziu-se o número de consultas, o que determinou um aumento da taxa de morbimortalidade por outras patologias, o que tem sido chamado de "segunda pandemia". Objetivo: descrever a atividade assistencial da Unidade de Mastologia (UM) no período março de 2020 - março de 2022 e compará-la com a do período março de 2019 - março de 2020. Material e método: estudo observacional retrospectivo que incluiu pacientes atendidos pelo CM no período março de 2019 - março de 2022. Resultados: no ano anterior à pandemia foram atendidos 30 novos pacientes. Em relação ao tempo entre o diagnóstico patológico e o primeiro tratamento: em 73,3% foi ≤2 meses, 16,6% >2 meses e ≤4 meses e em 10% foi >4 meses. Durante a pandemia, foram atendidos 50 novos pacientes, o que se traduz em uma queda de 16,6%no número de novos pacientes atendidos. Quanto ao tempo entre o diagnóstico patológico e o primeiro tratamento: em 41% foi ≤2 meses, 33% >2 meses e ≤4 meses e em 25% foi >4 meses. Conclusão: embora tenha conseguido manter a atividade assistencial e dar continuidade à maioria dos tratamentos, durante a pandemia de COVID-19 o número de pacientes encaminhados para o Serviço diminuiu cerca de 16,6% e houve um aumento do tempo decorrido entre o diagnóstico e o primeiro tratamento.

Extracellular Application of CRMP2 Increases Cytoplasmic Calcium through NMDA Receptors.

Collapsin Response Mediator Protein 2 (CRMP2) is an intracellular protein involved in axon and dendrite growth and specification. In this study, CRMP2 was identified in a conditioned media derived from degenerated sciatic nerves (CM). On cultured rat hippocampal neurons, acute extracellular application of CM or partially purified recombinant CRMP2 produced an increase in cytoplasmic calcium. The increase in cytoplasmic calcium was mostly mediated through NMDA receptors, with a minor contribution of N-type VDCC, and it was maintained as long as CM was present. By using live-labeling of CRMP2, Ca2+ channel binding domain 3 (CBD3) peptide derived from CRMP2, and recombinant CRMP2, we demonstrated that that this effect was mediated by an action on the extracellular side of the NMDA receptor. This is the first report of an extracellular action of CRMP2. Prolonged exposure to extracellular CRMP2, may contribute to neuronal calcium dysregulation and neuronal damage.