Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Down-regulation of human papillomavirus E6 oncogene and antiproliferative effect of Schisandra chinensis and Pueraria lobata natural extracts on Hela cell line.

ETHNOPHARMACOLOGICAL RELEVANCE: Cervical cancer is one of the most common malignancies in women that continues to be a public health problem worldwide. Human papillomavirus (HPV) infection is closely related as the causative agent of almost all cases of cervical cancer. Currently, there is no effective treatment for the persistence of HPV. Although vaccines have shown promising results in recent years, they are still a costly strategy for developing countries and have no therapeutic effect on existing infections, which is why the need arises to search for new strategies that can be used in treatment, suppressing oncogenic HPV and disease progression. Extracts of Schisandra Chinensis and Pueraria lobata have been used in traditional medicine, and it has been shown in recent years that some of their bioactive compounds have pharmacological, antioxidant, antitumor, apoptotic, and proliferation effects in HPV-positive cells. However, its mechanism of action has yet to be fully explored. AIM OF THE STUDY: The following study aimed to determine the chemical composition, antioxidant activity, and potential antiproliferative and viral oncogene effects of natural extracts of S. chinensis and P. lobata on HPV-18 positive cervical cancer cells. MATERIALS AND METHODS: The HPV-18-positive HeLa cells were treated for 24 and 48 h with the ethanolic extracts of S chinensis and P. lobata. Subsequently, cell viability was evaluated using the resazurin method, the effect on the cell cycle of the extracts (1.0, 10, and 100 µg/mL) was measured by flow cytometry, the gene of expression of the E6/E7, P53, BCL-2, and E2F-1 were determined by RT-PCR and the protein expression of p53, Ki-67, x|and Bcl-2 by immunohistochemistry. Additionally, the chemical characterization of the two extracts was carried out using LC-MS, and the total phenolics content (TPC), Total flavonoid content (TFC), and DPPH radical scavenging capacity were determined. Data were analyzed using the Mann-Whitney and Kruskal Wallis U test with GraphPad Prism 6 software. RESULTS: The natural extracts of Schisandra chinensis and Pueraria lobata induced down-regulation of E6 HPV oncogene (p<0.05) and a strong up-regulation of P53 (p<0.05), E2F-1 (p<0.05), and Bcl-2 (p<0.05) gene expression. Simultaneously, the natural extracts tend to increase the p53 protein levels and arrest the cell cycle of HeLa in the G1/S phase (p<0.05). Investigated extracts were characterized by the occurrence of bioactive lignans and isoflavones in S. chinensis and P. lobata, respectively. CONCLUSION: The extracts of S. chinensis and P. lobata within their chemical characterization mainly present lignan and isoflavone-type compounds, which are probably responsible for inhibiting the expression of the HPV E6 oncogene and inducing an increase in the expression of p53, Bcl -2 and E2F-1 producing cell cycle detection in S phase in HeLa cells. Therefore, these extracts are good candidates to continue studying their antiviral and antiproliferative potential in cells transformed by HPV.

HLA-G 14 bp Ins/Del (rs66554220) Variant Is Not Associated with Breast Cancer in Women from Western Mexico.

HLA-G is a physiology and pathologic immunomodulator detrimentally related to cancer. Its gene is heavily transcriptionally and post-transcriptionally regulated by variants located in regulator regions like 3'UTR, being the most studied Ins/Del of 14-bp (rs66554220), which is known to influence the effects of endogen cell factors; nevertheless, the reports are discrepant and controversial. Herein, the relationship of the 14-bp Ins/Del variant (rs66554220) with breast cancer (BC) and its clinical characteristics were analyzed in 182 women with non-familial BC and 221 disease-free women as a reference group. Both groups from western Mexico and sex-age-matched (sm-RG). The rs66554220 variant was amplified by SSP-PCR and the fragments were visualized in polyacrylamide gel electrophoresis. The variant rs66554220 was not associated with BC in our population. However, we suggest the Ins allele as a possible risk factor for developing BC at clinical stage IV (OR = 3.05, 95% CI = 1.16-7.96, p = 0.01); nevertheless, given the small stratified sample size (n = 11, statistical power = 41%), this is inconclusive. In conclusion, the 14-bp Ins/Del (rs66554220) variant of HLA-G is not associated with BC in the Mexican population, but might be related to advanced breast tumors. Further studies are required.

Improved Wisdom Tooth Diagnosis Can Reduce Dental Disease and Nonbattle Injuries.

INTRODUCTION: Wisdom teeth are a frequent cause for dental disease and nonbattle injuries (D-DNBIs) during expeditionary deployments. Improved diagnosis and timely treatment before deployment can reduce the need to evacuate a D-DNBI while in a theater. This study proposed key identifiers to diagnose wisdom teeth as Dental Readiness Classification (DRC) 3. MATERIALS AND METHODS: This study was a retrospective chart review conducted to measure concurrence among Army dentists when assigning DRC for wisdom teeth. This study also recorded demographic data and physical findings among the observed patients. Concurrence, or inter-rater reliability, was measured using Cohen's kappa (κ). RESULTS: A Cohen's κ of 0.04 suggested that there was no concurrence among Army dental providers in the diagnosis of wisdom teeth. The study concluded that caries and pericoronitis accounted for 37% and 13% of class 3 nondeployable troops, respectively. Forty-one percent of tobacco users had caries. Fifty-eight percent of the population was diagnosed as DRC 3. CONCLUSIONS: This study proposed DRC 3 criteria for wisdom teeth and measured concurrence among dental providers' diagnoses. Dental Readiness Classification 3 criteria include caries, pericoronitis, infection, and pathology. A Cohen's κ of 0.04 indicated there was a lack of concurrence in examining dentists compared to the DRC 3 criteria. Caries and pericoronitis were the most frequent diagnoses for third molars. Early diagnosis and treatment of these key identifiers can help reduce a significant source of D-DNBIs in the deployed environment.

Chronic pain and continuity of analgesic treatment during the COVID-19 pandemic.

INTRODUCTION: Chronic pain can trigger both physical and mental health complications. During the COVID-19 pandemic, patients with chronic diseases have had reduced access to some medications. OBJECTIVE: To determine the pharmacological management of patients with chronic pain and its continuity during the COVID-19 pandemic. METHODS: This was a retrospective longitudinal study of the continuity of analgesic use in patients with chronic pain between September 1, 2019 and February 28, 2021 based on a drug dispensing database. Survival analysis was performed until the discontinuation of chronic analgesics. RESULTS: A total of 12,701 patients who were being treated for chronic pain were identified. Their median age was 70.3 years, and 74.4% were women. The pain of rheumatological origin was the most frequent etiology (46.1%); the most used medications were nonopioid analgesics (78.9%), pain modulators (24.8%) and opioid analgesics (23.3%). A total of 76.1% of the patients experienced interruptions in their management during the study period. The median time to the first interruption of treatment was 5.0 months (95% CI: 4.8-5.2). Those who were treated for oncological pain experienced a greater number of interruptions in their management. CONCLUSIONS: The pharmacological management of patients with chronic pain is heterogeneous, and this real-world study showed that a high proportion of patients experienced an interruption of pain management during the 12 months following the onset of the COVID-19 pandemic.

Study of Prescription-Indication of Outpatient Systemic Anti-Fungals in a Colombian Population. A Cross-Sectional Study.

The inappropriate use of antifungals is associated with greater antimicrobial resistance, costs, adverse events, and worse clinical outcomes. The aim of this study was to determine prescription patterns and approved and unapproved indications for systemic antifungals in a group of patients in Colombia. This was a cross-sectional study on indications for the use of systemic antifungals in outpatients from a drug dispensing database of approximately 9.2 million people affiliated with the Colombian Health System. Sociodemographic, pharmacological, and clinical variables were considered. Descriptive, bivariate, and multivariate analyses were performed. A total of 74,603 patients with antifungal prescriptions were identified; they had a median age of 36.0 years (interquartile range: 22.0−53.0 years), and 67.3% of patients were women. Fluconazole (66.5%) was the most prescribed antifungal for indications such as vaginitis, vulvitis, and vulvovaginitis (35.0%). A total of 29.3% of the prescriptions were used in unapproved indications. A total of 96.3% of ketoconazole users used the medication in unapproved indications. Men (OR: 1.91; CI95%: 1.79−2.04), <18 years of age (OR: 1.20; CI95%: 1.11−1.31), from the Caribbean region (OR: 1.26; CI95%: 1.18−1.34), with chronic obstructive pulmonary disease (OR: 1.80; CI95%: 1.27−2.54), prescriptions made by a general practitioner (OR: 1.17; CI95%: 1.04−1.31), receiving comedications (OR: 1.58; CI95%: 1.48−1.69), and the concomitant use of other antimicrobials (OR: 1.77; CI95%: 1.66−1.88) were associated with a higher probability that the antifungal was used for unapproved indications; deep mycosis (OR: 0.49; CI95%: 0.41−0.58), prescribing fluconazole (OR: 0.06; CI95%: 0.06−0.06), and having diabetes mellitus (OR: 0.33; CI95%: 0.29−0.37), cancer (OR: 0.13; CI95%: 0.11−0.16), or HIV (OR: 0.07; CI95%: 0.04−0.09) reduced this risk. Systemic antifungals were mostly used for the management of superficial mycoses, especially at the gynecological level. In addition, more than a quarter of patients received these medications in unapproved indications, and there was broad inappropriate use of ketoconazole.

Effectiveness and safety in the management of chronic inflammatory diseases with etanercept and infliximab biosimilars in Colombian patients

Objective: To determine the effectiveness and safety of infliximab and etanercept biosimilar drugs in patients diagnosed with rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, and psoriasis in a specialized institution in Colombia, between 2015 and 2019. Methods: A retrospective study in patients treated with infliximab and etanercept biosimilar drugs treated in an institution specializing in the management of rheumatological diseases, to verify the clinimetric indicators of effectiveness and reports of adverse drug reactions. Clinical, sociodemographic, and pharmacological variables were identified over 5 years of follow-up. Results: 207 patients were identified with a mean age of 48.7 ± 15.1 years, 61.4% were women. Of the patients, 58.0% (n = 120) used infliximab and 42.0% (n = 87) etanercept. It was found that 46 (22.2%) patients had adverse drug reactions. At the end of the observation period, 61.6% (n = 72) of the patients with RA had achieved control of the disease (mild activity or remission), and 57.9% (n = 117) had problems with access to and persistence with therapy. Conclusion: In a group of patients treated in Colombia, the biosimilars of infliximab and etanercept showed proportions of effectiveness and safety comparable to the reference drugs, but lack of adherence to treatment was quite common.

Objetivo: Determinar la efectividad y la seguridad de medicamentos biosimilares de infliximab y etanercept en pacientes con diagnóstico de artritis reumatoide, espondilitis anquilosante, colitis ulcerativa y psoriasis en una institución especializada de Colombia, entre los arios 2015 y 2019. Métodos: Estudio retrospectivo, en pacientes tratados con infliximab y etanercept biosimilares, atendidos en una institución especializada en el manejo de enfermedades reumatológicas, para verificar los indicadores clinimétricos de efectividad y reportes de reacciones adversas medicamentosas. Se identificaron variables clínicas, sociodemográficas y farmacológicas durante cinco años de seguimiento. Resultados: Se identificaron 207 pacientes, con una edad media de 48,7 ± 15,1 años, el 61,4% de los cuales eran mujeres. El 58% (n = 120) de los pacientes utilizó infliximab y el 42% (n = 87) etanercept. Se encontró que 46 (22,2%) pacientes presentaron reacciones adversas al medicamento. Al final del periodo de observación, un 61,6% (n = 72) de los pacientes con AR había alcanzado el control de la enfermedad (actividad leve o remisión) y, en general, el 57,9% (n = 117) tuvo problemas de acceso y persistencia a la terapia. Conclusión: En un grupo de pacientes tratados en Colombia, los biosimilares de infliximab y etanercept mostraron proporciones de efectividad y seguridad comparables a los medicamentos de referencia, pero fue bastante común la falta de adherencia al tratamiento.

A gene expression signature in HER2+ breast cancer patients related to neoadjuvant chemotherapy resistance, overall survival, and disease-free survival.

Breast cancer ranks first in terms of mortality and incidence rates worldwide among women. The HER2+ molecular subtype is one of the most aggressive subtypes; its treatment includes neoadjuvant chemotherapy and the use of a HER2 antibody. Some patients develop resistance despite positive results obtained using this therapeutic strategy. OBJECTIVE: To identify prognostic markers for treatment and survival in HER2+ patients. METHODS: Patients treated with neoadjuvant chemotherapy were assigned to sensitive and resistant groups based on their treatment response. Differentially expressed genes (DEGs) were identified using RNA-seq analysis. KEGG pathway, gene ontology, and interactome analyses were performed for all DEGs. An enrichment analysis Gene set enrichment analysis was performed. All DEGs were analyzed for overall (OS) and disease-free survival (DFS). RESULTS: A total of 94 DEGs were related to treatment resistance. Survival analysis showed that 12 genes (ATF6B, DHRS13, DIRAS1, ERAL1, GRIN2B, L1CAM, IRX3, PRTFDC1, PBX2, S100B, SLC9A3R2, and TNXB) were good predictors of disease-free survival, and eight genes (GNG4, IL22RA2, MICA, S100B, SERPINF2, HLA-A, DIRAS1, and TNXB) were good predictors of overall survival (OS). CONCLUSION: We highlighted a molecular expression signature that can differentiate the treatment response, overall survival, and DFS of patients with HER2+ breast cancer.

Laparoscopic Hartmann's reversal has better clinical outcomes compared to open surgery: An international multicenter cohort study involving 502 patients.

Background: Hartmann's procedure (HP) is used in surgical emergencies such as colonic perforation and colonic obstruction. "Temporary" colostomy performed during HP is not always reversed in part due to potential morbidity and mortality associated with reversal. There are several contributing factors for patients requiring a permanent colostomy following HP. Therefore, there is still some discussion about which technique to use. The aim of this study was to evaluate perioperative variables of patients undergoing Hartmann's reversal using a laparoscopic and open approach. Methods: The multicenter retrospective cohort study was done between January 2009 and December 2019 at 14 institutions globally. Patients who underwent Hartmann's reversal laparoscopic (LS) and open (OS) approaches were evaluated and compared. Sociodemographic, preoperative, intraoperative variables, and surgical outcomes were analyzed. The main outcomes evaluated were 30-day mortality, length of stay, complications, and postoperative outcomes. Results: Five hundred and two patients (264 in the LS and 238 in the OS group) were included. The most prevalent sex was male in 53.7%, the most common indication was complicated diverticular disease in 69.9%, and 85% were American Society of Anesthesiologist (ASA) II-III. Intraoperative complications were noted in 5.3% and 3.4% in the LS and OS groups, respectively. Small bowel injuries were the most common intraoperative injury in 8.3%, with a higher incidence in the OS group compared with the LS group (12.2% vs. 4.9%, p < 0.5). Inadvertent injuries were more common in the small bowel (3%) in the LS group. A total of 17.2% in the OS versus 13.3% in the LS group required intensive care unit (ICU) admission (p = 0.2). The most frequent postoperative complication was ileus (12.6% in OS vs. 9.8% in LS group, p = 0.4)). Reintervention was required mainly in the OS group (15.5% vs. 5.3% in LS group, p < 0.5); mortality rate was 1%. Conclusions: Laparoscopic Hartmann's reversal is safe and feasible, associated with superior clinical outcomes compared with open surgery.

Indicación y prescripción de macrólidos en una población colombiana / Study of the indications for macrolide prescriptions in a Colombian population

Introducción. El uso inadecuado de antibióticos se asocia con aumento de la resistencia antimicrobiana, mayores costos de atención médica, más efectos adversos y peores resultados clínicos. Objetivo. Determinar los patrones de prescripción y las indicaciones aprobadas y no aprobadas para macrólidos en un grupo de pacientes en Colombia. Materiales y métodos. Se hizo un estudio de corte transversal sobre las indicaciones de uso de macrólidos en pacientes ambulatorios a partir de una base de datos de dispensación de medicamentos de 8,5 millones, aproximadamente, de personas afiliadas al sistema de salud de Colombia. Se consideraron variables sociodemográficas, farmacológicas y clínicas. Resultados. Se encontraron 9.344 pacientes que habían recibido prescripción de macrólidos; su mediana de edad era de 40,1 años (rango intercuartílico: 27,1-53,3 años) y el 58,3 % correspondía a mujeres. El macrólido más prescrito fue la azitromicina (38,8 %) y los usos más frecuentes fueron el tratamiento de la infección por Helicobacter pylori (15,9 %) y la neumonía (15,8 %). El 31,3 % de las prescripciones correspondía a indicaciones no aprobadas, destacándose el resfriado común (7,8 %), la Covid-19 (4,0 %) y la bronquitis aguda (3,5 %). La residencia en la región Caribe (OR=1,17; IC95% 1,05-1,31), las prescripciones odontológicas (OR=2,75; IC95% 1,91-3,96), las comorbilidades respiratorias crónicas (OR=1,30; IC95% 1,08-1,56), y la prescripción de eritromicina (OR=3,66; IC95% 3,24-4,14) o azitromicina (OR=2,15; IC95% 1,92 2,41), se asociaron con una mayor probabilidad de recibir macrólidos para indicaciones no aprobadas, en tanto que tener entre 18 y 64 años (OR=0,81; IC95% 0,71-0,93), 65 o más años (OR=0,77; IC95% 0,63-0,94) y residir en Bogotá-Cundinamarca (OR=0,74; IC95% 0,65 0,85) reducían dicho riesgo. Conclusiones. La mayoría de los pacientes recibieron macrólidos para infecciones del sistema respiratorio; la eritromicina y la azitromicina se prescribieron en indicaciones no aprobadas en menores de 18 años y en quienes presentaban enfermedades respiratorias crónicas.

Introduction: The inappropriate use of antibiotics is associated with a greater risk for antimicrobial resistance, high health care costs, adverse events, and worse clinical outcomes. Objective: To determine the prescription patterns and approved and nonapproved indications for macrolides in a group of patients from Colombia. Materials and methods: This was a cross-sectional study on the indications for the use of macrolides in outpatients registered in a drug-dispensing database of approximately 8.5 million people affiliated with the Colombian health system. Sociodemographic, pharmacological, and clinical variables were considered. Results: A total of 9.344 patients had received a macrolide prescription; their median age was 40.1 years (interquartile range: 27.1-53.3 years) and 58.3% were women. The most commonly prescribed macrolide was azithromycin (38.8%) most frequently for Helicobacter pylori infection (15.9%) and pneumonia treatment (15.8%). A total of 31.3% of the prescriptions were used for unapproved indications: common cold (7.8%), COVID-19 (4.0%), and acute bronchitis (3.5%). Residence in the Caribbean region (OR=1.17; 95%CI 1.05-1.31), dental prescriptions (OR=2.75; 95%CI 1.91-3.96), presence of chronic respiratory comorbidities (OR=1.30; 95%CI 1.08-1.56), and prescription of erythromycin (OR=3.66; 95%CI 3.24-4.14) or azithromycin (OR=2.15; 95%CI 1,92-2.41) were associated with a higher probability of macrolide use for unapproved indications while being 18-64 years old (OR=0.81; 95%CI 0.71-0.93) or 65 years or older (OR=0.77; 95%CI 0.63-0.94) and residing in Bogotá-Cundinamarca (OR=0.74; 95%CI 0.65-0.85) were associated with reduced risk. Conclusions: Most patients received macrolides for respiratory tract infections; erythromycin and azithromycin were used for unapproved indications in people under 18 years of age and those with chronic respiratory diseases.

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women.

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).

Transcriptomic Analysis of Breast Cancer Patients Sensitive and Resistant to Chemotherapy: Looking for Overall Survival and Drug Resistance Biomarkers.

Worldwide breast cancer ranks first in mortality and incidence rates in women over 20 years old. Rather than one disease, breast cancer is a heterogeneous group of diseases that express distinct molecular profiles. Neoadjuvant chemotherapy is an important therapeutic strategy for breast cancer patients independently of their molecular subtype, with the drawback of resistance development. In addition, chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. Although great efforts have been made to find diagnostic and prognostic biomarkers for breast cancer and for response to targeted and immune therapy for this pathology, little has been explored regarding biomarkers of response to anthracyclines and taxanes based neoadjuvant chemotherapy. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy to identify differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Breast cancer patients who were candidates for neoadjuvant chemotherapy were enrolled in this study. After treatment and according to their pathological response, they were assigned as sensitive or resistant. To evaluate DEGs, Gene Ontology, Kyoto Encyclopedia Gene and Genome (KEGG), and protein-protein interactions, RNA-seq information from all patients was obtained by next-generation sequencing. A total of 1985 DEGs were found, and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine-cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs was used further for an analysis of overall survival using the METABRIC study and the ductal carcinoma dataset of The Cancer Genome Atlas (TCGA) database. Nine DEGs correlated with overall survival, of which the subexpression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN, KRT15, HLA-A, and the overexpression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival.

Chemopreventive and Anti-tumor Potential of Natural Products in Oral Cancer.

Oral cancer (OC) is a multifactorial disease caused by isolated or combined risk factors related to tobacco, alcohol consumption, and human papillomavirus infection. It is an aggressive pathology with a low five-year survival rate after surgery, chemotherapy, and/or radiotherapy, frequently associated with severe side effects. Drugs with the highest anti-tumor effect are obtained from natural products with diverse biological and molecular activities and potential chemopreventive and anticancer properties. This review summarizes the natural products reported to have the chemopreventive and anti-tumor potential for OC treatment, showing that several of these compounds are promising candidates as chemopreventive agents, and those with the highest anti-tumor potential induce apoptosis and inhibit proliferation and metastasis-related processes. For this reason, natural products have the potential to be important preventive and therapeutic options for OC in the future.

Minimal invasive surgery for multiple adhesive small bowel obstruction: Results of a comparative multicenter study.

AIM OF THE STUDY: Laparoscopic adhesiolysis in small bowel obstruction (SBO) is getting increasingly normal. In patients with multiple adhesive SBOs (MASBO), laparoscopic approaches might increase the risk of bowel injury due to the distended and potentially compromised small bowel. It remains a challenge to the surgeons, entails an interdisciplinary team, trying to achieve the least complications as possible. The study aimed to compare surgical outcomes of laparoscopic procedures (multi-port vs. single-port) in the management of MASBO. PATIENTS AND METHODS: Comparative study of 68 patients with post-operative MASBO treated with Single-Port single incision laparoscopic surgery (SILS) and Multi-port Laparoscopic Surgery in two centers of Bogota, Colombia between January 2013 and June 2018. RESULTS: All patients underwent laparoscopic management, 27 patients by SILS, and 41 patients by multi-port. The average surgical time in the multiport approach was 167 min versus SILS with 129 min. Laparoscopic intestinal resection was performed in 4.4% of patients, through multi-port using intracorporeal anastomosis. Mean hospital stay of 3.2 days for the SILS approach versus multi-port in 2.2 days. CONCLUSIONS: Both laparoscopic approaches, in MASBO treatment is feasible in qualified hands. Patient selection and medical judgment seem to be the most essential factors for a positive result.

OBJETIVOS DEL ESTUDIO: Cada día es más frecuente la adherensiolisis laparoscópica en obstrucción del intestino delgado. En pacientes con obstrucciones debidas a múltiples adherencias del intestino delgado (OMAID), los abordajes laparoscópicos pueden incrementar el riesgo de daño de víscera hueca debido a la presencia de asas distendidas. Continúa siendo un reto para el cirujano, requiriendo un grupo interdisciplinario para disminuir las posibles complicaciones. Este estudio busca comparar los desenlaces de abordajes laparoscópicos (Multipuerto vs. monopuerto) en el manejo del OMAID. PACIENTES Y MÉTODOS: Se realizó un estudio de 68 pacientes con OMAID postoperatorio tratado con cirugía laparoscópica de monopuerto y múltipuerto en dos centros de Bogotá, Colombia entre enero de 2013 y junio de 2018. RESULTADOS: Pacientes llevados a manejo laparoscópico, 27 por monopuerto y 41 por múltipuerto, con tiempo quirúrgico promedio de 129 y 167 minutos respectivamente. 4.1% de los pacientes requirieron resección intestinal, todas en pacientes con abordaje múltipuerto con anastomosis intracorpóreas. El tiempo medio de hospitalización fue de 3.2 días para monopuerto y 2.2 días para multipuerto. CONCLUSIONES: Ambos abordajes laparoscópicos son factibles para el manejo del OMAID en manos calificadas. La selección del paciente y el juicio médico parecen ser factores fundamentales en el resultado positivo.

Uso ambulatorio de cefalosporinas en una población colombiana: estudio de prescripción-indicación / Outpatient cephalosporin use in a Colombian population: prescription-indication study

INTRODUCCIÓN: El uso indebido de cefalosporinas puede provocar resistencia de las bacterias. OBJETIVO: Determinar el perfil de prescripción e indicación de cefalosporinas en un grupo de pacientes afiliados al Sistema de Salud de Colombia. MÉTODOS: Estudio transversal. A partir de una base de datos poblacional se obtuvo una muestra aleatoria de pacientes atendidos en consulta ambulatoria para identificar las indicaciones de cefalosporinas en registros clínicos. Se evaluaron variables farmacológicas relacionadas con formulación no indicada según guías de práctica clínica. RESULTADOS: En 381 pacientes, con edad media 41,2 ± 15,4 años, el 61,4% (n = 234) eran mujeres. Cefalexina fue la más utilizada (n=318; 83,5%), con duración media del tratamiento de 7,3 ± 3,2 días, seguida de cefradina (n = 43, 11,3%) y ceftriaxona (n = 20, 5,2%). Se prescribieron para infecciones de piel y tejidos blandos (n = 177; 46,4%, de las cuales 47,5% eran purulentas), del tracto urinario (n = 70; 18,4%), de vías respiratorias superiores (n = 57; 15,0%), e infecciones de transmisión sexual (n = 21; 5,5%). Estaban indicadas en 169 pacientes (44,4%), pero sólo 103 (60,9%) tenían prescripciones que cumplían las recomendaciones de dosificación. CONCLUSIONES: Más de la mitad de pacientes prescritos con cefalosporinas en un contexto ambulatorio tenían prescripciones consideradas no indicadas, en particular por su uso en infecciones de piel y tejidos blandos purulentas.

BACKGROUND: Misuse of cephalosporins can lead to bacterial resistance. Aim: To determine the prescription profile and indication of cephalosporins in the patients affiliated to the Colombian Health System. METHODS: Cross-sectional study. From a population database, a random sample of patients treated in an outpatient consultation was obtained, to identify the indications of the prescribed cephalosporins in their clinical record. Pharmacological variables, and those related to non-indicated formulations were evaluated according to the clinical practice guidelines. RESULTS: In 381 patients, the mean age was 41.2 ± 15.4 years, and 61.4% (n = 234) were women. Cefalexin was the most widely used (n=318; 83.5%), with a mean duration of treatment of 7.3 ± 3.2 days; followed by cefradine (n = 43; 11.3%), and ceftriaxone (n = 20; 5.2%). The most common uses were for skin and soft tissue infections (n = 177; 46.4% of which 47.5% were purulent), urinary tract infections (n = 70; 18.4%), upper respiratory airway infections (n = 57; 15.0%) and sexually transmitted diseases (n = 21; 5.5%). The use was considered indicated in 169 patients (44.4%), but only 103 (60.9%) had prescriptions that met the dosage recommendations from the clinical practice guidelines. CONCLUSIONS: More than half of the patients prescribed with cephalosporins in the outpatient setting had prescriptions considered not indicated, particularly for their use in purulent skin and soft tissue infections.

Trends of vasopressor use in intensive care units in Colombia / Tendencias de consumo de vasopresores en unidades de cuidados intensivos de Colombia

Abstract Introduction Vasopressors are essential in the management of various types of shock. Objective To establish the trend of vasopressors use in the intensive care units (ICU) in a population of patients affiliated with the Colombian Health System, 2010-2017. Methods Observational trial using a population database of patients hospitalized in eleven ICUs in various cities in Colombia. The drugs dispensed to hospitalized patients over 18 years old, from January 2010 until December 2017 were considered. A review and analysis of the vasopressors dispensed per month was conducted, taking into account sociodemographic and pharmacological variables (vasopressor used and daily doses defined per 100/beds/day (DBD). Results 81,348 dispensations of vasopressors, equivalent to 26,414 treatments in 19,186 patients receiving care in 11 hospitals from 7 cities were reviewed. The mean age of patients was 66.3±18.1 years and 52.6 % were males. Of the total number of treatments recorded, 17,658 (66.8 %) were with just one vasopressor. Norepinephrine was the most frequently prescribed drug (75.9 % of the prescriptions dispensed; 60.5 DBD), followed by adrenaline (26.6 %; 41.6 DBD), dopamine (19.4%), dobutamine (16.0 %), vasopressin (8.5 %) and phenylephrine (0.9 %). The use of norepinephrine increased from 2010 to 2017 (+6.19 DBD), whilst the use of other drugs decreased, particularly the use of adrenaline (-60.6 DBD) and dopamine (-10.8 DBD). Conclusions Norepinephrine is the most widely used vasopressor showing a growing trend in terms of its use during the study period, which is supported by evidence in favor of its effectiveness and safety in patients with shock.

Resumen Introducción Los fármacos vasopresores son fundamentales en el manejo de los diferentes tipos de choque. Objetivo Determinar la tendencia de utilización de fármacos vasopresores en unidades de cuidados intensivos (UCI) en una población de pacientes afiliados al Sistema de Salud de Colombia, 2010-2017. Métodos Estudio observacional, a partir de una base de datos poblacional con pacientes hospitalizados en once UCI de diferentes ciudades de Colombia. Se obtuvieron las dispensaciones de pacientes mayores de 18 años hospitalizados desde enero de 2010 hasta diciembre de 2017. Se hizo revisión y análisis de la dispensación mensual de vasopresores. Se consideraron variables sociodemográficas y farmacológicas (medicamento vasopresor usado y dosis diarias definidas por 100 camas/día [DCD]). Resultados Se revisaron 81.348 dispensaciones de vasopresores, equivalentes a 26.414 terapias en 19.186 pacientes atendidos en 11 hospitales de 7 ciudades, cuya edad promedio fue 66,3±18,1 años y el 52,6 % eran hombres. Del total de terapias registradas, 17.658 (66,8 %) fueron con un solo vasopresor. La norepinefrina fue el más comúnmente prescrito (75,9 % de las dispensaciones; 60,5 DCD), seguido por adrenalina (26,6 %; 41,6 DCD), dopamina (19,4 %), dobutamina (16,0 %), vasopresina (8,5 %) y fenilefrina (0,9 %). El uso de norepinefrina se incrementó de 2010 a 2017 (+6,19 DCD), mientras que el de otros fármacos disminuyó, especialmente adrenalina (-60,6 DCD) y dopamina (-10,8 DCD). Conclusiones La norepinefrina es el fármaco vasopresor más utilizado y el que ha demostrado una tendencia de uso incremental durante el periodo de estudio, lo cual está respaldado por evidencia a favor de su efectividad y seguridad en pacientes con choque.

Prescription profile of antiarrhythmic drugs in a group of patients in Colombia / Perfil de prescripción de fármacos antiarrítmicos en un grupo de pacientes en Colombia

Abstract Objective: To determine the prescription patterns of antiarrhythmic drugs and variables associated with their use in a population of patients affiliated with the Colombian Health System. Methods: A cross-sectional study was performed on a population database with patients who received antiarrhythmics from March to May 2016. Sociodemographic, pharmacological and comedication variables were included. SPSS-24 was used for data analysis using X2 tests and multivariate analyses. Results: In total, 2772 patients were treated with antiarrhythmics in the evaluated period. The mean age was 70.1 ± 13.1 years, and 51.2% were women. In total, 79.4% used a β-blocker, 58.5% amiodarone and 2.9% a calcium channel blocker. Moreover, 1192 (43.0%) patients were prescribed a single antiarrhythmic, and 1580 (57.0%) received two or more. There were 2603 patients (93.9%) with comedication, including lipid-lowering drugs (62.6%), inhibitors of the renin angiotensin aldosterone system (62.6%) and antiplatelet drugs (42.0%). Age older than 65 years increased the probability of comedication (odds ratio [OR]: 2.48; 95% confidence interval [95% CI]: 1.59-3.85), and the risk was proportional to age. We identified 1364 patients treated with conditional risk medications for QT prolongation (49.2%), 68 with a possible risk (2.5%) and 171 (6.2%) with a known risk. Conclusion: Antiarrhythmic drugs recommended by clinical practice guidelines are mainly used; however, risk interactions interactions of QT prolongation were identified and should be taken into account by physicians to avoid adverse events or complications.

Resumen Objetivo: determinar los patrones de prescripción de fármacos antiarrítmicos y variables asociadas a su utilización en una población de pacientes afiliados al sistema de salud de Colombia. Métodos: estudio de corte transversal sobre una base de datos poblacional con pacientes que recibieron antiarrítmicos entre marzo y mayo de 2016. Se incluyeron variables sociodemográficas, farmacológicas y de comedicación. Para el análisis de datos se utilizó SPSS-24, realizando pruebas X2 y análisis multivariado. Resultados: se encontraron 2 772 pacientes en tratamiento con antiarrítmicos en el periodo evaluado, la edad promedio fue 70,1 ± 13,1 años, 51,2 % eran mujeres. El 79,4% utilizó algún β-bloqueador, 58,5% amiodarona y 2,9 % algún bloqueante de canales de calcio. Al 43 % se les prescribió un solo antiarrítmico y 57 % recibieron dos o más. El 93,9 % tenía con alguna comedicación, especialmente hipolipemiantes (62,6 %), inhibidores del sistema renina angiotensina aldosterona (62,6 %) y antiagregantes (42 %). Ser mayor de 65 años aumentó la probabilidad de comedicación (OR:2,48; IC95 %:1,59-3,85) y el riesgo fue proporcional al incremento de la edad. El 49,2 % (n=1364) estaban tratados con medicamentos de riesgo condicional de prolongación del QT, 2,5 % (n=68) con riesgo posible y 6,2% (n=171) de riesgo conocido. Conclusión: se están utilizando los mismos fármacos recomendados por las guías de práctica clínica; sin embargo, se encontraron interacciones de riesgo de prolongación del intervalo QT que deben ser tenidas en cuenta para evitar eventos o complicaciones en los pacientes.

ADXS11-001 LM-LLO as specific immunotherapy in cervical cancer.

Human papillomavirus (HPV) infection is a well-known cause of cervical cancer. Therapeutic cancer vaccines are part of the current therapeutic options for HPV-associated cancers. Axalimogen filolisbac (ADXS11-001) is an immunotherapy based on live attenuated Listeria monocytogenes-listeriolysin O (Lm-LLO), designed by biological engineering to secrete an antigen-adjuvant fusion protein, composed of a truncated fragment of LLO fused to HPV. The proposed mechanism of action is that Lm-based vectors infect antigen-presenting cells (APC) and secrete HPV-LLO fusion proteins within the APC cytoplasm, these proteins are processed and presented to cytotoxic T lymphocytes (CTL), thus generating a new population of CTLs specific to HPV antigens. These HPV-specific CTLs destroy HPV infected cells. ADXS11-001 has demonstrated safety results in phase I-II studies in women with cervical cancer and is being assessed in clinical trials in patients with HPV-positive anal canal and head and neck cancers.

Detección de errores de medicación mediante un programa de seguimiento y minimización en pacientes ambulatorios de Colombia, 2018-2019 / Identification of medication errors through a monitoring and minimization program in outpatients in Colombia, 2018-2019

Resumen | Introducción. El uso de medicamentos puede conllevar errores de medicación que desemboquen en la hospitalización del paciente, el aumento de los costos relacionados con la atención e, incluso, la muerte. Objetivos. Determinar la prevalencia de errores de medicación notificados en un sistema de información de farmacovigilancia en Colombia entre el 2018 y el 2019. Materiales y métodos. Se hizo un estudio observacional a partir del registro de errores de medicación de un sistema de farmacovigilancia que cubre a 8,5 millones de pacientes ambulatorios afiliados al sistema de salud de Colombia. Los errores se categorizaron en ocho grupos de la A (situaciones potenciales de error) hasta la I (error que pudo llevar a la muerte). Se hizo el análisis descriptivo y se estableció la prevalencia de los errores de medicación. Resultados. Durante los años 2018 y 2019, se reportaron 29.538 errores de medicación en pacientes ambulatorios, con una prevalencia general de 1,93 por cada 10.000 medicamentos dispensados. En el 0,02 % (n=6) de los casos, se presentaron errores que llegaron a afectar a los pacientes y causaron daño (tipos E, F e I). La mayoría de los errores se asoció con la dispensación (n=20.636; 69,9 %) y la posible causa más común fue la falta de concentración en el momento de dispensar los medicamentos (n=9.185; 31,1 %). Los grupos farmacológicos más implicados en errores de medicación fueron los antidiabéticos (8,0 %), los inhibidores del sistema renina-angiotensina (7,6 %) y los analgésicos (6,0 %). Conclusiones. Los errores de medicación son relativamente poco frecuentes y con mayor frecuencia se catalogan como circunstancias o eventos capaces de generar un error de tipo A. Muy pocas veces, pueden causarle daño al paciente, incluso, hasta la muerte.

Abstract | Introduction: The use of drugs may involve medication errors leading to hospitalization, increased costs related to care, and even death. Objective: To determine the prevalence of medication errors reported in a pharmacovigilance information system in Colombia between 2018 and 2019. Materials and methods: We conducted an observational study based on the records of medication errors from a pharmacovigilance system covering 8.5 million outpatients affiliated with the Colombian health system. The errors were categorized from A (potential situations to error) to I (an error that could lead to death). We performed a descriptive analysis and established the prevalence of medication errors. Results: During 2018 and 2019, 29,538 medication errors in outpatients were reported with a general prevalence of 1.93 per 10,000 drugs dispensed. The errors that reached the patient and caused damage (types E, F, and I) occurred in 0.02% (n=6) of the patients. Most of them were related to the dispensation (n=20,636; 69.9%) and the possible most common cause was the lack of concentration at the time of dispensing (n=9185; 31.1%). The pharmacological groups most involved in medication errors were antidiabetics (8.0%), renin-angiotensin system inhibitors (7.6%), and analgesics (6.0%). Conclusions: Medication errors are relatively rare situations, generally classified as circumstances or events capable of generating the error (type A error). In low proportion, they can reach the patient and cause damage or even death.