Detrimental effect of an early exposure to antibiotics on the outcomes of immunotherapy in a multi-tumor cohort of patients.

BACKGROUND: Immune checkpoint inhibitors (ICI) have changed the therapeutic landscape of many solid tumors. Modulation of the intestinal microbiota by antibiotics (Abx) has been suggested to impact on ICI outcomes. METHODS: Retrospective analysis of 475 patients with advanced solid tumors treated with ICI from 2015 to 2022. For each patient, the use of Abx was recorded from 1 month before ICI initiation until disease progression or death. The impact of Abx on objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), and overall survival (OS) was analyzed. Kaplan-Meier and log-rank tests were used to compare survival outcomes. RESULTS: In total 475 patients with advanced solid tumors were evaluated. Median age was 67.5 years and performance status (PS) was 0-1 in 84.6%. 66.5% of patients received Abx during treatment with ICI, mainly beta-lactams (53.8%) and quinolones (35.9%). The early exposure to Abx (from 60 days before to 42 days after the first cycle of ICI) was associated with a lower ORR (27.4% vs 39.4%; P < .01), a lower DCR (37.3% vs 57.4%; P < .001), lower PFS (16.8 m vs 27.8 m; HR 0.66; P < .001]) and lower OS (2.5 m vs 6.6 m; HR 0.68; P = .001]). The negative impact of Abx on OS and PFS was confirmed by a multivariable analysis. This effect was not observed among patients receiving Abx after 6 weeks from ICI initiation. CONCLUSIONS: Our results validate the hypothesis of a detrimental effect of an early exposure to Abxon the efficacy of ICI in a multi-tumor cohort of patients.

Negative association of steroids with immunotherapy efficacy in a multi-tumor cohort: time and dose-dependent.

Previous studies have suggested a negative impact of steroids on the efficacy of immune checkpoint inhibitors (ICI), but how this effect is modulated by the dosage and time of administration is yet to be clarified. We have performed a retrospective analysis of 475 patients with advanced solid tumors treated with ICI as monotherapy from 2015 to 2022. Data regarding immune-related adverse events (irAEs) and clinical outcomes were collected. For each patient, the daily steroid dose (in mg/kg of prednisone) was registered until disease progression or death. The impact of cumulative doses on response rates and survival outcomes was analyzed within different periods. The objective response rate (ORR) was significantly lower among patients exposed to steroids within 30 days before the first cycle of ICI (C1) (20.3% vs. 36.7%, p < 0.01) and within the first 90 days of treatment (25.7% vs. 37.7%, p = 0.01). This negative association was confirmed by multivariable analysis. Higher mean steroid doses were observed among non-responders, and cumulative doses were inversely correlated with the disease control rate (DCR) around ICI initiation. Remarkably, poorer outcomes were observed even in patients belonging to the lowest dose quartile compared to the steroid-naïve population. The exposure to steroids after 6 months of ICI was not associated with worse survival outcomes. Our results suggest that the potential impact of steroids on ICI efficacy may be time-dependent, prevailing around ICI initiation, and dose-dependent, with modulation of neutrophil-to-lymphocyte ratio as a possible underlying mechanism.

Her-2 Targeted Therapy in Advanced Urothelial Cancer: From Monoclonal Antibodies to Antibody-Drug Conjugates.

Metastatic urothelial cancer, associated with a poor prognosis, is still major cause of cancer-related death, with scarce options of effective treatment after progression to platinum-based chemotherapy and immunotherapy. The human epithelial growth factor receptor 2 (Her-2) has been identified as a new therapeutic target in medical oncology. However, despite the encouraging results in breast and gastric cancers, clinical trials with anti-Her-2 monoclonal antibodies and tyrosine-kinase inhibitors have shown limited efficacy of this strategy in urothelial tumors. Notably, more favorable data have been recently shown that antibody-drug conjugates are currently emerging as a novel promising approach for Her-2 targeted therapy in advanced urothelial cancer.

Receptor Tyrosine Kinase Inhibitors for the Treatment of Recurrent and Unresectable Bone Sarcomas.

Bone sarcomas are a heterogeneous group of rare tumors with a predominance in the young population. Few options of systemic treatment are available once they become unresectable and resistant to conventional chemotherapy. A better knowledge of the key role that tyrosine kinase receptors (VEGFR, RET, MET, AXL, PDGFR, KIT, FGFR, IGF-1R) may play in the pathogenesis of these tumors has led to the development of multi-target inhibitors (TKIs) that are progressively being incorporated into our therapeutic arsenal. Osteosarcoma (OS) is the most frequent primary bone tumor and several TKIs have demonstrated clinical benefit in phase II clinical trials (cabozantinib, regorafenib, apatinib, sorafenib, and lenvatinib). Although the development of TKIs for other primary bone tumors is less advanced, preclinical data and early trials have begun to show their potential benefit in advanced Ewing sarcoma (ES) and rarer bone tumors (chondrosarcoma, chordoma, giant cell tumor of bone, and undifferentiated pleomorphic sarcoma). Previous reviews have mainly provided information on TKIs for OS and ES. We aim to summarize the existing knowledge regarding the use of TKIs in all bone sarcomas including the most recent studies as well as the potential synergistic effects of their combination with other systemic therapies.

Dillapiole in Piper holtonii as an Inhibitor of the Symbiotic Fungus Leucoagaricus gongylophorus of Leaf-Cutting Ants.

Plants of the Piperaceae family are studied for their diverse secondary metabolism with a vast array of compounds that act as chemical defense agents against herbivores. Of all the agricultural pests, the management of insects is a highly significant challenge in the Neotropics, and ants of the Attini tribe pose a major problem. Due to their symbiotic association with the fungus Leucoagaricus gongylophorus (Möller) Singer (Agaricaceae), the species of Atta and Acromyrmex have exhaustive foraging activity which has intensified as deforestation and monoculture farming have increased. The control of leaf-cutting ants is still carried out with synthetic products with negative consequences to the environment and human health. In search for natural and sustainable alternatives to synthetic pesticides, Piper holtonii C. DC. was selected among other plant species after field observations of the foraging activity of Atta cephalotes, which revealed that P. holtonii was never chosen by ants. In vitro evaluation of an ethanol extract of the leaves of P. holtonii resulted in promising inhibitory activity (IC50 102 ppm) against L. gongylophorus. Subsequently, bioassay-guided fractionation led to the isolation of the phenylpropanoid dillapiole, which was also detected in the essential oil. This compound demonstrated inhibition of the fungus with an IC50 of 38 ppm. Considering the symbiotic relationship between the Attini ants and L. gongylophorus, the negative effect on the survival of one of the organisms will affect the survival of the other, so dillapiole or standardized essential oil extracts of P. holtonii containing this active principle could be a unique and useful source as a control agent for leaf cutting-ants.

Adoptive T cell therapy for solid tumors: current landscape and future challenges.

Adoptive cell therapy (ACT) comprises different strategies to enhance the activity of T lymphocytes and other effector cells that orchestrate the antitumor immune response, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR) gene-modified T cells, and therapy with tumor-infiltrating lymphocytes (TILs). The outstanding results of CAR-T cells in some hematologic malignancies have launched the investigation of ACT in patients with refractory solid malignancies. However, certain characteristics of solid tumors, such as their antigenic heterogeneity and immunosuppressive microenvironment, hamper the efficacy of antigen-targeted treatments. Other ACT modalities, such as TIL therapy, have emerged as promising new strategies. TIL therapy has shown safety and promising activity in certain immunogenic cancers, mainly advanced melanoma, with an exciting rationale for its combination with immune checkpoint inhibitors. However, the implementation of TIL therapy in clinical practice is hindered by several biological, logistic, and economic challenges. In this review, we aim to summarize the current knowledge, available clinical results, and potential areas of future research regarding the use of T cell therapy in patients with solid tumors.

Case-control study assessing the impact of COVID19 in advanced kidney cancer patients treated with antiangiogenics or immunotherapy: the COVID-REN study.

BACKGROUND: Cancer is a risk factor for developing severe COVID19. Additionally, SARS-CoV2 has a special tropism for renal cells and complications like thrombosis or cytokine storm could be enhanced by standard treatments in kidney cancer (i.e., antiangiogenics or immunotherapy). Thus, understanding the impact of COVID19 in patients with this tumor is key for their correct management. METHODS: We designed a retrospective case-control study comparing the outcome of three groups of advanced kidney cancer patients on systemic treatment: cohort A (developed COVID19 while on antiangiogenics), cohort B (developed COVID19 while on immunotherapy) and cohort C (non-infected). Matching factors were age, gender, and treatment. RESULTS: 95 patients were recruited in 16 centers in Spain from September 2020 to May 2021. Finally, 85 were deemed as eligible (23 cohort A, 21 cohort B, 41 cohort C). Patients with COVID required more dose interruptions (25 vs. six) and hospitalizations (10 vs. none) than those without COVID (both p = 0.001). No difference between cohorts A and B was observed regarding hospitalization or length of stay. No ICU admission was registered and one patient in cohort B died due to COVID19. Regarding cancer evolution, three patients in cohort A presented progressive disease after COVID19 compared to two in cohort B. One case in cohort B, initially deemed as stable disease, achieved a partial response after COVID19. CONCLUSIONS: Kidney cancer patients who developed COVID19 while on systemic therapy required more treatment interruptions and hospitalizations than those non-infected. However, no significant impact on cancer outcome was observed. Also, no difference was seen between cases on antiangiogenics or immunotherapy.

Recurrent Glioblastoma: A Review of the Treatment Options.

Glioblastoma is a disease with a poor prognosis. Multiple efforts have been made to improve the long-term outcome, but the 5-year survival rate is still 5-10%. Recurrence of the disease is the usual way of progression. In this situation, there is no standard treatment. Different treatment options can be considered. Among them would be reoperation or reirradiation. There are different studies that have assessed the impact on survival and the selection of patients who may benefit most from these strategies. Chemotherapy treatments have also been considered in several studies, mainly with alkylating agents, with data mostly from phase II studies. On the other hand, multiple studies have been carried out with target-directed treatments. Bevacizumab, a monoclonal antibody with anti-angiogenic activity, has demonstrated activity in several studies, and the FDA has approved it for this indication. Several other TKI drugs have been evaluated in this setting, but no clear benefit has been demonstrated. Immunotherapy treatments have been shown to be effective in other types of tumors, and several studies have evaluated their efficacy in this disease, both immune checkpoint inhibitors, oncolytic viruses, and vaccines. This paper reviews data from different studies that have evaluated the efficacy of different forms of relapsed glioblastoma.

Discordant Humoral and T-Cell Response to mRNA SARS-CoV-2 Vaccine and the Risk of Breakthrough Infections in Women with Breast Cancer, Receiving Cyclin-Dependent Kinase 4 and 6 Inhibitors.

Few data are available about the immune response to mRNA SARS-CoV-2 vaccines in patients with breast cancer receiving cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). We conducted a prospective, single-center study of patients with breast cancer treated with CDK4/6i who received mRNA-1273 vaccination, as well as a comparative group of healthcare workers. The primary endpoint was to compare the rate and magnitude of humoral and T-cell response after full vaccination. A better neutralizing antibody and anti-S IgG level was observed after vaccination in the subgroup of women receiving CDK4/6i, but a trend toward a reduced CD4 and CD8 T-cell response in the CDK4/6i group was not statistically significant. There were no differences in the rate of COVID-19 after vaccination (19% vs. 12%), but breakthrough infections were observed in those with lower levels of anti-S IgG and neutralizing antibodies after the first dose. A lower rate of CD4 T-cell response was also found in those individuals with breakthrough infections, although a non-significant and similar level of CD8 T-cell response was also observed, regardless of breakthrough infections. The rate of adverse events was higher in patients treated with CDK4/6i, without serious adverse events. In conclusion, there was a robust humoral response, but a blunted T-cell response to mRNA vaccine in women receiving CDK4/6i, suggesting a reduced trend of the adaptative immune response.

Maintained complete response to talazoparib in a BRCA-2 mutated metastatic luminal breast cancer: case report and review of literature.

PARP inhibitors are progressively becoming a part of our therapeutic arsenal against BRCA-defective tumors, because of their capacity to induce synthetic lethality in cells with a deficiency in the homologous recombination repair system. Olaparib and talazoparib have been approved for metastatic breast cancer in carriers of germline BRCA mutations, which are found in approximately 6% of patients with breast cancer. We report the case of a patient with metastatic breast cancer, carrier of a germline mutation in BRCA2, with a complete response to first-line treatment with talazoparib, maintained after 6 years. To the best of our knowledge, this is the longest response reported with a PARP inhibitor in a BRCA-mutated tumor. We have made a review of literature, regarding the rationale for PARP inhibitors in carriers of BRCA mutations and their clinical relevance in the management of advanced breast cancer, as well as their emerging role in early stage disease, alone and in combination with other systemic therapies.

Current Landscape of Immunotherapy for Advanced Sarcoma.

There is substantial heterogeneity between different subtypes of sarcoma regarding their biological behavior and microenvironment, which impacts their responsiveness to immunotherapy. Alveolar soft-part sarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma show higher immunogenicity and better responses to checkpoint inhibitors. Combination strategies adding immunotherapy to chemotherapy and/or tyrosine-kinase inhibitors globally seem superior to single-agent schemes. Therapeutic vaccines and different forms of adoptive cell therapy, mainly engineered TCRs, CAR-T cells and TIL therapy, are emerging as new forms of immunotherapy for advanced solid tumors. Tumor lymphocytic infiltration and other prognostic and predictive biomarkers are under research.

Neurologic Toxicity of Immune Checkpoint Inhibitors: A Review of Literature.

Immune checkpoint inhibitors have entailed a change of paradigm in the management of multiple malignant diseases and are acquiring a key role in an increasing number of clinical sceneries. However, since their mechanism of action is not limited to the tumor microenvironment, their systemic activity may lead to a wide spectrum of immune-related side effects. Although neurological adverse events are much less frequent than gastrointestinal, hepatic, or lung toxicity, with an incidence of <5%, their potential severity and consequent interruptions to cancer treatment make them of particular importance. Despite them mainly implying peripheral neuropathies, immunotherapy has also been associated with an increased risk of encephalitis and paraneoplastic disorders affecting the central nervous system, often appearing in a clinical context where the appropriate diagnosis and early management of neuropsychiatric symptoms can be challenging. Although the pathogenesis of these complications is not fully understood yet, the blockade of tumoral inhibitory signals, and therefore the elicitation of cytotoxic T-cell-mediated response, seems to play a decisive role. The aim of this review was to summarize the current knowledge about the pathogenic mechanisms, clinical manifestations, and therapeutic recommendations regarding the main forms of neurotoxicity related to checkpoint inhibitors.

Limited T cell response to SARS-CoV-2 mRNA vaccine among patients with cancer receiving different cancer treatments.

INTRODUCTION: Patients with cancer (PC) are at high risk of acquiring COVID-19 and can develop more serious complications. Deeper understanding of vaccines immunogenicity in this population is crucial for adequately planning vaccines programs. The ONCOVac study aimed to comprehensively assess the immunogenicity of mRNA-1273 vaccine in terms of humoral and cellular response. METHODS: We conducted a prospective, single-center study including patients with solid tumours treated with cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), immunotherapy (IT) or chemotherapy (CT). Patients were enrolled previously to vaccination with mRNA-1273. We also involved health care workers (HCW) to serve as a control group. We took blood samples before first dose administration (BL), after first dose (1D), and after second dose (2D). The primary objective was to compare the rate and magnitude of T cell response after second dose whereas safety and humoral response were defined as secondary objectives. We also collected patient reported outcomes after both the first and second vaccine dose and a six-month follow-up period to diagnose incident COVID-19 cases was planned. RESULTS: The rate of specific anti-S serologic positivity (anti-S IgG cut-off point at 7,14 BAU/mL) was significantly higher in HCW compared to PC after 1D (100% versus 83.8%; p = 0.04), but similar after 2D (100% versus 95.8%; p = 0.5). This difference after 1D was driven by PC treated with CT (100% versus 64.5%; p = 0.001). Cellular response after 2D was significantly lower in PC than in HCW for both CD4+ (91.7% versus 59.7%; p = 0.001) and CD8+ (94.4% versus 55.6%; p < 0.001) T cells. We found a difference on pre-existing CD4+ T cell response in HCW comparing to PC (36% and 17%, p = 0.03); without difference in pre-existing CD8+ T cell response (31% and 23%, p = 0.5). After excluding patients with pre-existing T cell response, PC achieved even lower CD4+ (50.9% versus 95.5%, p < 0.001) and CD8+ (45.5% versus 95.5%, p < 0.001) T cell response compared with HCW. Regarding safety, PC reported notably more adverse events than HCW (96.6% versus 69.2%, p < 0.001). CONCLUSION: We demonstrated that PC showed a similar humoral response but a lower T cell response following two doses of mRNA-1273 vaccination. Further studies are needed to complement our results and determine the implication of low T cell response on clinical protection of PC against COVID-19.

Relationship between death and admission of pediatric patients to intensive care due to Staphylococcus aureus bacteremia acquired in the community, 2014-2017 / Relación entre la muerte y el ingreso a cuidados intensivos de pacientes pediátricos con bacteriemia por Staphylococcus aureus adquirido en la comunidad, 2014-2017.

Introduction: The bacteremia caused by Staphylococcus aureus acquired in the community (SA-AC) is a frequent pathology in pediatrics and it is considered a public health problem generating high rates of morbidity, mortality, and bacterial resistance. Objectives: To analyze the factors related to death and admission to intensive care units of patients under 18 years of age with AC-SA bacteremia admitted to the Hospital Infantil Los Ángeles, Pasto, Colombia, from 2014 to 2017. Material and methods: We conducted a descriptive, transversal, cross-sectional observational study. We analyzed 86 patients with bacteremia due to AC-SA that met the inclusion criteria for the study using a multivariate logistic regression model. Results: Of the 86 cases, 25.6% died and 40.7% entered the intensive care unit. The resistance to methicillin was 52.3%. The main foci of infection were the soft tissues and the osteoarticular and respiratory systems; 32.6% of patients came from the Pacific area of Nariño. The predominant ethnic groups were the mestizo and the indigenous. Indigenous patients had higher mortality compared to the mestizo and Afro-Colombian ethnic groups. The multivariate analysis showed significance in terms of death for endocarditis (adjusted OR=20; CI: 1.5-254; p=0.02) while no statistical significance was registered for the admission to the intensive care unit. Conclusions: The AC-SA led to high mortality and admission to the intensive care unit; 52.3% of strains were resistant and resistance to methicillin showed higher mortality, although the mortality with sensitive strains was considerable. Endocarditis showed fairly high mortality. The empirical therapy should be adjusted when bacteremia due to AC-SA is suspected.

Introducción. La bacteriemia por Staphylococcus aureus adquirida en la comunidad (SAAC) es una condición frecuente en pediatría que, además, constituye un problema de salud pública por las altas tasas de morbimortalidad y de resistencia bacteriana. Objetivos. Analizar los factores relacionados con la muerte y el ingreso a cuidados intensivos de pacientes menores de 18 años con bacteriemia por SA-AC que ingresaron al Hospital Infantil Los Ángeles de Pasto, Colombia, entre el 2014 y el 2017. Materiales y métodos. Se hizo un estudio observacional descriptivo y transversal. Se analizaron 86 pacientes con bacteriemia por SA-AC que cumplían los criterios de inclusión en el estudio utilizando un modelo multivariado de regresión logística. Resultados. El 25,6 % de los 86 pacientes falleció y el 40,7 % ingresó a la unidad de cuidados intensivos. La resistencia a la meticilina fue de 52,3 %. Los focos principales de infección fueron los tejidos blandos, el sistema osteoarticular y el respiratorio. El 32,6 % de los pacientes provenía de la zona del Pacífico de Nariño. Las etnias predominantes fueron la mestiza y la indígena. Entre los indígenas hubo mayor mortalidad que entre mestizos y afrocolombianos. En el análisis multivariado de la variable de muerte, se registró significación de la endocarditis (odds ratio, OR ajustado=20; IC95%1,5-254; p=0,02); no se registró significación estadística en cuanto al ingreso en la unidad de cuidados intensivos. Conclusiones. La bacteriemia por SA-AC determinó altas tasas de mortalidad e ingreso a la unidad de cuidados intensivos. Las cepas resistentes representaron el 52,3 %, y la resistencia a la meticilina desembocó en una mayor mortalidad, aunque la mortalidad con cepas sensibles también fue considerable. La endocarditis fue responsable de una mortalidad bastante elevada. Se debe ajustar el tratamiento empírico cuando se sospeche bacteriemia por SA-AC.

Outcomes and complications of S2 alar iliac fixation technique in patients with neuromuscular scoliosis: experience in a third level pediatric hospital.

BACKGROUND: Multiple techniques are utilized for distal fixation in patients with neuromuscular scoliosis. Although there is evidence of benefit with S2 alar iliac (S2AI) fixation, this remains controversial. The objective of this study is to evaluate the radiological outcomes and complications associated with this surgical technique in a pediatric population. METHODS: An observational retrospective case series study was performed. All pediatric patients between January 2011 and February 2014 diagnosed with neuromuscular scoliosis associated with pelvic obliquity, which required surgery with fixation unto S2AI, were included. Clinical, radiological findings, and adverse events were presented with measures of central tendency. Comparison of deformity correction was carried out using a non-parametric analysis for related samples (Wilcoxon signed-rank test). Significance was set at P<0.05. RESULTS: A total of 31 patients diagnosed with neuromuscular scoliosis that met inclusion criteria were analyzed. The leading cause of neuromuscular scoliosis in 23 (74.2%) patients was spastic cerebral palsy (CP). The correction of pelvic obliquity in the immediate postoperative period was of 76%, which is statistically significant. The extent of correction that patients maintained at the end of the follow-up was analyzed, and it was found that there were no significant differences in this magnitude, compared with the immediate postoperative pelvic obliquity. The mean follow-up time was 9±7 months. Regarding postoperative adverse events, occurred in 64.5% of patients, the most common outcome was pneumonia (14.8%). The overall rate of complications related to instrumentation was low (1.9%), which corresponds to one patient with an intra-articular screw in the left hip that required repositioning. CONCLUSIONS: S2AI fixation for the treatment of neuromuscular scoliosis is a safe alternative, in which the onset of adverse events is related to the comorbidities of patients instead of the surgical procedure itself. An approximate correction of 76% of pelvic obliquity is maintained during the follow-up.

Relación entre la muerte y el ingreso a cuidados intensivos de pacientes pediátricos con bacteriemia por Staphylococcus aureus adquirido en la comunidad, 2014-2017 / Relationship between death and admission of pediatric patients to intensive care due to Staphylococcus aureus bacteremia acquired in the community, 2014-2017

Resumen | Introducción. La bacteriemia por Staphylococcus aureus adquirida en la comunidad (SA-AC) es una condición frecuente en pediatría que, además, constituye un problema de salud pública por las altas tasas de morbimortalidad y de resistencia bacteriana. Objetivos. Analizar los factores relacionados con la muerte y el ingreso a cuidados intensivos de pacientes menores de 18 años con bacteriemia por SA-AC que ingresaron al Hospital Infantil Los Ángeles de Pasto, Colombia, entre el 2014 y el 2017. Materiales y métodos. Se hizo un estudio observacional descriptivo y transversal. Se analizaron 86 pacientes con bacteriemia por SA-AC que cumplían los criterios de inclusión en el estudio utilizando un modelo multivariado de regresión logística. Resultados. El 25,6 % de los 86 pacientes falleció y el 40,7 % ingresó a la unidad de cuidados intensivos. La resistencia a la meticilina fue de 52,3 %. Los focos principales de infección fueron los tejidos blandos, el sistema osteoarticular y el respiratorio. El 32,6 % de los pacientes provenía de la zona del Pacífico de Nariño. Las etnias predominantes fueron la mestiza y la indígena. Entre los indígenas hubo mayor mortalidad que entre mestizos y afrocolombianos. En el análisis multivariado de la variable de muerte, se registró significación de la endocarditis (odds ratio, OR ajustado=20; IC95%1,5-254; p=0,02); no se registró significación estadística en cuanto al ingreso en la unidad de cuidados intensivos. Conclusiones. La bacteriemia por SA-AC determinó altas tasas de mortalidad e ingreso a la unidad de cuidados intensivos. Las cepas resistentes representaron el 52,3 %, y la resistencia a la meticilina desembocó en una mayor mortalidad, aunque la mortalidad con cepas sensibles también fue considerable. La endocarditis fue responsable de una mortalidad bastante elevada. Se debe ajustar el tratamiento empírico cuando se sospeche bacteriemia por SA-AC.

Abstract | Introduction: The bacteremia caused by Staphylococcus aureus acquired in the community (SA-AC) is a frequent pathology in pediatrics and it is considered a public health problem generating high rates of morbidity, mortality, and bacterial resistance. Objectives: To analyze the factors related to death and admission to intensive care units of patients under 18 years of age with AC-SA bacteremia admitted to the Hospital Infantil Los Ángeles, Pasto, Colombia, from 2014 to 2017. Materials and methods: We conducted a descriptive, transversal, cross-sectional observational study. We analyzed 86 patients with bacteremia due to AC-SA that met the inclusion criteria for the study using a multivariate logistic regression model. Results: Of the 86 cases, 25.6% died and 40.7% entered the intensive care unit. The resistance to methicillin was 52.3%. The main foci of infection were the soft tissues and the osteoarticular and respiratory systems; 32.6% of patients came from the Pacific area of Nariño. The predominant ethnic groups were the mestizo and the indigenous. Indigenous patients had higher mortality compared to the mestizo and Afro-Colombian ethnic groups. The multivariate analysis showed significance in terms of death for endocarditis (adjusted OR=20; CI: 1.5-254; p=0.02) while no statistical significance was registered for the admission to the intensive care unit. Conclusions: The AC-SA led to high mortality and admission to the intensive care unit; 52.3% of strains were resistant and resistance to methicillin showed higher mortality, although the mortality with sensitive strains was considerable. Endocarditis showed fairly high mortality. The empirical therapy should be adjusted when bacteremia due to AC-SA is suspected.

Complicaciones postoperatorias del manejo quirúrgico de escoliosis / Post-operative complications after surgical management of scoliosis

Introducción La tasa de complicaciones en cirugía de escoliosis sigue siendo alta. Lo que buscamos con este estudio es saber que características de los pacientes se relacionan con la presentación de complicaciones perioperatorias y poder usar esta informacion para la toma de medidas preventivas. Materiales y métodos Estudio descriptivo de corte transversal retrospectivo. Se incluyeron pacientes con escoliosis llevados a cirugía para corrección de su deformidad, obteniendo 230 pacientes y 318 procedimientos. Variables sociodemográficas fueron evaluadas con medidas de tendencia central, posteriormente se realizó un análisis bivariado y finalmente un análisis de regresión logística multinomial. Resultados Con una p<0,005 se encontró por diagnostico: escoliosis neuromuscular y sindromática un 28,8 y 16,66% de neumonías y una prevalencia de 15,87 y 33,33% de derrame pleural respectivamente. Escoliosis Congénita 1,88% tuvo Infección de vías urinarias. Se realizó un modelo de regresión logística obteniendo a la edad como principal predictor para presentación de complicaciones, siendo más frecuentes en los pacientes más jóvenes (p<0,000). Discusión Se encontró que a menor edad mas frecuente era la presentación de complicaciones, resultado no reportado previamente, pero que sirve para respaldar la conducta conservadora en pacientes con escoliosis de inicio temprano. Las complicaciones mas comunes fueron las pulmonares. Escoliosis neuromuscular es el diagnostico que mas complicaciones reportó. Datos comparables con la literatura que se deben tener en cuenta para tomar medidas de prevención y el desarrollo de planes de mejoramiento.

Background The rate of complications in scoliosis surgery remains high. This study intends to determine the characteristics of the patients that are related to the presentation of perioperative complications, and to be able to use this information to take preventive measures. Material and Method Descriptive cross-sectional retrospective study, including 230 patients and 318 procedures, was conducted on patients with scoliosis who underwent surgery to correct their deformity. Socio-demographic variables were evaluated using measures of central tendency measurements, followed by a bivariate analysis, and finally a multinomial logistic regression analysis. Results A significance of P<.005 was found for diagnosis: neuromuscular and syndromic scoliosis presented with 28.8 and 16.66% of pneumonias, and a prevalence of 15.87 and 33.33% for pleural effusion, respectively. A urinary tract infection (1.88%) was observed in Congenital Scoliosis. A logistic regression model was performed, observing age as the main predictor for presenting with complications, and being more frequent in younger patients (P<.000). Discussion It was found that more complications were present in younger patients. This outcome has not been previously reported, but can be used to support conservative behaviour in patients with early-onset scoliosis. The most common complication was pulmonary, with neuromuscular scoliosis being the diagnosis with more complications reported. These data are comparable with those in the literature, and should be taken into account when taking preventive measures and for the development of improvement plans.

Case–control study assessing the impact of COVID19 in advanced kidney cancer patients treated with antiangiogenics or immunotherapy: the COVID-REN study

Background Cancer is a risk factor for developing severe COVID19. Additionally, SARS-CoV2 has a special tropism for renal cells and complications like thrombosis or cytokine storm could be enhanced by standard treatments in kidney cancer (i.e., antiangiogenics or immunotherapy). Thus, understanding the impact of COVID19 in patients with this tumor is key for their correct management. Methods We designed a retrospective case–control study comparing the outcome of three groups of advanced kidney cancer patients on systemic treatment: cohort A (developed COVID19 while on antiangiogenics), cohort B (developed COVID19 while on immunotherapy) and cohort C (non-infected). Matching factors were age, gender, and treatment. Results 95 patients were recruited in 16 centers in Spain from September 2020 to May 2021. Finally, 85 were deemed as eligible (23 cohort A, 21 cohort B, 41 cohort C). Patients with COVID required more dose interruptions (25 vs. six) and hospitalizations (10 vs. none) than those without COVID (both p = 0.001). No difference between cohorts A and B was observed regarding hospitalization or length of stay. No ICU admission was registered and one patient in cohort B died due to COVID19. Regarding cancer evolution, three patients in cohort A presented progressive disease after COVID19 compared to two in cohort B. One case in cohort B, initially deemed as stable disease, achieved a partial response after COVID19. Conclusions Kidney cancer patients who developed COVID19 while on systemic therapy required more treatment interruptions and hospitalizations than those non-infected. However, no significant impact on cancer outcome was observed. Also, no difference was seen between cases on antiangiogenics or immunotherapy (AU)

The effect of correspondence between descriptions of contingencies and contingencies on the conduct of election under the self-control paradigm / Efeito da correspondência entre descrições de contingências e contingências sobre o comportamento de escolha sob o paradigma de autocontrole / Efecto de la correspondencia entre descripciones de contingencias y contingencias sobre la conducta de elección bajo paradigma de autocontrol

Abstract In this paper, the effect of correspondence history between contingency and contingency descriptions on the behavior of choice under the self-control paradigm is analyzed in 85 participants between the ages of 10 and 11, through two intrasubject experiments, one carried out in a laboratory context and another in a simulated natural situation. The results indicate that it is possible to affect the behavior of choice between an immediate reinforcer of lesser magnitude and a delayed one of greater magnitude in favor of the second alternative, from an experimental history of correspondence between descriptions of contingencies and contingencies. In both experiments, most of participants chose the delayed reinforcer after undergoing correspondence tests between descriptions and contingencies, and the immediate reinforcer after facing the correspondence absent trials, even though the training situations were formally and functionally different in relation with the task established to evaluate the conduct of choice. The results are analyzed in light of the "Relational Frame Theory", specifically, in relation with the alteration of the functions of the language.

Resumo Neste trabalho, analisa-se o efeito da história de correspondência entre as descrições de contingências e contingências sobre o comportamento de escolha sob o paradigma de autocontrole com 85 participantes entre 10 e 11 anos de idade, por meio de duas experiências intrassujeito, uma realizada em contexto de laboratório, e outra, numa situação natural simulada. Os resultados indicam que é possível afetar o comportamento de escolha entre um reforçador imediato -de menor magnitude- e outro demorado -de maior proporção- em favor da segunda alternativa a partir de uma história experimental de correspondência entre as descrições de contingências e contingências. Em ambas as experiências, a maioria de participantes escolheu o reforçador demorado depois de experimentar os ensaios de correspondência entre descrições e contingências, e o reforçador imediato depois de enfrentar os ensaios de correspondência ausente, embora as situações de treinamento tenham sido formal e funcionalmente diferentes com relação à tarefa estabelecida para avaliar o comportamento de escolha. Os resultados foram analisados à luz da Teoria das Molduras Relacionais, especificamente quanto à alteração das funções da linguagem.

Resumen En este trabajo se analiza el efecto de la historia de correspondencia entre las descripciones de contingencias y las contingencias sobre la conducta de elección bajo paradigma de autocontrol en 85 participantes de entre 10 y 11 años de edad, por medio de dos experimentos intrasujeto, uno realizado en contexto de laboratorio y otro en una situación natural simulada. Los resultados indican que es posible afectar la conducta de elección entre un reforzador inmediato -de menor magnitud- y otro demorado -de mayor proporción- en favor de la segunda alternativa a partir de una historia experimental de correspondencia entre las descripciones de contingencias y las contingencias. En ambos experimentos, la mayoría de participantes eligió el reforzador demorado después de experimentar los ensayos de correspondencia entre descripciones y contingencias, y el reforzador inmediato después de enfrentar los ensayos de correspondencia ausente pese a que las situaciones de entrenamiento fueron formal y funcionalmente diferentes en relación con la tarea establecida para evaluar la conducta de elección. Los resultados se analizan a la luz de la Teoría de los Marcos Relaciónales, específicamente en relación con la alteración de las funciones del lenguaje.

Conducta de elección bajo paradigma de autocontrol y desempeño académico en una situación grupal / Choice behavior under self-control paradigm and academic performance in a group situation

El objetivo del presente estudio fue establecer la relación entre autocontrol y las variables: desempeño académico, grado escolar y sexo en 87 estudiantes de transición, segundo y cuarto grado de primaria. Para medir la variable autocontrol, se planteó una tarea de elección entre un reforzador inmediato de baja magnitud y un reforzador postergado de mayor proporción. Esta tarea se presentó de forma grupal simulando los eventos de elección que se presentan en la realidad. Los resultados indican que las variables desempeño académico y grado escolar se relacionaron de manera positiva con autocontrol, mostrando diferencias estadísticamente significativas. Adicionalmente se encontró que en términos de proporción las mujeres tienden a postergar el refuerzo en mayor medida en comparación con los hombres.

The aim of this article was to establish the relation between self-control and a group of variables: academic performance, grade and gender, in 87 students of transition, second and fourth grade. To measure self-control, it was selected an election task between a delayed reinforcer and an immediate reinforce. This task was presented in a group activity simulating real election events. The results indicate that the academic performance and grade variables were associated positively with self-control, indicating statistically significant differences. In addition it was observed that women tend to delay the reinforcement at higher rates than men do.