Analysis of LRBA pathogenic variants and the association with functional protein domains and clinical presentation.

LRBA is a cytoplasmic protein that is ubiquitously distributed. Almost all LRBA domains have a scaffolding function. In 2012, it was reported that homozygous variants in LRBA are associated with early-onset hypogammaglobulinemia. Since its discovery, more than 100 pathogenic variants have been reported. This review focuses on the variants reported in LRBA and their possible associations with clinical phenotypes. In this work LRBA deficiency cases reported more than 11 years ago have been revised. A database was constructed to analyze the type of variants, age at onset, clinical diagnosis, infections, autoimmune diseases, and cellular and immunoglobulin levels. The review of cases from 2012 to 2023 showed that LRBA deficiency was commonly diagnosed in patients with a clinical diagnosis of Common Variable Immunodeficiency, followed by enteropathy, neonatal diabetes mellitus, ALPS, and X-linked-like syndrome. Most cases show early onset of presentation at <6 years of age. Most cases lack protein expression, whereas hypogammaglobulinemia is observed in half of the cases, and IgG and IgA levels are isotypes reported at low levels. Patients with elevated IgG levels exhibited more than one autoimmune manifestation. Patients carrying pathogenic variants leading to a premature stop codon show a severe phenotype as they have an earlier onset of disease presentation, severe autoimmune manifestations, premature death, and low B cells and regulatory T cell levels. Missense variants were more common in patients with low IgG levels and cytopenia. This work lead to the conclusion that the type of variant in LRBA has association with disease severity, which leads to a premature stop codon being the ones that correlates with severe disease.

Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

Tiempo hasta la modificación de la terapia antiparkinsoniana en un grupo de pacientes de Colombia / Time until modification of antiparkinsonian therapy in a group of patients from Colombia

Introducción: Se buscó determinar el tiempo transcurrido desde el inicio del tratamiento con fármacos antiparkinsonianos hasta la modificación en la terapia y establecer sus factores relacionados en un grupo de pacientes con enfermedad de Parkinson de Colombia. Pacientes y métodos: Estudio de cohorte retrospectiva que recolectó información sobre el tratamiento de pacientes con enfermedad de Parkinson que iniciaron terapia farmacológica entre junio de 2011 y diciembre de 2013; se realizó seguimiento a cinco años. Se generaron análisis de sobrevida para el tiempo trascurrido hasta la modificación de la terapia y se determinaron los factores relacionados con estos cambios utilizando modelos de regresión de Cox. Resultados: Un total de 3.224 pacientes (51,8%, hombres), con edad media de 73,1 ± 13,5 años, iniciaron tratamiento con fármacos antiparkinsonianos. Después de cinco años, 2.046 pacientes (63,5%) tuvieron modificaciones en la terapia farmacológica, con un promedio de tiempo de 36,4 meses (intervalo de confianza al 95%: 35,7-37,1). Un total de 1.216 pacientes (37,8%) requirió adición de otro principio activo, mientras que 830 (25,7%) tuvieron un cambio por otro medicamento. En el análisis multivariado, el sexo masculino, la edad mayor de 65 años y el inicio de amantadina se identificaron como factores que aumentaron la probabilidad de modificar la terapia. El uso de bromocriptina y biperideno, y la monoterapia como tratamiento inicial redujeron dicho riesgo. Conclusión: Después de cinco años de tratamiento, el 63,5% de los pacientes con enfermedad de Parkinson requirió modificaciones de la terapia, con un tiempo promedio de tres años. El sexo masculino, la edad mayor de 65 años y recibir terapia inicial con amantadina afectaron a la probabilidad de cambio de terapia en estos pacientes en Colombia.(AU)

Introduction: The aim was to determine the time elapsed between the start of treatment with antiparkinsonian agents and the modification of the pharmacological therapy, and to establish its related factors, in a group of patients with Parkinson’s disease from Colombia. Patients and methods: Retrospective cohort study that collected information about the treatment of patients with Parkinson’s disease who started drug therapy between June, 2011 and December, 2013; a five-year follow-up was performed. Survival analyses for time to therapy modification were generated, and factors related to these changes were determined using Cox regression models. Results: A total of 3,224 patients (51.8% men) with a mean age of 73.1 ± 13.5 years started treatment with antiparkinsonian agents. After five years, 2,046 patients (63.5%) had modifications in drug therapy, in a mean time of 36.4 months (95% confidence interval: 35.7-37.1). A total of 1,216 patients (37.8%) required the addition of another active principle, while 830 (25.7%) had a switch to another drug. In the multivariate analysis, male sex, age over 65 years, and the start of amantadine were identified as factors that increased the likelihood of therapy modification. The use of bromocriptine, biperiden, and monotherapy as an initial treatment were associated with a reduction in this likelihood. Conclusions: After five years of treatment, 63.5% of the patients with Parkinson’s disease required modifications to their therapy, with a mean time of three years. Male sex, age over 65 years, and receiving initial therapy with amantadine affected the likelihood of switching therapy in these patients in Colombia.(AU)

Time until modification of antiparkinsonian therapy in a group of patients from Colombia. / Tiempo hasta la modificación de la terapia antiparkinsoniana en un grupo de pacientes de Colombia.

INTRODUCTION: The aim was to determine the time elapsed between the start of treatment with antiparkinsonian agents and the modification of the pharmacological therapy, and to establish its related factors, in a group of patients with Parkinson's disease from Colombia. PATIENTS AND METHODS: Retrospective cohort study that collected information about the treatment of patients with Parkinson's disease who started drug therapy between June, 2011 and December, 2013; a five-year follow-up was performed. Survival analyses for time to therapy modification were generated, and factors related to these changes were determined using Cox regression models. RESULTS: A total of 3,224 patients (51.8% men) with a mean age of 73.1 ± 13.5 years started treatment with antiparkinsonian agents. After five years, 2,046 patients (63.5%) had modifications in drug therapy, in a mean time of 36.4 months (95% confidence interval: 35.7-37.1). A total of 1,216 patients (37.8%) required the addition of another active principle, while 830 (25.7%) had a switch to another drug. In the multivariate analysis, male sex, age over 65 years, and the start of amantadine were identified as factors that increased the likelihood of therapy modification. The use of bromocriptine, biperiden, and monotherapy as an initial treatment were associated with a reduction in this likelihood. CONCLUSIONS: After five years of treatment, 63.5% of the patients with Parkinson's disease required modifications to their therapy, with a mean time of three years. Male sex, age over 65 years, and receiving initial therapy with amantadine affected the likelihood of switching therapy in these patients in Colombia.

TITLE: Tiempo hasta la modificación de la terapia antiparkinsoniana en un grupo de pacientes de Colombia.Introducción. Se buscó determinar el tiempo transcurrido desde el inicio del tratamiento con fármacos antiparkinsonianos hasta la modificación en la terapia y establecer sus factores relacionados en un grupo de pacientes con enfermedad de Parkinson de Colombia. Pacientes y métodos. Estudio de cohorte retrospectiva que recolectó información sobre el tratamiento de pacientes con enfermedad de Parkinson que iniciaron terapia farmacológica entre junio de 2011 y diciembre de 2013; se realizó seguimiento a cinco años. Se generaron análisis de sobrevida para el tiempo trascurrido hasta la modificación de la terapia y se determinaron los factores relacionados con estos cambios utilizando modelos de regresión de Cox. Resultados. Un total de 3.224 pacientes (51,8%, hombres), con edad media de 73,1 ± 13,5 años, iniciaron tratamiento con fármacos antiparkinsonianos. Después de cinco años, 2.046 pacientes (63,5%) tuvieron modificaciones en la terapia farmacológica, con un promedio de tiempo de 36,4 meses (intervalo de confianza al 95%: 35,7-37,1). Un total de 1.216 pacientes (37,8%) requirió adición de otro principio activo, mientras que 830 (25,7%) tuvieron un cambio por otro medicamento. En el análisis multivariado, el sexo masculino, la edad mayor de 65 años y el inicio de amantadina se identificaron como factores que aumentaron la probabilidad de modificar la terapia. El uso de bromocriptina y biperideno, y la monoterapia como tratamiento inicial redujeron dicho riesgo. Conclusión. Después de cinco años de tratamiento, el 63,5% de los pacientes con enfermedad de Parkinson requirió modificaciones de la terapia, con un tiempo promedio de tres años. El sexo masculino, la edad mayor de 65 años y recibir terapia inicial con amantadina afectaron a la probabilidad de cambio de terapia en estos pacientes en Colombia.

Exogenous growth hormone promotes an epithelial-mesenchymal hybrid phenotype in cancerous HeLa cells but not in non-cancerous HEK293 cells.

In cancer, the Epithelial to Mesenchymal Transition (EMT) is the process in which epithelial cells acquire mesenchymal features that allow metastasis, and chemotherapy resistance. Growth hormone (GH) has been associated with melanoma, breast, and endometrial cancer progression through an autocrine regulation of EMT. Since exogenous and autocrine expression of GH is known to have different molecular effects, we investigated whether exogenous GH is capable of regulating the EMT of cancer cells. Furthermore, we investigated whether exogenous GH could promote EMT in non-cancerous cells. To study the effect of GH (100 ng/ml) on cancer and non-cancer cells, we used HeLa and HEK293 cell lines, respectively. We evaluated the loss of cell-cell contacts, by cell scattering assay and migration by wound-healing assay. Additionally, we evaluated the morphological changes by phalloidin-staining. Finally, we evaluated the molecular markers E-cadherin and vimentin by flow cytometry. GH enhances cell scattering and the migratory rate and promotes morphological changes such as cell area increase and actin cytoskeleton filaments formation on HeLa cell line. Moreover, we found that GH favors the expression of the mesenchymal protein vimentin, followed by an increase in E-cadherin's epithelial protein expression, characteristics of an epithelial-mesenchymal hybrid phenotype that is associated with metastasis. On HEK293cells, GH promotes morphological changes, including cell area increment and filopodia formation, but not affects scattering, migration, nor EMT markers expression. Our results suggest that exogenous GH might participate in cervical cancer progression favoring a hybrid EMT phenotype but not on non-cancerous HEK293 cells.

Prescription patterns of somatostatin analogs in patients with acromegaly and neuroendocrine tumors.

PURPOSE: Acromegaly and neuroendocrine tumors are rare diseases that, under certain conditions, can be treated with somatostatin analogs. The aim was to determine the prescription patterns of somatostatin analogs in a group of patients with acromegaly and neuroendocrine tumors affiliated with the Colombian Health System. METHODS: A retrospective study. A cohort of patients from a drug dispensing database that collected all prescriptions of long-acting somatostatin analogs (octreotide, lanreotide, pasireotide). Sociodemographic variables, clinical variables (diagnosis and comorbidities) and pharmacological therapy variables (dose, changes, persistence of use, comedications) were considered. RESULTS: A total of 213 patients were identified, including 139 (65.3%) with acromegaly and 74 (34.7%) with neuroendocrine tumors. There was a predominance of women (58.7%) and a mean age of 59.7 ± 14.5 years. The most commonly used medications were lanreotide autogel (n = 107; 50.2%), octreotide LAR (n = 102; 47.9%) and pasireotide LAR (n = 4; 1.9%). During follow-up, 11.3% of patients experienced modifications of therapy, with a mean duration from the beginning of treatment to the change in medication of 25 ± 15.9 months. A total of 48.9% of the patients with acromegaly and 87.1% of individuals with neuroendocrine tumors received maximum approved doses of the drug. CONCLUSION: Patients with acromegaly and neuroendocrine tumors in Colombia are mainly women and are most frequently treated with lanreotide autogel for acromegaly and with octreotide LAR for neuroendocrine tumors. In addition, a high proportion are managed with maximum doses of long-acting somatostatin analogs.

Assessment of Angiogenesis and Cell Survivability of an Inkjet Bioprinted Biological Implant in an Animal Model.

The rapidly growing field of tissue engineering hopes to soon address the shortage of transplantable tissues, allowing for precise control and fabrication that could be made for each specific patient. The protocols currently in place to print large-scale tissues have yet to address the main challenge of nutritional deficiencies in the central areas of the engineered tissue, causing necrosis deep within and rendering it ineffective. Bioprinted microvasculature has been proposed to encourage angiogenesis and facilitate the mobility of oxygen and nutrients throughout the engineered tissue. An implant made via an inkjet printing process containing human microvascular endothelial cells was placed in both B17-SCID and NSG-SGM3 animal models to determine the rate of angiogenesis and degree of cell survival. The implantable tissues were made using a combination of alginate and gelatin type B; all implants were printed via previously published procedures using a modified HP inkjet printer. Histopathological results show a dramatic increase in the average microvasculature formation for mice that received the printed constructs within the implant area when compared to the manual and control implants, indicating inkjet bioprinting technology can be effectively used for vascularization of engineered tissues.

HOLA COVID-19 Study: Evaluating the Impact of Caring for Patients With COVID-19 on Cancer Care Delivery in Latin America.

PURPOSE: The HOLA COVID-19 study sought to evaluate the impact of COVID-19 on oncology practices across Latin America (LATAM), challenges faced by physicians, and how practices and physicians adapted while delivering care to patients with cancer. METHODS: This international cross-sectional study of oncology physicians in LATAM included a 43-item anonymous online survey to evaluate changes and adaptations to clinical practice. Multivariable logistic regression analyses were used to evaluate the association of caring for patients with COVID-19 and changes to clinical practice. RESULTS: A total of 704 oncology physicians from 19 countries completed the survey. Among respondents, the most common specialty was general oncology (34%) and 56% of physicians had cared for patients with COVID-19. The majority of physicians (70%) noted a decrease in the number of new patients evaluated during the COVID-19 pandemic when compared with prepandemic, and 73% reported adopting the use of telemedicine in their practice. More than half (58%) of physicians reported making changes to the treatments that they offered to patients with cancer. In adjusted models, physicians who had cared for patients with COVID-19 had higher odds of changing the type of chemotherapy or treatments that they offered (adjusted odds ratio 1.81; 95% CI, 1.30 to 2.53) and of delaying chemotherapy start (adjusted odds ratio 2.05; 95% CI, 1.49 to 2.81). Physicians identified significant delays in access to radiation and surgical services, diagnostic tests, and supportive care. CONCLUSION: The COVID-19 pandemic has significantly disrupted global cancer care. Although changes to health care delivery are a necessary response to this global crisis, our study highlights the significant disruption and changes to the treatment plans of patients with cancer in LATAM resulting from the COVID-19 health care crisis.

Outcomes and Predictors of 28-Day Mortality in Patients With Hematologic Malignancies and Septic Shock Defined by Sepsis-3 Criteria.

BACKGROUND: To describe short-term outcomes and independent predictors of 28-dayx mortality in adult patients with hematologic malignancies and septic shock defined by the new Third International Consensus Definitions (Sepsis-3) criteria. METHODS: We performed a retrospective cohort study of patients admitted to the medical ICU with septic shock from April 2016 to March 2019. Demographic and clinical features and short-term outcomes were collected. We used descriptive statistics to summarize patient characteristics, logistic regression to identify predictors of 28-day mortality, and Kaplan-Meier plots to assess survival. RESULTS: Among the 459 hematologic patients with septic shock admitted to the ICU, 109 (23.7%) had received hematopoietic stem cell transplant. The median age was 63 years (range, 18-89 years), and 179 (39%) were women. Nonsurvivors had a higher Charlson comorbidity index (P=.007), longer length of stay before ICU admission (P=.01), and greater illness severity at diagnosis and throughout the hospital course (P<.001). The mortality rate at 28 days was 67.8% and increased with increasing sequential organ failure assessment score on admission (odds ratio [OR], 1.11; 95% CI, 1.03-1.20), respiratory failure (OR, 3.12; 95% CI, 1.49-6.51), and maximum lactate level (OR, 1.16; 95% CI, 1.10-1.22). Aminoglycosides administration (OR, 0.42; 95% CI, 0.26-0.69), serum albumin (OR, 0.51; 95% CI, 0.31-0.86), and granulocyte colony-stimulating factor (G-CSF) (OR, 0.40; 95% CI, 0.24-0.65) were associated with lower 28-day mortality. Life support limitations were present in 81.6% of patients at death. At 90 days, 19.4% of the patients were alive. CONCLUSIONS: Despite efforts to enhance survival, septic shock in patients with hematologic malignancies is still associated with high mortality rates and poor 90-day survival. These results demonstrate the need for an urgent call to action with higher awareness, including the further evaluation of interventions such as earlier ICU admission, aminoglycosides administration, and G-CSF treatment.

Prospects for beyond the Standard Model physics searches at the Deep Underground Neutrino Experiment: DUNE Collaboration.

The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE's sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.

Massive digestive bleeding as a result of gastric heterotopy: a case report. / Sangrado digestivo masivo por heterotopia gástrica. Reporte de un caso.

INTRODUCTION: Gastric heterotopy is a rare entity in the pediatric population. It occurs in the gastrointestinal tract, leading to digestive bleeding. CLINICAL CASE: This is the case of a 10-year-old boy with gastric tissue in the proximal jejunum, which caused two massive digestive bleeding episodes. Diagnostic techniques included endoscopic capsule, enteroscopy, and biopsy. The patient was scheduled for laparotomy and resection. After one year of follow-up, he remained asymptomatic. DISCUSSION: Gastric heterotopy approach represents a diagnostic challenge. Owing to how rare it is, there is no global consensus in terms of treatment. However, surgery is the definitive therapy. In this case, decision was made not to perform intestinal resection and anastomosis, but resection of the compromised intestinal wall. No malignity was reported in the literature reviewed.

INTRODUCCION: La heterotopia gástrica es una entidad infrecuente en la población pediátrica. Se presenta en el tracto gastrointestinal llevando a cuadros clínicos de sangrado digestivo. CASO CLINICO: Se reporta el caso de un escolar de 10 años, el cual presentó tejido gástrico en el yeyuno proximal, originando sangrado digestivo masivo en dos ocasiones. La secuencia de apoyos diagnósticos requirió cápsula endoscópica, enteroscopia y biopsia. Fue llevado a laparotomía y resección de la lesión. En el seguimiento al año se mantuvo asintomático. DISCUSION: Su abordaje genera un reto diagnóstico. Debido a su infrecuente presentación no hay un consenso global para el tratamiento, sin embargo, la intervención quirúrgica es la terapia definitiva. En este caso no se hizo resección intestinal y anastomosis sino resección de la pared intestinal comprometida. No se reportó malignidad en la literatura revisada.

The role of gut microbiome in modulating response to immune checkpoint inhibitor therapy in cancer.

Immunotherapy has led to a paradigm shift in the treatment of several cancers. There have been significant efforts to identify biomarkers that can predict response and toxicities related to immune checkpoint inhibitor (ICPI) therapy. Despite these advances, it has been challenging to tease out why a subset of patients benefit more than others or why certain patients experience immune-related adverse events (irAEs). Although the immune-modulating properties of the human gut bacterial ecosystem are yet to be fully elucidated, there has been growing interest in evaluating the role of the gut microbiome in shaping the therapeutic response to cancer immunotherapy. Considerable research efforts are currently directed to utilizing metagenomic and metabolic profiling of stool microbiota in patients on ICPI-based therapies. Dysbiosis or loss of microbial diversity has been associated with a poor treatment response to ICPIs and worse survival outcomes in cancer patients. Emerging data have shown that certain bacterial strains, such as Faecalibacterium that confer sensitivity to ICPI, also have a higher propensity to increase the risk of irAEs. Additionally, the microbiome can modulate the local immune response at the intestinal interface and influence the trafficking of bacterial peptide primed T-cells distally, influencing the toxicity patterns to ICPI. Antibiotic or diet induced alterations in composition of the microbiome can also indirectly alter the production of certain bacterial metabolites such as deoxycholate and short chain fatty acids that can influence the anti-tumor tolerogenesis. Gaining sufficient understanding of the exact mechanisms underpinning the interplay between ICPI induced anti-tumor immunity and the immune modulatory role gut microbiome can be vital in identifying potential avenues of improving outcomes to cancer immunotherapy. In the current review, we have summarized and highlighted the key emerging data supporting the role of gut microbiome in regulating response to ICPIs in cancer.

Sangrado digestivo masivo por heterotopia gástrica. Reporte de un caso / Massive digestive bleeding as a result of gastric heterotopy: a case repor

Introducción: La heterotopia gástrica es una entidad infrecuente enla población pediátrica. Se presenta en el tracto gastrointestinal llevandoa cuadros clínicos de sangrado digestivo. Caso clínico: Se reporta el caso de un escolar de 10 años, el cualpresentó tejido gástrico en el yeyuno proximal, originando sangradodigestivo masivo en dos ocasiones. La secuencia de apoyos diagnósti-cos requirió cápsula endoscópica, enteroscopia y biopsia. Fue llevadoa laparotomía y resección de la lesión. En el seguimiento al año semantuvo asintomático. Discusión: Su abordaje genera un reto diagnóstico. Debido a suinfrecuente presentación no hay un consenso global para el tratamien-to, sin embargo, la intervención quirúrgica es la terapia definitiva. Eneste caso no se hizo resección intestinal y anastomosis sino resecciónde la pared intestinal comprometida. No se reportó malignidad en laliteratura revisada.(AU)

Introduction: Gastric heterotopy is a rare entity in the pediatricpopulation. It occurs in the gastrointestinal tract, leading to digestivebleeding. Clinical case: This is the case of a 10-year-old boy with gastrictissue in the proximal jejunum, which caused two massive digestivebleeding episodes. Diagnostic techniques included endoscopic capsule,enteroscopy, and biopsy. The patient was scheduled for laparotomyand resection. After one year of follow-up, he remained asymptomatic. Discussion: Gastric heterotopy approach represents a diagnosticchallenge. Owing to how rare it is, there is no global consensus in termsof treatment. However, surgery is the definitive therapy. In this case,decision was made not to perform intestinal resection and anastomosis,but resection of the compromised intestinal wall. No malignity wasreported in the literature reviewed.(AU)

Years of Potential Life Lost Because of Breast and Cervical Cancers in Guatemala.

PURPOSE: Worldwide cervical and breast cancers are among the most commonly diagnosed cancers and are leading cause of cancer deaths among females in low- and middle-income countries. In Guatemala, breast and cervical cancers are the main cause of cancer-related deaths among women. Therefore, the aim of this study was to determine the years of potential life lost (YPLL) as an indicator of premature deaths as a result of breast and cervical cancers. METHODS: Data on the number of deaths as a result of breast and cervical cancers (International Classification of Diseases [10th revision] codes C50 and C53) between 2012 and 2016 and age composition by quinquennials were retrieved from the Health Information System of the Guatemalan Health Ministry. On the basis of each individual's age at death, YPLL was estimated for females between 20 and 70 years of age. RESULTS: A total of 1,476 deaths related to breast and cervical cancers was reported over the study period. The trend in breast cancer mortality rate and YPLL did not change from 2012 to 2016. The cervical cancer mortality rate has decreased to 10 deaths per 1 million habitants (P = .046). There has been a reduction in YPLL because of cervical cancer, from 50.18 YPLL in 2012 to 29.19 YPLL by 2016, mainly in women between 30 and 34 years of age, in whom YPLL decreased from 600 to 112.50 (P = .046). CONCLUSION: Cervical cancer screening has significantly reduced the mortality rate of this malignancy, and screening of breast cancer must include creating awareness of the disease and providing access to women at risk.

Prevalence of peripheral neuropathy associated with chemotherapy in four oncology centers of Colombia. / Prevalencia de neuropatia periferica asociada a quimioterapia en cuatro centros oncologicos de Colombia.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy is a common adverse reaction in a variety of medications frequently used for a great number of cancer treatments. This condition consists of mainly sensory-type symptoms, motor components and autonomic changes. Reported prevalence ranges from 30-68%, after the completion of chemotherapy in non-Latin American people with different populations and socioeconomic levels. AIM: To determine the prevalence of chemotherapy-induced peripheral neuropathy in a Colombian population. PATIENTS AND METHODS: A real-world evidence cross-sectional retrospective study was performed in all patients from oncological clinical centers in Colombia, which received pharmacological therapy for any cancer between January 2015 and December 2016, with taxanes (paclitaxel, docetaxel), alkylators (oxaliplatin), proteasome inhibitors (bortezomib), and epothilone B analogs (ixabepilone). RESULTS: A total of 1,551 patients in four cities were included, and 11,280 doses were applied; predominantly females (n = 1,094; 70.5%), with a mean age of 57 ± 13 years old. Paclitaxel was the most commonly prescribed drug (n = 788; 50.8%). Chemotherapy-induced peripheral neuropathy was developed in 48.9% of paclitaxel, 58.5% of oxaliplatin, 50.5% of docetaxel, 43.7% of bortezomib and 95.2% of ixabepilone patients. Thirty-three patients were treated with two of these medications simultaneously. CONCLUSIONS: Chemotherapy-induced peripheral neuropathy is a frequent adverse reaction to daily cancer therapy in Colombian patients managed with taxanes, alkylators, proteasome inhibitors, and epothilone B analogs. Hence, it is necessary to establish more successful diagnostic methods and incorporate validated scales in the routine evaluation of all patients receiving these medications in our environment.

TITLE: Prevalencia de neuropatia periferica asociada a quimioterapia en cuatro centros oncologicos de Colombia.Introduccion. La neuropatia periferica inducida por quimioterapia es una reaccion comun a una variedad de medicamentos usados en el tratamiento del cancer, que consiste principalmente en sintomas sensitivos, con componentes motores y cambios autonomicos. La prevalencia es del 30-68% despues de terminar la quimioterapia en paises no latinoamericanos. Objetivo. Determinar la prevalencia de la neuropatia periferica inducida por quimioterapia en la poblacion colombiana. Pacientes y metodos. Estudio retrospectivo con evidencia del mundo real en la totalidad de pacientes atendidos en cuatro centros oncologicos de Colombia, quienes recibieron terapia farmacologica para algun tipo de cancer entre enero de 2015 y diciembre de 2016 con taxanos (paclitaxel, docetaxel), agentes alquilantes (oxaliplatino), inhibidores de proteasoma (bortezomib) y analogos de epotilona B (ixabepilona). Resultados. Se siguio a un total de 1.551 pacientes en cuatro ciudades a quienes se les aplicaron 11.280 dosis, con predominio femenino (n = 1.094; 70,5%) y una edad media de 57 ± 13 años. El paclitaxel fue el farmaco mas prescrito (n = 788; 50,8%). La neuropatia inducida por quimioterapia se presento en el 48,9% de los pacientes con paclitaxel, el 58,5% de los pacientes con oxaliplatino, el 50,5% de los pacientes con docetaxel, el 43,7% de los pacientes con bortezomib y el 95,2% de los pacientes con ixabepilona. Se trato a 33 pacientes con dos de estos medicamentos simultaneamente. Conclusiones. La neuropatia periferica inducida por quimioterapia es una reaccion adversa frecuente en pacientes con cancer en Colombia tratados con taxanos, alquilantes, inhibidores de proteasoma e ixabepilona. Es necesario establecer metodos diagnosticos efectivos e incorporar escalas validadas en la evaluacion rutinaria de los pacientes que reciben estas medicaciones.

[Patterns of antidemential drug use in a group of patients from Colombia]. / Patrones de uso de farmacos antidemencia en un grupo de pacientes de Colombia.

INTRODUCTION: The benefits of pharmacological therapy with anti-dementia drugs are not yet fully demonstrated and there is even a lack of publications describing their use profile. The present work sought to determine the prescription patterns of anti-dementia drugs in a Colombian population. PATIENTS AND METHODS: Descriptive cross-sectional study. Through a systematized database of 3.5 million affiliates to the Colombian health system, patients with uninterrupted dispensing of anti-dementia drugs between August-October/2016 were selected. Sociodemographic, pharmacological and comedication variables were analyzed. The costs of the therapies were estimated from the reference price of the medicines. RESULTS: We identified 8372 patients with a mean age of 79.5 ± 8.7 years and 65.3% (n = 5471) were women. The most widely used medication was rivastigmine (69.6%), mainly in transdermal presentation, followed by memantine (31.4%). In general, the average dose administered per day was lower than the defined daily dose. Only 568 patients (6.7%) used combination therapy. 84.3% of patients (n = 7061) used some additional medication and 54.2% (n = 4535) had another neurologic medication. The cost per 1000 inhabitants/day of rivastigmine was 3.47 USD and for memantine 0.30 USD. CONCLUSION: Patients with anti-dementia drugs are using them at doses lower than those defined and they present an important frequency of comorbidities and comedications.

TITLE: Patrones de uso de farmacos antidemencia en un grupo de pacientes de Colombia.Introduccion. Los beneficios del manejo farmacologico con medicamentos antidemencia aun no estan del todo demostrados, e incluso hay carencia de trabajos que describan su perfil de utilizacion. El presente trabajo busco determinar los patrones de prescripcion de farmacos antidemencia en una poblacion de Colombia. Pacientes y metodos. Estudio descriptivo de corte transversal. Mediante una base de datos sistematizada de 3,5 millones de afiliados al sistema de salud colombiano, se selecciono a pacientes con dispensaciones ininterrumpidas de farmacos antidemencia entre agosto y octubre de 2016. Se analizaron variables sociodemograficas, farmacologicas y comedicaciones. Se estimaron los costes de las terapias a partir del precio de referencia de los medicamentos. Resultados. Se identifico a 8.372 pacientes con una edad media de 79,5 ± 8,7 años; el 65,3% (n = 5.471) fueron mujeres. El farmaco mas utilizado fue la rivastigmina (69,6%), principalmente en presentacion transdermica, seguida de la memantina (31,4%). En general, la dosis media administrada por dia fue inferior a la dosis diaria definida. Solamente 568 pacientes (6,7%) usaron terapia combinada. El 84,3% de los pacientes (n = 7.061) uso medicamentos para alguna comorbilidad y el 54,2% (n = 4.535) tenia otro neurofarmaco. El coste por 1.000 habitantes/dia de la rivastigmina fue de 3,47 dolares, y de la memantina, de 0,30 dolares. Conclusion. Los pacientes con medicamentos antidemencia los estan empleando en dosis inferiores a las definidas y presentan una importante frecuencia de comorbilidades y comedicaciones.

Liver Cancer in Guatemala: An Analysis of Mortality and Incidence Trends From 2012 to 2016.

PURPOSE: Guatemala has the highest mortality and incidence of liver cancer in Central and South America. The aim of this study is to describe the extent of liver cancer in the country from 2012 to 2016 and the associated risk factors. METHODS: A secondary analysis was performed using liver cancer mortality and morbidity data and data on risk factors, such as hepatitis B virus infection, cirrhosis, and alcoholism. RESULTS: Analysis revealed that liver cancer causes approximately 20% of cancer deaths in the country, is more frequent in the population older than age 65 years old, and is increasing in those age 30 to 44 years. More than 25% of deaths occurred in the North and West regions. The incidence of major risk factors for development of liver cancer has decreased. CONCLUSION: The high mortality of liver cancer compared with its incidence indicates that most patients are diagnosed at late stages. To reduce the burden of liver cancer, creation of strategies for earlier detection is needed.

CD38 protein deficiency induces autoimmune characteristics and its activation enhances IL-10 production by regulatory B cells.

CD38 is a transmembrane protein expressed in B lymphocytes, and is able to induce responses as proliferation, differentiation or apoptosis. Several reports propose that CD38 deficiency accelerates autoimmune processes in murine models of autoimmune diabetes, lymphoproliferation and rheumatoid arthritis. Other reports have shown elevated CD38 expression in B and T cells from patients with autoimmunity; however, the role of CD38 is still unclear in the development of autoimmunity. Recently, it has been characterized as CD1dhi CD5+ regulatory B cell subpopulation able to produce IL-10, and the loss of these cells exacerbates the autoimmunity in murine models. Here, we report that CD38-/- mice exhibited elevated titres of ANAS, anti-dsDNA autoantibodies from 12 months of age and were higher by 16 months of age and mice presented kidney damage. Interestingly, there is a reduction in the survival of CD38-/- mice compared to the WT. Furthermore, CD38 is highly expressed by CD1dhigh CD5+ regulatory B cells, and the agonistic anti-CD38 stimulus plus LPS was able to increase the percentage of this cell subset and its ability to induce IL-10 production. Together, these results suggest that CD38 could play a role in the control of autoimmune diseases through their expression on regulatory B cells.

Occurrence of Harmful Cyanobacteria in Drinking Water from a Severely Drought-Impacted Semi-arid Region.

Harmful cyanobacterial blooms have become increasingly common in freshwater ecosystems in recent decades, mainly due to eutrophication and climate change. Water becomes unreliable for human consumption. Here, we report a comprehensive study carried out to investigate the water quality of several Campina Grande reservoirs. Our approach included metagenomics, microbial abundance quantification, ELISA test for three cyanotoxins (microcystin, nodularins, and cylindrospermopsin), and in vivo ecotoxicological tests with zebrafish embryos. Cytometry analysis showed high cyanobacterial abundance, while metagenomics identified an average of 10.6% of cyanobacterial sequences, and demonstrated the presence of Microcystis, Cylindrospermopsis, and toxin coding genes in all ponds. Zebrafish embryos reared with pond water had high mortality and diverse malformations. Among the ponds analyzed, Araçagi showed the highest lethality (an average of 62.9 ± 0.8%), followed by Boqueirão (lethality average of 62.5 ± 0.8%). Here, we demonstrate that water from ponds undergoing extremely drought conditions have an abundance of potentially harmful cyanobacteria and their toxins. Our findings are consistent with a scenario in which polluted drinking water poses a great risk to human health.

D-Meson Azimuthal Anisotropy in Midcentral Pb-Pb Collisions at sqrt[s]_{NN}=5.02 TeV.

The azimuthal anisotropy coefficient v_{2} of prompt D^{0}, D^{+}, D^{*+}, and D_{s}^{+} mesons was measured in midcentral (30%-50% centrality class) Pb-Pb collisions at a center-of-mass energy per nucleon pair sqrt[s_{NN}]=5.02 TeV, with the ALICE detector at the LHC. The D mesons were reconstructed via their hadronic decays at midrapidity, |y|<0.8, in the transverse momentum interval 1