Car T Cells in Solid Tumors: Overcoming Obstacles.

Chimeric antigen receptor T cell (CAR T cell) therapy has emerged as a prominent adoptive cell therapy and a therapeutic approach of great interest in the fight against cancer. This approach has shown notorious efficacy in refractory hematological neoplasm, which has bolstered its exploration in the field of solid cancers. However, successfully managing solid tumors presents considerable intrinsic challenges, which include the necessity of guiding the modified cells toward the tumoral region, assuring their penetration and survival in adverse microenvironments, and addressing the complexity of identifying the specific antigens for each type of cancer. This review focuses on outlining the challenges faced by CAR T cell therapy when used in the treatment of solid tumors, as well as presenting optimizations and emergent approaches directed at improving its efficacy in this particular context. From precise localization to the modulation of the tumoral microenvironment and the adaptation of antigen recognition strategies, diverse pathways will be examined to overcome the current limitations and buttress the therapeutic potential of CAR T cells in the fight against solid tumors.

Mortality Rate and Acute Kidney Injury Prevalence Reduction in COVID-19 Critical Patients Treated with Hemoperfusion.

Introduction: Coronavirus disease 2019 (COVID-19) induces organic damage mainly through the patient's immune overreaction. Hemoperfusion (HPF) can remove inflammatory cytokines and can reduce the negative effects of cytokine storm in COVID-19. We compared the mortality rate, inflammatory response, and acute kidney injury (AKI) prevalence among patients suffering from respiratory insufficiency secondary to COVID-19 treated with and without HPF with HA330 cartridge. Methods: Mortality rate, serum creatinine, and ferritin values were compared between patients suffering from respiratory insufficiency secondary to COVID-19 who received conventional treatment and another group of patients who additionally received four sessions of HPF with HA330. Results: Of 116 patients suffering from acute respiratory insufficiency secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), one group (n: 84) received support treatment and the other group (n: 32) additionally received HPF with HA330 cartridge. Both groups had no renal disease and similar age and comorbidities at admission, except for obesity and mechanical ventilation requirement, which were significantly higher in the HPF group. Mortality rate (61% vs. 31%, P: 0.008), serum creatinine (1.4 vs. 0.5 mg/dl, P < 0.001), and post-HPF serum ferritin (2868 vs. 1675, P < 0.001) were significantly lower in the HPF group. Conclusion: Mortality rate, serum ferritin, and AKI were significantly reduced in critical COVID-19 patients who received HPF with HA330 cartridge than in those who did not receive it. These results were obtained despite the HPF group risk factors, such as obesity and mechanical ventilation, worsening its prognosis.

Pregnancy-Associated Atypical Hemolytic Uremic Syndrome: A Case Report with MCP Gene Mutation and Successful Eculizumab Treatment.

Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare condition characterized by microangiopathic hemolytic anemia and kidney injury from thrombotic microangiopathy. P-aHUS occurs in approximately 1 in 25,000 pregnancies and is strongly related to complement dysregulation and pregnancy-related disorders, such as preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome, resulting in adverse perinatal and fetal outcomes. Complement dysregulation in P-aHUS is commonly attributed to genetic mutations or autoantibodies affecting complement factors, including CFH , CFI , and MCP. We present a case of a 25-year-old primigravida who experienced severe preeclampsia and HELLP syndrome followed by the development of complicated P-aHUS during the early postpartum period. The patient exhibited severe clinical manifestations, including hypertensive emergency, central nervous system involvement, renal impairment, and microangiopathic hemolytic anemia. Timely initiation of eculizumab therapy resulted in successful disease remission. Further genetic analysis revealed a likely rare pathogenic MCP gene variant.

Frailty status improvement after kidney transplantation.

INTRODUCTION: Frailty is a clinical syndrome characterized by a decrease in strength, resistance and body physiological condition, making the individual more vulnerable, and increasing his/her risk of dependence and death. Kidney transplant (KT) is currently the best end-stage renal disease therapeutic alternative for certain individuals. Frailty status occurs in approximately 20% of KT patients. Thus, it was evaluated if there would be any change in frailty status level in a population of adult patients on chronic HD after receiving KT. MATERIAL AND METHOD: A cross-sectional study was conducted on a population of adult hemodialysis patients (n: 57), with the objective of evaluating if there was a significant change in their clinical frailty score (CFS) after 6 months of KT. For the statistical analysis, the Student's t-test, and the test of statistical significance between two proportions were applied. RESULTS: Mean CFS before KT was 4 (vulnerable), and after KT was 3 (robust). CFS value was significantly lower after KT (p value < 0.01). CONCLUSION: A significant improvement was found between pre- and post-transplant clinical frailty scores in hemodialysis adult patients.

Comparative Analysis of In-House RT-qPCR Detection of SARS-CoV-2 for Resource-Constrained Settings.

We developed and standardized an efficient and cost-effective in-house RT-PCR method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated sensitivity, specificity, and other statistical parameters by different RT-qPCR methods including triplex, duplex, and simplex assays adapted from the initial World Health Organization- (WHO) recommended protocol. This protocol included the identification of the E envelope gene (E gene; specific to the Sarvecovirus genus), RdRp gene of the RNA-dependent RNA polymerase (specific for SARS-CoV-2), and RNase P gene as endogenous control. The detection limit of the E and the RdRp genes were 3.8 copies and 33.8 copies per 1 µL of RNA, respectively, in both triplex and duplex reactions. The sensitivity for the RdRp gene in the triplex and duplex RT-qPCR tests were 98.3% and 83.1%, respectively. We showed a decrease in sensitivity for the RdRp gene by 60% when the E gene acquired Ct values > 31 in the diagnostic tests. This is associated with the specific detection limit of each gene and possible interferences in the protocol. Hence, developing efficient and cost-effective methodologies that can be adapted to various health emergency scenarios is important, especially in developing countries or settings where resources are limited.

Decreasing microbiota-derived uremic toxins to improve CKD outcomes.

Chronic kidney disease (CKD) is set to become the fifth-leading global cause of death by 2040. This illustrates the many unknowns regarding its pathogenesis and therapy. A key unknown relates to the therapeutic impact of the interaction between CKD and the gut microbiome. The normal gut microbiome is essential for body homeostasis. There is evidence for multiple interactions between the microbiota and CKD-its causes, comorbidities and therapeutic interventions-that are only starting to be unraveled. Thus uremic retention products, such as urea itself, modify the gut microbiota biology and both dietary and drug prescriptions modify the composition and function of the microbiota. Conversely, the microbiota may influence the progression and manifestations of CKD through the production of biologically active compounds (e.g. short-chain fatty acids such as butyrate and crotonate) and precursors of uremic toxins. The present review addresses these issues and their relevance for novel therapeutic approaches ranging from dietary interventions to prebiotics, probiotics, synbiotics and postbiotics, to the prevention of the absorption of microbial metabolites and to increased clearance of uremic toxins of bacterial origin through optimized dialysis techniques or blockade of tubular cell transporters.

Immune Lymphocyte Infiltrate and its Prognostic Value in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) occurs more frequently in young (<50 years) non-Hispanic black and Hispanic/Latina women. It is considered the most aggressive subtype of breast cancer, although, recently, immune infiltrate has been associated with long-term survival, lower risk of death and recurrence, and response to neoadjuvant chemotherapy. The aim of this review was to evaluate the clinical impact of the immune infiltrate in TNBC by discussing whether its prognostic value varies across different populations. A comprehensive systematic search in databases such as PubMed and Web of Science was conducted to include papers focused on tumor-infiltrating lymphocytes (TILs) in TNBC in different population groups and that were published before January 2021. TNBC patients with higher levels of TILs had longer overall survival and disease-free survival times compared with TNBC patients with low TIL levels. Similar results were observed for CD4+, CD8+ TIL populations. On the other hand, patients with high TIL levels showed a higher rate of pathological complete response regardless of the population group (Asian, European, and American). These results altogether suggest that TIL subpopulations might have a prognostic role in TNBC, but the underlying mechanism needs to be elucidated. Although the prognosis value of TILs was not found different between the population groups analyzed in the revised literature, further studies including underrepresented populations with different genetic ancestries are still necessary to conclude in this regard.

Chronic kidney disease (CKD) and chronic kidney insufficiency (CKI) diagnosing equation in cirrhotic patients.

Cirrhotic patients can develop acute kidney injury (AKI), and chronic kidney disease (CKD). Therefore, renal functional evaluation is crucial in cirrhotic patients. However, serum creatinine and urea levels, as well as measured or estimated glomerular filtration rate is not reliable renal functional markers in these patients compared to other patient groups. In the present study, four original equations are designed and tested for screening chronic kidney disease (CKD) and chronic kidney insufficiency (CKI) in stable cirrhotic patients. MATERIAL & METHOD: estimated GFR (CKD-EPI creatinine and cystatin equations) were recorded in 175 adult stable patients suffering from cirrhosis, and these patients were classified as presenting or not CKD and CKI after evaluation by two independent nephrologists. Based on these data, the variables with the significant discriminating capability to identify CKD and CKI (based on creatinine and cystatin) were detected by applying the Student's t-test for two independent groups, later confirmed by the lambda test of Wilks, in order to obtain the renal function equations. RESULTS: CKD equation (creatinine) = 7.094238-0.043104 × CKD-EPI creatinine - 0.057537 × haematocrit. CKD equation (cystatin) = 8.375074-0.117218 × CKD-EPI cystatin. CKI equation (creatinine) = 0.428389-0.043214 × CKD-EPI creatinine +0.183051 × Child-Pugh score + 0.050162 × age (in years). CKI equation (cystatin) = 9.169579-0.139319 × CKD-EPI cystatin. CONCLUSION: Simple and reliable equations have been obtained for screening chronic kidney disease and chronic kidney insufficiency in cirrhotic patients.

Atypical hemolytic uremic syndrome in the Colombian Caribbean: its particular characteristics.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is a rare and genetically mediated systemic disease most often caused by uncontrolled and chronic complement activation that leads to systemic thrombotic microangiopathy, renal and extra-renal damage. MATERIALS AND METHODS: This is descriptive, retrospective and multicenter study, which reports demographic, clinical, laboratory, and genetic characteristics, as well as their treatment response and outcome of 20 aHUS patients diagnosed between 2014 and 2018. RESULTS: Most patients were female adults (75%) and 30% were associated to pregnancy/postpartum, 15% to autoimmune disease, and 65% to infections. Gastrointestinal involvement (75%) was the most frequent extra-renal organ damage. Antenatal mortality and mortality rate were 5% and 10%, respectively. 25% of the patients progressed to end-stage renal disease. In 4/8 of patients treated within 1 week of presentation, eculizumab treatment restored multi-organ function after 4 weeks of treatment. CFH (37%) and CFI (25%) mutations were the most frequent. CONCLUSION: This is the first series of aHUS cases of Colombian Caribbean region which reports the clinical and epidemiological characteristics of this condition in this region.

Glomerular Diseases in the Colombian Caribbean: Data from the Colombian Nephropathy Registry (NEFRORED®).

Our study aimed to describe the glomerular diseases, both primary glomerular disease (PGD) and secondary glomerular disease (SGD) in the Colombian Caribbean based on the first regional Colombian Nephropathy Registry (NEFRORED®). A descriptive and retrospective study of adult patients with glomerular diseases from the Colombian Caribbean region was made. All diagnoses by renal biopsy with light microscopy and immunofluorescence obtained between January 2008 and June 2018 were recorded. Eight hundred and seventy-one renal biopsies were obtained. The main clinical indication for biopsy was nephritic syndrome (36%). SGD was more frequent than PGD (55% vs. 45%). Within SGD group, lupus nephritis (LN) was the most frequent etiology (83%). Within PGD group, membranous nephropathy (33%) and focal segmental glomerulosclerosis (FSGS) (19%) were the most common glomerular diseases. At a 24-month follow-up, the patients with FSGS and paraproteinemia-mediated glomerular disease had the worst renal survival prognosis. This is the first Colombian Nephropathy Registry in a Caribbean population, demonstrating a high predominance of SGD due to LN.

Optimizing dialysis dose in the context of frailty: an exploratory study.

INTRODUCTION: Frailty is a multicausal syndrome characterized by a decrease in strength, resistance and physiological function, which makes the individual vulnerable and dependent, and increases his/her mortality. This syndrome is more prevalent among older individuals, and chronic kidney disease patients, particularly those on dialysis. Dialysis dose is currently standardized for hemodialysis (HD) patients regardless of their age and functional status. However, it has been postulated that the dialysis dose required in older patients, especially frail ones, should be lower, since it could increase their degree of frailty. Then, the purpose of this study was to evaluate if there would be a correlation between the dose of Kt/V and the degree of frailty in a population of adult patients on HD. MATERIALS AND METHODS: A cross-sectional study with 82 patients on HD in Barranquilla (Colombia) and Lobos (Argentina) was conducted. Socio-demographic and laboratory data, as well as dialysis doses (Kt/V) were recorded and scales of fragility, physical activity, gait and grip strength were applied. Then these data were correlated by a Spearman's correlation and a logistic regression. RESULTS: CFS, social isolation, physical activity, gait speed, and prehensile strength tests were outside the reference ranges in the studied group. No significant correlation was found between dialysis dose and all the above mentioned functional tests. However, a significant and inverse correlation between physical activity and CFS was documented (score - 1.41 (CI - 2.1 to - 0.7). CONCLUSION: No significant correlation was documented between Kt/V value and different parameters of the frailty status, but this status correlated significantly and inversely with physical activity in this group. Frailty status in hemodialysis patients was significantly higher in older individuals, although young individuals were not exempt from it.

Impact of frailty and viral load on acute kidney injury evolution in patients affected by Coronavirus Disease 2019.

This paper describes the main characteristics of coronavirus diseases 2019 (COVID-19) patients suffering from acute kidney injury (AKI) assisted at a high complexity clinic in Barranquilla, Colombia. The patients included in this study (n = 48) were those with a positive diagnosis of COVID-19 confirmed by polymerase chain reaction detection of severe acute respiratory syndrome coronavirus 2, who had developed AKI during their hospital stay. Serum and urine parameters, as well as patient's viral load and clinical frailty scale (CFS) were recorded. A statistical analysis of the recorded parameters, such as comparisons, and correlations between variables of interest, were explored. The prevalence of COVID-19 induced AKI was 41%, being the majority of them classified as AKI network classification 3, with a renal replacement therapy requirement of 29%, and an associated mortality of 73%. AKI patients' mortality showed a significant positive correlation (33%) with patients' CFS score but not with their viral load. COVID-19 induced AKI significantly correlated with patients' frailty status but not to their viral load.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i): renal implications.

Type 2 diabetes mellitus (DM2) is a chronic condition that affects more than 400 million individuals worldwide. In DM2 patients, an appropriate glycemic control slows the onset and delays the progression of all its micro and macrovascular complications. Even though there are several glucose-lowering drugs, only approximately half of patients achieve glycemic control, while undesirable adverse effects (e.g., low serum glucose) normally affect treatment. Therefore, there is a need for new types of treatments. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have just been developed for treating DM2. Renal hyperfiltration as a marker of increased intraglomerular pressure in diabetic patients, and the role of renin-angiotensin-aldosterone system (RAAS) in this phenomenon have been studied. Nevertheless, RAAS blockade does not completely reduce hyperfiltration or diabetic renal damage. In this sense, the contribution of renal tubular factors to the hyperfiltration state, including sodium-glucose cotransporter (SGLT), has been currently studied. SGLT2i reduce proximal tubular sodium reabsorption, therefore increasing distal sodium delivery to the macula densa, causing tubule-glomerular feedback activation, afferent vasoconstriction, and reduced hyperfiltration in animal models. In humans, SGLT2i was recently shown to reduce hyperfiltration in normotensive, normoalbuminuric patients suffering from type 1 diabetes mellitus. In DM2 clinical trials, SGLT2 is associated with significant hyperfiltration and albuminuria reduction. The aim of this article is to compile the information regarding SGLT2i drugs, emphasizing its mechanism of renal repercussion.

Reporte de cuatro casos COVID-19 hospitalizados en unidad de cuidados intensivos en una institución hospitalaria en Barranquilla, Colombia / Original article: Case-Serie of 4 COVID-19 patients hospitalized in an intensive care unit in a hospital institution in Barranquilla, Colombia

Resumen Presentar una serie de casos de COVID-19 con requerimiento de ingreso a Unidad de Cuidados Intensivos. La información fue tomada de las historias clínicas, y su evaluación y diagnóstico fue realizado mediante estudios paraclínicos en sangre, orina, PCR e imágenes diagnósticas en 4 pacientes con diferentes comorbilidades y nexo epidemiológico presente para desarrollo de la enfermedad. Los cuatro casos fueron manejados con cloroquina 300 mg vía oral, cada 12 horas, y azitromicina 1 gr vía oral, cada 24 horas, durante 5 días, sin complicaciones ni toxicidad asociada. El caso 1 desarrolló falla orgánica múltiple, incluyendo injuria renal aguda con una estancia en UCI de 4 días antes de su fallecimiento, mientras los casos 2, 3 y 4 tuvieron una evolución favorable y fueron dados de alta de UCI. Se requieren estudios multicéntricos rápidos que orienten científicamente hacia un mejor abordaje diagnóstico y manejo, en el contexto de una enfermedad con un comportamiento clínico-epidemiológico que debe estudiarse en profundidad y que probablemente cobrará muchas vidas; además, debido a la ausencia de pruebas diagnósticas rápidas, la utilización de una clasificación basada en la severidad de lesiones radiológicas llamada CO-RADS (Covid-19 Imaging Reporting and Data System) podría ser de gran importancia para instalar de manera temprana los tratamientos farmacológicos disponibles y la asistencia respiratoria mecánica precoz.

Abstract To present a COVID-19 case series with clinical admission criteria to Intensive Care Unit. Patients information was obtained from medical records, and daily clinical evaluation whereas diagnosis was carried out through paraclinical studies in blood, urine, PCR and diagnostic images in 4 patients with different comorbidities and epidemiological link for the development of COVID-19. All four cases were managed with chloroquine 300 mg orally every 12 hours and azithromycin orally every 24 hours for 5 days without complications or associated toxicity. The case 1 developed multiple organ failure, including acute kidney injury with an ICU stay of 4 days before his death, while cases 2, 3 and 4 had a favorable evolution and were discharged from the ICU. Rapid multicenter studies are required to scientifically guide a better diagnostic and management approach, in the context of a disease with a clinical-epidemiological behavior that must be studied in depth and will probably take many lives. In addition, due to the absence of sufficiently rapid tests, the use of a classification based on the severity of radiological lesions called CO-RADS (Covid-19 Imaging Reporting and Data System) could be of great importance to install available pharmacological treatments early and early mechanical respiratory support.

The Importance of Tubular Function in Chronic Kidney Disease.

Glomerular filtration rate (GFR) and proteinuria-albuminuria are the renal functional parameters currently used to evaluate chronic kidney disease (CKD) severity. However, tubular secretion is another important renal functional parameter to be taken into account since proximal tubule (PT) secretion, in particular, is a crucial renal mechanism for endogenous organic cations, anions and drug elimination. The residual diuresis is a relevant survival predictor in patients on dialysis, since their urine is produced by the glomerular and tubular functions. It has been hypothesized that drugs which up-regulate some renal tubular transporters could contribute to uremic toxin excretion, and nephroprevention. However, if tubular transporters' down-regulation observed in CKD patients and experimental models is a PT adaptation to avoid intracellular accumulation and damage from uremic toxins, consequently the increase of toxin removal by inducing tubular transporters' up-regulation could be deleterious to the kidney. Therefore, a deeper understanding of this phenomenon is currently needed. In conclusion, tubular function has an important role for endogenous organic cations, anions and drug excretion in CKD patients, and a deeper understanding of its multiple mechanisms could provide new therapeutic alternatives in this population.

Trastorno por déficit de atención e hiperactividad (TDAH) en niños escolarizados de 6 a 17 años / Attention deficit hyperactivity disorder (ADHD) in schoolchildren aged 6 to 17 years

Objetivo: se buscó determinar la prevalencia del trastorno por déficit de atención e hiperactividad (TDAH) en niños de entre 6 a 17 años escolarizados en Barranquilla, para hacer una caracterización epidemiológica del trastorno en la región Caribe colombiana. Materiales y métodos: se tomaron 383 niños de una institución educativa a los que se les aplicaron pruebas de tamizaje (Checklist y BASC). Aquellos sujetos que registraron una puntuación sugestiva de alguna alteración fueron reprogramados para la realización de la evaluación por medio de la entrevista estructurada (MINI). Resultados: de los 383 sujetos evaluados inicialmente, 178 resultaron ser casos de algún tipo de alteración, de estos se confirmó que 59 (15%) tenían diagnóstico de TDAH, con una proporción de 38 varones y 21 mujeres, lo que arroja una relación 2:1, la distribución por subtipos se dio en 7,3% combinado, 5% inatento y 3,1% hiperactivo. En total, el 23% de los sujetos evaluados presentaron algún trastorno neuropsiquiátrico y se encontró una relación estadísticamente significativa entre el subtipo inatento con la agorafobia y los episodios depresivos, entre el subtipo hiperactivo con el trastorno oposicionista desafiante y el trastorno de angustia y entre la depresión y el riesgo de suicidio con el subtipo combinado. Conclusiones: la prevalencia del TDAH en Barranquilla presenta un comportamiento similar a otras regiones del país, tanto en la prevalencia como en la distribución por subtipos, relación por sexo, tipos de comorbilidades. Estos datos no están sujetos a factores psicosociales, lo que confirmaría la teoría de tener una etiología multifactorial

Objective: we aimed to establish the prevalence of attention-deficit hyperactivity disorder (ADHD) in schoolchildren aged 6 to 17 years in Barranquilla, to obtain an epidemiological perspective of this disorder in the Caribbean region of Colombia. Materials and methods: we selected 383 children enrolled in a single school and administered screening tests (symptoms checklist and BASC). In children with scores that suggested the presence of abnormalities, we scheduled another assessment by means of a structured interview (MINI). Results: of the 383 children that underwent the initial assessment, 178 exhibited abnormalities, of which 59 (15%) received a final diagnosis of ADHD (38 male and 21 women, corresponding to a 2:1 ratio). The distribution by subtypes was 7.3% combined, 5% inattentive and 3.1% hyperactive. Overall, 23% of the children in the sample had some form of neuropsychiatric disorder, and we found that the inattentive type was significantly associated with agoraphobia and episodes of depression and the hyperactive type with oppositional defiant disorder and anxiety disorder, while in the combined type, depression was associated with an increased risk of suicide. Conclusions: the prevalence of ADHD in Barranquilla was similar to the prevalence reported in other regions of Colombia, both overall and for each of the subtypes, and in its distribution by sex or comorbidities. These proportions were not associated to psychosocial factors, which supports the hypothesis of a multifactorial aetiology of ADHD

Impacto sobre la resistencia bacteriana de la revisión previa de la prescripción de antibióticos por el servicio farmacéutico en hospitales del Atlántico(Colombia) / Impact on the bacterial resistance of the previous revision of the prescription of antibiotics by the pharmaceutical service in hospitals of Atlántico (Colombia)

RESUMEN Objetivo: Determinar el impacto sobre la resistencia bacteriana de la revisión previa de la prescripción de antibióticos por parte del servicio farmacéutico en hospitales de mediana y alta complejidad del departamento del Atlántico (Colombia). Metodología: Se analizaron los valores de resistencia de bacterias Gram positivas, Enterobacterias y Gram negativos no fermentadores reportados en cinco institutos prestadores de salud (IPS) del departamento del Atlántico, en dos periodos (preintervención e intervención), de 12 meses cada uno, entre junio de 2015 y mayo de 2017. Resultados: Durante los dos periodos de estudio se identificaron 68 microorganismos en 8590 aislamientos microbiológicos provenientes de muestras de orina (40,3 %), sangre (21,7 %), tejidos (8,5 %) y otras (29,5 %). Los microorganismos aislados más frecuentemente fueron Escherichia coli (28,9 %), Staphylococcus coagulasa negativo (12,1%), Klebsiella pneumoniae (12,0 %), Pseudomonas aeruginosa (11,1 %) y Staphylococcus aureus (7,2 %). Durante los dos periodos la resistencia global osciló entre 27 y 40 %. Durante la Preintervención la resistencia osciló entre el 33 y el 39 %, mientras que durante la Intervención estuvo entre el 27 y 40 %. Al comparar los periodos de estudio solo hubo disminución significativa de la resistencia en los primeros nueve meses del periodo de intervención (p < 0.05). Conclusiones: Los valores de resistencia bacteriana reportados en el periodo de intervención fueron menores que en el periodo de preintervención. Se evidenció que la revisión previa de la prescripción por parte del servicio farmacéutico en las instituciones participantes influye en una disminución significativa de la resistencia bacteriana, pero que esta debe ser tanto continua como incremental.

ABSTRACT Objective: To determine the impact on bacterial resistance of the previous review of the prescription of antibiotics by the pharmaceutical service in medium and high complexity hospitals of the Department of Atlántico (Colombia). Methodology: Resistance values were analyzed for Gram-positive bacteria, Enterobacte-rial and non-fermenting Gram-negative bacteria reported in five health care institutions (IPS) of the Atlántico Department, in two periods (pre-intervention and intervention), of 12 months each between the months of June 2015 and May 2017. Results: During the two study periods, 68 microorganisms were identified in 8,590 microbiological isolates from urine samples (40.3 %), blood samples (21.7 %), tissues (8.5%) and others (29.5 %). The most frequently isolated microorganisms were Escherichia coli (28.9 %), Coagulase Negative Staphylococcus (12.1 %), Klebsiella pneumoniae (12.0 %), Pseudomonas aeruginosa (11.1 %) and S. aureus (7.2 %). During both periods the global resistance ranged between 27 and 40 %. During the Pre-intervention the resistance ranged between 33 and 39 %, while during the Intervention it was between 27 and 40 %. When comparing study periods, there was only significant decrease in resistance in the first nine months of the intervention period (p <0.05). Conclusions: the bacterial resistance values reported during the intervention period were lower than in the pre-intervention period. It was evidenced that the previous revision of the prescription by the pharmaceutical service in the participating institutions influences a significant decrease of the bacterial resistance; but that this must be both continuous and incremental.

Integrated analysis of microRNA regulation and its interaction with mechanisms of epigenetic regulation in the etiology of systemic lupus erythematosus.

The aim of this study was to identity in silico the relationships among microRNAs (miRNAs) and genes encoding transcription factors, ubiquitylation, DNA methylation, and histone modifications in systemic lupus erythematosus (SLE). To identify miRNA dysregulation in SLE, we used miR2Disease and PhenomiR for information about miRNAs exhibiting differential regulation in disease and other biological processes, and HMDD for information about experimentally supported human miRNA-disease association data from genetics, epigenetics, circulating miRNAs, and miRNA-target interactions. This information was incorporated into the miRNA analysis. High-throughput sequencing revealed circulating miRNAs associated with kidney damage in patients with SLE. As the main finding of our in silico analysis of miRNAs differentially expressed in SLE and their interactions with disease-susceptibility genes, post-translational modifications, and transcription factors; we highlight 226 miRNAs associated with genes and processes. Moreover, we highlight that alterations of miRNAs such as hsa-miR-30a-5p, hsa-miR-16-5p, hsa-miR-142-5p, and hsa-miR-324-3p are most commonly associated with post-translational modifications. In addition, altered miRNAs that are most frequently associated with susceptibility-related genes are hsa-miR-16-5p, hsa-miR-374a-5p, hsa-miR-34a-5p, hsa-miR-31-5p, and hsa-miR-1-3p.