Intravenous antibiotic therapy after laparoscopic appendectomy in acute complicated appendicitis: the patient clinical response is the key.

INTRODUCTION: The guidelines about acute complicated appendicitis (ACA) recommend 3-5 days of postoperative intravenous antibiotics (IVA). Nevertheless, the time selected by the surgeon can vary according to patient clinical response, ACA type, and professional experience. Once an adequate clinical response is obtained, the change from IVA to oral antibiotic (OA) could be realized without the waiting time established with satisfactory results. OBJECTIVE: Determine if a short course of IVA and/or switch to oral route is safe based on the patient clinical response. MATERIALS AND METHODS: Observational prospective cohort study from a general surgery reference center database since July 2019. RESULTS AND CONCLUSION: 48 patients with ACA intraoperative findings were included. Regarding postoperative antibiotic management, only preoperative IVA: 7 (14.58%), IVA 1-3 days: 1 (20.83%), IVA 1-3 days and change to OA: 21 (43.75%), IVA > 3 days: 6 (12.5%), and only OA: 3 (27.08%). The bivariate analysis did not show statistically significant differences in reconsultation (p = 0.81), rehospitalization (p = 0.44), and surgical site infection (p = 0.56) between the antibiotic scheme based on the postoperative clinical response and the traditional one regarding intra-abdominal collection rate, the hospital stays, and hospitalization costs.

INTRODUCTION: Las guías sobre apendicitis aguda complicada (ACA) recomiendan 3-5 días de antibióticos intravenosos (IVA) postoperatorios. No obstante, el tiempo seleccionado por el cirujano puede variar según la respuesta clínica del paciente, tipo de ACA y experiencia profesional. Una vez obtenida una adecuada respuesta clínica, el cambio de IVA a antibiótico oral (OA) podría realizarse sin esperar el tiempo establecido con resultados satisfactorios. OBJETIVO: Determinar si un ciclo corto de IVA y/o el cambio a OA según la respuesta clínica del paciente es seguro. MATERIALES Y MÉTODOS: Estudio observacional de cohorte prospectivo a partir de la base de datos de un centro de referencia en cirugía general desde julio del 2019. RESULTADOS Y CONCLUSIÓN: Se incluyeron 48 pacientes con hallazgos intraoperatorios de ACA. En cuanto al manejo antibiótico postoperatorio, solo IVA preoperatorio: 7 (14.58%), IVA 1-3 días: 1 (20.83%), IVA 1-3 días y cambio OA: 21 (43.75%), IVA > 3 días: 6 (12.5%) y solo OA: 3 (27.08%). El análisis bivariado no mostró diferencias estadísticamente significativas en la reconsulta (p = 0.81), la rehospitalización (p = 0.44) y la infección del sitio operatorio (p = 0.56) entre el esquema de antibióticos basado en la respuesta clínica postoperatoria y el tradicional con respecto a tasa de colección intrabdominal, estancia hospitalaria y costos de hospitalización.

A multi-centre randomized controlled trial investigating Consolidation Chemotherapy with and without oxaliplatin in distal rectal cancer and Watch & Wait.

BACKGROUND: Neoadjuvant chemoradiation(nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait-WW). Consolidation chemotherapy(cCT) regimens using fluoropyrimidine-based with or without oxalipatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCT compared to fluoropirimidine alone regimens in terms of primary tumor response remains unclear. Since oxalipatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine + oxaliplatin) for patients with distal rectal cancer. METHODS: In this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54 Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine + oxaliplatin. Magnetic resonance(MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1 cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy(RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) may be enrolled in an organ-preservation program(WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Secondary endpoints are 3-year surgery-free survival, TME-free survival, distant metastases-free survival, local regrowth-free survival and colostomy-free survival. DISCUSSION: Long-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05000697; registered on August 11th, 2021.

First-line biologic therapy with tumor necrosis factor inhibitors for psoriatic arthritis: a prospective observational study

ABSTRACT BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects multiple joints. It is associated with psoriasis and treated with synthetic and biologic drugs. OBJECTIVE: The objective of this study was to assess the outcomes of patients who received biologic therapy with tumor necrosis factor (TNF) inhibitors in terms of effectiveness, safety, functionality, and quality of life. DESIGN AND SETTING: A prospective observational study was performed at a single center in Belo Horizonte, Brazil. METHODS: Patients with PsA who received their first TNF inhibitor treatment were followed up for 12 months. Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease Activity Index (CDAI). Functionality was measured using the Health Questionnaire Assessment (HAQ), and quality of life was evaluated using the European Quality of Life Five Dimensions (EQ-5D). Multiple linear regression was used to identify predictors of the clinical response at 12 months. RESULTS: A total of 143 patients treated with adalimumab or etanercept were evaluated. Most of the clinical measures were significantly improved at 12 months. However, 31%-51% of the patients did not achieve good clinical control. No differences were observed between adalimumab and etanercept, except for poor functionality at 12 months among patients treated with etanercept. The main predictors of a worse clinical response were female sex, etanercept use, poor functionality, or lower quality of life at baseline. The main adverse reactions were alopecia, headache, injection site reaction, sinusitis, flu, dyslipidemia, and infections. CONCLUSION: TNF inhibitor therapy was effective and safe. However, despite improvements in clinical measures, most patients did not achieve satisfactory control of the disease.

Long-term outcomes of transanal endoscopic microsurgery for clinical complete response after neoadjuvant treatment in T2-3 rectal cancer.

BACKGROUND: Organ sparing by the transanal endoscopic microsurgery (TEM) procedure is a treatment for patients with locally advanced rectal cancer after chemoradiotherapy (CRT) and complete clinical response (cCR). AIMS: To assess the surgical and long-term oncological outcomes of TEM for the treatment in T2-3 rectal cancer after CRT and cCR. METHODS: This study was a retrospective review of a prospective database of patients with rectal cancer who underwent TEM after CRT and cCR from April 2011 to March 2020. RESULTS: 52 patients underwent TEM during a period of 9 years. This group of patients included 27 females and 25 males. The median age was 62 (32-86) years, lesion size was 2.5 (1-4) cm, and lesion distance from the anal verge 7.3 (4-10) cm. Median operative time was 79.5 (25-120) min and hospital stay was 1 day (14 h-4 days). Morbidity rate was 13.5% and reoperation rate due to major complications was 3.8%. Final histological findings confirmed 34 (65.4%) patients with ypT0, 7 (13.5%), 6 (11.5%), and 5 (9.6%) patients with carcinoma ypT1, ypT2, and ypT3, respectively. After a median follow-up period of 86 (5-107) months, 1 (2.4%) patient had local recurrences and 3 (7.3%) distant metastases. The 5-year disease-free survival was 91.7% and 5-year overall survival 89.5%. CONCLUSION: Our experience has shown significant rates of ypT0 and ypT1 associated with excellent long-term results. Performing TEM to treat T2-3N0 rectal cancer after CRT and cCR appears to be an oncologically safe and effective procedure.

Impact of treatment optimization in patients with gastroesophageal reflux disease who do not respond to esomeprazole / Impacto de la optimización del tratamiento en pacientes con enfermedad por reflujo gastroesofágico que no responden a esomeprazol

Abstract Introduction: gastroesophageal reflux disease (GERD) affects one out of eight people in Colombia. Its characteristic symptoms are heartburn and reflux. The cornerstone of treatment is proton pump inhibitors (PPIs), with a clinical response in 58-80% of patients. Of those who do not respond, 75-90% have a superimposed functional disorder and could be treated by adding visceral neuromodulators. Objective: to evaluate the impact of optimizing the treatment of patients with GERD when there is no response to esomeprazole (ESO). Materials and methods: a prospective study in patients with no clinical response (more than two reflux episodes per week) who were treated with 40 mg of ESO half an hour before breakfast along with the recommendation to lose weight if BMI >25, stop smoking and manage stress; and, finally, increasing the ESO dose to 40 mg on an empty stomach and before dinner. When all of this was done and symptoms persisted, 12.5 mg of amitriptyline were added at night. The response was evaluated every 12 weeks. Results: a total of 529 patients were eligible and 149 met the inclusion criteria. With treatment optimization, 111 patients had a clinical response without using amitriptyline (74.5%; 95%CI 67.2 81.4). Amitriptyline was added in 22 patients (14.8%), 15 of whom responded (68.2%; 95%CI 47.04-89.32%). Eight patients experienced drowsiness (53.3%). A relationship was found between PPI treatment compliance and clinical response (p<0.0001). Conclusions: in patients with GERD, PPI treatment optimization improves 74.5% (95%CI 67.2 81.4) of the patients, and adding amitriptyline for those who do not improve achieves improvement in 68.2% of those who did not improve with two doses of ESO. Sequential management achieved a cumulative improvement in symptom control in 85% (95%CI 78.6-90.4) of the patients. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.2041).

Resumen Introducción: la enfermedad por reflujo gastroesofágico (ERGE) afecta a una de cada ocho personas en Colombia. Sus síntomas característicos son pirosis y regurgitación. La piedra angular del tratamiento son los inhibidores de bomba de protones (IBP) con respuesta clínica en 58-80%. En quienes no responden 75-90% tienen un trastorno funcional superpuesto y se podrían tratar adicionando neuromoduladores viscerales. Objetivo: evaluar el impacto que tiene optimizar el tratamiento en pacientes con ERGE cuando no hay respuesta a esomeprazol (ESO). Material y métodos: estudio prospectivo en pacientes sin respuesta clínica (más de dos episodios de reflujo por semana) tratados con ESO 40 mg media hora antes del desayuno y simultáneamente recomendaciones para bajar de peso si IMC >25, dejar de fumar y controlar el estrés, y finalmente aumentado la dosis de ESO a 40 mg en ayunas y antes de la cena. Cuando se cumplió todo lo anterior y persistían los síntomas, se adicionó amitriptilina 12.5 mg por la noche. Cada 12 semanas se evaluaba la respuesta. Resultados: hubo 529 pacientes elegibles y 149 cumplieron los criterios de inclusión. Optimizando el tratamiento 111 pacientes tuvieron respuesta clínica sin la utilización de amitriptilina (74.5%; IC95% 67.2-81.4). En 22 se adicionó amitriptilina (14.8%) y de estos respondieron 15 pacientes, 68.2% (IC95% 47.04-89.32%). En ocho pacientes hubo somnolencia (53.3%). Se encontró relación entre el cumplimiento del tratamiento con IBP y la respuesta clínica (p<0.0001). Conclusiones: en pacientes con ERGE la optimización del tratamiento con IBP mejora el 74.5% (IC95% 67.2-81.4) de los pacientes y la adición de amitriptilina a quienes no mejoran, logra mejorar el 68.2% de quienes no mejoraban con dos dosis de ESO. Con el manejo secuencial se logró mejoría acumulativa en el control de los síntomas de 85% (IC95% 78.6-90.4) de los pacientes. (Acta Med Colomb 2021; 46. DOI:https://doi.org/10.36104/amc.2021.2041).

Clinical utility of ABCB1 and ABCG2 genotyping for assessing the clinical and pathological response to FAC therapy in Mexican breast cancer patients.

PURPOSE: Resistance to neoadjuvant chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in some patients with locally advanced breast cancer remains one of the main obstacles to first-line treatment. We investigated clinical and pathological responses to FAC neoadjuvant chemotherapy in Mexican women with breast cancer and their possible association with SNPs present in ABC transporters as predictors of chemoresistance. MATERIALS: A total of 102 patients undergoing FAC neoadjuvant chemotherapy were included in the study. SNP analysis was performed by RT-PCR from genomic DNA. Two SNPs were analyzed: ABCB1 rs1045642 (3435 C > T) and ABCG2 rs2231142 (421 G > T). RESULTS: In clinical response evaluation, significant associations were found between the ABCB1 C3435T genotype and breast cancer chemoresistant and chemosensitive patients (p < 0.05). In the early clinical response, patients with genotype C/C or C/T were more likely to be chemosensitive to neoadjuvant therapy than patients with genotype T/T (OR = 4.055; p = 0.0064). Association analysis between the ABCB1 gene polymorphism and the pathologic response to FAC chemotherapy showed that the C/C + C/T genotype was a protective factor against chemoresistance (OR = 3.714; p = 0.0104). Polymorphisms in ABCG2 indicated a lack of association with resistance to chemotherapy (p = 0.2586) evaluating the clinical or pathological response rate to FAC neoadjuvant chemotherapy. CONCLUSION: The early clinical response and its association with SNPs in the ABCB1 transporter are preserved until the pathological response to neoadjuvant chemotherapy; therefore, it could be used as a predictor of chemoresistance in locally advanced breast cancer patients of the Mexican population.

Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice.

PURPOSE: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. MATERIALS AND METHODS: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression. RESULTS: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001). CONCLUSION: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

Correlation of ultrasonography synovitis with disease activity and clinical response to etanercept treatment in juvenile idiopathic arthritis patients

This study aimed to investigate the correlation of ultrasonography (US) of synovitis with disease activity and clinical response to etanercept (ETN) in juvenile idiopathic arthritis (JIA) patients. Eighty-two JIA patients who underwent ETN treatment for 24 weeks were consecutively enrolled. US evaluations of 28 joints (shoulder, elbow, wrist, metacarpophalangeal, and proximal interphalangeal of hands and knee) at baseline were performed using grey-scale US and power doppler (PD) US, and US synovitis was defined as grey-scale abnormalities or PD abnormalities. Clinical response was assessed according to the ACRpedi 50 response criteria. In total, 2296 joints were scanned and 608 (26.5%) joints presented US synovitis, which was numerically higher than clinical synovitis (513 (22.3%)). The mean number of joints showing synovitis on US was 7.42±3.35, which was also numerically higher than that of clinical synovitis (6.26±2.70). The number of joints showing synovitis on US was positively correlated with C-reactive protein, erythrocyte sedimentation rate, number of joints with active disease, number of joints with limited range of motion, physician's global assessment of disease activity, parent/patient global assessment of overall well-being, and childhood health assessment questionnaire score. Most interestingly, the baseline number of joints showing synovitis on US was increased in ACRpedi 50 response JIA patients compared to non-response JIA patients, and it serves as an independent predictive factor for higher clinical response to ETN treatment. In conclusion, US is a more sensitive test to evaluate subclinical synovitis and disease activity in JIA patients, and US synovitis might serve as a marker for predicting increased clinical response rate to ETN treatment.

Efficacy of photobiomodulation on oral lichen planus: a protocol study for a double-blind, randomised controlled clinical trial.

INTRODUCTION: Oral lichen planus (OLP) is an idiopathic chronic mucocutaneous disease with a wide range of clinical manifestations, including white reticular patches, erosive/ulcerative and atrophic lesions, both associated with intense symptomatology. Topical corticosteroids are commonly used as standard therapy. However, patients frequently present relapses after the discontinuation of treatment as well as developing resistance to corticosteroid therapy. Photobiomodulation (PBM) has been shown to be a potential therapeutic tool to treat inflammatory disorders, including OLP. The aim of this study was to compare the efficacy of PBM (660 nm) with corticosteroid therapy with clobetasol propionate 0.05% for the treatment of OLP. METHODS AND ANALYSIS: Forty-four patients with symptomatic and histopathological diagnosis of OLP will be randomised into two experimental groups in a double-blind manner: control group (n=22): clobetasol propionate 0.05%+placebo PBM, and experimental group (n=22): PBM (λ=660 nm, power 100 mW, radiant exposure: 177 J/cm2 and 0.5J per point)+placebo gel. Laser will be applied 2×/week for 1 month and clobetasol propionate three times a day for 30 days and the same for placebo treatments. The primary variable (pain) and the secondary variables (clinical score, evaluation of functional scores, clinical resolution, OLP recurrence, quality of life and anxiety and depression) will be evaluated at the baseline, once a week during treatment (depending on the variables) and after 30 days and 60 days of follow-up. Pain will be evaluated using visual analogue scale and clinical characteristics will be scored using the Thongprasom Index. The quality of life and anxiety and depression will be evaluated by Oral Health Impact Profile-14 questionnaire and by Hospital Anxiety and Depression Scale for anxiety scale, respectively. The serum and salivary levels of interleukin (IL)-6, IL-10, IL-1ß, INF-γ and tumour necrosis factor-α will be evaluated by ELISA at baseline and at the end of treatment. ETHICS AND DISSEMINATION: This protocol was approved (#2.375.410) by the Nove de Julho University (UNINOVE) Research Ethics Committee. The data gathered using this protocol will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03320460.

Clinical and microbiological response of mice to intranasal inoculation with Lactococcus lactis expressing Group A Streptococcus antigens, to be used as an anti-streptococcal vaccine.

Protein subunit vaccines are often preferred because of their protective efficacy and safety. Lactic acid bacteria expressing heterologous antigens constitute a promising approach to vaccine development. However, their safety in terms of toxicity and bacterial clearance must be evaluated. Anti-Streptococcus pyogenes (S. pyogenes) vaccines face additional safety concerns because they may elicit autoimmune responses. The assessment of toxicity, clearance and autoimmunity of an anti-streptococcal vaccine based on Lactococcus lactis (L. lactis) expressing 10 different M protein fragments from S. pyogenes (L. lactis-Mx10) is here reported. Clearance of L. lactis from the oropharynges of immunocompetent mice and mice devoid of T/B lymphocytes mice was achieved without using antibiotics. The absence of autoimmune responses against human tissues was demonstrated with human brain, heart and kidney. Assessment of toxicity showed that leucocyte counts and selected serum biochemical factors were not affected in L. lactis-Mx10-immunized mice. In contrast, mice immunized with L. lactis wild type vector (L. lactis-WT) showed increased neutrophil and monocyte counts and altered histopathology of lymph nodes, lungs and nasal epithelium. Two days after immunization, L. lactis-Mx10-immunized and L. lactis-WT-immunized mice weighed significantly less than unimmunized mice. However, both groups of immunized mice recovered their body weights by Day 6. Our results demonstrate that L. lactis-WT, but not the vaccine L. lactis-Mx10, induces alterations in certain hematologic and histopathological variables. We consider these data a major contribution to data on L. lactis as a bacterial vector for vaccine delivery.

Predictors of Pathological Complete Response in Women with Clinical Complete Response to Neoadjuvant Chemotherapy in Breast Carcinoma.

OBJECTIVE: There is insufficient information on predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast carcinoma that also presented clinical complete response (cCR) evaluated in breast, axilla and breast and axilla. METHODS: This retrospective study included 310 women with breast carcinoma who received NAC from 1/1/13 to 12/31/15 with follow-up until 8/31/16. The factors analyzed to predict pCR and cCR were menopausal status, Ki67, estrogen receptor, histologic grade, molecular subtype, tumor size, axilla status, and stage. RESULTS: The cCR/pCR rates were 53.2/16.5% (breast), 76.3/36.8% (axilla) and 50.6/13.9% (breast and axilla). Molecular subtype and HER2-positive were independent predictors to confirm pCR in women with cCR, mainly triple negative (TN) in breast (OR 22.81, 95% CI 7.13-72.96) and breast and axilla (OR 36.06, 95% CI 8.77-148.26), but not in axilla. Ki67 ≥50% expression was predictor of cCR in breast (OR 2.00, 95% CI 1.31-3.06) and breast and axilla (OR 1.67, 95% CI 1.10-1.45). CONCLUSION: TN subtype and HER2-positive were the main independent predictors of pCR in women who also had cCR to NAC in breast and breast and axilla, but none was predictor in axilla. The Ki67 ≥50% was the independent predictor of cCR in breast and breast and axilla.

Desenlaces del manejo no quirúrgico posterior a neoadyuvancia del cáncer localmente avanzado de recto / Outcomes of the nonsurgical management of locally advanced rectal cancer after neoadjuvant treatment / Outcomesofthenon-surgicalmanagementoflocallyadvancedrectalcancerafterneoadjuvanttreatment

Objetivos: Describir características clínicas, histopatológicas y desenlaces de pacientes con cáncer localmente avanzado de recto y respuesta clínica completa posterior a la neoadyuvancia, sin manejo quirúrgico. Métodos: Estudio de cohorte retrospectiva de pacientes con cáncer de recto estadios II y III, llevados a quimiorradiación, en seguimiento clínico. Se evaluó supervivencia libre de enfermedad, global y tasa de recaída. Se describen características biológicas (Kras, Ki67, p53) y morfológicas del tumor (grado, invasión linfovascular y perineural). Resultados: Entre enero de 2003 y junio de 2013, 19 pacientes con cáncer localmente avanzado de recto y respuesta clínica completa postneoadyuvancia, no aceptaron el tratamiento quirúrgico radical. Con mediana de seguimiento de 21 meses (4-92 meses), se presentaron recaídas del: 21% en el primer año, 36% a los 3 años y 42% a los 5 años (total: 8 pacientes). Se presentó recaída local en 50% de casos, regional en 50% y no hubo recaída sistémica. La tasa estimada de recaída local fue 2,3 recaídas por 100 pacientes/mes (IC 95%:1,21-4,5) y de recaída regional 1,3 recaídas por 100 pacientes/mes (IC 95%:0,5-3,1). No se estableció relación, entre la expresión de factores biológicos del tumor primario y los desenlaces. Conclusiones: Se ratifica la indicación del tratamiento quirúrgico radical, posterior a la neoadyuvancia, en todos los pacientes con cáncer localmente avanzado de recto. Las bajas tasas de recaída local y regional de nuestra serie, sugieren la posibilidad de resección local u observación, en casos seleccionados. La individualización y deseo del paciente, debe orientar la toma de decisiones.

Objectives: To describe the clinical and histopathological characteristics and outcomes of patient with non-surgically managed locally advanced rectal cancer and a complete clinical response to neoadjuvant treatment. Methods: A retrospective study was conducted on a cohort of patients with stages II and III rectal cancer, on clinical follow up after subjected to chemoradiotherapy. The overall disease free survival and recurrence rates were evaluated. The biological (Kras, Ki67, p53) and morphological (grade, lymphovascular and perineural invasion) characteristics of the tumor were recorded. Results: Between January 2003 and June 2013, a total of 19 patients with locally advanced rectal cancer and a complete clinical response after neoadjuvant treatment, did not accept radical surgical treatment. With a median follow-up of 21 months (range 4-92 months), the recurrences were: 21% in the first year, 36% at 3 years, and 42% at 5 years (total: 8 patients). There was local recurrence in 50% of the cases, regional in 50%, and there were no systemic recurrences. The estimated local recurrence rate was 2.3 recurrences per 100 patients/month (95% CI; 1.21 - 4.5), and a regional recurrence of 1.3 recurrences per 100 patients/month (95% CI: 0.5 - 3.1). No relationship was found between the expression of biological factors of the primary tumor and the outcomes. Conclusions: The indication for radical surgical treatment after neoadjuvant treatment is demonstrated in all patients with locally advanced rectal cancer. The low local and regional recurrence rates of this series suggest the possibility of local resection or observation in selected cases. Individualization and the wishes of the patient must be taken into account when making decisions.

Staging and neuroprogression in bipolar disorder: a systematic review of the literature

INTRODUCTION: The use of clinical staging models is emerging as a novel and useful paradigm for diagnosing severe mental disorders. The term "neuroprogression" has been used to define the pathological reorganization of the central nervous system along the course of severe mental disorders. In bipolar disorder (BD), neural substrate reactivity is changed by repeated mood episodes, promoting a brain rewiring that leads to an increased vulnerability to life stress. METHOD: A search in the PubMed database was performed with the following terms: "staging", "neuroprogression", "serum", "plasma", "blood", "neuroimaging", "PET scan", "fMRI", "neurotrophins", "inflammatory markers" and "oxidative stress markers", which were individually crossed with "cognition", "functionality", "response to treatments" and "bipolar disorder". The inclusion criteria comprised original papers in the English language. Abstracts from scientific meetings were not included. RESULTS: We divided the results according to the available evidence of serum biomarkers as potential mediators of neuroprogression, with brain imaging, cognition, functioning and response to treatments considered as consequences. CONCLUSION: The challenge in BD treatment is translating the knowledge of neuronal plasticity and neurobiology into clinical practice. Neuroprogression and staging can have important clinical implications, given that early and late stages of the disorder appear to present different biological features and therefore may require different treatment strategies.

Antígenos de Plasmodium falciparum, blancos de la respuesta inmunitaria humoral en pacientes tratados con cloroquina / Antigens of Plasmodium falciparum, target of humoral immune response in patients treated with chloroquine

Se planteó identificar antígenos que pudieran ser reconocidos por los anticuerpos IgG1 e IgG3, descritos como protectores en la infección malárica, en personas con respuesta clínica adecuada (RCA) o falla al tratamiento (FT) antimalárico, provenientes de localidades con diferentes grados de endemicidad. Se evaluaron por Immunoblotting muestras de sueros de individuos provenientes de tres localidades del Edo. Amazonas (Venezuela): Puerto Ayacucho (Atures), San Juan de Manapiare (Manapiare) y Platanal (Alto Orinoco). La reactividad de IgG, IgG1 e IgG3 frente a componentes antigénicos del extracto de P. falciparum (FCB2), permitió identificar un mayor número de moléculas específicas en los pacientes con RCA que en los pacientes con FT. La frecuencia de reconocimiento de polipéptidos fue baja en las tres localidades, algunas moléculas con una frecuencia de reconocimiento igual o mayor al 20% pertenecían a sueros de individuos de las localidades de Puerto Ayacucho y Platanal, ambas con exposición permanente a P. falciparum. Dado el reconocimiento de polipéptidos por IgG, IgG1 e IgG3 en sueros de pacientes con RCA, estos podrían ser considerados como posibles blancos relevantes de la respuesta inmunológica protectora que coadyuven con el tratamiento antimalárico. Esto contribuiría al desarrollo y diseño de vacunas más efectivas, que prevengan la infección malárica y/o potencien la eficacia a la quimioterapia.

Here we studied the presence of antigens recognized by IgG1 and IgG3 antibodies, thought as protective, in patients with adequate clinical response (RCA) or treatment failure (FT), living in areas of different degrees of endemicity. Immunoblotting was evaluated from serum samples of individuals from three locations in the State Amazonas (Venezuela): Puerto Ayacucho (Atures), San Juan de Manapiare (Manapiare) and Pantanal (Alto Orinoco). The reactivity of IgG, IgG1 and IgG3 against antigenic components of the extract of P. falciparum (FCB2) identified a greater number of specific molecules in patients with RCA in patients with AFT. The frequency of recognition of polypeptides was low in all three locations, with some molecules having a recognition rate of greater than or equal to 20% sera of individuals belonging to the towns of Puerto Ayacucho and Platanal, both with cases of P. falciparum. Given the recognition of polypeptides by IgG, IgG1 and IgG3 in sera of patients with RCA, they could be considered as possible targets for relevant protective immune responses that contribute to malaria treatment. This would contribute to the development and design of more effective vaccines that prevent malaria infection and/or enhance the efficacy of chemotherapy.

HIV Genetic Diversity and Drug Resistance.

Most of the current knowledge on antiretroviral (ARV) drug development and resistance is based on the study of subtype B of HIV-1, which only accounts for 10% of the worldwide HIV infections. Cumulative evidence has emerged that different HIV types, groups and subtypes harbor distinct biological properties, including the response and susceptibility to ARV. Recent laboratory and clinical data highlighting such disparities are summarized in this review. Variations in drug susceptibility, in the emergence and selection of specific drug resistance mutations, in viral replicative capacity and in the dynamics of resistance acquisition under ARV selective pressure are discussed. Clinical responses to ARV therapy and associated confounding factors are also analyzed in the context of infections by distinct HIV genetic variants.