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 watch&wait (W&W) after neoadjuvant treatment in patients with rectal cancer / 中华放射肿瘤学杂志

Objective:To compare the outcomes of watch&wait (W&W) strategy in patients with locally advanced rectal cancer who achieved complete clinical response (cCR) after neoadjuvant therapy, with those who obtained pathological complete response (pCR) after total mesorectal excision (TME).Methods:This is a retrospective cohort analysis study. Patients histologically proven with locally advanced rectal adenocarcinoma (stage Ⅱ-Ⅲ) who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing neoadjuvant therapy and follow-up ≥1 year (W&W group), and patients who did not have cCR but pCR after TME (pCR group). The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (NR-DFS), and organ preservation rate. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM).Results:A total of 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (12.1-79.9 months). No difference was observed in the 3-year OS (97.1% vs. 96.7%) and 5-year OS (93.8% vs. 90.9%, P=0.696) between the W&W and pCR groups. Patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs. 43.5%, P<0.001), better 3-year DFS (83.6% vs. 97.0%) and 5-year DFS (83.6% vs. 91.2%, P=0.047) compared with those achieving pCR. The 3-year NR-DFS (95.9% vs. 97.0%) and 5-year NR-DFS (92.8% vs. 97.0%, P=0.407) did not significantly differ between the W&W and pCR groups. Local regeneration occurred in six cases, and 87.7% of patients had successful rectum preservation in the W&W group. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs. 26.5%, P<0.001) was noted in the W&W group. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19.0 vs. 9.8 weeks, P<0.001). Conclusions:The oncological outcomes of W&W strategy in patients with locally advanced rectal cancer are safe and effective, significantly improving the quality of life. Longer interval for cCR evaluation may improve rectal organ preservation rate.

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).

Variables Impacting Gfr Estimation Method For Drug Dosing In Ckd: Artificial Neural Network Prediction Model

Objective: This study aimed to measure concordance between different renal function estimates in terms of drug doses and determine the potential significant clinical differences. Methods: Around one hundred and eighty patients (≥ 18 y) with chronic kidney disease (CKD) were eligible for inclusion in this study. A paired-proportion cohort design was utilized using an artificial intelligence model. CKD patients refined into those who have drugs adjusted for renal function. For superiority of Cockcroft-Gault (CG) vs. modified diet in renal disease (MDRD) guided with references for concordance or discordance of the two equations and determined the dosing tiers of each drug. Validated artificial neural networks (ANN) was one outcome of interest. Variable impacts and performed reassignments were compared to evaluate the factors that affect the accuracy in estimating the kidney function for a better drug dosing. Results: The best ANN model classified most cases to CG as the best dosing method (79 vs. 72). The probability was 85% and the top performance was slightly above 93%. Creatinine levels and CKD staging were the most important factors in determining the best dosing method of CG versus MDRD. Ideal and actual body weights were second (24%). Whereas drug class or the specific drug was an important third factor (14%). Conclusion: Among many variables that affect the optimal dosing method, the top three are probably CKD staging, weight, and the drug. The contrasting CKD stages from the different methods can be used to recognize patterns, identify and predict the best dosing tactics in CKD patients.

Predictive Value of Serum Survivin Level for Clinical Efficacy of Tumor Necrosis Factor-α Inhibitor Treatment in Patients with Rheumatoid Arthritis / 中国医科大学学报

Objective To investigate the predictive value of serum survivin for clinical efficacy of tumor necrosis factor-α (TNF-α) inhibitor treatment in rheumatoid arthritis (RA) patients. Methods This study enrolled 63 consecutive patients with moderate or severe RA who received TNF-α inhibitor via subcutaneous injection 2 times/week, 25 mg/dose, for 24 weeks. According to disease activity, patients were also administered a disease-modifying antirheumatic drug. Serum survivin level was measured by enzyme-linked immunosorbent assay. The Disease Activity Score 28 was assessed, and clinical response and clinical remission were investigated. Results After treatment, 41 patients had a clinical response and 22 had no response. Baseline serum survivin level was reduced in the responder group compared to that in the non-responder group (P = 0.004). Receiver operating characteristic curve analysis showed that survivin level had good predictive value for non-response to TNF-α inhibitor treatment in RA patients (area under the curve:0.717, 95％ confidence interval:0.583-0.852). High survivin level (≥672.75 pg/mL) was an independent predictor of non-response to TNF-α inhibitor treatment in RA patients (P = 0.011), while a high C-reactive protein (CRP) level was an independent predictor of a better response to TNF-α inhibitor treatment (P = 0.011). High survivin level predicted non-response to TNF-α inhibitor treatment, independent of CRP level. However, baseline survivin level showed no difference between remission (16 cases) and non-remission groups (47 cases) (P = 0.265). A high survivin level did not affect remission in RA patients after TNF-α inhibitor treatment. Conclusion Baseline serum survivin level can predict the response of RA patients to TNF-α inhibitor treatment.

Transition of treatment strategy for locally advanced rectal cancer towards "watch and wait" / 中华胃肠外科杂志

Therapeutic goal for locally advance rectal cancer (LARC) patients includes long-term survival and function preservation of pelvic organs. During the recent two decades, treatment strategy for LARC is gradually shifing to minimally invasive surgery, even avoiding a major surgery. "Watch and wait (W&W)" strategy is effective in dramatically decreasing surgical trauma and significantly improving preservation of defecation, urination and sexual function. Total neoadjuvant therapy (TNT) shifts all or part of adjuvant chemotherapy to the neoadjuvant phase and has showed obvious advantage in tumor shrinkage and complete clinical response (cCR) achievement. This article will summarize the transition of treatment strategy of LARC towards W&W from standard treatment. After more than ten years of development, both NCCN and ESMO guidelines recommend stratified neoadjuvant treatment considerations based on distinct risk classifications and especially suggest TNT for LARC patients with advanced diseases, which affirms the value of TNT in tumor shrinkage. Although accumulating data show that pelvic control and organ preservation using W&W strategy after cCR is equal or non-inferior to standard surgery, impact on long-term survival still needs prospective randomized controlled study; no consensus has been achieved for the detail of the W&W strategy. Thus W&W strategy is suggested to applied in hospitals specialized in the treatment of rectal cancer within the framework of multiple disciplinary treatment. In view of special medical conditions of our country, we still need to accumulate more experience and data of W&W strategy for rectal cancer patients with appeals for sphincter preservation and actively participate in international researches.

Thoughts on prediction of pathological response and strategies of esophageal preservation in the era of neoadjuvant therapy for esophageal cancer / 中华消化外科杂志

In recent years,neoadjuvant treatment followed by esophagectomy has been the standard treatment strategy for locally advanced esophageal cancer.Pathological response,especially complete pathological response (pCR),indicates better overall survival.With respect to complete clinical response (cCR) after neoadjuvant treatment,some researchers propose that definitive chemoradiotherapy could be an alternative to esophageetomy.The authors analyze and summarize correlation between cCR and pCR,and survival benefits of watch and wait after cCR.The authors think cCR alone could not be the precondition for the debate,unless combined with an effective predition of pCR based on clinical and molecular biomarkers.In this way,a prudent selection of patients followed by optimal therapy could be an important direction of individual management for locally advanced esophageal cancer.

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.

Correlation of Serum Calprotectin Expression with Clinical Response in Juvenile Idiopathic Arthritis Patients Treated with a Tumor Necrosis Factor Inhibitor / 中国医科大学学报

Objective To investigate the correlation of serum calprotectin (MRP8/14) expression with clinical response in Chinese juvenile idiopathic arthritis (JIA) patients treated with a tumor necrosis factor (TNF) inhibitor.Methods Seventy-two JIA patients and 30 health volunteers (HCs) were enrolled in this prospective study.All JIA patients received etanercept for 24 weeks.Serum was collected from JIA patients at baseline before treatment and from HCs.Clinical response was defined according to the American College of Rheumatology (ACR) Pedi 50 criteria.Results Serum MRP8/14 expression was greater in JIA patients than in HCs (P ＜ 0.001).Serum MRP8/14 level was greater in responders than in non-responders (area under the receiver operating characteristic curve,0.823;95％ CI:0.706-0.939).Univariate and multivariate logistic analysis showed that high serum MRP8/14 expression was an independent predictive factor for clinical response (P =0.003).Conclusion Serum MRP8/14 level can be used as a convincing and novel biomarker for clinical response in JIA patients treated with a TNF inhibitor.

Axillary Lymph Node to Primary Breast Tumor Standardized Uptake Value Ratio from FDG-PET/CT Imaging for Predicting the Necessity for Nodal Dissection in Primary Breast Tumors

PURPOSE: Accurate preoperative detection by radiologic assessment is necessary to specifically identify patients with at least three positive nodes, who can directly undergo axillary lymph node (ALN) dissection, and avoid unnecessary surgical procedures. We evaluated the usefulness of the standardized uptake value (SUV) ratio of ALN in primary breast tumor, using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) and magnetic resonance imaging (MRI) to predict the necessity of ALN dissection during breast cancer surgery. METHODS: In this retrospective study we enrolled 316 consecutive patients with invasive breast cancer. The SUV ratio of ALN to primary breast tumor uptake was calculated. Optimal cutoff values were determined by receiver operating characteristic curve analysis for predicting the presence of ≥3 ALN metastases. Diagnostic performance of FDG-PET and MRI features for the prediction of ≥3 ALN metastases were determined by sensitivity, specificity, and diagnostic odds ratio (DOR). A subgroup analysis for FDG-avid tumors was also performed. RESULTS: Of the 316 patients, 36 (11.4%) showed involvement of ≥3 ALNs, with 101 (32%) having at least one metastatic lymph node. Axillary 18F-FDG uptake was positive in 75 patients (23.7%), and the optimal ratio of maximum SUV of axillary lymph node and primary tumor for determining ALN dissection was 0.3. MRI scans revealed suspicious ALN involvement in 147 patients (46.6%). The sensitivity and specificity of MRI detection were 88.9% and 56.2%, respectively, while for SUVLN/T ratio, they were 69.4% and 86.8%, respectively. DOR values for MRI and SUVLN/T ratio were 10.37 and 9.7, respectively. The area under the curve (AUC) was improved to 0.896 (95% confidence interval [CI], 0.817–0.975) for the SUVLN/T ratio in patients with FDG-avid primary tumors (FDG ≥3.9, n=108), but the MRI AUC was worsened (0.681; 95% CI, 0.569–0.793). The DOR, sensitivity, and specificity for the SUVLN/T ratio of FDG-avid cancers were 25.68, 89.0% and 86.0%, respectively. CONCLUSION: SUVLN/T ratio outperformed MRI features in predicting the need for ALN dissection in FDG-avid primary breast cancer. PET/CT may be a potential noninvasive diagnostic technique for identifying the presence of ≥3 ALN metastases.

Clinical Efficacy of Beclomethasone Dipropionate in Korean Patients with Ulcerative Colitis

PURPOSE: Our aim was to evaluate the efficacy and safety of oral beclomethasone dipropionate (BDP) in Korean patients with ulcerative colitis (UC). MATERIALS AND METHODS: The medical records of patients with active UC who were treated with BDP were retrospectively reviewed. Partial Mayo Clinic score (pMS) was calculated to determine disease activity. After 4 weeks of therapy, clinical remission, clinical response, and response failure rates were evaluated. Clinical remission was defined as a post-treatment pMS of 0 or 1, clinical response as a decrease of two of three points in pMS and >30% from baseline, and response failure as a lack of clinical response. Also, we considered that clinical remission was included in clinical response. RESULTS: Between July 2013 and April 2015, 95 patients with UC received BDP therapy at our institution (median age, 44 years; range, 12–81 years). After 4 weeks of therapy, clinical remission and clinical response rates were 50.5% and 73.7%, respectively. Mean change of pMS before and after BDP therapy was 2.4. There was no significant side effect reported. In multivariate analysis, disease activity was the only factor associated with a favorable response. Clinical remission rate was significantly higher in the mild disease activity group (66.7%) than that in the moderate or severe disease activity group (41.9%) (p=0.024). CONCLUSION: BDP is efficacious in inducing a clinical response or remission in Korean patients with UC. Patients with mild UC were more likely to be in remission than those with moderate or severe UC after receiving BDP for 4 weeks. BDP exhibited a good safety profile.

Clinical Response to Valproate in Patients with Migraine

BACKGROUND AND PURPOSE: Valproate is used as a prophylactic drug for migraine, but it is not be effective in all patients. We used medical records to investigate which clinical factors affected the response to valproate in patients with migraine as an original headache, and established a scoring system for predicting the clinical response to prophylactic therapy. METHODS: We investigated clinical factors from the medical records of 95 consistent responders (CRs) and 24 inconsistent responders (IRs) to valproate. RESULTS: Multivariate stepwise logistic regression analysis revealed that a history of hyperlipidemia and hay fever and the complication of depression or other psychiatric disorder were significant factors that independently contributed to a negative response, with odds ratios of 6.024 [no vs. yes; 95% confidence interval (CI)=1.616–22.222], 2.825 (no vs. yes; 95% CI=1.046–7.634), and 2.825 (no vs. yes; 95% CI=1.052–7.576), respectively. A predictive index (PI) of the clinical response to valproate in patients with migraine was calculated using the regression coefficients of these three factors as an integer, and the index was significantly higher for IRs than for CRs (1.46±1.10 vs. 0.69±0.74, mean±SD, p<0.001). CONCLUSIONS: The obtained PI may represent an appropriate scoring system for predicting the responses in these patients.

Association of blood lipid with distant metastases and clinical response in patients with hormone receptor negative breast cancer / 实用肿瘤学杂志

Objective To investigate the relationship between dyslipidemia and distant metastases in pa-tients with hormone receptor( HR) negative breast cancer,and to explore the impact of blood lipid change during chemotherapy on clinical response.Methods We collected the complete clinicopathological data and fasting blood lipid in 154 patients with HR negative breast cancer.The secondary blood lipid level were measured on day14 after two cycles of chemotherapy in patients with distant metastases.Single factor chi -square test was choosen to analyze the relationship between clinicopathological characteristics,including baseline lipid level,and distant metastases,then independent risk factor for distant metastases were evaluated by logistic regression model. Data about altered blood lipid and clinical response analysis were performed using paired t-test pre-or post-chemotherapy.Results Our results from single chi-square test showed that distant metastasis from breast canc-er was significantly associated with tumor size,local lymph node metastases,grade,higher total cholesterol( TC) , higher triglycerides(TG)and higher low-density lipoprotein(LDL)(P<0.05).For distant metastases,inde-pendent risk factors were tumor size(OR=1.563),local lymph node metastases(OR=1.983),higher TC(OR=1.502),higher TG(OR=1.877).Decreased trend of TC,TG and LDL and increased trend of HDL were showed in disease control( PR+SD) group,and TG had significantly tend in objective response( PR) group.Conclusion Hyperlipidmia is significantly associated with distant metastases in patients with HR negative breast cancer,andblood lipid levels decrease with effective anti -tumor chemotherapy.Dynamic monitoring of blood lipid levelscould be a candidate surrogate biomarker for outcome prediction and distant metastases in patients with HR negativebreast cancer.

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.

Histopathologic changes following neoadjuvant chemotherapy in locally advanced breast cancer.

Aims: To compare the clinical and pathologic assessment of response to neoadjuvant chemotherapy and describe the various histopathologic changes observed. Materials and Methods: We studied a group of 40 patients with locally advanced breast cancer who had their initial workup in the form of clinico-imaging assessment of the size and pretreatment biopsy from the lesion. All the patients received two to six cycles of neoadjuvant chemotherapy, either cyclophosphamide 50 to 60 mg/m 2 IV, doxorubicin 40 to 50 mg/m 2 IV and 5-fluorouracil 500 to 800 mg/m 2 IV (CAF) or cyclophosphamide, epirubicin, and 5-fluorouracil (CEF). Clinical and pathologic assessment of response to chemotherapy was done based on the UICC guidelines. Result: Complete clinical response (cCR) was seen in 10% cases (4/40), thirty percent patients had (12/40) partial response and 60% (24/40) had stable disease after neoadjuvant chemotherapy. Pathologic complete response (pCR) with no evidence of viable tumor was observed in 20% patients (8/40). Fifteen patients (37.5%) showed partial response and 42.5% patients (17/40) had a stable disease. No patient progressed during the course of chemotherapy. Changes in the tumor type were observed following chemotherapy, most common being the mucinous change. Histologic changes like dyscohesion, shrinkage of tumor cells, elastosis, collagenization, necrosis, lymphocytic reaction, giant cell response are some of the common observations seen following treatment with neoadjuvant chemotherapy. Conclusion: Pathologic assessment of response to neoadjuvant chemotherapy is a better predictor than the clinical response. The chemotherapy drugs can be modified based on the response observed after 1-2 cycles of neoadjuvant, the response being based on both tumor and patient's responsiveness.

Outcomes of the Early Psychosis Intervention Programme (EPIP) Singapore

Psychoses are serious and potentially chronic mental disorders with a profound impact, in terms of economic cost and human suffering, on patients, their families and society. Early detection and treatment, through reducing the duration of untreated psychosis, however, could lead to a better outcome. In 2001, the Early Psychosis Intervention Programme (EPIP), Singapore was started with the following key strategies: (1) early detection of psychosis through outreach to and network with the community and our partners; (2) provision of clinical treatment that is evidence-based; and (3) conducting clinically relevant research to evaluate our service to be accountable to the stake-holders and to ensure cost-effectiveness. A myriad of structure, process and outcome measures offering a multi-dimensional evaluation were chosen to make us accountable to a broad range of stakeholders, from our funders, other service providers, to our patients and their families. EPIP has shown good outcomes in terms of number of patients accepted into the programme, as well as our clinical service provision. Such outcomes are achieved with our community partners playing an important role. General Practitioners, in particular, are vital not only in the detection, management of such individuals, but also in the re-integration of our patients back to community.

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.

Assessment of clinical and laboratory parameters that reflect inflammatory response and organ function in sepsis.

Sepsis is a spectrum of clinical conditions caused by the host immune response to infection or other inflammatory stimuli characterized by systemic inflammation. Clinical response to sepsis could be varies according to compensate or decompensate state, inflammatory process and host condition. Aims of this study is to assess the role of some parameters (clinical and biochemical, hematology, arterial blood gas analysis and coagulation) in supporting the diagnosis of sepsis. A cross-sectional study was performed in the Internal Medicine Inpatient Unit of Dr. Cipto Mangunkusumo National General Hospital, Jakarta, from February to July 2002. Forty-two patients who fulfilled the criteria of sepsis, severe sepsis, and septic shock were enrolled in this study. Clinical details and blood specimens for hematological, biochemical, arterial blood gas analysis and coagulation were collected. There were 42 subjects who participated in the study, aged from 19 to 78 years old. Eleven subjects fulfilled the criteria for early sepsis, 20 severe sepsis and 11 septic shock. Clinical examination showed that the Glasgow coma scale (GCS) was significantly reduced in severe sepsis and septic shock. Heart rate, respiration rate and body temperature were increased in all groups. Hemoglobin levels mostly below 10 g/dl and hematocrite levels below 30 %. The leucocyte counts were increased in more than 80%, mostly above 15.000/mm3. The platelet count were low (below 50.000/mm3) especially in septic shock. The serum creatinine were significantly increased (>2 mg/dl) in severe sepsis and septic shock. Albumin was decreased, lactate dehydrogenase/LDH and procalcitonin were increased. The arterial blood gas analysis showed that: pH and HCO3 were decreased especially in septic shock; the PO2 was lower in severe sepsis and septic shock; and PCO2 was below 32 mmHg in all groups. Coagulation examinations showed that fibrinogen was significantly decreased in septic shock; PT and APTT were prolong in severe sepsis and septic shock more than 18.8 and 48 seconds respectively. The d-dimer was also increased mostly in all groups. In conclusions that clinical examinations include level of consciousness, heart rate, mean arterial pressure, temperature and respiration rate and additional laboratory examinations include hamatological, biochemical, blood gas analysis and coagulation examinations can be used as parameters in diagnosis of sepsis. Some parameters include level of consciousness (Glasgow coma scale), serum creatinine, hemoglobin, platelet count and fibrinogen can differ sepsis according to severity.

Neoadjuvant Chemotherapy for the Local Advanced Breast Cancer / 한국유방암학회지

PURPOSE: The definition of locally advanced breast cancer (LABC) includes stage III breast cancer. In order to investigate the factors influencing on the final outcome we analysed the data of LABC patients that received neoadjuvant chemotherapy prior to definitive surgery. METHODS: 122 LABC patients, who underwent neoadjuvant chemotherapy between 1980 and 1997, were included for the analysis. Clinical responses to neoadjuvant chemother apy were classified as complete response (CR), partial response (PR), and no response (NR). Overall survival (OS), Loco-regional relapse free survival (LRRFS), and distant relapse free survival (DRRFS) probabilities were investigated according to initial clinical stage, clinical response to neoadjuvant chemotherapy, and pathologic stage after neo adjuvant chemotherapy. Statistical analyses were performed with chi2-test, Kaplan-Meier, and Cox-regression methods using SPSS. RESULTS: The mean age at diagnosis was 47 years old (range 31~73) and median follow-up period was 61.6 months (range 3~227 months). Among 122 LABC patients, 69 (56.6%) were included in stage IIIA, 37 (30.3%) in stage IIIB, and 16 (13.1%) in IIIC at diagnosis. 10 patients (8.2%) have shown CR, 85 (69.7%) patients PR, and the remaining 27 (22.1%) patients showed NR. The overall response rate to neoadjuvant chemotherapy was 77.5%. However, only 51 (41.8%) were demonstrated to have pathologically down-staged results. There were 32 loco-regional recurrences and 59 distant metastases. All of the initial clinical stage, clinical response to neoadjuvant chemotherapy, and pathologic stage influenced the final outcome of 10 year OS, LRRFS, DRFS. However, in multivariate analysis pathologic stage after neoadjuvant chemotherapy was the most influencing factor on the final outcome. CONCLUSION: Pathologic stage after neoadjuvant chemotherapy could be the most important prognostic factor of the LABC.