Diagnostic performance of machine learning models using cell population data for the detection of sepsis: a comparative study.

OBJECTIVES: To compare the artificial intelligence algorithms as powerful machine learning methods for evaluating patients with suspected sepsis using data from routinely available blood tests performed on arrival at the hospital. Results were compared with those obtained from the classical logistic regression method. METHODS: The study group consisted of consecutive patients with fever and suspected infection admitted to the Emergency Department. The complete blood counts (CBC) were acquired using the Mindray BC-6800 Plus analyser (Mindray Diagnostics, Shenzhen, China). Cell Population Data (CPD) were also recorded. The ML and artificial intelligence (AI) models were developed; their performance was evaluated using several indicators, such as the area under the receiver operating curve (AUC), calibration plots and decision curve analysis (DCA). RESULTS: Overall, all the tested approaches obtained an AUC>0.90. The logistic regression (LR) performed well compared to the ML/AI models. The naïve Bayes and the K-nearest neighbour (KNN) methods did not show good calibration properties. The multi-layer perceptron (MLP) model was the best in terms of discrimination, calibration and clinical usefulness. CONCLUSIONS: The best performance in the early detection of sepsis was achieved using the ML and AI models. However, external validation studies are needed to strengthen model derivation and procedure updating.

Five-year follow-up mortality prognostic index for colorectal patients.

PURPOSE: To identify 5-year survival prognostic variables in patients with colorectal cancer (CRC) and to propose a survival prognostic score that also takes into account changes over time in the patient's health-related quality of life (HRQoL) status. METHODS: Prospective observational cohort study of CRC patients. We collected data from their diagnosis, intervention, and at 1, 2, 3, and 5 years following the index intervention, also collecting HRQoL data using the EuroQol-5D-5L (EQ-5D-5L), European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Multivariate Cox proportional models were used. RESULTS: We found predictors of mortality over the 5-year follow-up to be being older; being male; having a higher TNM stage; having a higher lymph node ratio; having a result of CRC surgery classified as R1 or R2; invasion of neighboring organs; having a higher score on the Charlson comorbidity index; having an ASA IV; and having worse scores, worse quality of life, on the EORTC and EQ-5D questionnaires, as compared to those with higher scores in each of those questionnaires respectively. CONCLUSIONS: These results allow preventive and controlling measures to be established on long-term follow-up of these patients, based on a few easily measurable variables. IMPLICATIONS FOR CANCER SURVIVORS: Patients with colorectal cancer should be monitored more closely depending on the severity of their disease and comorbidities as well as the perceived health-related quality of life, and preventive measures should be established to prevent adverse outcomes and therefore to ensure that better treatment is received. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02488161.

Influence of depression on survival of colorectal cancer patients drawn from a large prospective cohort.

OBJECTIVE: The prevalence of depressive symptoms immediately after the diagnosis of colorectal cancer (CRC) is high and has important implications both psychologically and on the course of the disease. The aim of this study is to analyse the association between depressive symptoms and CRC survival at 5 years after diagnosis. METHODS: This multicentre, prospective, observational cohort study was conducted on a sample of 2602 patients with CRC who completed the Hospital Anxiety and Depression Scale (HADS-D) at 5 years of follow-up. Survival was analysed using the Kaplan-Meier method and Cox regression models. RESULTS: According to our analysis, the prevalence of depressive symptoms after a CRC diagnosis was 23.8%. The Cox regression analysis identified depression as an independent risk factor for survival (HR = 1.47; 95% CI: 1.21-1.8), a finding which persisted after adjusting for sex (female: HR = 0.63; 95% CI: 0.51-0.76), age (>70 years: HR = 3.78; 95% CI: 1.94-7.36), need for help (yes: HR = 1.43; 95% CI: 1.17-1.74), provision of social assistance (yes: HR = 1.46; 95% CI: 1.16-1.82), tumour size (T3-T4: HR = 1.56; 95% CI: 1.22-1.99), nodule staging (N1-N2: HR = 2.46; 95% CI: 2.04-2.96), and diagnosis during a screening test (yes: HR = 0.71; 95% CI: 0.55-0.91). CONCLUSIONS: There is a high prevalence of depressive symptoms in patients diagnosed with CRC. These symptoms were negatively associated with the survival rate independently of other clinical variables. Therefore, patients diagnosed with CRC should be screened for depressive symptoms to ensure appropriate treatment can be provided.

Anxiety, depression, health-related quality of life, and mortality among colorectal patients: 5-year follow-up.

PURPOSE: Health-related quality of life (HRQoL) measurement represents an important outcome in cancer patients. We describe the evolution of HRQoL over a 5-year period in colorectal cancer patients, identifying predictors of change and how they relate to mortality. METHODS: Prospective observational cohort study including colorectal cancer (CRC) patients having undergone surgery in nineteen public hospitals who were monitored from their diagnosis, intervention and at 1-, 2-, 3-, and 5-year periods thereafter by gathering HRQoL data using the EuroQol-5D-5L (EQ-5D-5L), European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Multivariable generalized linear mixed models were used. RESULTS: Predictors of Euroqol-5D-5L (EQ-5D-5L) changes were having worse baseline HRQoL; being female; higher Charlson index score (more comorbidities); complications during admission and 1 month after surgery; having a stoma after surgery; and needing or being in receipt of social support at baseline. For EORTC-QLQ-C30, predictors of changes were worse baseline EORTC-QLQ-C30 score; being female; higher Charlson score; complications during admission and 1 month after admission; receiving adjuvant chemotherapy; and having a family history of CRC. Predictors of changes in HADS anxiety were being female and having received adjuvant chemotherapy. Greater depression was associated with greater baseline depression; being female; higher Charlson score; having complications 1 month after intervention; and having a stoma. A deterioration in all HRQoL questionnaires in the previous year was related to death in the following year. CONCLUSIONS: These findings should enable preventive follow-up programs to be established for such patients in order to reduce their psychological distress and improve their HRQoL to as great an extent as possible. GOV IDENTIFIER: NCT02488161.

Effect of comorbidities on long-term outcomes of colorectal cancer patients.

OBJECTIVE: The objective of this work is to evaluate the association of comorbidities with various outcomes in patients diagnosed with colon or rectal cancer. METHODS: We conducted a prospective cohort study of patients diagnosed with colon or rectal cancer who underwent surgery. Data were gathered on sociodemographic, clinical characteristics, disease course, and the EuroQol EQ-5D and EORTC QLQ-C30 scores, up to 5 years after surgery. The main outcomes of the study were mortality, complications, readmissions, reoperations, and changes in PROMs up to 5 years. Multivariable multilevel logistic regression models were used in the analyses. RESULTS: Mortality at some point during the 5-year follow-up was related to cardiocerebrovascular, hemiplegia and/or stroke, chronic obstructive pulmonary disease (COPD), diabetes, cancer, and dementia. Similarly, complications were related to cardiovascular disease, COPD, diabetes, hepatitis, hepatic or renal pathologies, and dementia; readmissions to cardiovascular disease, COPD, and hepatic pathologies; and reoperations to cerebrovascular and diabetes. Finally, changes in EQ-5D scores at some point during follow-up were related to cardiocerebrovascular disease, COPD, diabetes, pre-existing cancer, hepatic and gastrointestinal pathologies, and changes in EORTC QLQ-C30 scores to cardiovascular disease, COPD, diabetes, and hepatic and gastrointestinal pathologies. CONCLUSIONS: Optimising the management of the comorbidities most strongly related to adverse outcomes may help to reduce those events in these patients.

Leukocyte differential and reactive lymphocyte counts from Sysmex XN analyzer in the evaluation of SARS-CoV-2 infection.

BACKGROUND: Leukocyte differential present certain features in COVID 19 patients. RE-LYMP (reactive lymphocytes) is an extended inflammation parameter (EIP) reported by XN analyzer (Sysmex Corporation, Kobe, Japan) reflect the activation of lymphocytes triggered by infections. We aimed to assess the clinical utility of these parameters as biomarkers for the rapid detection of COVID 19. METHODS: The study group included 200 COVID 19 and 167 patients with other infections at admission. Differences of leukocyte differential, neutrophil/lymphocyte ratio (NLR) and EIP among groups were assessed with the Kruskal-Wallis test; parameters statiscally different in the groups were tested with Receiver operating characteristic (ROC) curve analysis to assess their diagnostic performance in distinguishing SARS-CoV-2 infections. The reliability of the selected parameters was evaluated in a validation group of 347 patients (160 COVID 19 and 187 other infections). RESULTS: NLR performed well to discard viral infections, area under curve (AUC) 0.988 (95%CI 0.973 - 0.991) and RE-LYMP was useful to distinguish COVID 19 and bacterial infections AUC 0.920 (95%CI 0.884 - 0.948); the two conditions NLR> 3.3 RE-LYMP> 0.6% was applied to the validation group and 153 out of 160 COVID 19 patients were correctly distinguished (95.6%). CONCLUSIONS: Early diagnosis of SARS-CoV-2 infection is critical for better caring of patients and to reduce the threat of nosocomial infection for professionals. Leukocyte differential and RE-LYMPH could assist in a preliminary differential diagnosis of the disease.

Risk scores to predict mortality 2 and 5 years after surgery for colorectal cancer in elderly patients.

BACKGROUND: The aim of this study was to identify predictors of mortality in elderly patients undergoing colorectal cancer surgery and to develop a risk score. METHODS: This was an observational prospective cohort study. Individuals over 80 years diagnosed with colorectal cancer and treated surgically were recruited in 18 hospitals in the Spanish National Health Service, between June 2010 and December 2012, and were followed up 1, 2, 3, and 5 years after surgery. Sociodemographic and clinical data were collected. The primary outcomes were mortality at 2 and between 2 and 5 years after the index admission. RESULTS: The predictors of mortality 2 years after surgery were haemoglobin ≤ 10 g/dl and colon locations (HR 1.02; CI 0.51-2.02), ASA class of IV (HR 3.55; CI 1.91-6.58), residual tumour classification of R2 (HR 7.82; CI 3.11-19.62), TNM stage of III (HR 2.14; CI 1.23-3.72) or IV (HR 3.21; CI 1.47-7), LODDS of more than - 0.53 (HR 3.08; CI 1.62-5.86)) and complications during admission (HR 1.73; CI 1.07-2.80). Between 2 and 5 years of follow-up, the predictors were no tests performed within the first year of follow-up (HR 2.58; CI 1.21-5.46), any complication due to the treatment within the 2 years of follow-up (HR 2.47; CI 1.27-4.81), being between 85 and 89 and not having radiotherapy within the second year of follow-up (HR 1.60; CI 1.01-2.55), no colostomy closure within the 2 years of follow-up (HR 4.93; CI 1.48-16.41), medical complications (HR 1.61; CI 1.06-2.44), tumour recurrence within the 2 years of follow-up period (HR 3.19; CI 1.96-5.18), and readmissions at 1 or 2 years of follow-up after surgery (HR 1.44; CI 0.86-2.41). CONCLUSION: We have identified variables that, in our sample, predict mortality 2 and between 2 and 5 years after surgery for colorectal cancer older patients. We have also created risks scores, which could support the decision-making process. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02488161 .

Gender differences in stage at diagnosis and preoperative radiotherapy in patients with rectal cancer.

BACKGROUND: Few studies have examined gender differences in the clinical management of rectal cancer. We examine differences in stage at diagnosis and preoperative radiotherapy in rectal cancer patients. METHODS: A prospective cohort study was conducted in 22 hospitals in Spain including 770 patients undergoing surgery for rectal cancer. Study outcomes were disseminated disease at diagnosis and receiving preoperative radiotherapy. Age, comorbidity, referral from a screening program, diagnostic delay, distance from the anal verge, and tumor depth were considered as factors that might explain gender differences in these outcomes. RESULTS: Women were more likely to be diagnosed with disseminated disease among those referred from screening (odds ratio, confidence interval 95% (OR, CI = 7.2, 0.9-55.8) and among those with a diagnostic delay greater than 3 months (OR, CI = 5.1, 1.2-21.6). Women were less likely to receive preoperative radiotherapy if they were younger than 65 years of age (OR, CI = 0.6, 0.3-1.0) and if their tumors were cT3 or cT4 (OR, CI = 0.5, 0.4-0.7). CONCLUSIONS: The gender-specific sensitivity of rectal cancer screening tests, gender differences in referrals and clinical reasons for not prescribing preoperative radiotherapy in women should be further examined. If these gender differences are not clinically justifiable, their elimination might enhance survival.

Factors associated with colon cancer early, intermediate and late recurrence after surgery for stage I-III: A 5-year prospective study.

OBJECTIVE: To identify factors associated with early, intermediate or late recurrence colon cancer recurrence. METHODS: A total of 1,732 consecutive patients with colon cancer were recruited and followed for a period of 5 years. Recurrence at 1 year (early), from 1 to 2 (early), from 2 to 3 (intermediate) and from 3 to 5 years (late) was the main outcome measures. RESULTS: Predictors of early recurrence (AUC (95% CI):0.74 (0.70-0.78) were as follows: TNM stage II and III, more than one type of invasion, haemoglobin <10 g/dl, residual tumour (R1), ASA IV, log odds of positive lymph nodes ratio ≥-0.53, perforation, neoadjuvant chemotherapy, infectious complications within 1 year and CEA pre- and post-intervention. These factors remained significant for predicting intermediate (AUC [95% CI]: 0.72 [0.67-0.77]) and late (AUC [95% CI]: 0.68 [0.63-0.74]) recurrence, except for ASA class, log lymph node ratio, perforation and neoadjuvant chemotherapy. Additionally, laterality (left) and medical complications up to 2 years were significant. CONCLUSIONS: These risk factors show good predictive ability of early, intermediate and late recurrence, confirming factors established by guidelines and adding some others. They could serve to provide more appropriate and accurate treatment and follow-up tailored to patient characteristics.

Gastrointestinal infection with Aeromonas: incidence and relationship to inflammatory bowel disease. / Infección gastrointestinal por Aeromonas: incidencia y su posible relación con la enfermedad inflamatoria intestinal.

INTRODUCTION: Aeromonas can cause several diseases in humans, with gastroenteritis accounting for most cases. The role of Aeromonas as a pathogen in human enterocolitis has been questioned in recent years. OBJECTIVE: To determine the incidence of gastrointestinal infection caused by Aeromonas in our area and its possible relationship to inflammatory bowel disease. PATIENTS AND METHODS: This was a retrospective observational study. All adult patients with a positive stool culture for Aeromonas were identified between January 2015 and December 2017 at Hospital Galdakao-Usansolo (Vizcaya, Spain). RESULTS: Ninety-eight patients were identified (median age 62 years; 51% women). Therefore, the incidence in our area was 32 cases per 105 inhabitants per year. Eleven per cent of them had been previously diagnosed with inflammatory bowel disease (four with ulcerative colitis and seven with Crohn's disease). Patients with inflammatory bowel disease more often received immunosuppressive therapy. Conversely, patients without inflammatory bowel disease suffered from more comorbidities. We also found comorbidity to be the risk factor most associated with Aeromonas infection. CONCLUSION: Aeromonas infection is a common gastrointestinal infection that may occur in both immunocompetent and immunocompromised patients. Immunosuppression is a significant factor in inflammatory bowel disease patients, while comorbidity seems to confer a higher risk on patients without this disease.

Revision hip arthroplasty with a rectangular tapered cementless stem: a retrospective study of the SLR-Plus stem at a mean follow-up of 4.1 years.

PURPOSE: Demand for revision total hip arthroplasty (THA) is growing, and this type of surgery remains challenging for orthopedic surgeons. Our objectives were to assess clinical and radiographic outcomes, survivorship and complications with the SLR-Plus stem in revision THA. METHODS: We retrospectively reviewed 65 patients (66 hips) who had undergone revision THA with the SLR-Plus stem between 2008 and 2015 at two medical institutions with a minimum 2-year follow-up. The clinical outcome was assessed using the Harris hip score and the Merlé D'Aubigné score preoperatively and at final follow-up. A postoperative visual analogue scale for pain and satisfaction was also used. Radiographic subsidence and fixation, Kaplan-Meier survivorship and complications were analyzed. RESULTS: The mean follow-up was 4.1 years (SD 2.1). Aseptic loosening (57.6%) was the main indication for surgery. The mean Harris Hip Score improved from 50.4 (SD 16.5) to 83 (SD 12.7) (p < 0.001) and mean Merlé D'Aubigné score improved from 9.5 (SD 2.7) to 14.3 (SD 2.2) (p < 0.001). A total of 98.4% of stems showed radiographically stable fixation. No aseptic loosening of the stem was seen. Radiolucent lines > 1 mm were observed in 33.3% of stems. Three stems were re-revised: two due to infection and one due to instability. At 7 years, estimated stem survival was 95.5% for revision for any reason and 100% for revision for aseptic loosening. Dislocation occurred in 7.6% of hips. CONCLUSION: We have shown significant clinical improvement, 98.4% of stable fixation and 100% stem survivorship for aseptic loosening in revision THA with the SLR-Plus stem.

Granulocyte-monocyte apheresis: an alternative combination therapy after loss of response to anti-TNF agents in ulcerative colitis.

Objective: To evaluate the effectiveness and safety of the combination of granulocyte-monocyte apheresis (GMA) after loss of response (LOR) to anti-tumor necrosis factor (TNF) agents in ulcerative colitis (UC). Materials and methods: A retrospective, multicenter study was performed in 11 inflammatory bowel disease (IBD) Units. Clinical remission was defined as a partial Mayo score ≤2. The effectiveness of the treatment was evaluated by the partial Mayo score and the rate of anti-TNF intensification, switch, swap or colectomy. Results: Forty-seven patients with ulcerative colitis were included (mean age 35 years, mean disease duration 52 months, 66% male and 59% extensive colitis). Twenty-three subjects were receiving infliximab, eighteen adalimumab and six golimumab. GMA was combined after a primary non-response (49%) or secondary loss of response (51%) to anti-TNF therapy. We observed a significant decrease in partial Mayo score and fecal calprotectin after GMA. Fifteen patients (32%) responded to the combination therapy without anti-TNF intensification, switch, swap or colectomy. Eight patients (17%) underwent colectomy. Two patients (4%) presented adverse events related to the technique. Conclusions: Combination of GMA and anti-tumor necrosis factor is a safe and effective treatment after the loss of response to these biologic agents, with a significant decrease of the clinical disease activity and biomarkers, in a population with limited therapeutic alternatives.

Improvement in detecting sepsis using leukocyte cell population data (CPD).

Background The cell population data (CPD) parameters reported by XN analyzers (Sysmex Corporation, Kobe, Japan) reflect the size and internal structure of leukocytes. We explored whether CPD values could contribute to recognize those patients with fever at risk to develop sepsis. A profile of sepsis was developed combining CPD parameters and other markers. Methods We recruited 295 patients at the onset of fever, with infection confirmed by positive cultures. We studied the diagnostic performance of the CPD parameters in the differential diagnosis of sepsis vs. non-systemic bacterial infection using receiver operating characteristic (ROC) curve analysis. Additionally, the K-means unsupervised clustering method was applied. Once the clusters had been defined, the relationship between them and the CPD parameter values was assessed with the non-parametric Wilcoxon test. Lastly, the relationship between the clusters obtained and the categorical variables was examined with the χ2-test (or Fisher's exact test). Results ROC analysis demonstrated that NE-FSL, NE-WY, NE-WZ and MO-WZ had areas under the curve (AUCs) >0.700 for predicting sepsis. Using the K-means clustering algorithm, 80 patients (66.67%) were assigned to Cluster 1 and the others to Cluster 2. Out of 80 of patients in Cluster 1, 45 (56.25%) presented a PCT value ≥2 ng/mL, whereas almost 80% of Cluster 2 patients had a PCT <2 ng/mL. Cluster 1 was characterized by high NE-SFL, NE-WY, MO-X, MO-WX and MO-Z values (p<0.05). Conclusions CPD related to monocyte complexity and neutrophil activation were found to be significant, with high values suggesting sepsis.

Risk factors affecting hospital stay among patients undergoing colon cancer surgery: a prospective cohort study.

PURPOSE: To identify and validate risk factors that contribute to prolonged length of hospital stay (LOS) in patients undergoing resection for colorectal cancer. METHODS: This prospective cohort study included 1955 patients admitted to 22 hospitals for primary resection of colorectal cancer. Multivariate analyses were used to identify and validate risk factors, randomizing patients into a derivation and a validation cohort. Multiple correspondence and cluster analysis were performed to identify clinical subtypes based on LOS. RESULTS: The strongest independent predictors of prolonged LOS were postoperative reintervention, surgical site infection, open surgery, and distant metastasis. The multiple correspondence and cluster analysis provided three groups of patients in relation to prolonged LOS: patients with the longest LOS included the highest percentage of patients with open surgery, distant metastasis, deep surgical site infections, emergency admissions, additional diagnostic factors, and highly contaminated surgical sites. Patients with prolonged LOS (> 14 days) were more likely to develop adverse outcomes within 30 days after discharge. CONCLUSIONS: Patients undergoing resection of colorectal cancer cluster into different groups based on LOS of the index admission. Those with prolonged LOS were more likely to develop adverse outcomes within 30 days after discharge. Some of the strongest independent predictors of prolonged LOS, such as surgical infections or open surgery, could be modified to reduce LOS and, in turn, other adverse outcomes. TRIAL REGISTRATION: NCT02488161.

Characteristics and Progression of Preclinical Inflammatory Bowel Disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a chronic disease usually diagnosed after the appearance of gastrointestinal symptoms. Little is known about IBD progression during its early and even preclinical phases. We aimed to determine the number of new incidental diagnoses of IBD in an older population, and evaluate disease progression from its early stages. METHODS: We performed a retrospective analysis of 31,005 colonoscopies performed during colorectal cancer screening of patients with positive results from fecal immunochemical tests, at 11 centers in the Basque Country (Spain) from 2009 through 2014. We collected clinical and laboratory data from all asymptomatic individuals suspected to have IBD during screening colonoscopies, with histologic confirmation. RESULTS: Colonoscopy screening led to 79 new diagnoses of ulcerative colitis, 24 of Crohn's disease, and 7 of unclassified colitis (average patient age, 57 y; interquartile range, 52-62 y; 57% male). Eleven patients had symptoms before colonoscopy and were excluded from the analysis. Among those patients who were asymptomatic at diagnosis, 36% developed symptoms after a follow-up period of 25 months (interquartile range, 10.5-42 mo), mostly rectal bleeding and diarrhea. Treatment was prescribed for 81 patients (88%), and 2 cases required surgery. CONCLUSIONS: We analyzed data from a large cohort of patients with IBD diagnosed at early or even preclinical stages, from an older population. New incidental diagnoses of IBD were made in 0.35% of individuals undergoing a population-based screening colonoscopy-most were classified as ulcerative colitis. Approximately one third of patients developed symptoms during the follow-up period.

Only full adherence to proton pump inhibitors protects against drug-induced upper gastrointestinal bleeding.

PURPOSE: The use of gastroprotective agents has allowed significant progress in the prevention of upper gastrointestinal bleeding (UGIB) associated with non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents. Nevertheless, some concerns remain regarding the gastroprotective dosage and treatment duration. Our aim was to study the effect of gastroprotective agents in UGIB induced by NSAIDs and single- or dual-antiplatelet therapy. METHODS: A multicenter case-control study was conducted including 577 cases diagnosed with UGIB and 1343 sex-, age-, and hospital-matched controls. To estimate exposure to NSAIDs and gastroprotective agents, consumption was calculated for the 4 weeks prior to hospital admission in terms of defined daily doses (DDDs). Risk groups for UGIB induced by NSAIDs and single- or dual-antiplatelet therapy were defined as a function of each drug dose, use of gastrointestine-damaging drugs, and risk factors for UGIB. Odds ratios (ORs) with 95% confidence intervals (CIs) were adjusted for single- (model 1) and dual- (model 2) antiplatelet therapy. RESULTS: Full adherence (> 0.80DDD) to proton pump inhibitors (PPIs) was the only gastroprotective therapy that significantly reduced the risk of UGIB, considering NSAID risk (OR: 0.53; 95% CI: 0.30-0.95) and dose (OR: 0.48; 95% CI: 0.27-0.87) with ORs adjusted for single-antiplatelet therapy (model 1) and NSAID risk (OR: 0.55; 95% CI: 0.31-0.98) and dose (OR: 0.49; 95% CI: 0.28-0.89) with ORs adjusted for dual-antiplatelet therapy (model 2). CONCLUSIONS: These results reinforce the recommendation of adding a PPI at effective doses (full adherence) to prevent UGIB induced by NSAIDs, or single- or dual-antiplatelet therapy.

Colorectal cancer health services research study protocol: the CCR-CARESS observational prospective cohort project.

BACKGROUND: Colorectal cancers are one of the most common forms of malignancy worldwide. But two significant areas of research less studied deserve attention: health services use and development of patient stratification risk tools for these patients. DESIGN: a prospective multicenter cohort study with a follow up period of up to 5 years after surgical intervention. Participant centers: 22 hospitals representing six autonomous communities of Spain. Participants/Study population: Patients diagnosed with colorectal cancer that have undergone surgical intervention and have consented to participate in the study between June 2010 and December 2012. Variables collected include pre-intervention background, sociodemographic parameters, hospital admission records, biological and clinical parameters, treatment information, and outcomes up to 5 years after surgical intervention. Patients completed the following questionnaires prior to surgery and in the follow up period: EuroQol-5D, EORTC QLQ-C30 (The European Organization for Research and Treatment of Cancer quality of life questionnaire) and QLQ-CR29 (module for colorectal cancer), the Duke Functional Social Support Questionnaire, the Hospital Anxiety and Depression Scale, and the Barthel Index. The main endpoints of the study are mortality, tumor recurrence, major complications, readmissions, and changes in health-related quality of life at 30 days and at 1, 2, 3 and 5 years after surgical intervention. STATISTICAL ANALYSIS: In relation to the different endpoints, predictive models will be used by means of multivariate logistic models, Cox or linear mixed-effects regression models. Simulation models for the prediction of discrete events in the long term will also be used, and an economic evaluation of different treatment strategies will be performed through the use of generalized linear models. DISCUSSION: The identification of potential risk factors for adverse events may help clinicians in the clinical decision making process. Also, the follow up by 5 years of this large cohort of patients may provide useful information to answer different health services research questions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02488161 . Registration date: June 16, 2015.

Previous exposure to biologics and C-reactive protein are associated with the response to tacrolimus in inflammatory bowel disease.

BACKGROUND AND AIMS: Inflammatory bowel disease is a chronic disorder of the gastrointestinal tract. Tacrolimus is a calcineurin inhibitor used in the prophylaxis of rejection after a solid organ transplant. There is some evidence for its use in inflammatory bowel disease, although there is a lack of information about the patients who will benefit the most with this drug and the prognostic factors for a favorable response. MATERIAL AND METHODS: We performed a multicentric retrospective study evaluating all the patients who have received tacrolimus in the last 10 years as a treatment for IBD in our area. RESULTS: A total of 20 patients, 12 with Crohn's disease and 8 with ulcerative colitis, were included in four hospitals. The two most common indications were steroid-dependency and fistulizing Crohn's disease. The median time receiving tacrolimus was 11 months. In 12 patients the treatment was stopped. The main reasons for drug withdrawal were absence or loss of response. The median clinical follow-up was 35.5 months. Overall, a 25% achieved clinical remission and 40% were in partial response. Biologics-naïve patients demonstrated a significantly better remission rate as compared with those that were not (80 vs 7%). Patients who achieved remission were more likely to have a significant reduction in C-reactive protein values 1 month after starting the drug. Seven patients required surgery during the follow- up period. CONCLUSIONS: Patients naïve to biologics showed a significantly better response to tacrolimus. A reduction in C-reactive protein one month after starting this drug was associated with clinical remission.