Cryptococcal meningoencephalitis presenting as cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is characterized by its variety of neurological manifestations and difficulty in diagnosis. In subacute cases, the main symptoms are secondary to increased intracranial pressure. This condition is associated with an extensive range of medical disorders, but only 2% are caused by a CNS infection in recent series. We report a 45-year-old patient, with no previous medical history, who developed a syndrome of increased intracranial pressure as the presentation of a cryptococcal meningoencephalitis (CM) complicated with a CVT. The patient was first diagnosed of a CVT, and later on, the VIH infection and the CM diagnosis were made. Despite being treated with anticoagulation, liposomal amphotericin B, and a therapeutic lumbar puncture, the patient continued to deteriorate and suffered a respiratory arrest secondary to the increased intracranial pressure, with subsequent brain death. Cryptococcus is an infrequent cause of CNS infection in developed countries, despite being the most frequent cause of meningits in adults in several countries with high rates of HIV infection. CVT is a very rare complication of CM which can contribute to worsen the increased intracranial pressure and in consequence, its prognosis and outcome. A high level of suspicion is needed for diagnosing CM as the underlying cause of CVT and the subsequent increased intracranial pressure should be managed exhaustively.

Association of lifestyle, inflammatory factors, and dietary patterns with the risk of suffering a stroke: A case-control study.

BACKGROUND: Lifestyle, including dietary patterns, could involve specific factors participating in inflammation that confer a higher risk of suffering a stroke. However, little attention has been apparently given to habitual food consumption in patients suffering a cerebrovascular event. OBJECTIVE: To assess the influence of dietary habits as well as other lifestyle-related variables on the risk of suffering a stroke. DESIGN: A case-control study was designed. Fifty-one cases (age: 59.1 ± 9.1y.o; BMI; 30.8 ± 3.4 kg/m2) and 51 controls (age: 61.1 ± 9.1y.o; BMI; 30.4 ± 3.6 kg/m2) were enrolled in the study. Anthropometric and body composition variables were measured. Dietary information was obtained from a validated food frequency questionnaire. Physical activity and lifestyle-related factors were assessed. Blood samples were drawn. RESULTS: Patients suffering a stroke showed higher prevalence of diabetes (30 vs. 7.7%; P = 0.020) and hypertension (74.5 vs. 40.3%; P < 0.001) and were less physically active (36.7 vs. 66.6%; P = 0.024) than controls. Patients registered worse glucose and lipid profiles, higher levels of hepatic biomarkers, and higher blood cell counts than controls. Stroked patients showed lower adherence to a statistically derived healthy dietary pattern than controls (23.5 vs. 42.3%; P = 0.017). A logistic regression model was built up considering hypertension, diabetes, smoking, physical activity, adherence to a 'healthy dietary pattern' and C-reactive protein concentration. The final model strongly associated with the risk of suffering a stroke (R2: 44.6%; Pmodel < 0.0001). CONCLUSION: Lifestyle variables such as physical activity, smoking habit, and a dietary pattern including foods with low inflammatory potential play an important role in the reduction of the risk of suffering a stroke.

Mixed adenoneuroendocrine carcinoma (MANEC) of the gastroesophageal junction: a case report and review of the literature.

Esophageal cancer is the fourth most common neoplasm of the gastrointestinal tract. It is responsible for 1.7% of all deaths related with cancer. The two main types of esophageal cancer are squamous cell carcinoma and adenocarcinoma. Other types of esophageal cancer are uncommon. We present a 57-year-old man admitted to the hospital with nausea and vomiting due to a high-grade malignant mixed adenoneuroendocrine carcinoma of the gastroesophageal junction. The patient underwent Ivor-Lewis esophagectomy and adyuvant chemoradiotherapy. At 8-month follow-up he was alive without evidence of recurrence.

Pretreatment predictive value of blood neutrophil/lymphocyte ratio in R0 gastric cancer resectability. / Valor predictivo pretratamiento del cociente neutrófilos/linfocitos circulantes sobre la posibilidad de resección R0 en el cáncer gástrico.

INTRODUCTION: New parameters complementary to clinical TNM classification are needed, to orient preoperative on the possibility of a R0 gastric cancer resection. We analysed the possible predictive value of blood neutrophil/lymphocytic ratio (N/L) in relation to resectability. METHODS: Two hundred and fifty-seven gastric cancers consecutively diagnosed and without neoadjuvant treatment were retrospectively studied. Univariate and multivariate analysis of the frequency of R0 cases was performed between groups with a normal N/L ratio (<5) and pathological N/L ratio (≥5). Furthermore, we studied the subgroup of operated patients (n=156) analysing the frequency of R0 resection according to N/L ratio<5 or≥5. RESULTS: One hundred and fifty-six patients underwent surgical intervention, of which 139 had R0 resections. A high N/L ratio was registered in 46 cases (17.9%). Globally, resectability was higher in patients with a N/L ratio<5: 59.7% vs. N/L ratio≥5: 28.6% (P<.001; OR=3.76; 95% CI=1.78-8.04). The relation between N/L ratio<5 and R0 resection was confirmed in the multivariate (P=.006; OR=3.86; 95% CI=1.46-10.22). In the operated subgroup, the higher frequency of R0 resection achievement is maintained in cases with N/L ratio<5: 91.3% vs. 72.2% (P=.015; OR=4.04; 95% CI=1.23-13.26). CONCLUSIONS: The presence of a N/L ratio<5 at the diagnosis of a gastric carcinoma is related in a significant and independent way with a higher frequency of R0 tumoral resection, globally. This higher proportion of R0 resection cases in patients with a N/L<5 ratio is confirmed in the subgroup of operated patients.

[Prognostic value of preoperative carcinoembryogenic antigen: Is it useful in all stages of colorectal cancer?]. / Valor pronóstico pretratamiento del antígeno carcinoembrionario en el cáncer colorrectal operado. ¿Es útil en todos los estadios del tumor?

INTRODUCTION: Recent reports have reopened discussion of the prognostic value of elevated pre-treatment carcinoembryonic antigen (CEA) levels in colorectal cancer. Due to the discrepancies in the published results, we aimed to analyze the possible predictive value of CEA, both overall and in different tumoral stages in our environment. PATIENTS AND METHODS: We retrospectively studied 303 consecutive patients with colorectal cancer resected with curative intent by analysing tumor-related mortality. The frequency of patients with increased CEA levels (> 5mg/l) was registered. Univariate and multivariate analyses of survival curves were performed, comparing patients with increased CEA levels and those with CEA levels within normal limits, both in the overall series and in the different pTNM tumoral stages. RESULTS: Frequency of patients with CEA>5mg/l was 31%. The median clinical follow-up was 83 months. A poor survival rate was registered in the multivariate analysis of the whole series in patients with high CEA levels: hazard ratio (HR)=1.81; 95% confidence interval (95% CI)=(1.15-3.10); P=.012. This predictive value was only maintained in stage II in the survival analysis of the distinct tumoral stages (n=104): HR=3.02; 95% CI=(1.22-7.45); P=.017. CONCLUSIONS: Before treatment, 31% of our patients with colorectal cancer resected with curative intent had pathological CEA values. In the overall series, a high pretreatment CEA level showed an independent prognostic value for poor survival. When pTNM tumoral stages were analyzed separately, CEA level had predictive value only in pTNM II tumors.

[Does endoscopist fatigue play a role in incomplete colonoscopies and detection of polypoid lesions?]. / ¿Influye el posible cansancio del endoscopista en la frecuencia de colonoscopias incompletas y de las lesiones polipoideas diagnosticadas?

INTRODUCTION: Nowadays, the possible effect of endoscopist fatigue on the results of colonoscopies is under discussion. We aimed to analyze possible differences in cecal intubation and the polyp and adenoma detection rate, depending on whether colonoscopies were performed at the beginning or at the end of the daily endoscopy session and to analyze the influence of the queue position on the detection rate. PATIENTS AND METHODS: A retrospective study was performed with 1,000 ambulatory and consecutive colonoscopies, divided into 2 groups: «early¼ and «late¼ procedures. A total of 95 colonoscopies were excluded due to poor colon cleansing. After confirming that patient characteristics were homogenous in the two groups, we compared the frequency of complete colonoscopies and the polyp and adenoma detection rate. Possible differences between the 2 groups in the polyp detection rate according to the colonoscopy schedule were analyzed. RESULTS: The overall polyp and adenoma detection rates were 44.2 and 30.5%, respectively, with no significant differences among 13 different endoscopists; polyps: p = 0.21; adenomas: p=0.63. No significant differences were found between the «early group¼ (n= 532) and the «late group¼ (n = 373) in the rates of complete colonoscopies [97.2 vs 99.4% (p=0.92)], the polyp detection rate [45.9 vs 41.8% (p=0.23)], the adenoma detection rate [30.8 vs 30% (p=0.80)] or the serrated adenoma rate [2.1% vs 1.6% (p=0.62)]. The lesion detection rate did not vary in relation to the «queue position¼: polyps [p = 0.60, and adenomas: p = 0.83. CONCLUSIONS: In our series, endoscopist fatigue at the end of the day had no influence on the complete colonoscopy rate or on the polyp and adenoma detection rate. There were no differences in the number of polypoid lesions detected according to the timing of the colonoscopy schedule.

[Predictive value of pre-treatment hypoalbuminemia in prognosis of resected colorectal cancer]. / Valor predictivo de la hipoalbuminemia pre-tratamiento sobre el pronóstico del cáncer colorrectal resecado.

INTRODUCTION: Albuminemia is part of the antitumoral systemic inflammatory response. We therefore analyzed its possible value in establishing the preoperative prognosis of colorectal carcinoma (CRC). PATIENTS AND METHODS: We conducted a retrospective, observational study of a series of consecutive patients who underwent CRC resection. Univariate and multivariate analyses of survival curves were performed in patients with and without pre-treatment hypoalbuminemia (<3.5g/dl), both in the overall group of patients and in the subgroup of those with pTNM stage ii tumors. In addition, we compared the 5-year tumor-related mortality in patients with and without hypoalbuminemia. RESULTS: A total of 207 patients were reviewed (median follow-up: 81 months). In the overall multivariate analysis, survival curves were better in patients with normal albumin levels than in those with hypoalbuminemia (HR=2.82; CI 95%=[1.54-5.19]; P=.001). This better prognostic value of normal albumin levels was also significant in pTNM stage ii tumors: (HR=3.76; CI 95%=[1.40-10.08]; P=.009). The 5-year mortality index was lower in patients with normal albumin levels: overall series=18.8% vs 42.9% (OR=3.24; CI 95%=[1.48-7.12]; p=0.001); pTNM stage ii=13.3% vs 44.4% (OR=5.2; CI 95%=[1.36-20.34]; P=0.004). CONCLUSIONS: Pre-treatment hypoalbuminemia (<3.5g/dl) was independently related to shorter survival after tumor resection, both in the overall series of patients and in pTNM stage ii CRC. If these results are confirmed, hypoalbuminemia would be a simple and significant marker of poor prognosis, available at the initial diagnosis.

Drawing up an individual risk index for development of metachronous neoplastic lesions in resected colorectal cancer.

AIM: to identify possible risk factors for the development of metachronous lesions in colorectal cancer (CRC) which would allow to establish a post-surgical individual prognostic index. PATIENTS AND METHODS: three hundred eighty-two surgically treated CRC were reviewed. We compared the incidence of metachronous lesions in 40 variables concerning patient clinical data and initial neoplastic findings. An individual risk index for metachronicity was drawn up including those variables which presented significant differences in multivariate logistic regression, dividing patients into three groups. RESULTS: variables with prognostic value for metachronicity were distal cancer location: OR = 2.30 (1.03-5.13), alcohol intake: OR = 2.20 (1.08-4.48), presence of synchronous adenomas: isolated: OR = 2.47 (1.03-4.48), multiple: OR = 4.26 (1.78-10.17), and presence of synchronous advanced adenoma: OR = 2.91 (1.52-12.60). Tumor MUC-5 expression proved to have a protective role: OR = 0.23 (0.08-0.66). An individual risk score was established considering these variables and patients could be classified into three groups, with a discrimination power for metachronicity of p < 0.0000001. Classification in high and low risk groups had a sensitivity = 75.32%, specificity = 84.21%, positive predictive value = 75.34%, negative predictive value = 92.31% and global diagnostic accuracy = 80.75%. CONCLUSIONS: the identification of risk factors for the development of metachronous lesions allow to calculate, at the time of surgical treatment, an individual prognostic index and to classify patients into three different risk groups. In high and low risk groups, both specificity and accuracy were acceptable for the prognosis of metachronous lesions, being remarkable the negative predictive power of our classification, which could become relevant when planning a different endoscopic follow up of these patients.

[Predictive value of intraepithelial (CD3) T-lymphocyte infiltration in resected colorectal cancer]. / Valor predictivo de la infiltración por linfocitos T intraepiteliales (CD3) en el pronóstico del cáncer colorrectal resecado.

INTRODUCTION: Colorectal cancer (CRC) can induce an anti-tumoral immune response mediated by T-lymphocytes, which express CD3. OBJECTIVES: To analyze the prognostic value of tissue expression of intraepithelial CD3 (CD3I) both overall and in the early tumoral stages. METHODS: We revised 251 patients with resected CRC and favorable clinical course. CD3I expression was analyzed by immunohistochemistry. Multivariate analysis was used to analyze the variables independently associated with survival. We analyzed CD3I(+) expression in relation to survival and tumoral progression, both overall and in patients with pTNM(I-II) stage tumors. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of CD3I expression were analyzed. RESULTS: A total of 25.9% of patients with CRC were CD3I(+). After a mean follow-up of 74 months, CD3I(+) expression showed a favorable prognostic value for survival in the multivariate analysis (p=0.045). Survival curves and absence of tumoral progression were more favorable in CD3I(+) cases, both overall (p=0.009 and p=0.004, respectively), and in stages I-II (p=0.029 and p=0.015). The specificity and positive predictive value of CD3I(+) were as follows: Survival: overall: specificity =0.89; positive predictive value =0.91. Stage (I-II): specificity =0.94; positive predictive value =0.98. Absence of tumoral progression: overall: specificity=0.89; positive predictive value =0.88. Stage (I-II): specificity =0.92; positive predictive value =0.96. CONCLUSIONS: CD3I expression has an favorable independent prognostic value, with statistically significantly higher percentages of survival and absence of tumoral progression. This more favorable outcome is maintained in the less advanced stages (I-II). CD3I expression shows high specificity and positive predictive value.

Does capsule endoscopy impact clinical management in established Crohn's disease?

BACKGROUND: Capsule endoscopy (SBCE) has developed a relevant role in patients with established Crohn's Disease (CD). However, evaluation of the impact in clinical management has been scarce. AIMS: To evaluate therapeutic impact of SBCE in an 11-year real-life cohort of known CD patients. METHODS: Retrospective single center study including all patients with established CD submitted to SBCE procedure from 01/01/2008 to 31/12/2019. Patency capsule was used in selected patients. Small bowel mucosal inflammation was quantified using Lewis score. Therapeutic impact was defined as a change in CD-related treatment recommended based on SBCE results. Patients were assigned to four groups regarding SBCE indication: staging, flare, post-op and remission. RESULTS: From the 432 SBCE performed 87.5% were conclusive. Active disease was present in 63.7 of patients; 41.6% mild inflammation and 21.9% moderate-to-severe activity. A change of management was guided by SBCE in 51.3% of procedures: 199 (46.1%) escalation and 23 (5.3%) de-escalation, with significant changes in all groups. Escalation increased with disease activity: 57.8% in mild and 89.5% in moderate-to-severe disease. De-escalation was conducted in 13.9% procedures with mucosal healing and 1.1% with mild disease. CONCLUSION: SBCE is a useful tool for guiding therapeutic management in CD patients both for treatment escalation and de-escalation.

EUS is superior to secretin-enhanced cholangio-MRI to establish the etiology of idiopathic acute pancreatitis.

Background and study aims The etiology of idiopathic acute pancreatitis (IAP) should always be defined. Our aim was to compare the diagnostic value of endoscopic ultrasound (EUS) versus secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) in patients with IAP. Patients and Methods Patients admitted to a single tertiary care University hospital with IAP were invited to participate in the study. Enrolled patients underwent EUS and S-MRCP in a single-blinded comparative study. EUS and S-MRCP were performed no sooner than 4 weeks after discharge. The diagnostic yield of EUS and S-MRCP and demographic variables were included in the analysis. Additional follow-up, results of subsequent serology, radiographic exams, and relevant histological analysis were considered in determination of the final diagnosis. Results A total of 34 patients were enrolled; EUS was normal in six, cholelithiasis was defined in 15, choledocholithiasis in two, pancreas divisum in three, branch-type intraductal papillary mucinous tumor (IPMT) in three, and chronic pancreatitis in five. S-MRCP identified choledocholithiasis in one, divisum in four, branch-type IPMT in three, chronic pancreatitis in two; 24 subjects diagnosed as normal by S-MRCP. Diagnostic correlation between EUS and S-MRCP was slight (kappa = 0.236, 95 % confidence interval: 0.055-0.416). EUS provided a statistically significantly higher diagnostic yield than S-MRCP: 79.4 % (CI95 %: 65 %-94 %) vs 29.4 % (CI95 %: 13 %-46 %) (P = 0.0002). The sensitivity, specificity, and positive and negative predictive values of EUS and S-MRCP were 90 %, 80 %, 96 %, 57 % and 33 %, 100 %, 100 % and 16 %, respectively. Conclusion The diagnostic yield of EUS is higher than S-MRCP in patients with IAP.

MRI predicts intracranial hemorrhage in patients who receive long-term oral anticoagulation.

OBJECTIVE: We tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI. METHODS: Patients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses. RESULTS: We recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1-7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6-20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66-0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62-7.4). CONCLUSION: Patients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke. CLINICALTRIALSGOV IDENTIFIER: NCT02238470.

Statins do not increase Markers of Cerebral Angiopathies in patients with Cardioembolic Stroke.

We investigated whether pre-treatment with statins is associated with surrogate markers of amyloid and hypertensive angiopathies in patients who need to start long-term oral anticoagulation therapy. A prospective multicenter study of patients naive for oral anticoagulants, who had an acute cardioembolic stroke. MRI was performed at admission to evaluate microbleeds, leukoaraiosis and superficial siderosis. We collected data on the specific statin compound, the dose and the statin intensity. We performed bivariate analyses and a logistic regression to investigate variables associated with microbleeds. We studied 470 patients (age 77.5 ± 6.4 years, 43.7% were men), and 193 (41.1%) of them received prior treatment with a statin. Microbleeds were detected in 140 (29.8%), leukoaraiosis in 388 (82.5%) and superficial siderosis in 20 (4.3%) patients. The presence of microbleeds, leukoaraiosis or superficial siderosis was not related to pre-treatment with statins. Microbleeds were more frequent in patients with prior intracerebral hemorrhage (OR 9.7, 95% CI 1.06-90.9) and in those pre-treated antiplatelets (OR 1.66, 95% CI 1.09-2.53). Prior treatment with statins was not associated with markers of bleeding-prone cerebral angiopathies in patients with cardioembolic stroke. Therefore, previous statin treatment should not influence the decision to initiate or withhold oral anticoagulation if these neuroimaging markers are detected.

Early risk of recurrent stroke in patients with symptomatic carotid near-occlusion: Results from CAOS, a multicenter registry study.

Background The risk of recurrent stroke among patients with symptomatic carotid near-occlusion is not well established, and management of the condition remains controversial. Symptomatic carotid near-occlusion with full collapse has been identified as a strong predictor of early recurrence. We aimed to analyze the 90-day risk of recurrent ipsilateral ischemic stroke in medically treated patients with symptomatic carotid near-occlusion. Methods We performed a multicenter, nationwide, prospective study from January 2010 to May 2016. Patients with angiography-confirmed symptomatic carotid near-occlusion were included. The primary endpoint was ipsilateral ischemic stroke or transient ischemic attack (TIA) within 90 days after the presenting event. For this analysis, patients who underwent revascularization within 90 days after stroke were excluded. Results The study population comprised 141 patients from 17 Spanish centers; 83 patients were treated medically. Primary endpoint occurred in eight patients, resulting in a cumulative rate of 10.6% (95% CI, 3.7-17.5). Previous history of stroke or transient ischemic attack was identified as an independent predictor for recurrence in the multivariate Cox regression analysis (HR, 4.37 [95% CI, 1.05-18.18]; p = 0.043), while the presence of full collapse was not associated with an increased risk (HR, 0.81 [95% CI, 0.17-3.92]; p = 0.793). The risk of recurrence was also not affected by the presence of significant stenosis or occlusion of the contralateral carotid artery, or by the collateral circulation. Conclusions Patients with symptomatic carotid near-occlusion seem to have an increased risk of early ipsilateral recurrent stroke. Our results contrast with the low risk of symptomatic carotid near-occlusion reported to date. Full collapse did not increase the risk of recurrent stroke in our study.

Capsule endoscopy capture rate: has 4 frames-per-second any impact over 2 frames-per-second?

AIM: To compare the current capsule and a new prototype at 2 and 4 frames-per-second, respectively, in terms of clinical and therapeutic impact. METHODS: One hundred patients with an indication for capsule endoscopy were included in the study. All procedures were performed with the new device (SB24). After an exhaustive evaluation of the SB24 videos, they were then converted to "SB2-like" videos for their evaluation. Findings, frames per finding, and clinical and therapeutic impact derived from video visualization were analyzed. Kappa index for interobserver agreement and χ (2) and Student's t tests for qualitative/quantitative variables, respectively, were used. Values of P under 0.05 were considered statistically significant. RESULTS: Eighty-nine out of 100 cases included in the study were ultimately included in the analysis. The SB24 videos detected the anatomical landmarks (Z-line and duodenal papilla) and lesions in more patients than the "SB2-like" videos. On the other hand, the SB24 videos detected more frames per landmark/lesion than the "SB2-like" videos. However, these differences were not statistically significant (P > 0.05). Both clinical and therapeutic impacts were similar between SB24 and "SB2-like" videos (K = 0.954). The time spent by readers was significantly higher for SB24 videos visualization (P < 0.05) than for "SB2-like" videos when all images captured by the capsule were considered. However, these differences become non-significant if we only take into account small bowel images (P > 0.05). CONCLUSION: More frames-per-second detect more landmarks, lesions, and frames per landmark/lesion, but is time consuming and has a very low impact on clinical and therapeutic management.

Colon capsule endoscopy.

Wireless capsule endoscopy has become the first imaging tool for small bowel examination. Recently, new capsule endoscopy applications have been developed, such as esophageal capsule endoscopy and colon capsule endoscopy. Clinical trials results have shown that colon capsule endoscopy is feasible, accurate and safe in patients suffering from colonic diseases. It could be a good alternative in patients refusing conventional colonoscopy or when it is contraindicated. Upcoming studies are needed to demonstrate its utility for colon cancer screening and other indications such us ulcerative colitis. Comparative studies including both conventional and virtual colonoscopy are also required.

Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants.

OBJECTIVES: After the withdrawal of some cyclooxygenase-2 (COX-2) selective inhibitors, traditional nonsteroidal anti-inflammatory drug (NSAID) use has increased, but without additional prevention strategies against upper gastrointestinal (GI) complications in many cases. Here, we report the effect of antisecretory drugs and nitrates on the risk of upper GI peptic ulcer bleeding (UGIB) associated with nonselective NSAIDs, aspirin, antiplatelet agents, and anticoagulants. METHODS: This case-control study matched 2,777 consecutive patients with UGIB (confirmed by endoscopy) with 5,532 controls (2:1). Adjusted relative risks (RR) of UGIB are reported. RESULTS: Proton pump inhibitors (PPIs) (RR 0.33, 95% confidence interval [CI] 0.27-0.39), H2-receptor antagonists (H2-RAs) (RR 0.65, 95% CI 0.50-0.85), and nitrates (RR 0.52, 95% CI 0.38-0.70) reduced UGIB risk. PPI use was associated with greater reductions among both traditional NSAID (RR 0.13, 95% CI 0.09-0.19 vs RR 0.30, 95% CI 0.17-0.53 with H2-RAs; RR 0.48, 95% CI 0.19-1.24 with nitrates) and low-dose aspirin users (RR 0.32, 95% CI 0.22-0.51 vs RR 0.40, 95% CI 0.19-0.73 with H2-RA; RR 0.69, 95% CI 0.36-1.04 with nitrates), and among patients taking clopidogrel (RR 0.19, 95% CI 0.07-0.49). For patients taking anticoagulants, use of nitrates, H2-RA, or PPIs was not associated with a significant effect on UGIB risk. CONCLUSION: Antisecretory agent or nitrate treatment is associated with reduced UGIB RR in patients taking NSAID or aspirin. Only PPI therapy was associated with a marked, consistent risk reduction among patients receiving all types of agents (including nonaspirin antiplatelet agents). Protection was not apparent in patients taking anticoagulants.