Mistakes in the diagnosis and treatment of Helicobacter pylori infection in daily clinical practice.

BACKGROUND: An adequate diagnostic and therapeutic approach to Helicobacter pylori (H. pylori) infection is the cornerstone to avoid overdiagnosis, overuse of health resources, and increase in antibiotic resistances. The aim of the study was to evaluate the most common errors in clinical practice and the associated risk factors. MATERIALS AND METHODS: This is a retrospective observational study including patients with H. pylori infection and no previous treatment belonging to two defined areas of the National Health System in Spain; some of them were enrolled in the European Registry on H. pylori management (Hp-EuReg). Patients were attended by gastroenterologists between 2010 and 2019. According to current guidelines, we evaluated indications for H. pylori investigation, appropriateness of diagnostic test used in dyspeptic patients and discontinuation of surveillance after treatment. RESULTS: A total of 1730 patients were included, receiving 2260 eradication regimens. H. pylori infection was investigated in 1.7% cases in absence of a formal indication. Oral endoscopy was incorrectly used in 56% of patients with dyspepsia under 55 years without alarm signs, and urea breath test (UBT) was incorrectly used in 22.4% of patients with dyspepsia ≥55 years or red flags. Levofloxacin containing regimens were used as first-line therapy in 7.5% of non-allergic to penicillin patients. After first-line failure, clarithromycin was repeated in 2.6% of the patients who received second-line therapy. Confirmatory test of H. pylori status was absent in 2.5% cases. Men, patients under 55 years, and patients diagnosed by UBT had a higher risk of not undergoing a confirmatory test. CONCLUSIONS: Investigation of H. pylori infection by gastroenterologists is rare in absence of a formal indication; however, endoscopy is commonly used for dyspeptic patients <55 years without red flags and non-invasive tests are still used for dyspeptic patients ≥55 years or presenting alarm signs. Men, patients under 55 years, and patients diagnosed by UBT have an increased risk of being lost to follow-up after eradication treatment.

Pharmacokinetics and Changes in Lipid Mediator Profiling after Consumption of Specialized Pro-Resolving Lipid-Mediator-Enriched Marine Oil in Healthy Subjects.

Omega-3 polyunsaturated fatty acids (PUFAs) play a vital role in human health, well-being, and the management of inflammatory diseases. Insufficient intake of omega-3 is linked to disease development. Specialized pro-resolving mediators (SPMs) are derived from omega-3 PUFAs and expedite the resolution of inflammation. They fall into categories known as resolvins, maresins, protectins, and lipoxins. The actions of SPMs in the resolution of inflammation involve restricting neutrophil infiltration, facilitating the removal of apoptotic cells and cellular debris, promoting efferocytosis and phagocytosis, counteracting the production of pro-inflammatory molecules like chemokines and cytokines, and encouraging a pro-resolving macrophage phenotype. This is an experimental pilot study in which ten healthy subjects were enrolled and received a single dose of 6 g of an oral SPM-enriched marine oil emulsion. Peripheral blood was collected at baseline, 3, 6, 9, 12, and 24 h post-administration. Temporal increases in plasma and serum SPM levels were found by using LC-MS/MS lipid profiling. Additionally, we characterized the temporal increases in omega-3 levels and established fundamental pharmacokinetics in both aforementioned matrices. These findings provide substantial evidence of the time-dependent elevation of SPMs, reinforcing the notion that oral supplementation with SPM-enriched products represents a valuable source of essential bioactive SPMs.

Impact of the COVID-19 pandemic in colorectal cancer diagnosis and presentation.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic has been associated with a decrease in the colorectal cancer (CRC) incidence, due to the disruption of screening programmes and a downscaling of endoscopic activity. The endpoint of this study is to evaluate if the pandemic has led to a change in CRC diagnostic rate and presentation in our population. METHODS: Multicenter retrospective study of all public hospitals of the Aragon region, attending a population of 1,329,391 inhabitants. We have analyzed all CRC cases detected and endoscopic units workload the year before the pandemic onset (1 March 2019-14 March 2020) and the first year of the COVID-19 pandemic (15 March 2020-28 February 2021). RESULTS: The diagnosis of CRC cases dropped a 38.9% (888 pre-pandemic vs 542 pandemic cases). Also, there were 30.3% less colonoscopies performed (24,860 vs 17,337). During the pandemic, CRC cases were diagnosed in older patients (72.4±12.2 vs 71.2±12.1 years, p=0.021), and had more frequently severe complications at diagnosis (14.6% vs 10.4%, p=0.019). Moreover, most CRC cases were diagnosed in symptomatic patients (81.4%). No significant difference was found in CRC stage at diagnosis, although stage IV was more frequent (20.1% vs 16.1%). Most hospitals reported a lower workload of endoscopic activity. CONCLUSION: CRC diagnostic rate was lower after the onset of the pandemic. CRC was diagnosed in older patients and was more frequently associated with complications. After the onset of the pandemic, the endoscopic units did not reach the workload performed previously.

Predictive Value of Genetic Risk Scores in the Development of Colorectal Adenomas.

INTRODUCTION: Unlike colorectal cancer (CRC), few studies have explored the predictive value of genetic risk scores (GRS) in the development of colorectal adenomas (CRA), either alone or in combination with other demographic and clinical factors. METHODS: In this study, genomic DNA from 613 Spanish Caucasian patients with CRA and 829 polyp-free individuals was genotyped for 88 single-nucleotide polymorphisms (SNPs) associated with CRC risk using the MassArray™ (Sequenom) platform. After applying a multivariate logistic regression model, five SNPs were selected to calculate the GRS. Regression models adjusted by sex, age, family history of CRC, chronic use of NSAIDs, low-dose ASA, and consumption of tobacco were built in order to study the association between GRS and CRA risk. We evaluated the discriminatory capacity using the area under the receiver operating characteristic curve (AUC). The interactions between demographic information and GRS were also analyzed. RESULTS: Significant associations between high GRS values and risk of CRA for analyzed models were observed. In particular, patients with higher GRS values had 2.3-2.6-fold increase in risk of CRA compared to patients with middle values. Combining sex and age with the GRS significantly increased the discriminatory accuracy of the univariate model with GRS alone. The best model achieved an AUC value of 0.665 (95% CI: 0.63-0.69). The GRS showed a different behavior depending on sex and age. CONCLUSION: Our findings showed that, besides sex and age, GRS is an important risk factor for development of CRA and may be useful for CRC risk stratification and adaptation of screening programs.

Impact of the lockdown period due to the COVID-19 pandemic in patients with inflammatory bowel disease.

INTRODUCTION: The lockdown period due to the coronavirus disease 2019 (COVID-19) in Spain probably had a significant emotional impact on chronic patients and hence on those who are suffering from inflammatory bowel disease (IBD) due to their high risk of emotional disorders. The aim of this study was to learn how COVID-19 influenced patients suffering from IBD during the quarantine period, focusing in particular on psychological distress through the Perceived Stress Scale-10 (PSS-10) and also the impact of the pandemic on therapeutic adherence using the Visual Analogue Scale (VAS). PATIENTS AND METHODS: A prospective, single-centre and analytical observational study was carried out in the IBD unit in August 2020. Patients were contacted and interviewed by phone. A descriptive analysis was carried out and subsequently the factors associated with the loss of therapeutic adherence and higher-moderate levels of stress were analyzed through logistic regression multivariate analyses. RESULTS: A total of 426 patients were included with a median PSS-10 score of 12 (10-16). A higher level of stress was reported by those who were not married, women and those who experienced an increase in IBD-related symptoms. Adherence to treatment was not associated with stress based on the PSS-10 questionnaire. CONCLUSIONS: Although the lockdown period due to the COVID-19 pandemic has probably had a significant emotional impact on Spaniards with IBD, IBD patients in general had lower PSS-10 scores.

Genetic susceptibility in the development of colorectal adenomas according to family history of colorectal cancer.

Our study aimed to evaluate the relevance of genetic susceptibility in the development of colorectal adenomas (CRA) and its relationship with the presence of family history of colorectal cancer (CRC). Genomic DNA from 750 cases (first degree relatives of patients with CRC) and 750 controls (subjects with no family history of CRC) was genotyped for 99 single nucleotide polymorphisms (SNPs) previously associated with CRC/CRA risk by GWAS and candidate gene studies by using the MassArray™ (Sequenom) platform. Cases and controls were matched by gender, age and histological lesion. Eight hundred and fifty-eight patients showed no neoplastic lesions, whereas 288 patients showed low-risk adenomas, and 354 patients presented high-risk adenomas. Two SNPs (rs10505477, rs6983267) in the CASC8 gene were associated with a reduced risk of CRA in controls (log-additive models, OR: 0.67, 95%CI:0.54-0.83, and OR:0.66, 95%CI:0.54-0.84, respectively). Stratified analysis by histological lesion revealed the association of rs10505477 and rs6983267 variants with reduced risk of low- and high-risk adenomas in controls, being this effect stronger in low-risk adenomas (log-additive models, OR:0.63, 95%CI:0.47-0.84 and OR:0.64, 95%CI:0.47-0.86, respectively). Moreover, 2 SNPs (rs10795668, rs11255841) in the noncoding LINC00709 gene were significantly associated with a reduced risk of low-risk adenomas in cases (recessive models, OR:0.22, 95%CI:0.06-0.72, and OR:0.08, 95%CI:0.03-0.61) and controls (dominant models, OR:0.50, 95%CI:0.34-0.75, and OR:0.52, 95%CI:0.35-0.78, respectively). In conclusion, some variants associated with CRC risk (rs10505477, rs6983267, rs10795668 and rs11255841) are also involved in the susceptibility to CRA and specific subtypes. These associations are influenced by the presence of family history of CRC.

Acetylsalicylic Acid Exhibits Antitumor Effects in Esophageal Adenocarcinoma Cells In Vitro and In Vivo.

BACKGROUND AND AIM: Recent observational studies have shown therapeutic benefits of acetylsalicylic acid (ASA) in several types of cancer. We examined whether ASA exerts antitumor activity in esophageal adenocarcinoma (EAC). METHODS: Human EAC cells (OE33) were treated with ASA (0-5 mM) to evaluate proliferation, apoptosis, and migration. In vivo model: OE33-derived tumors were subcutaneously implanted into athymic mice which were allocated to ASA (5 or 50 mg/kg/day)/vehicle (5-6 animals/group). Tumor growth was assessed every 2-3 days, and after 40 days, mice were euthanized. Plasma drug levels were determined by high-performance liquid chromatography. Histological and immunohistochemical (Ki67, activated caspase-3) analysis of tumors were performed. The effect of ASA on tumor prostaglandin E2 (PGE2) levels was also evaluated. RESULTS: In vitro cell proliferation and migration were significantly inhibited while apoptosis increased (p < 0.05) by ASA. Although ASA did not induce tumor remission, tumor progression was significantly lower in ASA-treated mice when compared to non-treated animals (478 % in mice treated with 5 mg/kg/day ASA vs. 2696 % control; 748 % in mice treated with 50 mg/kg/day ASA vs. 2670 % control). Maximum tumor inhibition was 92 and 85 %, respectively. This effect was associated with a significant decrease of proliferation index in tumors. ASA 5 mg/kg/day did not modify tumor PGE2 levels. Whereas tumor PGE2 content in mice treated with ASA 50 mg/kg was lower than in control mice, the difference was not significant. CONCLUSION: Although these results need to be confirmed in other EAC cells, our data suggest a role for ASA in the treatment of this tumor.

[Health-care utilization in elderly (Spain 2006-2012): Influence of health status and social class]. / Utilización de servicios sanitarios en ancianos (España 2006-2012): influencia del nivel de salud y de la clase social.

OBJECTIVE: to explore health-care utilization (primary and specialized health-care, hospitalizations, day hospital and emergency services) and overuse in elderly in Spain, considering the influence of health status, sex, social class and its temporal trend. DESIGN: cross sectional study in two phases. SETTING: Spain. PARTICIPANTS: people surveyed in the National Health Surveys 2006 and 2011-12. MAIN MEASUREMENTS: Health status was measured using self-rated and diagnosed health (number and diagnoses). Social class was obtained from the last occupation of the main supporter (manual and non-manual workers). Logistic regression analyses were conducted adjusting by sex, age, health status, social class and year, obtaining its predictive capacity. RESULTS: the percentage of elderly population with health-care utilization decreased during the period analyzed. Women who belonged to the manual workers category presented the highest prevalence of low health (low self-rated health in 2006: 70.6%). Low health status was associated with a higher utilization of health-care services. Self-rated health was a better predictor of health-care utilization and overuse than diagnosed health, getting the highest predictive capacity for specialized health-care (C = 0.676). Old people from low social class used with higher frequency primary health-care and emergency services. On the other hand, specialized health-care and day hospital were more used by high social classes. CONCLUSIONS: inequalities in health and health-care utilization have been observed in elderly according social class. It is necessary to consider self-rated health as a health-care utilization predictor and to review our health-care services accessibility and equity.

Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease.

Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR-TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45-15.33] and nonsteroidal anti-inflammatory drugs (OR: 6.54; 95% CI: 3.19-12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33-0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63-2.34), smoking (OR: 1.93; 95% CI: 1.54-2.61), family history of GC (OR: 2.83; 95% CI: 2.01-3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07-1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12-1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16-1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse-type GC (hazard ratio: 1.85; 95% CI: 1.12-3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse-type of GC in Caucasians.

Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants.

BACKGROUND & AIMS: Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin is associated with increased risk of upper gastrointestinal bleeding. There is little evidence on the risk of lower gastrointestinal bleeding with NSAIDs, antiplatelet agents (APAs), or anticoagulants. We aimed to quantify the relative risk (RR) of upper and lower gastrointestinal bleeding associated with use of NSAIDs, APAs, or anticoagulants. METHODS: We performed a case-control study that used data collected from consecutive patients hospitalized for gastrointestinal bleeding (563 upper, mean age, 63.6 ± 16.7 years and 415 lower, mean age, 70.8 ± 13.8 years), confirmed by endoscopy or other diagnostic procedures. Unhospitalized patients were used as controls (n = 1008) and matched for age, hospital, and month of admission. Drug use was considered current when taken within 7 days or less before hospitalization. RRs and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis. RESULTS: Use of anticoagulants, low-dose aspirin, and other drugs (non-aspirin-APA, 82.3% thienopiridines) was associated with upper and lower gastrointestinal bleeding; the risk was 2-fold higher for anticoagulants (RR, 4.2; 95% CI, 2.9-6.2) than for low-dose aspirin (RR, 2.1; 95% CI, 1.4-3.3) or other non-aspirin-APA drugs (RR, 2.0; 95% CI, 1.6-2.6). NSAID use was also associated with increased risk of gastrointestinal bleeding and greater for upper (RR, 2.6; 95% CI, 2.0-3.5) than lower gastrointestinal bleeding (RR, 1.4; 95% CI, 1.0-1.9). Use of proton pump inhibitors was associated with reduced risk of upper, but not lower, gastrointestinal bleeding. CONCLUSIONS: Anticoagulants, low-dose aspirin, NSAIDs, and other non-aspirin-APA drugs are associated with increased risk of upper and lower gastrointestinal bleeding. Use of anticoagulants appears to be the strongest risk factor for gastrointestinal bleeding.

Outcomes of peptic ulcer bleeding following treatment with proton pump inhibitors in routine clinical practice: 935 patients with high- or low-risk stigmata.

OBJECTIVE: To assess rates of further bleeding, surgery and mortality in patients hospitalized owing to peptic ulcer bleeding. MATERIALS AND METHODS: Consecutive patients hospitalized for peptic ulcer bleeding and treated with a proton pump inhibitor (PPI) (esomeprazole or pantoprazole) were identified retrospectively in 12 centers in Spain. Patients were included if they had high-risk stigmata (Forrest class Ia-IIb, underwent therapeutic endoscopy and received intravenous PPI ≥120 mg/day for ≥24 h) or low-risk stigmata (Forrest class IIc-III, underwent no therapeutic endoscopy and received intravenous or oral PPI [any dose]). RESULTS: Of 935 identified patients, 58.3% had high-risk stigmata and 41.7% had low-risk stigmata. After endoscopy, 88.3% of high-risk patients and 22.1% of low-risk patients received intravenous PPI therapy at doses of at least 160 mg/day. Further bleeding within 72 h occurred in 9.4% and 2.1% of high- and low-risk patients, respectively (p < 0.001). Surgery to stop bleeding was required within 30 days in 3.5% and 0.8% of high- and low-risk patients, respectively (p = 0.007). Mortality at 30 days was similar in both groups (3.3% in high-risk and 2.3% in low-risk patients). CONCLUSION: Among patients hospitalized owing to peptic ulcer bleeding and treated with PPIs, patients with high-risk stigmata have a higher risk of further bleeding and surgery, but not of death, than those with low-risk stigmata.

Predictive Score for Advanced Colorectal Neoplasia Based on Cardiovascular and Colorectal Cancer Risk Factors.

Background and Aims: Cardiovascular disease and colorectal cancer (CRC) are significant health problems and share some risk factors. The aim of our study was to develop and validate a predictive score for advanced colorectal neoplasia (CRN) based on risk factors for cardiovascular disease and CRC. Materials and Methods: A cross-sectional study comprising a derivation cohort and an external validation cohort of 1049 and 308 patients, respectively. A prediction score for advanced CRN (CRNAS: Colorectal Neoplasia Advanced Score) was developed from a logistic regression model, comprising sex, age, first-degree family history for CRC, systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, body mass index, diabetes, smoking, and antihypertensive treatment. Other cardiovascular risk scores (Framingham-Wilson, REGICOR, SCORE, and FRESCO) were also used to predict the risk of advanced CRN. The discriminatory capacity of each score was evaluated using the area under the curve (AUC). Results: CRN were found in 379 subjects from the derivation cohort (36%), including 228 patients (22%) with an advanced CRN. Male sex, age, diabetes, and smoking were identified as independent risk factors for advanced CRN. The newly created score (CRNAS) showed an AUC of 0.68 (95% CI: 0.64-0.73) for advanced CRN, which was better than cardiovascular risk scores (p < 0.001). In the validation cohort, the AUC of CRNAS for advanced CRN was 0.67 (95% CI: 0.57-0.76). Conclusions: The newly validated CRNAS has a better discriminatory capacity to predict advanced CRN than cardiovascular scores. It may be useful for selecting candidates for screening colonoscopy, especially in those with cardiovascular risk factors.

[Medicine consumption in the adult population: Influence of self-medication]. / Consumo de medicamentos en población adulta: influencia del autoconsumo.

OBJECTIVE: The objective of this study is to determine the factors associated with medicine consumption and self-consumption in Aragón (Spain) DESIGN: Cross-sectional study from the National Health Survey 2006. SETTING: Aragón (Spain). PARTICIPANTS: Adult population in Aragón (Spain). MAIN MEASUREMENTS: Medicine consumption and the type of consumption. Demographic, health and health style variables were also considered. RESULTS: At least one drug was taken by the 65.1% of the adults in Aragón during the previous two weeks. Of this group, 11.7% were self-medicated. A higher frequency of consumption was observed in females and older people, and in those with a poor self-perceived health. People with a low educational level took drugs more often, but self-consumption was more frequent in the group with a high educational level. CONCLUSIONS: Medicine consumption and self-consumption in adults in Aragón is common. It is of great interest to know the consumption profile of these patients in order to develop specific interventions to reduce unnecessary consumption and to improve safety.

Serum lipid mediator profiles in COVID-19 patients and lung disease severity: a pilot study.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is highly heterogeneous, ranging from asymptomatic to severe and fatal cases. COVID-19 has been characterized by an increase of serum pro-inflammatory cytokine levels which seems to be associated with fatal cases. By contrast, the role of pro-resolving lipid mediators (SPMs), involved in the attenuation of inflammatory responses, has been scarcely investigated, so further studies are needed to understand SPMs metabolism in COVID-19 and other infectious diseases. Our aim was to analyse the lipid mediator metabolome, quantifying pro- and anti-inflammatory serum bioactive lipids by LC-MS/MS in 7 non-infected subjects and 24 COVID-19 patients divided into mild, moderate, and severe groups according to the pulmonary involvement, to better understand the disease outcome and the severity of the pulmonary manifestations. Statistical analysis was performed with the R programming language (R Foundation for Statistical Computing, Vienna, Austria). All COVID-19 patients had increased levels of Prostaglandin E2. Severe patients showed a significant increase versus controls, mild- and moderate-affected patients, expressed as median (interquartile range), in resolvin E1 [112.6 (502.7) vs 0.0 (0.0) pg/ml in the other groups], as well as in maresin 2 [14.5 (7.0) vs 8.1 (4.2), 5.5 (4.3), and 3.0 (4.0) pg/ml, respectively]. Moreover, 14-hydroxy docosahexaenoic acid (14-HDHA) levels were also increased in severe vs control and mild-affected patients [24.7 (38.2) vs 2.4 (2.2) and 3.7 (6.4) ng/mL, respectively]. Resolvin D5 was also significantly elevated in both moderate [15.0 (22.4) pg/ml] and severe patients [24.0 (24.1) pg/ml] versus controls [0.0 (0.0) pg/ml]. These results were confirmed by sparse partial least squares discriminant analysis which highlighted the contribution of these mediators to the separation between each of the groups. In conclusion, the potent inflammatory response to SARS-CoV-2 infection involves not only pro- but also anti-inflammatory lipid mediators that can be quantified in easily accessible serum samples, suggesting the need to perform future research on their generation pathways that will help us to discover new therapeutic targets.

Management of Helicobacter Pylori Infection and Effectiveness Rates in Daily Clinical Practice in Spain: 2010-2019.

The management and effectiveness of the treatment of Helicobacter pylori infection are heterogeneous worldwide, despite the publication of international consensus conferences and guidelines, which have been widely available for years. The aim of the study was to describe the clinical management and the eradication rates in a region of Southern Europe (Spain). Between 2010 and 2019, we conducted a retrospective analysis of patients with H. pylori infection attended by gastroenterologists in two defined areas of the National Health System in Aragón. We compared the appropriateness of therapies according to guidelines, and described the effectiveness of each treatment. A total of 1644 penicillin non-allergic patients were included. The most prescribed therapy between 2010 and 2013 was the 'classic' triple therapy PCA (80%), whereas the 'concomitant' therapy PCAM was chosen by 90% of the gastroenterologists in 2015. After 2016, the use of the quadruple bismuth-containing therapy in a single capsule (Pylera®) quickly increased, representing almost half of the overall prescriptions in 2019. Throughout the decade, adherence to guidelines was 76.4% and global efficacy was 70.7% (ITT). Triple therapies' eradication rates were lower than 70% (ITT), whereas eradication rates with quadruple therapies achieved or were over 80% (ITT). In conclusion, despite the use of quadruple therapies and optimized treatments, the effectiveness of H. pylori management in daily clinical practice is far from the target of 90%.

Blood-Cell-Based Inflammatory Markers as a Useful Tool for Early Diagnosis in Colorectal Cancer.

Background: Systemic inflammation seems to be involved in the pathogenetic pathways of colorectal cancer (CRC). Analytical markers that reflect the inflammatory status, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) or systemic immune-inflammation index (SII), have been proposed as tools for the prognosis of CRC. Nevertheless, their use for diagnosis has been scarcely investigated. Aims: To analyze the ability of these markers and of a new marker combining SII and hemoglobin concentration, named NP/LHb = [neutrophils x platelets]/[lymphocytes x hemoglobin], as tools for CRC diagnosis. Furthermore, we studied their association with CRC-related variables. Methods: Case-control study including 214 CRC patients and 214 controls without CRC, matched by age (±5 years) and sex. We collected demographic, CRC-related and laboratory variables to calculate NLR, PLR, SII, and NP/LHb. In the case group, the laboratory variables were collected at two different period times, 6 months (IQR 4-8) before the CRC diagnosis and at the time of the diagnosis. ROC analysis was performed to evaluate the discriminatory accuracy of each index and we calculated Se, Sp, PPV, NPV, and OR to identify the diagnostic performance of each positive marker. Results: NP/LHb showed high Sp (92.06%) and PPV (87.50%) to diagnose patients with CRC. This index exhibited an OR of 14.52 (8.26-25.52) and the best area under the curve (AUC: 0.78) for a positive CRC diagnosis. We found significant differences in all indices according to the presence of CRC, observing the highest values in CRC patients at time of diagnosis, in comparison with the analysis performed in the previous months to diagnosis or with control patients. There were significant differences in all ratios according to TNM stages (p < 0.05). PLR, SII and NP/LHb (but not NLR) showed significant differences according to tumor location (p < 0.05). Right-sided colon cancers presented the highest values, in comparison with left-sided and rectal cancers. Conclusions: Systemic inflammatory cell ratios (especially NP/LHb) change over time with the development of CRC, so they could be useful in its early diagnosis. We suggest that they could be routinely measured in patients with suspicion of CRC, to identify those ones with a higher risk of cancer, considering the high positive predictive value they have shown in our study.

Evidence-Based Selection on the Appropriate FIT Cut-Off Point in CRC Screening Programs in the COVID Pandemic.

Background: The COVID pandemic has forced the closure of many colorectal cancer (CRC) screening programs. Resuming these programs is a priority, but fewer colonoscopies may be available. We developed an evidence-based tool for decision-making in CRC screening programs, based on a fecal hemoglobin immunological test (FIT), to optimize the strategy for screening a population for CRC. Methods: We retrospectively analyzed data collected at a regional CRC screening program between February/2014 and November/2018. We investigated two different scenarios: not modifying vs. modifying the FIT cut-off value. We estimated program outcomes in the two scenarios by evaluating the numbers of cancers and adenomas missed or not diagnosed in due time (delayed). Results: The current FIT cut-off (20-µg hemoglobin/g feces) led to 6,606 colonoscopies per 100,000 people invited annually. Without modifying this FIT cut-off value, when the optimal number of individuals invited for colonoscopies was reduced by 10-40%, a high number of CRCs and high-risk adenomas (34-135 and 73-288/100.000-people invited, respectively) will be undetected every year. When the FIT cut-off value was increased to where the colonoscopy demand matched the colonoscopy availability, the number of missed lesions per year was remarkably reduced (9-36 and 29-145/100.000 people, respectively). Moreover, the unmodified FIT scenario outcome was improved by prioritizing the selection process based on sex (males) and age, rather than randomly reducing the number invited. Conclusions: Assuming a mismatch between the availability and demand for annual colonoscopies, increasing the FIT cut-off point was more effective than randomly reducing the number of people invited. Using specific risk factors to prioritize access to colonoscopies should be also considered.

Familial Colorectal Cancer and Genetic Susceptibility: Colorectal Risk Variants in First-Degree Relatives of Patients With Colorectal Cancer.

INTRODUCTION: Epidemiological studies estimate that having a first-degree relative (FDR) with colorectal cancer (CRC) increases 2-fold to 3-fold the risk of developing the disease. Because FDRs of CRC patients are more likely to co-inherit CRC risk variants, we aimed to evaluate potential differences in genotype distribution of single nucleotide polymorphisms (SNPs) related to CRC risk between FDRs of patients with nonsyndromic CRC (cases) and individuals with no family history of CRC (controls). METHODS: We designed a case-control study comprising 750 cases and 750 Spanish Caucasian controls matched by sex, age, and histological findings after colonoscopy. Genomic DNA from all participants was genotyped for 88 SNPs associated with CRC risk using the MassArray (Sequenom) platform. RESULTS: Ten of the 88 SNPs analyzed revealed significant associations (P < 0.05) with a family history of CRC in our population. The most robust associations were found for the rs17094983G>A SNP in the long noncoding RNA LINC01500 (odds ratio = 0.72; 95% confidence interval: 0.58-0.88, log-additive model), and the rs11255841T>A SNP in the long noncoding RNA LINC00709 (odds ratio = 2.04; 95% confidence interval: 1.19-3.51, dominant model). Of interest, the observed associations were in the same direction than those reported for CRC risk. DISCUSSION: FDRs of CRC patients show significant differences in genotype distribution of SNPs related to CRC risk as compared to individuals with no family history of CRC. Genotyping of CRC risk variants in FDRs of CRC patients may help to identify subjects at risk that would benefit from stricter surveillance and CRC screening programs.

Multiple Approaches at Admission Based on Lung Ultrasound and Biomarkers Improves Risk Identification in COVID-19 Patients.

BACKGROUND: Risk stratification of COVID-19 patients is fundamental to improving prognosis and selecting the right treatment. We hypothesized that a combination of lung ultrasound (LUZ-score), biomarkers (sST2), and clinical models (PANDEMYC score) could be useful to improve risk stratification. METHODS: This was a prospective cohort study designed to analyze the prognostic value of lung ultrasound, sST2, and PANDEMYC score in COVID-19 patients. The primary endpoint was in-hospital death and/or admission to the intensive care unit. The total length of hospital stay, increase of oxygen flow, or escalated medical treatment during the first 72 h were secondary endpoints. RESULTS: a total of 144 patients were included; the mean age was 57.5 ± 12.78 years. The median PANDEMYC score was 243 (52), the median LUZ-score was 21 (10), and the median sST2 was 53.1 ng/mL (30.9). Soluble ST2 showed the best predictive capacity for the primary endpoint (AUC = 0.764 (0.658-0.871); p = 0.001), towards the PANDEMYC score (AUC = 0.762 (0.655-0.870); p = 0.001) and LUZ-score (AUC = 0.749 (0.596-0.901); p = 0.002). Taken together, these three tools significantly improved the risk capacity (AUC = 0.840 (0.727-0.953); p ≤ 0.001). CONCLUSIONS: The PANDEMYC score, lung ultrasound, and sST2 concentrations upon admission for COVID-19 are independent predictors of intra-hospital death and/or the need for admission to the ICU for mechanical ventilation. The combination of these predictive tools improves the predictive power compared to each one separately. The use of decision trees, based on multivariate models, could be useful in clinical practice.

[Prevalence of SARS-CoV-2 coronavirus infection in patients and professional staff at a medium or long-stay hospital in Spain]. / Prevalencia de infección por coronavirus SARS-CoV-2 en pacientes y profesionales de un hospital de media y larga estancia en España.

BACKGROUND AND GOALS: The aim of the study is to know the prevalence of SARS-CoV-2 infection in patients and professional staff of a medium or long-stay hospital during the peak period of the pandemic in Spain, spring 2020. MATERIAL AND METHODS: At the end of February 2020, we developed at the hospital a strategy to diagnose the SARS-CoV-2 infection consisting of complementing the realization of PCR tests at real time with a quick technique of lateral flow immunochromatography to detect IgG and IgM antibodies against the virus. We also developed a protocol to realize those diagnostic tests and considered an infection (current or past) a positive result in any of the above tests. We included 524 participants in the study (230 patients and 294 hospital staff), and divided them into hospital patients and Hemodialysis outpatients. Furthermore, we divided the hospital staff into healthcare and non-healthcare staff. The documented period was from March, 20th to April, 21st, 2020. RESULTS: 26 out of 230 patients tested positive in any of the diagnostic techniques (PCR, antibodies IgG, IgM) with a 11.30% prevalence. According to patients groups, we got a 14.38% prevalence in hospital patients vs. 5.95% in outpatients, with a significantly higher risk in admitted patients after adjustment for age and gender (OR=3,309, 95%CI: 1,154-9,495). 24 out of 294 hospital staff tested positive in any of the diagnostic techniques, with a 8.16% prevalence. According to the groups, we got a 8.91% prevalence in healthcare staff vs. 4.26% in non-healthcare staff. Thus, we do not see any statistically significant differences between hospital staff and patients as far as prevalence is concerned (P=0,391), (OR=2,200, 95%CI: 0,500-9,689). CONCLUSIONS: The result of the study was a quite low prevalence rate of SARS-CoV-2 infection, in both patients and hospital staff, being the hospital patients' prevalence rate higher than the outpatients', and the healthcare staff higher than the non-healthcare's. Combining PCR tests (gold standard) with antibodies tests proved useful as a diagnostic strategy.