Optimizing aspirin dose for colorectal cancer patients through deep phenotyping using novel biomarkers of drug action.

Background: Low-dose aspirin's mechanism of action for preventing colorectal cancer (CRC) is still debated, and the optimal dose remains uncertain. We aimed to optimize the aspirin dose for cancer prevention in CRC patients through deep phenotyping using innovative biomarkers for aspirin's action. Methods: We conducted a Phase II, open-label clinical trial in 34 CRC patients of both sexes randomized to receive enteric-coated aspirin 100 mg/d, 100 mg/BID, or 300 mg/d for 3 ± 1 weeks. Biomarkers were evaluated in blood, urine, and colorectal biopsies at baseline and after dosing with aspirin. Novel biomarkers of aspirin action were assessed in platelets and colorectal tissues using liquid chromatography-mass spectrometry to quantify the extent of cyclooxygenase (COX)-1 and COX-2 acetylation at Serine 529 and Serine 516, respectively. Results: All aspirin doses caused comparable % acetylation of platelet COX-1 at Serine 529 associated with similar profound inhibition of platelet-dependent thromboxane (TX)A2 generation ex vivo (serum TXB2) and in vivo (urinary TXM). TXB2 was significantly reduced in CRC tissue by aspirin 300 mg/d and 100 mg/BID, associated with comparable % acetylation of COX-1. Differently, 100 mg/day showed a lower % acetylation of COX-1 in CRC tissue and no significant reduction of TXB2. Prostaglandin (PG)E2 biosynthesis in colorectal tumors and in vivo (urinary PGEM) remained unaffected by any dose of aspirin associated with the variable and low extent of COX-2 acetylation at Serine 516 in tumor tissue. Increased expression of tumor-promoting genes like VIM (vimentin) and TWIST1 (Twist Family BHLH Transcription Factor 1) vs. baseline was detected with 100 mg/d of aspirin but not with the other two higher doses. Conclusion: In CRC patients, aspirin 300 mg/d or 100 mg/BID had comparable antiplatelet effects to aspirin 100 mg/d, indicating similar inhibition of the platelet's contribution to cancer. However, aspirin 300 mg/d and 100 mg/BID can have additional anticancer effects by inhibiting cancerous tissue's TXA2 biosynthesis associated with a restraining impact on tumor-promoting gene expression. EUDRACT number: 2018-002101-65. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03957902.

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.

Endomapper dataset of complete calibrated endoscopy procedures.

Computer-assisted systems are becoming broadly used in medicine. In endoscopy, most research focuses on the automatic detection of polyps or other pathologies, but localization and navigation of the endoscope are completely performed manually by physicians. To broaden this research and bring spatial Artificial Intelligence to endoscopies, data from complete procedures is needed. This paper introduces the Endomapper dataset, the first collection of complete endoscopy sequences acquired during regular medical practice, making secondary use of medical data. Its main purpose is to facilitate the development and evaluation of Visual Simultaneous Localization and Mapping (VSLAM) methods in real endoscopy data. The dataset contains more than 24 hours of video. It is the first endoscopic dataset that includes endoscope calibration as well as the original calibration videos. Meta-data and annotations associated with the dataset vary from the anatomical landmarks, procedure labeling, segmentations, reconstructions, simulated sequences with ground truth and same patient procedures. The software used in this paper is publicly available.

Screening uptake of colonoscopy versus fecal immunochemical testing in first-degree relatives of patients with non-syndromic colorectal cancer: A multicenter, open-label, parallel-group, randomized trial (ParCoFit study).

BACKGROUND: Colonoscopy screening is underused by first-degree relatives (FDRs) of patients with non-syndromic colorectal cancer (CRC) with screening completion rates below 50%. Studies conducted in FDR referred for screening suggest that fecal immunochemical testing (FIT) was not inferior to colonoscopy in terms of diagnostic yield and tumor staging, but screening uptake of FIT has not yet been tested in this population. In this study, we investigated whether the uptake of FIT screening is superior to the uptake of colonoscopy screening in the familial-risk population, with an equivalent effect on CRC detection. METHODS AND FINDINGS: This open-label, parallel-group, randomized trial was conducted in 12 Spanish centers between February 2016 and December 2021. Eligible individuals included asymptomatic FDR of index cases <60 years, siblings or ≥2 FDR with CRC. The primary outcome was to compare screening uptake between colonoscopy and FIT. The secondary outcome was to determine the efficacy of each strategy to detect advanced colorectal neoplasia (adenoma or serrated polyps ≥10 mm, polyps with tubulovillous architecture, high-grade dysplasia, and/or CRC). Screening-naïve FDR were randomized (1:1) to one-time colonoscopy versus annual FIT during 3 consecutive years followed by a work-up colonoscopy in the case of a positive test. Randomization was performed before signing the informed consent using computer-generated allocation algorithm based on stratified block randomization. Multivariable regression analysis was performed by intention-to-screen. On December 31, 2019, when 81% of the estimated sample size was reached, the trial was terminated prematurely after an interim analysis for futility. Study outcomes were further analyzed through 2-year follow-up. The main limitation of this study was the impossibility of collecting information on eligible individuals who declined to participate. A total of 1,790 FDR of 460 index cases were evaluated for inclusion, of whom 870 were assigned to undergo one-time colonoscopy (n = 431) or FIT (n = 439). Of them, 383 (44.0%) attended the appointment and signed the informed consent: 147/431 (34.1%) FDR received colonoscopy-based screening and 158/439 (35.9%) underwent FIT-based screening (odds ratio [OR] 1.08; 95% confidence intervals [CI] [0.82, 1.44], p = 0.564). The detection rate of advanced colorectal neoplasia was significantly higher in the colonoscopy group than in the FIT group (OR 3.64, 95% CI [1.55, 8.53], p = 0.003). Study outcomes did not change throughout follow-up. CONCLUSIONS: In this study, compared to colonoscopy, FIT screening did not improve screening uptake by individuals at high risk of CRC, resulting in less detection of advanced colorectal neoplasia. Further studies are needed to assess how screening uptake could be improved in this high-risk group, including by inclusion in population-based screening programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02567045).

Fecal occult blood and calprotectin testing to prioritize primary care patients for colonoscopy referral: The advantage study.

BACKGROUND: Colonoscopy is the gold standard for colorectal cancer (CRC) diagnosis and screening, but endoscopy services are usually overburdened. This study aims to investigate the usefulness of fecal hemoglobin (fHb) and calprotectin (FC) for the identification of patients with high probability of CRC who need urgent referral. METHODS: In a multicenter prospective study, we enrolled symptomatic patients referred from primary care for colonoscopy. Prior to bowel preparation, fHb and FC quantitative tests were performed. The diagnostic performance was estimated for each biomarker/combination. We built a multivariable predictive model based on logistic regression, translated to a nomogram and a risk calculator to assist clinicians in the decision-making process. RESULTS: The study included 1224 patients, of whom 69 (5.6%) had CRC. At the fHb cut-offs of >0 and 10 µg/g, the negative predictive values for CRC were 98.8% (95% confidence interval 97.8%-99.3%) and 98.6% (95%CI 97.7%-99.1%), and the sensitivities were 85.5% (95%CI 75.0%-92.8%) and 79.7% (95%CI 68.3%-88.4%), respectively. When we added the cut-off of 150 µg/g of FC to both fHb thresholds, the sensitivity of fecal tests improved. In the multivariate logistic regression model, the concentration of fHb was an independent predictor for CRC; age and gender were also independently associated with CRC. CONCLUSIONS: fHb and FC are useful as part of a triage tool to identify those symptomatic patients with high probability of CRC. This can be easily applied by physicians to prioritize high-risk patients for urgent colonoscopy.

Drug-Associated Gastropathy: Diagnostic Criteria.

Drugs are widely used to treat different diseases in modern medicine, but they are often associated with adverse events. Those located in the gastrointestinal tract are common and often mild, but they can be serious or life-threatening and determine the continuation of treatment. The stomach is often affected not only by drugs taken orally but also by those administered parenterally. Here, we review the mechanisms of damage, risk factors and specific endoscopic, histopathological and clinical features of those drugs more often involved in gastric damage, namely NSAIDs, aspirin, anticoagulants, glucocorticosteroids, anticancer drugs, oral iron preparations and proton pump inhibitors. NSAID- and aspirin-associated forms of gastric damage are widely studied and have specific features, although they are often hidden by the coexistence of Helicobacter pylori infection. However, the damaging effect of anticoagulants and corticosteroids or oral iron therapy on the gastric mucosa is controversial. At the same time, the increased use of new antineoplastic drugs, such as checkpoint inhibitors, has opened up a new area of gastrointestinal damage that will be seen more frequently in the near future. We conclude that there is a need to expand and understand drug-induced gastrointestinal damage to prevent and recognize drug-associated gastropathy in a timely manner.

Diagnosis and Treatment of Helicobacter pylori Infection in Real Practice-New Role of Primary Care Services in Antibiotic Resistance Era.

Helicobacter pylori (H. pylori) is a key agent in several upper gastrointestinal diseases. Treatment of H. pylori infection is the main strategy for resolving the associated gastroduodenal damage in infected patients and for the prevention of gastric cancer development. Infection management is becoming complex due to the increase in antibiotic resistance, which already represents a global healthcare problem. Resistance to clarithromycin, levofloxacin or metronidazole have forced the adaptation of eradication regimens in this new reality to reach the eradication rate target recommended in most international guidelines (>90%). In this challenging scenario, molecular methods are revolutionizing the diagnosis of antibiotic-resistant infections and the detection of antibiotic resistance and opening a path towards personalized treatments, although their use is not yet widespread. Moreover, the infection management by physicians is still not adequate, which contributes to aggravating the problem. Both gastroenterologists and mainly primary care physicians (PCPs), who currently routinely manage this infection, perform suboptimal management of the diagnosis and treatment of H. pylori infection by not following the current consensus recommendations. In order to improve H. pylori infection management and to increase PCPs' compliance with guidelines, some strategies have been evaluated with satisfactory results, but it is still necessary to design and evaluate new different approaches.

Biomarkers of Response to Low-Dose Aspirin in Familial Adenomatous Polyposis Patients.

BACKGROUND: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial. METHODS: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas. RESULTS: In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B2 generation ex vivo (serum TXB2). However, enhanced residual urinary 11-dehydro-TXB2 and urinary PGEM, primary metabolites of TXA2 and prostaglandin (PG)E2, respectively, were detected in association with incomplete acetylation of COX-1 in normal colorectal biopsies and adenomas. Proteomics of adenomas showed that Aspirin significantly modulated only eight proteins. The upregulation of vimentin and downregulation of HBB (hemoglobin subunit beta) distinguished two groups with high vs. low residual 11-dehydro-TXB2 levels, possibly identifying the nonresponders and responders to Aspirin. CONCLUSIONS: Although low-dose Aspirin appropriately inhibited the platelet, persistently high systemic TXA2 and PGE2 biosynthesis were found, plausibly for a marginal inhibitory effect on prostanoid biosynthesis in the colorectum. Novel chemotherapeutic strategies in FAP can involve blocking the effects of TXA2 and PGE2 signaling with receptor antagonists.

Dissecting the genetic heterogeneity of gastric cancer.

BACKGROUND: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. METHODS: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. FINDINGS: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. INTERPRETATION: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. FUNDING: German Research Foundation (DFG).

Advances in the pharmacotherapeutic management of refractory peptic ulcers.

INTRODUCTION: Refractory peptic ulcer is now a rare disease since most peptic ulcers heal with appropriate treatment with proton pump inhibitors (PPIs) and/or Helicobacter pylori eradication. AREAS COVERED: The most frequent cause of apparent refractoriness is lack of adherence to treatment. Persistence of H. pylori infection, use or abuse (often surreptitious) of high dose non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin (ASA) are the two major causes of true refractory ulcers. There is a growing number of peptic ulcers which are not linked to either NSAIDs or H. pylori infection. Refractoriness in these ulcers can be linked to gastric acid hypersecretion, rapid PPI metabolization, ischemia, chemo-radiotherapy, immune diseases, more rarely to other drugs or be fully idiopathic. Treatment of the cause of the ulcer, if known, is essential. This review is based on pertinent publications retrieved by a selective search in PubMed, with particular attention to refractory peptic ulcer. EXPERT OPINION: High-dose PPI or the new potassium competitive acid blocker or the combination of PPIs with misoprostol can be recommended in these cases. Other more experimental treatments such the topical application of platelet-rich plasma or mesenchymal stem cells have also been suggested. Surgery is the last option, but there is no guarantee of success, especially in NSAID or ASA abusers.

Bowel Preparation for Colonoscopy Changes Serum Composition as Detected by Thermal Liquid Biopsy and Fluorescence Spectroscopy.

(1) Background: About 50% of prescribed colonoscopies report no pathological findings. A secondary screening test after fecal immunochemical test positivity (FIT+) would be required. Considering thermal liquid biopsy (TLB) as a potential secondary test, the aim of this work was to study possible interferences of colonoscopy bowel preparation on TLB outcome on a retrospective study; (2) Methods: Three groups were studied: 1/514 FIT(+) patients enrolled in a colorectal screening program (CN and CP with normal and pathological colonoscopy, respectively), with blood samples obtained just before colonoscopy and after bowel preparation; 2/55 patients from the CN group with blood sample redrawn after only standard 8-10 h fasting and no bowel preparation (CNR); and 3/55 blood donors from the biobank considered as a healthy control group; (3) Results: The results showed that from the 514 patients undergoing colonoscopy, 247 had CN and 267 had CP. TLB parameters in these two groups were similar but different from those of the blood donors. The resampled patients (with normal colonoscopy and no bowel preparation) had similar TLB parameters to those of the blood donors. TLB parameters together with fluorescence spectra and other serum indicators (albumin and C-reactive protein) confirmed the statistically significant differences between normal colonoscopy patients with and without bowel preparation; (4) Conclusions: Bowel preparation seemed to alter serum protein levels and altered TLB parameters (different from a healthy subject). The diagnostic capability of other liquid-biopsy-based methods might also be compromised. Blood extraction after bowel preparation for colonoscopy should be avoided.

A Point-of-Care Faecal Test Combining Four Biomarkers Allows Avoidance of Normal Colonoscopies and Prioritizes Symptomatic Patients with a High Risk of Colorectal Cancer.

Most colonoscopies performed to evaluate gastrointestinal symptoms detect only non-relevant pathologies. We aimed to evaluate the diagnostic accuracy of a qualitative point-of-care (POC) test combining four biomarkers (haemoglobin, transferrin, calprotectin, and lactoferrin), a quantitative faecal immunochemical test (FIT) for haemoglobin, and a quantitative faecal calprotectin (FC) test in symptomatic patients prospectively recruited. Colorectal cancer (CRC), adenoma requiring surveillance, inflammatory bowel disease (IBD), microscopic colitis, and angiodysplasia were considered significant pathologies. A total of 571 patients were included. Significant pathology was diagnosed in 118 (20.7%), including 30 CRC cases (5.3%). The POC test yielded the highest negative predictive values: 94.8% for a significant pathology and 100% for CRC or IBD if the four markers turned negative (36.8% of the patients). Negative predictive values of FIT, FC, and its combination for diagnosis of a significant pathology were 88.4%, 87.6%, and 90.8%, respectively. Moreover, the positive predictive value using the POC test was 82.3% for significant pathology when all biomarkers tested positive (6% of the patients), with 70.6% of these patients diagnosed with CRC or IBD. The AUC of the POC test was 0.801 (95%CI 0.754-0.848) for the diagnosis of a significant pathology. Therefore, this POC faecal test allows the avoidance of unnecessary colonoscopies and prioritizes high risk symptomatic patients.

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.

Antitumor effects of lactate transport inhibition on esophageal adenocarcinoma cells.

As a consequence of altered glucose metabolism, cancer cell intake is increased, producing large amounts of lactate which is pumped out the cytosol by monocarboxylate transporters (MCTs). MCT 1 and MCT4 are frequently overexpressed in tumors, and recently, MCT inhibition has been reported to exert antineoplastic effects. In the present study, MCT1 and MCT4 levels were assessed in esophageal adenocarcinoma (EAC) cells and the effects of the MCT-1 selective inhibitor AZD3965, hypoxia, and a glucose overload were evaluated in vitro. Two EAC cell lines (OE33 and OACM5.1C) were treated with AZD3965 (10-100 nM) under different conditions (normoxia/hypoxia) and also different glucose concentrations, and parameters of cytotoxicity, oxidative stress, intracellular pH (pHi), and lactate levels were evaluated. MCT1 was present in both cell lines whereas MCT4 was expressed in OE33 cells and only in a small proportion of OACM5.1C cells. Glucose addition did not have any effect on apoptosis nor cell proliferation. AZD3965 increased apoptosis and reduced proliferation of OACM5.1C cells, effects which were abrogated when cells were growing in hypoxia. MCT1 inhibition increased intracellular lactate levels in all the cells evaluated, but this increase was higher in cells expressing only MCT1 and did not affect oxidative stress. AZD3965 induced a decrease in pHi of cells displaying low levels of MCT4 and also increased the sodium/hydrogen exchanger 1 (NHE-1) expression on these cells. These data provide in vitro evidence supporting the potential of MCT inhibitors as novel antineoplastic drugs for EAC and highlight the importance of achieving a complete MCT inhibition.

Management of iron-deficiency anemia following acute gastrointestinal hemorrhage: A narrative analysis and review.

Many patients experiencing acute gastrointestinal bleeding (GIB) require iron supplementation to treat subsequent iron deficiency (ID) or iron-deficiency anemia (IDA). Guidelines regarding management of these patients are lacking. We aimed to identify areas of unmet need in patients with ID/IDA following acute GIB in terms of patient management and physician guidance. We formed an international working group of gastroenterologists to conduct a narrative review based on PubMed and EMBASE database searches (from January 2000 to February 2021), integrated with observations from our own clinical experience. Published data on this subject are limited and disparate, and those relating to post-discharge outcomes, such as persistent anemia and re-hospitalization, are particularly lacking. Often, there is no post-discharge follow-up of these patients by a gastroenterologist. Acute GIB-related ID/IDA, however, is a prevalent condition both at the time of hospital admission and at hospital discharge and is likely underdiagnosed and undertreated. Despite limited data, there appears to be notable variation in the prescribing of intravenous (IV)/oral iron regimens. There is also some evidence suggesting that, compared with oral iron, IV iron may restore iron levels faster following acute GIB, have a better tolerability profile, and be more beneficial in terms of quality of life. Gaps in patient care exist in the management of acute GIB-related ID/IDA, yet further data from large population-based studies are needed to confirm this. We advocate the formulation of evidence-based guidance on the use of iron therapies in these patients, aiding a more standardized best-practice approach to patient care.

Indications and hemoglobin thresholds for red blood cell transfusion and iron replacement in adults with gastrointestinal bleeding: An algorithm proposed by gastroenterologists and patient blood management experts.

Gastrointestinal (GI) bleeding is associated with considerable morbidity and mortality. Red blood cell (RBC) transfusion has long been the cornerstone of treatment for anemia due to GI bleeding. However, blood is not devoid of potential adverse effects, and it is also a precious resource, with limited supplies in blood banks. Nowadays, all patients should benefit from a patient blood management (PBM) program that aims to minimize blood loss, optimize hematopoiesis (mainly by using iron replacement therapy), maximize tolerance of anemia, and avoid unnecessary transfusions. Integration of PBM into healthcare management reduces patient mortality and morbidity and supports a restrictive RBC transfusion approach by reducing transfusion rates. The European Commission has outlined strategies to support hospitals with the implementation of PBM, but it is vital that these initiatives are translated into clinical practice. To help optimize management of anemia and iron deficiency in adults with acute or chronic GI bleeding, we developed a protocol under the auspices of the Spanish Association of Gastroenterology, in collaboration with healthcare professionals from 16 hospitals across Spain, including expert advice from different specialties involved in PBM strategies, such as internal medicine physicians, intensive care specialists, and hematologists. Recommendations include how to identify patients who have anemia (or iron deficiency) requiring oral/intravenous iron replacement therapy and/or RBC transfusion (using a restrictive approach to transfusion), and transfusing RBC units 1 unit at a time, with assessment of patients after each given unit (i.e., "don't give two without review"). The advantages and limitations of oral versus intravenous iron and guidance on the safe and effective use of intravenous iron are also described. Implementation of a PBM strategy and clinical decision-making support, including early treatment of anemia with iron supplementation in patients with GI bleeding, may improve patient outcomes and lower hospital costs.

The impact of COVID-19 pandemic in the diagnosis and management of colorectal cancer patients.

The novel coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to healthcare systems worldwide, causing downscaling of almost all other activities, especially in its early stages. Currently, the availability of vaccines along with the spread of new viral variants has modified the epidemiology of the disease, and the previous activity is being gradually resumed in most healthcare facilities. In this review, we have summarized the influence of the COVID-19 pandemic in the diagnosis and management of colorectal cancer (CRC) patients. Population-based screening with either colonoscopy or fecal occult blood tests has proven to reduce CRC incidence and mortality, so screening programs have been implemented in most western countries. However, during the first COVID-19 wave, most of these programs had to be disrupted temporarily. In this review, we have thoroughly analyzed the consequences of these disruptions of screening programs as well as of the forced delays in diagnostic and therapeutic services on CRC prognosis, although its exact impact cannot be exactly measured yet. In any way, strategies to minimize its effect, such as catch-up strategies expanding the colonoscopy capacity or using fecal occult blood concentration and other risk factors to prioritize patients, are urgently needed. The COVID-19 pandemic has also led to a change in CRC patient presentation, with an overall temporary decreased incidence due to postponed diagnoses, but with more patients presenting in need of an emergency admission or with symptoms. Finally, changes in treatment approaches in CRC patients have been reported during the pandemic, namely a drop in the proportion of laparoscopic surgeries or a rise in short-term radiotherapy courses. We have therefore aimed to summarize the available evidence to guide the healthcare professionals treating CRC patients to choose the best treatment options in the current pandemic situation.