Coffee and Microbiota: A Narrative Review.

Coffee is one of the most widely consumed beverages in the world, which has important repercussions on the health of the individual, mainly because of certain compounds it contains. Coffee consumption exerts significant influences on the entire body, including the gastrointestinal tract, where a central role is played by the gut microbiota. Dysbiosis in the gut microbiota is implicated in the occurrence of numerous diseases, and knowledge of the microbiota has proven to be of fundamental importance for the development of new therapeutic strategies. In this narrative review, we thoroughly investigated the link between coffee consumption and its effects on the gut microbiota and the ensuing consequences on human health. We have selected the most significant articles published on this very interesting link, with the aim of elucidating the latest evidence about the relationship between coffee consumption, its repercussions on the composition of the gut microbiota, and human health. Based on the various studies carried out in both humans and animal models, it has emerged that coffee consumption is associated with changes in the gut microbiota, although further research is needed to understand more about this link and the repercussions for the whole organism.

PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications.

Sepsis is a serious organ dysfunction caused by a dysregulated immune host reaction to a pathogen. The innate immunity is programmed to react immediately to conserved molecules, released by the pathogens (PAMPs), and the host (DAMPs). We aimed to review the molecular mechanisms of the early phases of sepsis, focusing on PAMPs, DAMPs, and their related pathways, to identify potential biomarkers. We included studies published in English and searched on PubMed® and Cochrane®. After a detailed discussion on the actual knowledge of PAMPs/DAMPs, we analyzed their role in the different organs affected by sepsis, trying to elucidate the molecular basis of some of the most-used prognostic scores for sepsis. Furthermore, we described a chronological trend for the release of PAMPs/DAMPs that may be useful to identify different subsets of septic patients, who may benefit from targeted therapies. These findings are preliminary since these pathways seem to be strongly influenced by the peculiar characteristics of different pathogens and host features. Due to these reasons, while initial findings are promising, additional studies are necessary to clarify the potential involvement of these molecular patterns in the natural evolution of sepsis and to facilitate their transition into the clinical setting.

Gut-Brain Axis: Focus on Sex Differences in Neuroinflammation.

In recent years, there has been a growing interest in the concept of the "gut-brain axis". In addition to well-studied diseases associated with an imbalance in gut microbiota, such as cancer, chronic inflammation, and cardiovascular diseases, research is now exploring the potential role of gut microbial dysbiosis in the onset and development of brain-related diseases. When the function of the intestinal barrier is altered by dysbiosis, the aberrant immune system response interacts with the nervous system, leading to a state of "neuroinflammation". The gut microbiota-brain axis is mediated by inflammatory and immunological mechanisms, neurotransmitters, and neuroendocrine pathways. This narrative review aims to illustrate the molecular basis of neuroinflammation and elaborate on the concept of the gut-brain axis by virtue of analyzing the various metabolites produced by the gut microbiome and how they might impact the nervous system. Additionally, the current review will highlight how sex influences these molecular mechanisms. In fact, sex hormones impact the brain-gut microbiota axis at different levels, such as the central nervous system, the enteric nervous one, and enteroendocrine cells. A deeper understanding of the gut-brain axis in human health and disease is crucial to guide diagnoses, treatments, and preventive interventions.

New Advances in Gastroenterology: The Crucial Role of Molecular Medicine.

The significant progress we have recently observed in the field of gastroenterology, both in the understanding of pathophysiological mechanisms and in the diagnosis and treatment of diseases, is closely related to the improvement and discovery of new biomolecular techniques [...].

The Interplay between Helicobacter pylori and Gut Microbiota in Non-Gastrointestinal Disorders: A Special Focus on Atherosclerosis.

The discovery of Helicobacter pylori (H. pylori) in the early 1980s by Nobel Prize winners in medicine Robin Warren and Barry Marshall led to a revolution in physiopathology and consequently in the treatment of peptic ulcer disease. Subsequently, H. pylori has also been linked to non-gastrointestinal diseases, such as autoimmune thrombocytopenia, acne rosacea, and Raynaud's syndrome. In addition, several studies have shown an association with cardiovascular disease and atherosclerosis. Our narrative review aims to investigate the connection between H. pylori infection, gut microbiota, and extra-gastric diseases, with a particular emphasis on atherosclerosis. We conducted an extensive search on PubMed, Google Scholar, and Scopus, using the keywords "H. pylori", "dysbiosis", "microbiota", "atherosclerosis", "cardiovascular disease" in the last ten years. Atherosclerosis is a complex condition in which the arteries thicken or harden due to plaque deposits in the inner lining of an artery and is associated with several cardiovascular diseases. Recent research has highlighted the role of the microbiota in the pathogenesis of this group of diseases. H. pylori is able to both directly influence the onset of atherosclerosis and negatively modulate the microbiota. H. pylori is an important factor in promoting atherosclerosis. Progress is being made in understanding the underlying mechanisms, which could open the way to interesting new therapeutic perspectives.

Recent Advances and Future Challenges in the Field of Digestive Diseases.

Digestive diseases are a rapidly evolving area of clinical and research [...].

Are Short-Stay Units Safe and Effective in the Treatment of Non-Variceal Upper Gastrointestinal Bleeding?

Introduction: Emergency Department (ED) overcrowding is a health, political, and economic problem of concern worldwide. The causes of overcrowding are an aging population, an increase in chronic diseases, a lack of access to primary care, and a lack of resources in communities. Overcrowding has been associated with an increased risk of mortality. The establishment of a Short Stay Unit (SSU) for conditions that cannot be treated at home but require treatment and hospitalization for up to 72 h may be a solution. SSU can significantly reduce hospital length of stay (LOS) for certain conditions but does not appear to be useful for other diseases. Currently, there are no studies addressing the efficacy of SSU in the treatment of non-variceal upper gastrointestinal bleeding (NVUGIB). Our study aims to evaluate the efficacy of SSU in reducing the need for hospitalization, LOS, hospital readmission, and mortality in patients with NVUGIB compared with admission to the regular ward. Materials and Methods: This was a retrospective, single-center observational study. Medical records of patients presenting with NVUGIB to ED between 1 April 2021, and 30 September 2022, were analyzed. We included patients aged >18 years who presented to ED with acute upper gastrointestinal tract blood loss. The test population was divided into two groups: Patients admitted to a normal inpatient ward (control) and patients treated at SSU (intervention). Clinical and medical history data were collected for both groups. The hospital LOS was the primary outcome. Secondary outcomes were time to endoscopy, number of blood units transfused, readmission to the hospital at 30 days, and in-hospital mortality. Results: The analysis included 120 patients with a mean age of 70 years, 54% of whom were men. Sixty patients were admitted to SSU. Patients admitted to the medical ward had a higher mean age. The Glasgow-Blatchford score, used to assess bleeding risk, mortality, and hospital readmission were similar in the study groups. Multivariate analysis after adjustment for confounders found that the only factor independently associated with shorter LOS was admission to SSU (p < 0.0001). Admission to SSU was also independently and significantly associated with a shorter time to endoscopy (p < 0.001). The only other factor associated with a shorter time to EGDS was creatinine level (p = 0.05), while home treatment with PPI was associated with a longer time to endoscopy. LOS, time to endoscopy, number of patients requiring transfusion, and number of units of blood transfused were significantly lower in patients admitted to SSU than in the control group. Conclusions: The results of the study show that treatment of NVUGIB in SSU can significantly reduce the time required for endoscopy, the hospital LOS, and the number of transfused blood units without increasing mortality and hospital readmission. Treatment of NVUGIB at SSU may therefore help to reduce ED overcrowding but multicenter randomized controlled trials are needed to confirm these data.

Translational, Precision, and Personalized Medicine in Gastroenterology.

In recent decades, tremendous progress has been made in the medicinal field in understanding the molecular mechanisms underlying human pathologies, due to the significant development of advanced laboratory techniques and technologies [...].

Gastrointestinal Bleeding Due to NOACs Use: Exploring the Molecular Mechanisms.

Novel oral anticoagulants (NOACs) are drugs approved for the prevention and treatment of many thromboembolic cardiovascular conditions as a safer alternative to warfarin. We reviewed studies published in PubMed®, UpToDate®, Web of Science®, and Cochrane® about NOACs' risks and benefits in patients requiring anticoagulation, with a focus on gastrointestinal bleeding and on molecular and pathophysiological mechanisms underlying the risk of bleeding in patients treated with them. Apixaban resulted in a lower rate of gastrointestinal bleeding compared to dabigatran and rivaroxaban. However, data reported that gastrointestinal bleeding in patients treated with NOACs was less severe compared to warfarin. Studies show promising results on the increased and widespread use of NOACs in patients who require anticoagulation (for example-in case of atrial fibrillation or high risk of venous thromboembolism), reporting an overall lower risk of major bleeding events. The profile of NOACs was more effective and secure compared to warfarin, but a more careful medical prescription is required in patients who are at high risk of gastrointestinal bleeding.

Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers.

Our digestive system, particularly our intestines, harbors a vast amount of microorganisms, whose genetic makeup is referred to as the microbiome. Clostridium difficile is a spore-forming Gram-positive bacterium, which can cause an infection whose symptoms range from asymptomatic colonization to fearsome complications such as the onset of toxic megacolon. The relationship between gut microbiota and Clostridium difficile infection has been studied from different perspectives. One of the proposed strategies is to be able to specifically identify which types of microbiota alterations are most at risk for the onset of CDI. In this article, we understood once again how crucial the role of the human microbiota is in health and especially how crucial it becomes, in the case of its alteration, for the individual's disease. Clostridium difficile infection is an emblematic example of how a normal and physiological composition of the human microbiome can play a very important role in immune defense against such a fearsome disease.

Autoimmune Pancreatitis: From Pathogenesis to Treatment.

Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological, serological, and pathological findings. Two different types of AIP have been identified: autoimmune pancreatitis type 1 (AIP-1), which is considered a pancreatic manifestation of multiorgan disease related to IgG4, and autoimmune pancreatitis type 2 (AIP-2), which is considered a pancreas-specific disease not related to IgG4. Although the pathophysiological conditions seem to differ between type 1 and type 2 pancreatitis, both respond well to steroid medications. In this review, we focused on the pathogenesis of the disease to develop a tool that could facilitate diagnosis and lead to the discovery of new therapeutic strategies to combat autoimmune pancreatitis and its relapses. The standard therapy for AIP is oral administration of corticosteroids. Rituximab (RTX) has also been proposed for induction of remission and maintenance therapy in relapsing AIP-1. In selected patients, immunomodulators such as azathioprine are used to maintain remission. The strength of this review, compared with previous studies, is that it focuses on the clear difference between the two types of autoimmune pancreatitis with a clearly delineated and separate pathogenesis. In addition, the review also considers various therapeutic options, including biologic drugs, such as anti-tumor necrosis factor (TNF) therapy, a well-tolerated and effective second-line therapy for AIP type 2 relapses or steroid dependence. Other biologic therapies are also being explored that could provide a useful therapeutic alternative to corticosteroids and immunosuppressants, which are poorly tolerated due to significant side effects.

Gastrointestinal Involvement in Extra-Digestive Disease: Which Is the Role of Fecal Calprotectin?

Fecal calprotectin (FC) is a very sensitive marker of inflammation of the gastrointestinal tract. Its clinical utility can be appreciated in both intestinal and extraintestinal diseases. Recent evidence suggests a link between intestinal inflammation and dermatological, rheumatic and neurological diseases. This review focuses on the role of FC in non-gastrointestinal disease, such as rheumatic, dermatologic, neurologic and last but not least SARS-CoV-2 infection.

Interaction between Lipopolysaccharide and Gut Microbiota in Inflammatory Bowel Diseases.

Lipopolysaccharides (LPSs) are bacterial surface glycolipids, produced by Gram-negative bacteria. LPS is known to determine acute inflammatory reactions, particularly in the context of sepsis. However, LPS can also trigger chronic inflammation. In this case, the source of LPS is not an external infection, but rather an increase in endogenous production, which is usually sustained by gut microbiota (GM), and LPS contained in food. The first site in which LPS can exert its inflammatory action is the gut: both GM and gut-associated lymphoid tissue (GALT) are influenced by LPS and shift towards an inflammatory pattern. The changes in GM and GALT induced by LPS are quite similar to the ones seen in IBD: GM loses diversity, while GALT T regulatory (Tregs) lymphocytes are reduced in number, with an increase in Th17 and Th1 lymphocytes. Additionally, the innate immune system is triggered, through the activation of toll-like receptor (TLR)-4, while the epithelium is directly damaged, further triggering inflammation. In this review, we will discuss the importance of the crosstalk between LPS, GM, and GALT, and discuss the possible implications.

Humoral Predictors of Malignancy in IPMN: A Review of the Literature.

Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5-9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.

Lactobacillus Reuteri DSM 17938 (Limosilactobacillus reuteri) in Diarrhea and Constipation: Two Sides of the Same Coin?

Background and Objectives: Lactobacillus reuteri DSM 17938 (L. reuteri) is a probiotic that can colonize different human body sites, including primarily the gastrointestinal tract, but also the urinary tract, the skin, and breast milk. Literature data showed that the administration of L. reuteri can be beneficial to human health. The aim of this review was to summarize current knowledge on the role of L. reuteri in the management of gastrointestinal symptoms, abdominal pain, diarrhea and constipation, both in adults and children, which are frequent reasons for admission to the emergency department (ED), in order to promote the best selection of probiotic type in the treatment of these uncomfortable and common symptoms. Materials and Methods: We searched articles on PubMed® from January 2011 to January 2021. Results: Numerous clinical studies suggested that L. reuteri may be helpful in modulating gut microbiota, eliminating infections, and attenuating the gastrointestinal symptoms of enteric colitis, antibiotic-associated diarrhea (also related to the treatment of Helicobacter pylori (HP) infection), irritable bowel syndrome, inflammatory bowel disease, and chronic constipation. In both children and in adults, L. reuteri shortens the duration of acute infectious diarrhea and improves abdominal pain in patients with colitis or inflammatory bowel disease. It can ameliorate dyspepsia and symptoms of gastritis in patients with HP infection. Moreover, it improves gut motility and chronic constipation. Conclusion: Currently, probiotics are widely used to prevent and treat numerous gastrointestinal disorders. In our opinion, L. reuteri meets all the requirements to be considered a safe, well-tolerated, and efficacious probiotic that is able to contribute to the beneficial effects on gut-human health, preventing and treating many gastrointestinal symptoms, and speeding up the recovery and discharge of patients accessing the emergency department.

Microbiota and Probiotics: The Role of Limosilactobacillus Reuteri in Diverticulitis.

The microbiota is the set of commensal microorganisms, residing in the organism, helping proper functioning of organs and systems. The role that the microbiota plays in maintaining the health of vertebrates is widely accepted, particularly in the gastrointestinal system, where it is fundamental for immunity, development, and conversion of nutrients. Dysbiosis is an alteration of the microbiota which refers to a disturbed balance, which can cause a number of pathologies. Probiotics have proven to be effective in modulating the microbiota of the gastrointestinal system and, therefore, in promoting the health of the individual. In particular, Lactobacilli are a group of Gram-positive bacteria, which are able to produce lactic acid through glucose metabolism. They are present in different microenvironments, ranging from the vagina, to the mouth, to different tracts of the small intestine. In the present review, we will discuss the use of Limosilactobacillus in human health in general and more specifically in diverticulitis. In particular we analyze the role of Limosilactobacillus reuteri and its anti-inflammatory action. For this review, articles were identified using the electronic PubMed database through a comprehensive search, conducted by combining key terms such as "diverticulitis", "Limosilactobacillus reuteri", "human health and disease", "probiotics". We selected all the articles published in the last 10 years and screened 1017 papers. Articles referenced in the screened papers were evaluated if considered interesting for our topic. Probiotics have proven to be effective in modulating the microbiota of the gastrointestinal system and, therefore, in promoting the health of the individual. The importance of probiotics in treating diverticular disease and acute diverticulitis can be further understood if taking into consideration some pathophysiological aspects, associated to the microbiota. L. reuteri plays an important role in human health and disease. The effectiveness of L. reuteri in stimulating a correct bowl motility partly explains its effectiveness in treating diverticulitis. The most important action of L. reuteri is probably its immunomodulating activity. Levels of IL-6, IL-8, and Tumor necrosis factor (TNF-alpha) are reduced after supplementation with different strands of Lactobacilli, while T-regulatory cells increase in number and activity. Anyway, new mechanisms of action of probiotics come to light from the many investigations currently taking place in numerous centres around the world and to improve how exactly probiotic administration could make the difference in the management of diverticular disease and acute diverticulitis.

The Role of Early Procalcitonin Determination in the Emergency Departiment in Adults Hospitalized with Fever.

Background and Objectives: Fever is one of the most common presenting complaints in the Emergency Department (ED). The role of serum procalcitonin (PCT) determination in the ED evaluation of adults presenting with fever is still debated. The aim of this study was to evaluate if, in adults presenting to the ED with fever and then hospitalized, the early PCT determination could improve prognosis. Materials and Methods. This is a retrospective, mono-centric study, conducted over a 10-year period (2009-2018). We analyzed consecutive patients ≥18 years admitted to ED with fever and then hospitalized. According to quick sequential organ failure assessment (qSOFA) at admission, we compared patients that had a PCT determination vs. controls. Primary endpoint was overall in-hospital mortality; secondary endpoints were in-hospital length of stay, and mortality in patients with bloodstream infection and acute respiratory infections. Results. The sample included 12,062 patients, median age was 71 years and 55.1% were men. In patients with qSOFA ≥ 2 overall mortality was significantly lower if they had a PCT-guided management in ED, (20.5% vs. 26.5%; p = 0.046). In the qSOFA < 2 group the mortality was not significantly different in PCT patients, except for those with a final diagnosis of bloodstream infection. Conclusions. Among adults hospitalized with fever, the PCT evaluation at ED admission was not associated with better outcomes, with the possible exception of patients affected by bloodstream infections. However, in febrile patients presenting to the ED with qSOFA ≥ 2, the early PCT evaluation could improve the overall in-hospital survival.

Factors Associated with ICU Admission in Patients with COVID-19: The GOL2DS Score.

Background and Objectives: The COVID-19 pandemic has been shaking lives around the world for nearly two years. The discovery of highly effective vaccines has not been able to stop the transmission of the virus. SARS-CoV-2 shows completely different clinical manifestations. A large percentage (about 40%) of admitted patients require treatment in an intensive care unit (ICU). This study investigates the factors associated with admission of COVID-19 patients to the ICU and whether it is possible to obtain a score that can help the emergency physician to select the hospital ward. Materials and Methods: We retrospectively recorded 313 consecutive patients who were presented to the emergency department (ED) of our hospital and had a diagnosis of COVID-19 confirmed by polymerase chain reaction (PCR) on an oropharyngeal swab. We used multiple logistic regression to evaluate demographic, clinical, and laboratory data statistically associated with ICU admission. These variables were used to create a prognostic score for ICU admission. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver-operating characteristic curve (ROC) of the score for predicting ICU admission during hospitalization were calculated. Results: Of the variables evaluated, only blood type A (p = 0.003), PaO2/FiO2 (p = 0.002), LDH (p = 0.004), lactate (p = 0.03), dyspnea (p = 0.03) and SpO2 (p = 0.0228) were significantly associated with ICU admission after adjusting for sex, age and comorbidity using multiple logistic regression analysis. We used these variables to create a prognostic score called GOL2DS (group A, PaO2/FiO2, LDH, lactate and dyspnea, and SpO2), which had high accuracy in predicting ICU admission (AUROC 0.830 [95% CI, 0.791-0.892). Conclusions: In our single-center experience, the GOL2DS score could be useful in identifying patients at high risk for ICU admission.

Proadrenomedullin in Sepsis and Septic Shock: A Role in the Emergency Department.

Sepsis and septic shock represent a leading cause of mortality in the Emergency Department (ED) and in the Intensive Care Unit (ICU). For these life-threating conditions, different diagnostic and prognostic biomarkers have been studied. Proadrenomedullin (MR-proADM) is a biomarker that can predict organ damage and the risk of imminent death in patients with septic shock, as shown by a large amount of data in the literature. The aim of our narrative review is to evaluate the role of MR-proADM in the context of Emergency Medicine and to summarize the current knowledge of MR-proADM as a serum indicator that is useful in the Emergency Department (ED) to determine an early diagnosis and to predict the long-term mortality of patients with sepsis and septic shock. We performed an electronic literature review to investigate the role of MR-proADM in sepsis and septic shock in the context of ED. We searched papers on PubMed®, Cochrane®, UptoDate®, and Web of Science® that had been published in the last 10 years. Data extracted from this literature review are not conclusive, but they show that MR-proADM may be helpful as a prognostic biomarker to stratify the mortality risk in cases of sepsis and septic shock with different degrees of organ damage, guiding emergency physicians in the diagnosis and the succeeding therapeutic workup. Sepsis and septic shock are conditions of high complexity and have a high risk of mortality. In the ED, early diagnosis is crucial in order to provide an early treatment and to improve patient survival. Diagnosis and prognosis are often the result of a combination of several tests. In our opinion, testing for MR-proADM directly in the ED could contribute to improving the prognostic assessment of patients, facilitating the subsequent clinical management and intensive treatment by the emergency physicians, but more studies are needed to confirm these results.

Presepsin as Early Marker of Sepsis in Emergency Department: A Narrative Review.

The diagnosis and treatment of sepsis have always been a challenge for the physician, especially in critical care setting such as emergency department (ED), and currently sepsis remains one of the major causes of mortality. Although the traditional definition of sepsis based on systemic inflammatory response syndrome (SIRS) criteria changed in 2016, replaced by the new criteria of SEPSIS-3 based on organ failure evaluation, early identification and consequent early appropriated therapy remain the primary goal of sepsis treatment. Unfortunately, currently there is a lack of a foolproof system for making early sepsis diagnosis because conventional diagnostic tools like cultures take a long time and are often burdened with false negatives, while molecular techniques require specific equipment and have high costs. In this context, biomarkers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT), are very useful tools to distinguish between normal and pathological conditions, graduate the disease severity, guide treatment, monitor therapeutic responses and predict prognosis. Among the new emerging biomarkers of sepsis, Presepsin (P-SEP) appears to be the most promising. Several studies have shown that P-SEP plasma levels increase during bacterial sepsis and decline in response to appropriate therapy, with sensitivity and specificity values comparable to those of PCT. In neonatal sepsis, P-SEP compared to PCT has been shown to be more effective in diagnosing and guiding therapy. Since in sepsis the P-SEP plasma levels increase before those of PCT and since the current methods available allow measurement of P-SEP plasma levels within 17 min, P-SEP appears a sepsis biomarker particularly suited to the emergency department and critical care.