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.
(
) is a key agent in several upper gastrointestinal diseases. Treatment of
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
infection by not following the current consensus recommendations. In order to improve
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.
Background Understanding the enduring respiratory consequences of severe COVID-19 is crucial for comprehensive patient care. This study aims to evaluate the impact of post-COVID conditions on ...respiratory sequelae of severe acute respiratory distress syndrome (ARDS). Methods We examined 88 survivors of COVID-19-associated severe ARDS six months post-intensive care unit (ICU) discharge. Assessments included clinical and functional evaluation as well as plasma biomarkers of endothelial dysfunction, inflammation, and viral response. Additionally, an in vitro model using human umbilical vein endothelial cells (HUVECs) explored the direct impact of post-COVID plasma on endothelial function. Results Post-COVID patients with impaired gas exchange demonstrated persistent endothelial inflammation marked by elevated ICAM-1, IL-8, CCL-2, and ET-1 plasma levels. Concurrently, systemic inflammation, evidenced by NLRP3 overexpression and elevated levels of IL-6, sCD40-L, and C-reactive protein, was associated with endothelial dysfunction biomarkers and increased in post-COVID patients with impaired gas exchange. T-cell activation, reflected in CD69 expression, and persistently elevated levels of interferon-beta (IFN-beta) further contributed to sustained inflammation. The in vitro model confirmed that patient plasma, with altered levels of sCD40-L and IFN-beta proteins, has the capacity to alter endothelial function. Conclusions Six months post-ICU discharge, survivors of COVID-19-associated ARDS exhibited sustained elevation in endothelial dysfunction biomarkers, correlating with the severity of impaired gas exchange. NLRP3 inflammasome activity and persistent T-cell activation indicate on going inflammation contributing to persistent endothelial dysfunction, potentially intensified by sustained viral immune response. Keywords: Acute respiratory distress syndrome, Post-COVID-19 syndrome, Endothelial dysfunction, ICAM-1, Inflammation
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
CD39/NTPDase1 has emerged as an important molecule that contributes to maintain inflammatory and coagulatory homeostasis. Various studies have hypothesized the possible role of CD39 in COVID-19 ...pathophysiology since no confirmatory data shed light in this regard. Therefore, we aimed to quantify CD39 expression on COVID-19 patients exploring its association with severity clinical parameters and ICU admission, while unraveling the role of purinergic signaling on thromboinflammation in COVID-19 patients. We selected a prospective cohort of patients hospitalized due to severe COVID-19 pneumonia (n=75), a historical cohort of Influenza A pneumonia patients (n=18) and sex/age-matched healthy controls (n=30). CD39 was overexpressed in COVID-19 patients' plasma and immune cell subsets and related to hypoxemia. Plasma soluble form of CD39 (sCD39) was related to length of hospital stay and independently associated with intensive care unit admission (adjusted odds ratio 1.04, 95%CI 1.0-1.08, p=0.038), with a net reclassification index of 0.229 (0.118-0.287; p=0.036). COVID-19 patients showed extracellular accumulation of adenosine nucleotides (ATP and ADP), resulting in systemic inflammation and pro-coagulant state, as a consequence of purinergic pathway dysregulation. Interestingly, we found that COVID-19 plasma caused platelet activation, which was successfully blocked by the P2Y
receptor inhibitor, ticagrelor. Therefore, sCD39 is suggested as a promising biomarker for COVID-19 severity. As a conclusion, our study indicates that CD39 overexpression in COVID-19 patients could be indicating purinergic signaling dysregulation, which might be at the basis of COVID-19 thromboinflammation disorder.
Introduction
Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. ...Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy.
Methods
The expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using
in vitro
models. In addition, PSGL-1 impact on T-cells function was evaluated by
ex vivo
models.
Results
Data showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia.
Discussion
In conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.
COVID-19 has emerged as a devastating disease in the last 2 years. Many authors appointed to the importance of kallikrein-kinin system (KKS) in COVID-19 pathophysiology as it is involved in ...inflammation, vascular homeostasis, and coagulation. We aim to study the bradykinin cascade and its involvement in severity of patients with COVID-19. This is an observational cohort study involving 63 consecutive patients with severe COVID-19 pneumonia and 27 healthy subjects as control group. Clinical laboratory findings and plasma protein concentration of KKS peptides bradykinin (BK), BK1-8, KKS proteins high–molecular weight kininogen (HK), and KKS enzymes carboxypeptidase N subunit 1 (CPN1), kallikrein B1 (KLKB1), angiotensin converting enzyme 2 (ACE2), and C1 esterase inhibitor (C1INH) were analyzed. We detected dysregulated KKS in patients with COVID-19, characterized by an accumulation of BK1-8 in combination with decreased levels of BK. Accumulated BK1-8 was related to severity of patients with COVID-19. A multivariate logistic regression model retained BK1-8, BK, and D-dimer as independent predictor factors to intensive care unit (ICU) admission. A Youden’s optimal cutoff value of −0.352 was found for the multivariate model score with an accuracy of 92.9%. Multivariate model score-high group presented an odds ratio for ICU admission of 260.0. BK1-8 was related to inflammation, coagulation, and lymphopenia. Our data suggest that BK1-8/BK plasma concentration in combination with D-dimer levels might be retained as independent predictors for ICU admission in patients with COVID-19. Moreover, we reported KKS dysregulation in patients with COVID-19, which was related to disease severity by means of inflammation, hypercoagulation, and lymphopenia.
Nutritional Support in Pancreatic Diseases Cañamares-Orbís, Pablo; García-Rayado, Guillermo; Alfaro-Almajano, Enrique
Nutrients,
10/2022, Letnik:
14, Številka:
21
Journal Article
Recenzirano
Odprti dostop
This review summarizes the main pancreatic diseases from a nutritional approach. Nutrition is a cornerstone of pancreatic disease and is sometimes undervalued. An early identification of malnutrition ...is the first step in maintaining an adequate nutritional status in acute pancreatitis, chronic pancreatitis and pancreatic cancer. Following a proper diet is a pillar in the treatment of pancreatic diseases and, often, nutritional counseling becomes essential. In addition, some patients will require oral nutritional supplements and fat-soluble vitamins to combat certain deficiencies. Other patients will require enteral nutrition by nasoenteric tube or total parenteral nutrition in order to maintain the requirements, depending on the pathology and its consequences. Pancreatic exocrine insufficiency, defined as a significant decrease in pancreatic enzymes or bicarbonate until the digestive function is impaired, is common in pancreatic diseases and is the main cause of malnutrition. Pancreatic enzymes therapy allows for the management of these patients. Nutrition can improve the nutritional status and quality of life of these patients and may even improve life expectancy in patients with pancreatic cancer. For this reason, nutrition must maintain the importance it deserves.
Obstructive sleep apnea (OSA) patients are at special risk of suffering atherosclerosis, leading to major cardiovascular diseases. Notably, the transforming growth factor (TGF-β) plays a crucial role ...in the development and progression of atherosclerosis. In this context, the central regulator of TGF-β pathway, SMAD4 (small mother against decapentaplegic homolog 4), has been previously reported to be augmented in OSA patients, which levels were even higher in patients with concomitant cardiometabolic diseases. Here, we analyzed soluble and intracellular SMAD4 levels in plasma and monocytes from OSA patients and non-apneic subjects, with or without early subclinical atherosclerosis (eSA). In addition, we used in vitro and ex vivo models to explore the mechanisms underlying SMAD4 upregulation and release. Our study confirmed elevated sSMAD4 levels in OSA patients and identified that its levels were even higher in those OSA patients with eSA. Moreover, we demonstrated that SMAD4 is overexpressed in OSA monocytes and that intermittent hypoxia contributes to SMAD4 upregulation and release in a process mediated by NLRP3. In conclusion, this study highlights the potential role of sSMAD4 as a biomarker for atherosclerosis risk in OSA patients and provides new insights into the mechanisms underlying its upregulation and release to the extracellular space.
Obstructive sleep apnea (OSA) has been identified as a cardiovascular (CV) risk factor. The potential of OSA promoting the synthesis of CV biomarkers in acute coronary syndrome (ACS) is unknown. ...Ischemia-modified albumin (IMA) has been identified as a specific CV biomarker. The aim of this study was to evaluate the role of IMA as a potential biomarker for determining the impact of OSA in ACS patients. A total of 925 patients (15.5% women, age: 59 years, body mass index: 28.8 kg/m
) from the ISAACC study (NCT01335087) were included. During hospitalization for ACS, a sleep study for OSA diagnosis was performed and blood samples extraction for IMA determination were obtained. IMA values were significantly higher in severe OSA (median (IQR), 33.7 (17.2-60.3) U/L) and moderate (32.8 (16.9-58.8) U/L) than in mild/no OSA (27.7 (11.8-48.6) U/L) (
= 0.002). IMA levels were very weakly related to apnea-hypopnea index (AHI) as well as hospital and intensive care unit stay, although they only maintained a significant relationship with days of hospital stay after adjusting for sex, age and BMI (ß = 0.410,
= 0.013). The results of the present study would suggest a potentially weaker role of OSA in the synthesis of the CV risk biomarker IMA in patients with ACS than in primary prevention.
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