The Elevated De Ritis Ratio on Admission Is Independently Associated with Mortality in COVID-19 Patients.

Liver damage in COVID-19 patients was documented as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels or an elevated AST/ALT ratio, known as the De Ritis ratio. However, the prognostic value of the elevated De Ritis ratio in COVID-19 patients is still unknown. The aim of our study was to evaluate the prognostic value of the De Ritis ratio compared to other abnormal laboratory parameters and its relation to mortality. We selected 322 COVID-19 patients in this retrospective study conducted between November 2020 and March 2021. The laboratory parameters were measured on admission and followed till patient discharge or death. Of the 322 COVID-19 patients, 57 (17.7%) had gastrointestinal symptoms on admission. The multivariate analysis showed that the De Ritis ratio was an independent risk factor for mortality, with an OR of 29.967 (95% CI 5.266-170.514). In ROC analysis, the AUC value of the the De Ritis ratio was 0.85 (95% CI 0.777-0.923, p < 0.05) with sensitivity and specificity of 80.6% and 75.2%, respectively. A De Ritis ratio ≥1.218 was significantly associated with patient mortality, disease severity, higher AST and IL-6 levels, and a lower ALT level. An elevated De Ritis ratio on admission is independently associated with mortality in COVID-19 patients, indicating liver injury and cytokine release syndrome.

A peculiar pancreatic lesion: nodular foci of trilineage differentiation and diffuse islet cell hyperplasia / Egy különleges pancreaselváltozás: kevert differenciációjú nodularitás és diffúz szigetsejtes hyperplasia.

Összefoglaló. A szerzok egy különleges pancreaselváltozás esetét ismertetik, melyben az acinusok neuroendokrin jellegu transzformációja diffúz, atípusos megjelenésu szigetsejtes hyperplasiával társult, valamint a pancreas mindhárom sejtvonalát (acinaris, ductalis, insularis) tartalmazó nodulusok képzodtek. A komplex megjelenés ellenére a kórfolyamat nem járt endokrin tünetekkel. Esetünkben a kiváltó ok hátterében a struktúrák kóros progenitorsejt-differenciációja állhatott. Az irodalomban ilyen közlés eddig nem ismert. Orv Hetil. 2021; 162(6): 227-232. Summary. The authors present a case of a peculiar pancreatic lesion, in which the neuroendocrine transformation of the acini was associated with a diffuse, atypical insular hyperplasia, and micronodules exhibiting trilineage differentiation. Despite the complex alteration, no endocrine symptoms were noted. The case may represent the result of an abnormal pancreatic differentiation raising the possibility of reprogramming of the progenitor cells. To the best of our knowledge, this is the first report of such a lesion in the literature. Orv Hetil. 2021; 162(6): 227-232.

Real-life efficacy of vedolizumab on endoscopic healing in inflammatory bowel disease - A nationwide Hungarian cohort study.

Background: GEMINI trials demonstrated the therapeutic efficacy of vedolizumab (VDZ) in Crohn's disease (CD) and ulcerative colitis (UC).Research design and methods: Aim of this study was to determine the real-life effectiveness of VDZ on endoscopic healing in the Hungarian nationwide cohort of inflammatory bowel disease (IBD) patients based on the changes on clinical and endoscopic scores. Every adult IBD patient in the country (121 UC and 83 CD) who completed the short-term VDZ therapy was enrolled, of which 72 UC and 52 CD patients could complete the long-term therapy.Results: The rates of endoscopic healing were substantially higher in UC compared with CD patients during the short- and long-term therapy (52.9% vs. 21.7%, p < 0.0001, and 51.4% vs. 21.2%, p = 0.015, respectively). In CD, the rate of endoscopic healing was lower at week 14 compared with week 22 (14.5% vs. 37.0%, p = 0.026). Prior anti-TNF-α therapy (88.73%) was not associated with a significant decrease in therapeutic response. The average disease duration was significantly lower in CD patients achieving endoscopic healing at week 52 (11.75 vs. 5.27 years, p = 0.007).Conclusions: VDZ therapy is an effective therapeutic option in anti-TNF-α refractory IBD. However, the endoscopic healing rate was substantially lower and showed a significant delay in CD compared with UC.

Have biologics changed the natural history of Crohn's disease?

Crohn's disease (CD) is a progressive condition, with most patients developing a penetrating or stricturing phenotype over time. The introduction of anti-tumor necrosis factor (TNF) therapies over the past 10-15 years, which was supported by accumulating evidence both from trials and clinical practice, has led to a significant change in patient management, monitoring, and treatment algorithms. Anti-TNF therapy was demonstrated to be effective for both luminal and fistulizing disease. Regular therapy with both infliximab and adalimumab was shown to increase the likelihood of clinical remission and mucosal healing, as well as to reduce the need for surgery and hospitalization in both clinical trials and clinical practice, especially in patients with pediatric-onset CD, shorter disease duration, and when used in combination with immunosuppressives. This has led to new treatment goals and to the use of early aggressive medical therapy in a selected group of patients with a worse prognosis. Exploratory clinical trials are underway to determine if further optimization of therapies and treatment beyond clinical remission leads to superior disease outcomes. However, more long-term clinical data are needed to assess whether an early, aggressive therapeutic strategy employing anti-TNF, alone or in combination with biologicals, can further improve long-term disease outcomes in both pediatric patients and young adults.

Probiotics in the management of Crohn's disease and ulcerative colitis.

Probiotics are nowadays frequently used by patients with inflammatory bowel disease, however literature data are conflicting related to their importance. In mild to moderate ulcerative colitis probiotics can be used effectively in induction and maintaining remission, and prevention of pouchitis. As the other side of the shield, there is not sufficient evidence to support the use of probiotics in daily clinical practice in Crohn's disease. The aim of the present review is to provide help for clinicians about the probiotic use in patients with inflammatory bowel disease. The comparison of literature data is limited by the large number of probiotic strains, various combined preparations, and different doses applied in the clinical studies. Small number of comparable protocols and lack of standardization encumber the analysis of study results.

Clinical aspects of mucosal healing in inflammatory bowel diseases: what is it and what is the real value for the everyday practice?

The course of inflammatory bowel diseases is heterogeneous and varies over time. Therefore, the search for predictive factors has increasingly become the focus of research. Mucosal healing has emerged as an important objective, as evidence indicates that it is associated with improved disease outcome. Nevertheless, many unsolved questions remain, including the definition of complete or partial healing as well as the best assessment method using endoscopic or imaging techniques, most of which are relatively invasive and expensive procedures, which therefore are not ideal for frequent monitoring and it is not clear. This review summarizes the available evidence in order to assist clinicians when assessing the mucosal status in the everyday practice.

Update on the pharmacogenomics of proton pump inhibitors.

Proton pump inhibitors (PPIs) are widely used for the treatment of gastroesophageal reflux disease as well as other acid-related disorders. PPIs are metabolized primarily via the CYP2C19 and CYP3A4 isoenzymes; their activity is influenced both by exogenous and endogenous (pharmacogenetic) factors. The CYP2C19 polymorphism affects the metabolism of PPIs, causing large individual pharmacokinetic variations. Differences in the CYP2C19-mediated metabolism can produce marked interpatient variability in acid suppression, in drug-interaction potential and in clinical efficacy. Understanding the pharmacokinetic properties of PPIs and examining the pharmacogenetic alterations may help clinicians optimize PPI therapy and administer individual treatment, especially to nonresponder patients with gastroesophageal reflux disease or ulcer or after failed eradication therapy.

Low bone mass in microscopic colitis.

BACKGROUND: Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis. AIMS: The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis. METHODS: Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively) were measured using immunoassays. RESULTS: Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm²; p < 0.01). Bone mineral density at the non-dominant radius was decreased in microscopic colitis patients (0.565 ± 0.093 vs. 0.667 ± 0.072 g/cm²; p < 0.05) but unaffected in Crohn's disease patients (0.672 ± 0.056 g/cm²). Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p < 0.05). A negative correlation between beta-crosslaps concentration and the femoral and radius t-scores was evident in microscopic colitis patients. CONCLUSIONS: Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.

[Sedation and analgesia during gastrointestinal endoscopy]. / Szedáció és fájdalomcsillapítás az emésztorendszer endoszkópiája során.

Sedative and analgesic premedication is frequently used during gastrointestinal endoscopy. Sedation improves patient's compliance, helping the examinations and their safe completion, but it lengthens the procedures, increases the costs, and complications can occur. Sedative drugs are applied during upper and lower gastrointestinal endoscopy, and also at ERCP. The review summarizes the different forms of sedation, drugs, future techniques and possibilities of improvements. Moreover, sedation practice in Hungary is also described.

[Clinical pharmacological aspects of the proton pump inhibitor therapy: importance of pharmacogenetic differences in the clinical practice]. / Klinikai farmakológiai szempontok a protonpumpa-gátlók használatában - farmakogenetikai eltérések jelentôsége a klinikai gyakorlatban.

Proton pump inhibitors (PPIs) are widely used for the treatment of gastroesophageal reflux disease, as well as other acid-related disorders. Omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole effectively suppress gastric acid secretion by blocking the gastric acid pump, H+/K+ -adenosine triphosphatase (ATPase). Understanding the pharmacokinetic properties of PPIs and examining the pharmacogenetic differences may help clinicians to optimize PPI therapy and to perform individual treatment, especially in non-responder patients with GERD or ulcer or after failed eradication therapy.

Age and monosodium glutamate treatment cause changes in the stimulation-induced [3H]-norepinephrine release from rat nucleus tractus solitarii-dorsal vagal nucleus slices.

In nucleus tractus solitarii-dorsal vagal nucleus slices prepared from young adult rats (180-260 g) 10(-3) M L-glutamate and 10(-5) M baclofen caused a 2-3-fold increase of field stimulation-induced [3H]-norepinephrine release without affecting the resting release. In slices prepared from rats treated neonatally with monosodium glutamate neither L-glutamate nor baclofen had any effect on stimulation-induced norepinephrine release, tested between postnatal days 74-99 (350-530 g). In untreated littermates used in the same period (460-580 g) L-glutamate was fully effective whereas baclofen was ineffective. The tritium content in tissue extracts did not differ significantly in the three experimental groups. It is concluded that i) the loss of GABA(B) receptor-mediated disinhibitory stimulation of norepinephrine release is an age-related phenomenon and ii) neonatal monosodium glutamate treatment causes a damage in the local neural circuitry characterized by the loss of glutamate receptor-mediated mechanism that stimulates the release of norepinephrine.

Gyrus cinguli transection abolishes delta-opioid receptor-induced gastroprotection and alters alpha 2 adrenoceptor activity in the lower brainstem in rats.

Previously, using the acidified ethanol-induced ulcer model in rats, we demonstrated that the mainly vagus-dependent gastroprotective effect of intracerebroventricularly injected clonidine was mediated by beta-endorphin release in the lower brainstem. Presently, retroarcuate transections were used to evaluate the contribution of forebrain beta-endorphinergic projection in this mechanism. Since the transection trajectory affected the cingulate cortex and other forebrain structures, matching lesions were also performed. In control and sham-operated rats intracisternal injection of clonidine and the direct opioid receptor (delta type) stimulant peptide (D-Ala(2), D-Leu(5))-enkephalin caused a potent and fully naloxone-reversible (i.e. opioid receptor-mediated) protection against acidified ethanol-induced mucosal damage. In gyrus cinguli-transected rats (as well as in groups with midline hippocampal, thalamic and hypothalamic lesions) gastric mucosal protection induced centrally by direct delta-opioid receptor stimulation in the lower brainstem was completely abolished. The protective effect of clonidine was significantly reduced but it was still present in these animals. The residual protection by clonidine was naloxone-resistant, i.e. independent of an opioid mediation. Transections of the cingulate gyrus as well as thalamic but not the retroarcuate transections elevated plasma corticosterone levels. The changes seen in the clonidine/opioid-induced gastroprotection did not show any correlation with the changes in plasma corticosterone levels. It was concluded that (i) the transection of the cingulate cortex strongly influences the neural input to the nucleus tractus solitarii-dorsal motor vagal nucleus complex that is required for the activation of gastroprotective vagus outflow by delta-opioid receptor stimulation; (ii) the transection uncovers a direct, clonidine-induced gastroprotective pathway which is probably suppressed in intact animals.

Involvement of central K(ATP) channels in the gastric antisecretory action of alpha2-adrenoceptor agonists and beta-endorphin in rats.

The intracerebroventricularly (i.c.v.) injected presynaptic alpha2-adrenoceptor agonists, clonidine and oxymetazoline, exerted a dose-dependent inhibition on the gastric acid secretion in pylorus-ligated rats; the ED50 values were 20 and 7.5 nmol/rat, respectively. Moreover, beta-endorphin, given i.c.v., also decreased acid secretion (ED50=0.25 nmol/rat i.c.v.). The antisecretory effect of these compounds was highly reduced by glibenclamide (10 nmol/rat i.c.v.), a selective blocker of K(ATP) channels. These results suggest that K(ATP) channels in the central nervous system are likely to be involved in the centrally initiated antisecretory action of both alpha2-adrenoceptor agonists and beta-endorphin.