Portal hypertension in patients with nonalcoholic fatty liver disease:Current knowledge and challenges

Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.

Could near focus endoscopy,narrow-band imaging,and acetic acid improve the visualization of microscopic features of stomach mucosa?

BACKGROUND Conventional magnifying endoscopy with narrow-band imaging(NBI)observation of the gastric body mucosa shows dominant patterns in relation to the regular arrangement of collecting venules,subepithelial capillary network,and gastric pits.AIM To evaluate the effectiveness of a new one-dual(near)focus,NBI mode in the assessment of the microscopic features of gastric body mucosa compared to conventional magnification.METHODS During 2021 and 2022,68 patients underwent proximal gastrointestinal endoscopy using magnification endoscopic modalities subsequently applying acetic acid(AA).The GIF-190HQ series NBI system with dual focus capability was used for the investigation of gastric mucosa.At the time of the endoscopy,the gastric body mucosa of all enrolled patients was photographed using the white light endoscopy(WLE),near focus(NF),NF-NBI,AA-NF,and AA-NF-NBI modes.RESULTS The WLE,NF and NF-NBI endoscopic modes for all patients(204 images)were classified in the same order into three groups.Two images from each patient for the AA-NF and AA-NF-NBI endoscopic modes were classified in the same order.According to all three observers who completed the work independently,NF magnification was significantly superior to WLE(P<0.01),and the NF-NBI mode was significantly superior to NF magnification(P<0.01).After applying AA,the three observers confirmed that AA-NF-NBI was significantly superior to AA-NF(P<0.01).Interobserver kappa values for WLE were 0.609,0.704,and 0.598,respectively and were 0.600,0.721,and 0.637,respectively,for NF magnification.For the NF-NBI mode,the values were 0.378,0.471,and 0.553,respectively.For AA-NF,they were 0.453,0.603,and 0.480,respectively,and for AA-NF-NBI,they were 0.643,0.506,and 0.354,respectively.CONCLUSION When investigating gastric mucosa in microscopic detail,NF-NBI was the most powerful endoscopic mode for assessing regular arrangement of collecting venules,subepithelial capillary network,and gastric pits among the five endoscopic modalities investigated in this study.AA-NF-NBI was the most powerful endoscopic mode for analyzing crypt opening and intervening part.

Spontaneous gastric hematoma as a rare cause of acute abdomen:A case report

BACKGROUND Spontaneous gastric hematoma is an exceedingly rare condition characterized by the accumulation of blood within the gastric wall without any apparent iatrogenic or traumatic cause.Coagulopathies are the most frequent cause of gastric he-matomas.However,other causes include amyloidosis,pancreatitis,visceral vas-cular aneurysms,endoscopy complications and others.The pathophysiology of spontaneous gastric hematoma is not completely understood.However,it is postulated that it is caused by disruption of submucosal vessels that leads to dissection of the muscularis layer and formation of false lumen.The rarity of this condition increases the challenge of diagnosis,and there is no standard treatment protocol.CASE SUMMARY We present the case of a spontaneous gastric hematoma in a 22-year-old male.He presented to our emergency department complaining of pain in the left flank area lasting for 2 wk.There was no history of trauma,antico-agulant medications or endoscopy procedures.His hemoglobin and hematocrit levels were slightly lower than normal.Multi-slice computed tomography,ultrasound and endoscopy confirmed a gastric intramural hematoma.We recommended conservative treatment because there was no hemodynamic instability nor significant bleeding.The patient responded well,and there were no unexpected events.At the 3-mo follow-up,the ultrasound exa-mination revealed complete regression of the hematoma.CONCLUSION After reviewing the literature and our experience,we recommend that more of these cases should be treated conservatively.The tendency to treat these cases with potentially burdensome procedures such as total or subtotal gastrectomy should be significantly reduced.

流感与COVID-19患者的免疫球蛋白G糖基化差异

The essential role of immunoglobulin G(IgG)in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine 297 of the fragment crystallizable(Fc)domain that occur under such circumstances.These glycans impact the antibody stability,half-life,secretion,immunogenicity,and effector functions.Therefore,in this study,we analyzed and compared the total IgG glycome—at the level of individual glycan structures and derived glycosylation traits(sialylation,galactosylation,fucosylation,and bisecting Nacetylglucosamine(GlcNAc))—of 64 patients with influenza,77 patients with coronavirus disease 2019(COVID-19),and 56 healthy controls.Our study revealed a significant decrease in IgG galactosylation,sialylation,and bisecting GlcNAc(where the latter shows the most significant decrease)in deceased COVID19 patients,whereas IgG fucosylation was increased.On the other hand,IgG galactosylation remained stable in influenza patients and COVID-19 survivors.IgG glycosylation in influenza patients was more time-dependent:In the first seven days of the disease,sialylation increased and fucosylation and bisecting GlcNAc decreased;in the next 21 days,sialylation decreased and fucosylation increased(while bisecting GlcNAc remained stable).The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses,while the observed changes in deceased COVID-19 patients may indicate its deviation.

Fear of hypoglycemia,a game changer during physical activity in type 1 diabetes mellitus patients

Hypoglycemia limits optimal glycemic management of patients with type 1 diabetes mellitus(T1DM).Fear of hypoglycemia(FoH)is a significant psychosocial consequence that negatively impacts the willingness of T1DM patients to engage in and profit from the health benefits of regular physical activity(e.g.,cardiometabolic health,improved body composition,cardiovascular fitness,quality of life).Technological advances,improved insulin regimens,and a better understanding of the physiology of various types of exercise could help ameliorate FoH.This narrative review summarizes the available literature on FoH in children and adults and tools to avoid it.

Effect of COVID-19 on management of type 1 diabetes:Pushing the boundaries of telemedical healthcare

The new coronavirus disease 2019(COVID-19)pandemic posed a great burden on health care systems worldwide and is an enormous and real obstacle in providing needed health care to patients with chronic diseases such as diabetes.Parallel to COVID-19,there have been great advances in technology used for management of type 1 diabetes,primarily insulin pumps,sensors,integrated and closed loop systems,ambulatory glucose profile software,and smart phone apps providing necessary essentials for telemedicine implementation right at the beginning of the COVID-19 pandemic.The results of these remote interventions are reassuring in terms of glycemic management and hemoglobin A1c reductions.However,data on long-term outcomes and cost reductions are missing as well as proper technical infrastructure and government health policy support.

A candidate identification questionnaire for postmenopausal osteoporosis patients switched from daily or weekly bisphosphonate to once-monthly ibandronate: An open, prospective, multicenter study—BONCURE study

A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once-monthly dosing. This was a prospective, open-label, multicenter international study in patients with postmenopausal osteoporosis who had been receiving once-daily or once-weekly alendronate or risendronate for at least 3 months. Patients completed a CIQ, then commenced 150 mg monthly ibandronate for 6 months. Patients completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-QTM) at baseline for 6 months. Scores were converted to composite satisfaction scores (CSS, scale 0-100). Totally 677 patients completed a CIQ, 645 were enrolled in the treatment phase and comprised the intent-to-treat (ITT) population, and 630 completed the study. In the ITT population, 68.1% patients answered “yes” to one or more CIQ questions. OPSAT-Q scores increased for the convenience, quality of life and overall satisfaction domains (p scores for the side effects domains were significant (p < 0.001) in the CIQ “yes” group, but not for the degree of bother (decrease in mean of 0.1 points, p = 0.50) or duration (no change, p = 0.84) of non-gastrointestinal side effects. Of 638 patients who completed the preference questionnaire, 93.0% of patients preferred the once-monthly dosing schedule and 563 patients (90.7%) found it more convenient. The most common adverse events were dyspepsia (1.9%), nausea (1.1%), and upper abdominal pain (0.9%). Patients are likely to prefer treatment with monthly ibandronate to a weekly or monthly bisphosphonate irrespective of their stated preference before switching treatment.

Noninvasive Fibrosis Assessment in Chronic Hepatitis C Infection: An Update

Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C patients.However,with the introduction and validation of noninvasive tests(NITs)to evaluate advanced fibrosis,and the direct-acting antiviral agents for treatment of chronic hepatitis C virus(HCV),the role of NITs have become even more complex.There is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological response.The aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.

Coagulation and Endothelial Dysfunction Associated with NAFLD:Current Status and Therapeutic Implications

Non-alcoholic fatty liver disease(NAFLD)is closely related to insulin resistance,type 2 diabetes mellitus,and obesity.It is nowadays considered a multisystem disease with a strong association with cardiovascular disease and arterial hypertension,which interfere with changes in the coagulation system.Coagulation disorders are common in patients with hepatic impairment and are dependent on the degree of liver damage.Patients with NAFLD may have preserved overall hemostatic profile,but many studies suggest a trend toward a procoagulant state.Hypercoagulable state in NAFLD patients may even induce progression of hepatic injury.Endothelial dysfunction is present in the systemic and portal vein circulation in NAFLD patients,and platelets are being recognized as modulators of liver diseases through various mechanisms.Through a literature review,we discuss possible disorders in the coagulation cascade and fibrinolysis,endothelial dysfunction,and platelet abnormalities in patients with NAFLD.Considering the processes and mechanisms involved in the hemostatic abnormalities associated with NAFLD,directly related to liver disease or indirectly related through inflam-matory processes and metabolic disorders,several potential therapeutic targets have been identified and reviewed here.

Pulmonary embolism due to the right atrial thrombus mymicking atrial myxoma

Detection of a cardiac mass has a direct therapeutic implication because of its potential for pulmonary or systemic embolization. The choice of treatment is dependent upon the time of the embolization, clinical presentation and type of embolic mass. Imaging features in combination with clinical and laboratory findings are usually helpful in the differentiation of various cardiac masses with high probability. The case we are presenting is a 73-year-old man with occlusion of both pulmonary arteries and a right atrial thrombus initially diagnosed as a myxoma.