COVID-19-induced gastrointestinal autonomic dysfunction:A systematic review

BACKGROUND It is common for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection to occur in the gastrointestinal tract,which can present itself as an initial symptom.The severity of coronavirus disease 2019(COVID-19)is often reflected in the prevalence of gastrointestinal symptoms.COVID-19 can damage the nerve supply to the digestive system,leading to gastrointestinal autonomic dysfunction.There is still much to learn about how COVID-19 affects the autonomic nervous system and the gastrointestinal tract.AIM To thoroughly explore the epidemiology and clinical aspects of COVID-19-induced gastrointestinal autonomic dysfunction,including its manifestations,potential mechanisms,diagnosis,differential diagnosis,impact on quality of life,prognosis,and management and prevention strategies.METHODS We conducted a thorough systematic search across various databases and performed an extensive literature review.Our review encompassed 113 studies published in English from January 2000 to April 18,2023.RESULTS According to most of the literature,gastrointestinal autonomic dysfunction can seriously affect a patient's quality of life and ultimate prognosis.Numerous factors can influence gastrointestinal autonomic nervous functions.Studies have shown that SARS-CoV-2 has a well-documented affinity for both neural and gastrointestinal tissues,and the virus can produce various gastrointestinal symptoms by reaching neural tissues through different pathways.These symptoms include anorexia,dysgeusia,heartburn,belching,chest pain,regurgitation,vomiting,epigastric burn,diarrhea,abdominal pain,bloating,irregular bowel movements,and constipation.Diarrhea is the most prevalent symptom,followed by anorexia,nausea,vomiting,and abdominal pain.Although COVID-19 vaccination may rarely induce autonomic dysfunction and gastrointestinal symptoms,COVID-19-induced autonomic effects significantly impact the patient's condition,general health,prognosis,and quality of life.Early diagnosis and proper recognition are crucial for improving outcomes.It is important to consider the differential diagnosis,as these symptoms may be induced by diseases other than COVID-19-induced autonomic dysfunction.Treating this dysfunction can be a challenging task.CONCLUSION To ensure the best possible outcomes for COVID-19 patients,it is essential to take a multidisciplinary approach involving providing supportive care,treating the underlying infection,managing dysfunction,monitoring for complications,and offering nutritional support.Close monitoring of the patient's condition is crucial,and prompt intervention should be taken if necessary.Furthermore,conducting thorough research on the gastrointestinal autonomic dysfunction caused by COVID-19 is vital to manage it effectively.

Abnormal Systemic and Ocular Responses to the Valsalva Manoeuvre in Primary Open-Angle Glaucoma:A Case for Autonomic Failure?

Objective This study aimed to examine the association of primary open-angle glaucoma(POAG)with autonomic dysfunction by assessing the differences in systemic and ocular responses to an autonomic provocation test,the Valsalva manoeuvre(VM),between POAG patients and normal subjects.Methods Forty POAG and forty control subjects were subjected to the VM.Systemic and ocular parameters were measured at baseline,phase 2,and phase 4 of the VM(VM2 and VM4),where VM2 and VM4 are sympathetic and parasympathetic nervous activation states,respectively.Heart rate variability was used to assess the autonomic nervous activity,among which the high-frequency component(HF)and the low-frequency(LF)/HF ratio were used as indices of parasympathetic and sympathetic activation,respectively.Results POAG patients demonstrated higher sympathetic activation(LF/HF ratio median:2.17 vs.1.53,P=0.000)than controls at baseline and exhibited attenuated sympathetic and parasympathetic responses(a smaller change in LF/HF and HF values)during the VM than controls.During VM,the intraocular pressure(IOP),mean blood pressure(MAP),mean ocular perfusion pressure(MOPP),and the Schlemm’s canal area(SCAR)increased from baseline to VM2 and then decreased from VM2 to VM4 in both the POAG and control groups(all P<0.05).However,when we compared the changes above,the fluctuations in IOP,MAP,and MOPP were more pronounced in POAG than in controls(all P<0.05),while the changes in amplitudes of SCAR were smaller in POAG(P<0.05).Furthermore,from VM2 to VM4,the choroid thickness(ChT)in the POAG group was significantly decreased,while it was unchanged in normal subjects(P=0.258).A regression analysis showed a significant correlation of the baseline LF/HF with IOP change values(ΔIOP)from baseline to VM2 in POAG(R^(2)=0.147,P=0.014).Conclusion Patients with POAG showed more pronounced fluctuations in IOP,MAP,MOPP and ChT during the VM than controls.These reactions could be associated with autonomic dysfunction in POAG.

Activities of autonomic neurotransmitters in meibomian gland tissues are associated with menopausal dry eye

The secretory activities of meibomian glands are regulated by the autonomic nervous system, The change in density and activity of autonomic nerves in meibomian glands during menopause play an important role in the pathogenesis of dry eye. In view of this, we established a dry eye rat model by removing the bilateral ovaries. We used neuropeptide Y and vasoactive intestinal polypeptide as markers of autonomic neurotransmitters. Our results showed that the concentration of estradiol in serum significantly decreased, the density of neuropeptide Y immunoreactivity in nerve fibers significantly increased, the density of vasoactive intestinal polypeptide immunoreactivity in nerve fibers significantly decreased, and the ratio of vasoactive intestinal polypeptide/neuropeptide Y positive staining significantly decreased. These results suggest that a decrease in ovary activity may lead to autonomic nervous system dysfunction, thereby affecting the secretory activity of the meibomian gland, which participates in sexual hormone imbalance-induced dry eye.

Cardiac implications in myasthenia gravis

This editorial aimed to consolidate the current evidence in literature on the association between myasthenia gravis(MG)and cardiac involvement,focusing on the impact of thymoma,antistriational antibodies,and late-onset MG.Additionally,the study aimed to explore the influence of genetic differences among populations on the association with cardiac disease.We conducted a review of existing literature in PubMed and Google Scholar to find relevant studies on cardiac involvement in MG.We created search criteria using a combination of free text words,including MG,antistriational antibodies,thymectomy,cardiomyopathy,myocarditis,arrhythmias,autonomic dysfunction.Relevant articles published in English language were analyzed and incorporated.The findings indicate a strong association between thymoma,myasthenic crisis,antistriational antibodies,and late-onset MG with cardiac involvement.The study also revealed that genetic differences among populations influence the risk of cardiac disease and electrocardiography(ECG)abnormalities in MG patients.Autonomic dysfunctions altered cardiac autonomic response and increased susceptibility to arrhythmias and sudden cardiac death in MG patients.The study supports the significance of thymoma,antistriational antibodies,and late-onset MG as key factors associated with cardiac involvement in MG patients.It emphasizes the importance of ECG as the initial test in managing MG patients,particularly in the perioperative period,to identify and genetic testing if needed to address their cardiac risk effectively.

Pressure pain sensitivity: A new stress measure in children and adolescents with type 1 diabetes?

Type 1 diabetes(T1D)is associated with general-and diabetes-specific stress which has multiple adverse effects.Hence measuring stress is of great importance.An algometer measuring pressure pain sensitivity(PPS)has been shown to correlate to certain stress measures in adults.However,it has never been investigated in children and adolescents.The aim of our study was to examine associations between PPS and glycated hemoglobin(HbA1c),salivary cortisol and two questionnaires as well as to identify whether the algometer can be used as a clinical tool among children and adolescents with T1D.Eighty-three participants aged 6-18 years and diagnosed with T1D were included in this study with data from two study visits.Salivary cortisol,PPS and questionnaires were collected,measured,and answered on site.HbA1c was collected from medical files.We found correlations between PPS and HbA1c(rho=0.35,P=0.046),cortisol(rho=-0.25,P=0.02)and Perceived Stress Scale(rho=-0.44,P=0.02)in different subgroups based on age.Males scored higher in PPS than females(P<0.001).We found PPS to be correlated to HbA1c but otherwise inconsistent in results.High PPS values indicated either measurement difficulties or hypersensibility towards pain.

Splanchnic vasodilation and hyperdynamic circulatory syndrome in cirrhosis

Portal hypertension is a clinical syndrome which leads to several clinical complications, such as the formation and rupture of esophageal and/or gastric varices, ascites, hepatic encephalopathy and hepato-renal syndrome. In cirrhosis, the primary cause of the increase in portal pressure is the enhanced resistance to portal outflow. However, also an increase in splanchnic blood flow worsens and maintains portal hypertension. The vasodilatation of arterial splanchnic vessels and the opening of collateral circulation are the determinants of the increased splanchnic blood flow. Several vasoactive systems/substances, such as nitric oxide, cyclooxygenase-derivatives, carbon monoxide and endogenous cannabinoids are activated in portal hypertension and are responsible for the marked splanchnic vasodilatation. Moreover, an impaired reactivity to vasoconstrictor systems, such as the sympathetic nervous system, vasopressin, angiotensin II and endothelin-1, plays a role in this process. The opening of collateral circulation occurs through the reperfusion and dilatation of preexisting vessels, but also through the generation of new vessels. Splanchnic vasodilatation leads to the onset of the hyperdynamic circulatory syndrome, a syndrome which occurs in patients with portal hypertension and is characterized by increased cardiac output and heart rate, and decreased systemic vascular resistance with low arterial blood pressure. Understanding the pathophysiology of splanchnic vasodilatation and hyperdynamic circulatory syndrome is mandatory for the prevention and treatment of portal hypertension and its severe complications.

Nonalcoholic fatty liver disease and aging: Epidemiology to management

Nonalcoholic fatty liver disease(NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic(nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications(cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment(diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients.

Cardiopulmonary,complications in chronic liver disease

Patients with cirrhosis and portal hypertension exhibit characteristic cardiovascular and pulmonary hemodynamic changes. A vasodilatatory state and a hyperdynamic circulation affecting the cardiac and pulmonary functions dominate the circulation. The recently defined cirrhotic cardiomyopathy may affect systolic and diastolic functions, and imply electromechanical abnormalities. In addition, the baroreceptor function and regulation of the circulatory homoeostasis is impaired. Pulmonary dysfunction involves diffusing abnormalities with the development of the hepatopulmonary syndrome and portopulmonary hypertension in some patients. Recent research has focused on the assertion that the hemodynamic and neurohumoral dysregulation are of major importance for the development of the cardiovascular and pulmonary complications in cirrhosis. This aspect is important to take into account in the management of these patients.

Spinal cord injury-induced cognitive impairment: a narrative review

Spinal cord injury is a serious damage to the spinal cord that can lead to life-long disability.Based on its etiology,spinal cord injury can be classified as traumatic or non-traumatic spinal cord injury.Furthermore,the pathology of spinal cord injury can be divided into two phases,a primary injury phase,and a secondary injury phase.The primary spinal cord injury phase involves the initial mechanical injury in which the physical force of impact is directly imparted to the spinal cord,disrupting blood vessels,axons,and neural cell membranes.After the primary injury,a cascade of secondary events begins,expanding the zone of neural tissue damage,and exacerbating neurological deficits.Secondary injury is a progressive condition characterized by pro-inflammatory cytokines,reactive oxygen species,oxidative damage,excitatory amino acids such as glutamate,loss of ionic homeostasis,mitochondrial dysfunction,and cell death.This secondary phase lasts for several weeks or months and can be further subdivided into acute,subacute,and chronic.One of the most frequent and devastating complications developed among the spinal cord injury population is cognitive impairment.The risk of cognitive decline after spinal cord injury has been reported to be 13 times higher than in healthy individuals.The exact etiology of this neurological complication remains unclear,however,many factors have been proposed as potential contributors to the development of this disorder,such as concomitant traumatic brain injury,hypoxia,anoxia,autonomic dysfunction,sleep disorders such as obstructive sleep apnea,body temperature dysregulation,alcohol abuse,and certain drugs.This review focuses on a deep understanding of the pathophysiology of spinal cord injury and its relationship to cognitive impairment.We highlight the main mechanisms that lead to the development of this neurological complication in patients with spinal cord injury.

Visceral and somatic hypersensitivity, autonomic cardiovascular dysfunction and low-grade inflammation in a subset of irritable bowel syndrome patients

The pathophysiology of irritable bowel syndrome（IBS） is complex and not fully understood, so the aim of this study was to evaluate whether visceral and somatic hypersensitivity, autonomic cardiovascular dysfunction, and low-grade inflammation of the gut wall are associated with diarrhea-predominant IBS（D-IBS）. Sixty-two patients with D-IBS and 20 control subjects participated in the study. Using the ascending method of limits（AML） protocol, we demonstrated that D-IBS patients had significantly lower sensory thresholds compared with healthy controls（P〈0.001）. Using diverse methods, especially the ischemic sensitivity test, for the first time in China, we confirmed that D-IBS patients have somatic hypersensitivity. They had a significantly higher systolic blood pressure and heart rate after a cold stimulus, indicative of autonomic cardiovascular dysfunction. Compared with the control group, D-IBS patients had a significantly higher level of calprotectin（P〈0.001）. We also found significant correlations between visceral and somatic hypersensitivity, visceral hypersensitivity and autonomic cardiovascular dysfunction, and somatic hypersensitivity and autonomic cardiovascular dysfunction. Our findings may provide valuable suggestions for the treatment of D-IBS.

Hereditary Transthyretin Amyloidosis in Eight Chinese Families

Background： Mutations of transthyretin （TTR） cause the most common type of autosomal-dominant hereditary systemic amyloidosis, which occurs worldwide. To date, more and more mutations in the TTR gene have been reported. Some variations in the clinical presentation are often observed in patients with the same mutation or the patients in the same family. The purpose of this study was to find out the clinicopathologic and genetic features of Chinese patients with hereditary TTR amyloidosis. Methods： Clinical and necessary examination materials were collected from nine patients of eight families with hereditary TTR amyloidosis at Peking University First Hospital from January 2007 to November 2014. Sural nerve biopsies were taken for eight patients and skin biopsies were taken in the calf/upper arm for two patients, for light and electron microscopy examination. The TTR genes from the nine patients were analyzed. Results： The onset age varied from 23 to 68 years. The main manifestations were paresthesia, proximal and/or distal weakness, autonomic dysfunction, cardiomyopathy, vitreous opacity, hearing loss, and glossohypertrophia. Nerve biopsy demonstrated severe loss ofmyelinated fibers in seven cases and amyloid deposits in three. One patient had skin amyloid deposits which were revealed from electron microscopic examination. Genetic analysis showed six kinds of mutations of TTR gene, including Val30Met, Phe33Leu, Ala36Pro, Val30Ala, Phe33Val, and Glu42Gly in exon 2. Conclusions： Since the pathological examinations ofsural nerve were negative for amyloid deposition in most patients, the screening for TTR mutations should be performed in all the adult patients, who are clinically suspected with hereditary TTR amyloidosis.