Pharmaceutical care of a patient with antibiotic-associated encephalopathy

Objective:To provide reference of pharmaceutical care for the clinical treatment of a severe patient with antibiotic-associated encephalopathy.Methods:Clinical pharmacists participated in the clinical treatment of the patient with antibiotic-associated encephalopathy,provided pharmaceutical care for clinicians,including the evaluation of adverse drug events and the prevention of adverse drug interaction and development of anti-infection programs by using Pharmacokinetics/pharmacodynamics theory and therapeutic drug monitoring technique.Results:Through active clinical treatment and pharmaceutical care,the symptoms of patients with encephalopathy were relieved,and the infection was effectively controlled.Conclusion:Clinical pharmacists play a positive role in the treatment for the case with antibiotic associated encephalopathy.

Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and electroencephalography.At present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy.This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent articles.This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy.Many challenges limit the timing consistency,particularly the need for intensive care and clinical monitoring.Conversely,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after birth.This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

Probiotics for antibiotic-associated diarrhea:Do we have a verdict?

Probiotics use has increased tremendously over the past ten years.This was coupled with a surge of data relating their importance in clinical practice.Antibioticassociated diarrhea,whose frequency has risen recently,was one of the earliest targets with data published more than ten years ago.Unfortunately,available trials suffer from severe discrepancies associated with variability and heterogeneity of several factors.Most published randomized controlled trials and subsequent meta-analyses suggest benefit for probiotics in the prevention of antibiotic-associated diarrhea.The same seems to also apply when the data is examined for Clostridium difficile-associated colitis.However,the largest randomized double-blind placebo-controlled trial to date examining the use of a certain preparation of probiotics in antibiotic-associated diarrhea showed disappointing results,but it was flawed with several drawbacks.The commonest species of probiotics studied across most trials is Lactobacillus;however,other types have also shown similar benefit.Probiotics have enjoyed an impeccable safety reputation.Despite a few reports of severe infections sometimes leading to septicemia,most of the available trials confirm their harmless behavior and show similaradverse events compared to placebo.Since a consensus dictating its use is still lacking,it would be advisable at this point to suggest prophylactic use of probiotics to certain patients at risk for antibiotic-associated diarrhea or to those who suffered previous episodes.

Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

Antibiotic-associated diarrhea(AAD) and Clostridum difficile infections(CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases Pub Med(June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications(required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar(discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.

Preventing pediatric antibiotic-associated diarrhea and Clostridium difficile infections with probiotics: A metaanalysis

AIM： To assess the effcacy and safety of probiotics for preventing pediatric： （1） antibiotic associated diarrhea and （2） Clostridium diffcile （C. diffcile） infections.METHODS： On June 3, 2013, we searched PubMed （1960-2013）, EMBASE （1974-2013）, Cochrane Da-tabase of Systematic Reviews （1990-2013）, CINAHL （1981-2013）, AMED （1985-2013）, and ISI Web of Science （2000-2013）. Additionally, we conducted an extensive grey literature search including contact with National Institutes of Health Clinical Trials Registry, abstracts from annual infectious disease and gastroen-terology meetings, experts in the feld and correspondence with authors. The primary outcomes were the incidence of antibiotic-associated diarrhea （AAD） and C. difficile infections （CDI）. Dichotomous outcomes （e.g. , incidence of AAD or CDI） were pooled using a random-effects model to calculate the relative risk and corresponding 95% confidence interval （95%CI） and weighted on study quality. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain type, daily dose, quality of study and safety of probiotics. The overall quality of the evidence supporting each outcome was assessed using the grading of recommendations, assessment, development and evaluation criteria.RESULTS： A total of 1329 studies were identifed with 22 trials （23 treatment arms and 4155 participants） meeting eligibility requirements for our review of prevention of AAD and 5 trials （1211 participants） for the prevention of CDI. Trials in adult populations, trials of uncertain antibiotic exposure or studies which did not provide incidence of AAD were excluded. We found 12 trials testing a single strain of probiotic and 10 trials testing a mixture of probiotic strains. Probiotics （all strains combined） signifcantly reduced the incidence of pediatric AAD （pooled RR = 0.42, 95%CI： 0.33-0.53） and significantly reduced pediatric CDI （pooled RR = 0.35, 95%CI： 0.13-0.92）. Of the two strains with multiple trials, both signifcantly reduced pediatric AAD： Sac-charomyces boulardii lyo （pooled RR = 0.43, 95%CI： 0.32-0.60） and Lactobacillus rhamnosus GG （pooled RR = 0.36, 95%CI： 0.19-0.69）. There was no significant effect by type of antibiotic, or by duration or dose of probiotic. No adverse events associated were found in the 22 controlled trials relating to the use of probiotics.CONCLUSION： This meta-analysis found that probiotics signifcantly prevented pediatric antibiotic associated diarrhea and pediatric CDI, but the effcacy varies signifcantly by the strain of the probiotic.

Magnetic resonance imaging scanning susceptibility weighted imaging sequences in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy

BACKGROUND Magnetic resonance imaging(MRI)scanning with susceptibility weighted imaging(SWI)sequences plays a significant role in the diagnosis and prognostic evaluation of neonatal hypoxic-ischemic encephalopathy(HIE).AIM To observe the role of MRI multi-parameter quantitative indexes in the diagnosis of neonatal HIE.METHODS The imaging data from 23 cases of neonatal HIE admitted to the Imaging Department of Ganyu District People's Hospital of Lianyungang City and 23 neonates without HIE admitted during the same period were analyzed retrospectively from August,2021 to December,2023.The results of clinical judgment were compared with the results of computed tomography(CT)and MRI examinations.RESULTS The degree of cerebral edema(more than moderate),the number of damaged brain regions(>2),the number of cerebral hemorrhages(>2),and the percentage of small venous dilatation detected were higher in MRI than in CT examination,and the differences were statistically significant(P<0.05).The total area of the largest region of cerebral damage and of cerebral hemorrhage observed by MRI examination were significantly larger than those of CT examination(P<0.01).Multiparametric quantitative MRI combined with diffusion weighted imaging and SWI had higher sensitivity and accuracy than CT diagnosis,and the difference was statistically significant(P<0.05).The difference in the specificity of the two modes of diagnosis was not significant(P>0.05).CONCLUSION The use of MRI multi-parameter quantitative indexes can accurately diagnose and evaluate neonatal HIE.

Efficacy of Xianglian pill for antibiotic-associated diarrhea: a protocol for systematic review and meta-analysis

Background:Antibiotic-associated diarrhea is a clinical common symptom of antibiotics overuse and occurs in 5%-70%of adults.Xianglian pill has been traditionally considered as an efficient treatment of diarrhea and gastrointestinal diseases for thousands of years.However,no systematic review and meta-analyses have focused on its positive effects.Hence,this protocol for systematic review and meta-analysis was developed to evaluate the effect and clinical safety of Xianglian pill on treating antibiotic-associated diarrhea.Methods:All randomized controlled trials published in Chinese and English and assessed use of Xianglian pill for antibiotic-associated diarrhea will be included.Databases of PubMed,EMBASE,Cochrane Library,China National Knowledge Infrastructure,Chinese Biomedical Literature,Wanfang,and Chinese Science and Technology Periodical Database will be searched for randomized controlled trials from their inception until November 16,2020.Primary outcomes will be the incidence of diarrhea and adverse events,and secondary outcomes will be bowel movements and microbiome characteristics.Two authors will extract data and assess the risk of bias independently.Risk ratio will be used to evaluate the results,and meta-analyses will be conducted using STATA 15.0 software.The review aims to demonstrate the effectiveness of Xianglian pill in the prevention and treatment of antibiotic-associated diarrhea.

Efficacy of a synbiotic chewable tablet in the prevention of antibiotic-associated diarrhea

Infection by Clostridium difficile, a complication of treatment with antibiotics, causes antibiotic- associated diarrhea (AAD) and can lead to colitis and pseudomembranous colitis. Incidence of C. difficile infection is increasing among the elderly undergoing antibiotics therapy confined to health care facilities, conditions that are expensive to treat, decrease the quality of life and are life threatening. Use of probiotics has been proposed as a method to decrease the incidence of AAD in health care facilities. To examine the efficacy of using probiotics, 120 nursing home residents undergoing antibiotic therapy were provided with a synbiotic tablet containing two probiotics, Saccharomyces boulardii and Bacillus coagulans, and a prebiotic, fructooligosaccharide. Residents were evaluated retrospectively for AAD and C. difficile infection. It was found that 95% of residents treated with antibiotics and taking the synbiotic tablet were free of AAD. More than 97% of the residents did not become infected with C. difficile. No adverse effects were reported. Minor side effects, gastrointestinal upset and nausea, were reported by less than 6% of the residents. The cause of the minor side effects was not known. Only 2.5% of the residents stopped taking the synbiotic tablet because of the gastrointestinal upset. These Results suggest that use of the synbiotic tablet prevents AAD and C. difficile infection in nursing home residents undergoing antibiotic therapy. It is concluded that this synbiotic tablet provides an easy to administer and safe approach to controlling AAD and C. difficile infection in residents in nursing homes.

Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions

Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.

Does MgSO_(4) protect the preterm brain?Dissecting its role in the pathophysiology of hypoxic ischemic encephalopathy

Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal medicine.Preterm encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a lifetime.The cost of disability associated with preterm brain injury continues to rise.Prevention of this injury,and disability,would significantly reduce this socioeconomic burden.

Assessment of rehabilitation treatment for patients with acute poisoning-induced toxic encephalopathy

BACKGROUND:Poisoned patients often suffer damage to multiple systems,and those experiencing central nervous system disorders present more severe conditions,prolonged hospital stays,and increased mortality rates.We aimed to assess the efficacy of rehabilitation interventions for patients with toxic encephalopathy.METHODS:This retrospective,observational,comparative cohort study was performed at the teaching hospital affiliated of Nanjing Medical University,from October 2020 to December 2022.Patients who met the diagnostic criteria for toxic encephalopathy and exclusion criteria were included,and patients were divided into three subgroups according to Glasgow Coma Scale(GCS).Demographic and clinical characteristics were collected.The effect of the rehabilitation intervention on patients were assessed in the improvement of consciousness status(Glasgow Coma Scale[GCS]score),muscle strength and movement and swallowing function(Fugl-Meyer Assessment[FMA]scale,Water Swallow Test[WST],and Standardized Swallowing Assessment[SSA]).Subgroup analysis was based on different toxic species.RESULTS:Out of the 464 patients with toxic encephalopathy,184 cases received rehabilitation treatments.For the severe toxic encephalopathy patients,patients without rehabilitation intervention have a 2.21 times higher risk of death compared to patients with rehabilitation intervention(Hazard ratio[HR]=2.21).Subgroup analysis revealed that rehabilitation intervention significantly increased the survival rate of patients with pesticide poisoning(P=0.02),while no significant improvement was observed in patients with drug/biological agent poisoning(P=0.44).After rehabilitation intervention,significant improvement in GCS and FMA were observed in severe patients with toxic encephalopathy(P<0.01).CONCLUSION:Active rehabilitation intervention for patients exposed to poisons that can potentially cause toxic encephalopathy may improve the prognosis and reduce the mortality rate in clinical practice.

Classical bovine spongiform encephalopathy and chronic wasting disease:two sides of the prion coin

Transmissible spongiform encephalopathies(TSEs)are a group of progressive and ultimately fatal neurologic diseases of man and animals,all resulting from the propagated misfolding of the host's normal cellular prion protein.These diseases can be spontaneous,heritable,anthropogenic/iatrogenic,or in some cases horizontally transmissible,and include such notable TSEs as bovine spongiform encephalopathy(BSE)of cattle and chronic wasting disease(CWD)of cervids.Although they are both unequivocally protein misfolding disorders,they differ markedly in their pathogenesis,transmissibility,and zoonotic potential.While the BSE epidemic has largely abated over the past three decades following global feed bans on ruminant meat and bone meal,CWD,which is readily transmitted through various forms of excreta,has rapidly expanded from its original endemic zone to encompass much of North America,along with recently identified foci in Scandinavia.Most importantly,although the classical form of BSE has proven transmissible to humans consuming contaminated beef or beef products,so far there have been no conclusive reports on the zoonotic transmission of cWD to humans.The underlying basis for these differences-whether host or agent directed-are not well understood,though may be due to inherent differences in the three-dimensional structure of the misfolded BSE or CWD prion proteins or the expression levels and tissue distribution of respective cellular prion proteins.With the uncontrolled geographic spread of CWD,it is imperative that we improve our understanding of the factors governing prion disease pathogenesis,transmission,and zoonotic potential.

Fecal microbiota transplantation in the treatment of hepatic encephalopathy:A perspective

Due to its complex pathogenesis,treatment of hepatic encephalopathy(HE)continues to be a therapeutic challenge.Of late,gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use.New evidence suggests that gut micro-biota plays a significant role in cerebral homeostasis.Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies.Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics,prebiotics and the latest fecal microbiota transplantation(FMT).Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE.However,questions over the appropriate dose,duration and route of administration for best treatment outcome remains unsettled.

Spectrum of delayed post-hypoxic leukoencephalopathy syndrome:A systematic review

BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome(DPHLS),also known as Grinker’s myelinopathy,is a rare but significant neurological condition that manifests days to weeks after a hypoxic event.Characterized by delayed onset of neurological and cognitive deficits,DPHLS presents substantial diagnostic and therapeutic challenges.AIM To consolidate current knowledge on pathophysiology,clinical features,diagnostic approaches,and management strategies for DPHLS,providing a comprehensive overview and highlighting gaps for future research.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines,we systematically searched PubMed,ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy.Inclusion criteria were original research articles,case reports,and case series involving human subjects with detailed clinical,neuroimaging,or pathological data on DPHLS.Data were extracted on study characteristics,participant demographics,clinical features,neuroimaging findings,pathological findings,treatment,and outcomes.The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist.RESULTS A total of 73 cases were reviewed.Common comorbidities included schizoaffective disorder,bipolar disorder,hypertension,and substance use disorder.The primary causes of hypoxia were benzodiazepine overdose,opioid overdose,polysubstance overdose,and carbon monoxide(CO)poisoning.Symptoms frequently include decreased level of consciousness,psychomotor agitation,cognitive decline,parkinsonism,and encephalopathy.Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter,sometimes involving the basal ganglia and the globus pallidus.Magnetic resonance spectroscopy often showed decreased N-acetylaspartate,elevated choline,choline-to-creatinine ratio,and normal or elevated lactate.Treatment is often supportive,including amantadine,an antioxidant cocktail,and steroids.Hyperbaric oxygen therapy may be beneficial in those with CO poisoning.Parkinsonism was often treated with levodopa.Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits.CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations.Early recognition and appropriate management are crucial to improving patient outcomes.Future research should focus on standardizing diagnostic criteria,using advanced imaging techniques,and exploring therapeutic interventions to improve understanding and treatment of DPHLS.Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.

Portocaval shunts'role in gut microbiota and hepatic encephalopathy:The gut-to-brain pathway

I read the study by Zhao et al with great interest.Although the study design was quite complicated,it was successful in raising awareness of science and relevant researchers.Thirty patients with liver cirrhosis and portal hypertension secondary to chronic hepatitis B were included in the study.They were treated for variceal bleeding and underwent trans-jugular intrahepatic portosystemic shunt to prevent the recurrence of variceal bleeding and to reduce portal pressure.The authors evaluated the effects of changes in gut microbiota(GM)on hepatic encephalopathy secondary to portocaval bypass.The GM is greatly affected by local and general factors,including herbal and medical drugs,a person's dietary characteristics(carnivorous,vegan,vegetarian),supplementary foods,drinking water sources,and living in a city center or town.Therefore,I congratulate Zhao et al for their concise and comprehensive study on a multifactorial subject.

Spleen volume is associated with overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with portal hypertension

BACKGROUND Portal shunt and immune status related to the spleen are related to the occurrence of hepatic encephalopathy(HE).It is unknown whether spleen volume before transjugular intrahepatic portosystemic shunt(TIPS)is related to postoperative HE.AIM To investigate the relationship between spleen volume and the occurrence of HE.METHODS This study included 135 patients with liver cirrhosis who underwent TIPS,and liver and spleen volumes were elevated upon computed tomography imaging.The Kaplan-Meier curve was used to compare the difference in the incidence rate of HE among patients with different spleen volumes.Univariate and multivariate Cox regression analyses were performed to identify the factors affecting overt HE(OHE).Restricted cubic spline was used to examine the shapes of the dose-response association between spleen volumes and OHE risk.RESULTS The results showed that 37(27.2%)of 135 patients experienced OHE during a 1-year follow-up period.Compared with preoperative spleen volume(901.30±471.90 cm3),there was a significant decrease in spleen volume after TIPS(697.60±281.0 cm^(3))in OHE patients.As the severity of OHE increased,the spleen volume significantly decreased(P<0.05).Compared with patients with a spleen volume≥782.4 cm^(3),those with a spleen volume<782.4 cm^(3) had a higher incidence of HE(P<0.05).Cox regression analysis showed that spleen volume was an independent risk factor for post-TIPS OHE(hazard ratio=0.494,P<0.05).Restricted cubic spline model showed that with an increasing spleen volume,OHE risk showed an initial increase and then decrease(P<0.05).CONCLUSION Spleen volume is related to the occurrence of OHE after TIPS.Preoperative spleen volume is an independent risk factor for post-TIPS OHE.

Rifaximin discontinuation during broad-spectrum antibiotic treatment in critically ill patients with hepatic encephalopathy

Hepatic encephalopathy(HE)is one of the main complications of cirrhosis,characterized by a wide spectrum of neuropsychiatric alterations that lead to an increase in mortality,morbidity and recurrent hospitalizations.Due to the central role in HE pathogenesis of ammonia and other neurotoxins primarily produced by the gut microbiota,the main therapeutic approaches for the treatment of HE are based on the modulation of the gut microbiota.Rifaximin is a non-absorbable broad-spectrum antibiotic,that is effective against ammonia-producing grampositive,gram-negative,and anaerobic species,approved for the treatment of HE in secondary prophylaxis.The chronic administration of rifaximin in this setting is associated with a lower risk of HE recurrence and mortality,while the role of rifaximin for the treatment of an overt-HE episode in inpatients is still unclear.Limited data exist about the coadministration of rifaximin and broad-spectrum antibiotics commonly used to treat concomitant infections,as patients receiving or recently treated with antibiotics were frequently excluded from clinical trials.In this editorial we comment on the article by Ward et al published in the recent issue of the World Journal of Hepatology.It is a single center,retrospective,quasiexperimental,pharmacist-driven protocol,with the aim to evaluate the feasibility and safety of rifaximin discontinuation in critically ill patients with HE and chronic liver disease receiving broad-spectrum antibiotic therapies in intensive care units.The study revealed no differences between the protocol and control group in terms of primary outcome(days alive and free of delirium and coma to day 14)and secondary outcomes which include:Intensive care mortality,intensive care length of stay,intravenous vasopressor requirement changes and adverse effects rate.Therefore,rifaximin discontinuation during broad-spectrum antibiotic therapy does not appear to negatively impact the clinical status of critically ill liver patients,with a similar safety profile and significant cost savings,as compared to the coadministration of rifaximin and broad-spectrum antibiotics.In agreement with Ward et al,a recently published double-blind,randomized controlled trial provided additional evidence to support the feasibility of withholding rifaximin during broad-spectrum antibiotic therapy in critically ill cirrhotic patients.However,given the limitations of these studies,further multicentric and prospective clinical trials,enrolling a larger sample of non-critically ill patients,are needed to better establish the role of rifaximin in this setting.

Calcineurin inhibitors-related posterior reversible encephalopathy syndrome in liver transplant recipients: Three case reports and review of literature

BACKGROUND Posterior reversible encephalopathy syndrome(PRES),characterized by acute neurological deterioration and extensive white matter lesions on T2-fluid attenuated inversion recovery magnetic resonance imaging(MRI),is increasingly associated with calcineurin inhibitors(CNI)-related neurotoxicity.Prompt diagnosis is crucial,as early intervention,including the modification or discontinuation of CNI therapy,strict blood pressure management,corticosteroid treatment,and supportive care can significantly improve patient outcomes and prognosis.The growing clinical recognition of CNI-related PRES underscores the importance of identifying and managing this condition in patients presenting with acute neurological symptoms.CASE SUMMARY This report describes three cases of liver transplant recipients who developed PRES.The first case involves a 60-year-old woman who experienced seizures,aphasia,and hemiplegia on postoperative day(POD)9,with MRI revealing ischemic foci followed by extensive white matter lesions.After replacing tacrolimus,her symptoms improved,and no significant MRI abnormalities were observed after three years of follow-up.The second case concerns a 54-year-old woman with autoimmune hepatitis who developed headaches,seizures,and extensive white matter demyelination on MRI on POD24.Following the switch to rapamycin and the initiation of corticosteroids,her symptoms resolved,and she was discharged on POD95.The third case details a 60-year-old woman with hepatocellular carcinoma who developed PRES,evidenced by brain MRI abnormal-ities on POD11.Transitioning to rapamycin and corticosteroid therapy led to her full recovery,and she was discharged on POD22.These cases highlight the critical importance of early diagnosis,CNI modification,and stringent management in improving outcomes for liver transplant recipients with CNI related PRES.CONCLUSION Clinical manifestations,combined with characteristic MRI findings,are crucial in diagnosing PRES among organ transplant recipients.However,when standard treatments are ineffective or MRI results are atypical,alternative diagnoses should be taken into considered.

Subdural effusion associated with COVID-19 encephalopathy: A case report

BACKGROUND The precise mechanism by which severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)impacts the central nervous system remains unclear,with manifestations spanning from mild symptoms(e.g.,olfactory and gustatory deficits,hallucinations,and headache)to severe complications(e.g.,stroke,seizures,encephalitis,and neurally demyelinating lesions).The occurrence of single-pass subdural effusion,as described below,is extremely rare.CASE SUMMARY A 56-year-old male patient presented with left-sided limb weakness and slurred speech as predominant clinical symptoms.Through comprehensive imaging and diagnostic assessments,he was diagnosed with cerebral infarction complicated by hemorrhagic transformation affecting the right frontal,temporal,and parietal regions.In addition,an intracranial infection with SARS-CoV-2 was identified during the rehabilitation process;consequently,an idiopathic subdural effusion developed.Remarkably,the subdural effusion underwent absorption within 6 d,with no recurrence observed during the 3-month follow-up.CONCLUSION Subdural effusion is a potentially rare intracranial complication associated with SARS-CoV-2 infection.