Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice

Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated mortality.This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease.This makes the management of patients more challenging,since physicians must take into consideration two different conditions,the chronic liver disease and the tumor.The underlying liver disease has several implications in clinical practice,because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC,obstacles in surveillance,and differences in the efficacy of the treatment against HCC.A shift in the prevalence of liver diseases has been evident over the last few years,with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance.Therefore,in an era of personalized medicine,it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.

Mental health in the virtual world:Are we ready for the metaverse era?

The advent of the metaverse,including virtual reality,augmented reality,andartificial intelligence,is an undeniable issue that health care scientists need toupdate.It influences all fields of knowledge,interpersonal relationships,andhealth.Regarding mental health since the post-coronavirus disease 2019 pandemic,it is necessary to consider and understand the potential,possibilities,weaknesses,and consequences arising from and provided by this new scenario.Due tothe increasing need for mental health monitoring and care,mental health treatmentsrequire in-depth training and preparation to achieve the maximum use of themetaverse advantages and possibilities.Currently,very little is known about theeffectiveness of remote mental health treatment,but it is certainly suggested thataccessibility and the characteristics associated with the use of metaverse technologiesmay represent new horizons for accessibility and approach tools,as long asmore studies are carried out and more evidence is collected to develop accurateguidelines,safe training,solve ethical concerns,and overcome limitations.

Impact of multidrug resistance on the management of bacterial infections in cirrhosis

Patients with cirrhosis have an increased risk of infection and differently from other complications,that over the years are improving in their outcomes,infections in cirrhotic patients are still a major cause of hospitalization and death(up to 50%in-hospital mortality).Infections by multidrug-resistant organisms(MDRO)have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact.About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years.MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution.An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects,such as the type of infection(spontaneous bacterial peritonitis,pneumonia,urinary tract infection and spontaneous bacteremia),bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition(community acquired,healthcare associated or nosocomial).Furthermore,regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology.Antibiotic treatment is the most effective measure to treat infections caused by MDRO.Therefore,optimizing antibiotic prescribing is critical to effectively treat these infections.Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality.On the other hand,the supply of new agents to treat these infections is very limited.Thus,specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.

Drug-induced liver injury and COVID-19:Use of artificial intelligence and the updated Roussel Uclaf Causality Assessment Method in clinical practice

BACKGROUND Liver injury is a relevant condition in coronavirus disease 2019(COVID-19)inpatients.Pathophysiology varies from direct infection by virus,systemic inflammation or drug-induced adverse reaction(DILI).DILI detection and monitoring is clinically relevant,as it may contribute to poor prognosis,prolonged hospitalization and increase indirect healthcare costs.Artificial Intelligence(AI)applied in data mining of electronic medical records combining abnormal liver tests,keyword searching tools,and risk factors analysis is a relevant opportunity for early DILI detection by automated algorithms.AIM To describe DILI cases in COVID-19 inpatients detected from data mining in electronic medical records(EMR)using AI and the updated Roussel Uclaf Causality Assessment Method(RUCAM).METHODS The study was conducted in March 2021 in a hospital in southern Brazil.The NoHarm©system uses AI to support decision making in clinical pharmacy.Hospital admissions were 100523 during this period,of which 478 met the inclusion criteria.From these,290 inpatients were excluded due to alternative causes of liver injury and/or due to not having COVID-19.We manually reviewed the EMR of 188 patients for DILI investigation.Absence of clinical information excluded most eligible patients.The DILI assessment causality was possible via the updated RUCAM in 17 patients.RESULTS Mean patient age was 53 years(SD±18.37;range 22-83),most were male(70%),and admitted to the non-intensive care unit sector(65%).Liver injury pattern was mainly mixed,mean time to normalization of liver markers was 10 d,and mean length of hospitalization was 20.5 d(SD±16;range 7-70).Almost all patients recovered from DILI and one patient died of multiple organ failure.There were 31 suspected drugs with the following RUCAM score:Possible(n=24),probable(n=5),and unlikely(n=2).DILI agents in our study were ivermectin,bicalutamide,linezolid,azithromycin,ceftriaxone,amoxicillin-clavulanate,tocilizumab,piperacillin-tazobactam,and albendazole.Lack of essential clinical information excluded most patients.Although rare,DILI is a relevant clinical condition in COVID-19 patients and may contribute to poor prognostics.CONCLUSION The incidence of DILI in COVID-19 inpatients is rare and the absence of relevant clinical information on EMR may underestimate DILI rates.Prospects involve creation and validation of alerts for risk factors in all DILI patients based on RUCAM assessment causality,alterations of liver biomarkers and AI and machine learning.

Correction:Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellularcholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant

Rereading the article“Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant”(DOI:10.5306/wjco.v13.i8.688),published on August 24,we observe,with concern,that figures 3 and 4 are wrong.The authors have attached the correct figures for correction.

Influence of proton pump inhibitors in the development of spontaneous bacterial peritonitis

AIM To investigate whether the use of proton pump inhibitors(PPIs) increases the incidence of spontaneous bacterial peritonitis(SBP) in patients with cirrhosis and ascites.METHODS An historical cohort study was carried out in cirrhotic outpatients with ascites followed in a specialized clinic at a tertiary hospital in Southern Brazil. Patient charts were reviewed to collect information on the variables of interest as the use of PPIs. Primary outcome was defined as development of SBP during the study period. SBP was diagnosed based on ascitic fluid polymorphonuclear cell count ≥ 250 cells/mm3 without evidence of an intraabdominal, surgically treatable source of infection.RESULTS Of 738 cirrhotic patients, 582(58.2% male) were enrolled, with mean age of 53.6 ± 12 years. Hepatitis C virus infection(36.2%) and alcohol abuse(25.6%) were the main etiologies of cirrhosis. The presence of ascites was detected in 299(51.4%) patients during the development of the study. Nineteen patients with previous diagnosis of SBP undergoing secondary prophylaxis and 22 patients with insufficient PPI data were further excluded. Of 258 patients with ascites, 151 used PPIs, and 34 developed SBP(22.5%). Among 107 non-users of PPIs, 23 developed SBP(21.5%)(HR = 1.44, 95%CI: 0.85-2.47, P = 0.176). The median follow-up time of patients using PPI was 27 mo vs 32 mo for non-users. Univariate analysis of the risk factors associated with the development of SBP revealed a significant association of SPB with the severity of liver disease according to the Child-Turcotte-Pugh(CTP) score. Multivariate analysis confirmed that CTP score was the only independent variable influencing the occurrence of SBP. Survival at 60 mo(Kaplan-Meier analysis) was similar in users and non-users of PPI, independently of the presence of SBP(58.4% vs 62.7% respectively, P = 0.66). For patients with SBP, survival at 60 mo was 55.1%, vs 61.7% in patients without SBP(P = 0.34). CONCLUSION In conclusion, the rate of SBP was not significantly different in users or non-users of PPIs in this cohort of cirrhotic with ascites.

Association between thrombomodulin and high mobility group box 1 in sepsis patients

BACKGROUND High mobility group box 1(HMGB1)has been studied as a molecule associated with severe outcomes in sepsis and thrombomodulin(TM)seems to decrease HMGB1 activity.AIM To investigate the role of the thrombomodulin/high mobility group box 1(T/H)ratio in patients with sepsis and their association with their clinic,testing the hypothesis that higher ratios are associated with better outcomes.METHODS Twenty patients diagnosed with sepsis or septic shock,according to the 2016 criteria sepsis and septic shock(Sepsis-3),were studied.Patients were followed until they left the intensive care unit or until they achieved 28 d of hospitalization(D28).The following clinical outcomes were observed:Sequential Organ Failure Assessment(SOFA)score;Need for mechanical pulmonary ventilation;Presence of septic shock;Occurrence of sepsis-induced coagulopathy;Need for renal replacement therapy(RRT);and Death.RESULTS The results showed that patients with SOFA scores greater than or equal to 12 points had higher serum levels of TM:76.41±29.21 pg/mL vs 37.41±22.55 pg/mL among those whose SOFA scores were less than 12 points,P=0.003.The T/H ratio was also higher in patients whose SOFA scores were greater than or equal to 12 points,P=0.001.The T/H ratio was,on average,three times higher in patients in need of RRT(0.38±0.14 vs 0.11±0.09),P<0.001.CONCLUSION Higher serum levels of TM and,therefore,higher T/H ratio in the first 24 h after the diagnosis of sepsis were associated with more severe disease and the need for renal replacement therapy,while those with better clinical outcomes and those who were discharged before D28 showed a tendency for lower T/H ratio values.

Immune aspects of hepatocellular carcinoma:From immune markers for early detection to immunotherapy

Hepatocellular carcinoma(HCC)is one of the most prevalent cancers and one of the main causes of cancer-related deaths worldwide.Most HCCs develop in an inflammatory microenvironment,and mounting evidence emphasizes the importance of immune aspects in hepatocarcinogenesis.In normal physiology,both innate and adaptive immune responses are responsible for eliminating malignantly transformed cells,thus preventing the development of liver cancer.However,in the setting of impaired natural killer cells and exhaustion of T cells,HCC can develop.The immunogenic features of HCC have relevant clinical implications.There is a large number of immune markers currently being studied for the early detection of liver cancer,which would be critical in order to improve surveillance programs.Moreover,novel immunotherapies have recently been proven to be effective,and the combination of atezolizumab and bevacizumab is currently the most effective treatment for advanced HCC.It is expected that in the near future different subgroups of patients will benefit from specific immunotherapy.The better we understand the immune aspects of HCC,the greater the benefit to patients through surveillance aiming for early detection of liver cancer,which allows for curative treatments,and,in cases of advanced disease,through the selection of the best possible therapy for each individual.

Drug-induced liver injury and COVID-19:A review for clinical practice

Coronavirus disease 2019(COVID-19)consists of a systemic disease that can present many complications.The infection presents broad clinical symptoms and a high rate of transmissibility.In addition to severe acute respiratory syndrome,the patients manifest complications beyond the respiratory system.The frequency of liver damage in COVID-19 patients ranges from 14.8% to 53% of patients.One should pay attention to drug-induced liver injury(DILI)in patients with COVID-19,especially considering the off-label use of drugs in prophylactic and therapeutic regimens applied on large scales.This review aims to present relevant information on the medication used so far in COVID-19 patients and its possible hepatotoxicity.We reviewed liver damage in patients with COVID-19 on PubMed and Virtual Health Library to investigate DILI cases.Four studies were selected,involving the medicines remdesivir,tocilizumab and a pharmacovigilance analysis study.The hepatotoxicity profile of drugs presented in the literature considers use in accordance to usual posology standards for treatment.However,drugs currently used in the management of COVID-19 follow different dosages and posology than those tested by the pharmaceutical industry.The deficiency of uniformity and standardization in the assessment of hepatotoxicity cases hinders the publication of information and the possibility of comparing information among healthcare professionals.It is suggested that severe liver injury in COVID-19 patients should be reported in pharmacovigilance institutions,and physicians should pay attention to any considerable abnormal liver test elevation as it can demonstrate unknown drug hepatotoxicity.Liver disorders in COVID-19 patients and the use of several concomitant off-label medications—with a potential risk of further damaging the liver-should at least be a warning sign for rapid identification and early intervention,thus preventing liver damage from contributing to severe impairment in patients.

Epidemiology of inflammatory bowel diseases in the state of Rio Grande do Sul,Brazil

BACKGROUND This is the first study on the epidemiology of inflammatory bowel diseases(IBDs)in Rio Grande do Sul(RS),the southernmost state of Brazil with the country’s fifth largest population.Crohn’s disease(CD)and ulcerative colitis(UC)are collectively termed IBDs.They have high incidence and prevalence rates in highincome countries,although in recent years there has been a change in the classic geographical distribution of IBDs,with growing rates in traditionally lowincidence regions.AIM To estimate the incidence and prevalence of IBDs in the RS state,Brazil,between 2014 and 2019.METHODS This is a cross-sectional descriptive observational study.Patients with IBD who had initiated treatment and met the inclusion criteria of the RS state free drug distribution program were included.Data were obtained from registration or renewal records of the RS state specialty pharmacy.The male,female,and total populations were estimated according to mid-year data from the Brazilian Institute of Geography and Statistics,which served as a reference for calculating the incidence and prevalence rates of IBDs during the study period.Results were described using mean,standard deviation,and range.RESULTS We included 1082 patients with IBD,of whom 57.5%were female and 42.5% were male.Patients with CD accounted for 72.45% of the sample,and those with UC accounted for 27.54%.IBD prevalence during the study period was 9.51 per 100000 population,of which 6.89 corresponded to people with CD and 2.62,to people with UC.Incidence rates per 100000 population/year were 2.54 in 2014,2.61 in 2015,1.91 in 2016,0.80 in 2017,0.83 in 2018,and 0.96 in 2019.The mean IBD incidence rate per 100000 population was 1.61,of which 1.17 corresponded to CD and 0.44,to UC.The mean age was 41 years,and patients were mostly aged 30-40 years.Prevalence by region was higher in the state capital metropolitan area:12.69 per 100000 population.CONCLUSION Our results demonstrated an IBD prevalence of 9.51% and incidence of 1.61 per 100000 population.The patients were predominantly female,and CD was more prevalent than UC.

Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database

AIM To evaluate the occurrence of resistant mutations in treatment-na?ve hepatitis C virus(HCV) sequences deposited in the European hepatitis C virus database(euH CVdb). METHODS The sequences were downloaded from the eu HCVdb(https://euhcvdb.ibcp.fr/eu HCVdb/). The search was performed for full-length NS3 protease, NS5 A and NS5 B polymerase sequences of HCV, separated by genotypes 1a, 1b, 2a, 2b and 3a, and resulted in 798 NS3, 708 NS5 A and 535 NS5 B sequences from HCV genotypes1a, 1b, 2a, 2b and 3a, after the exclusion of sequences containing errors and/or gaps or incomplete sequences, and sequences from patients previously treated with direct antiviral agents(DAA). The sequence alignment was performed with MEGA 6.06 MAC and the resulting protein sequences were then analyzed using the BioE dit 7.2.5. for mutations associated with resistance. Only positions that have been described as being associated with failure in treatment in in vivo studies, and/or as conferring a more than 2-fold change in replication in comparison to the wildtype reference strain in in vitro phenotypic assays were included in the analysis.RESULTS The Q80 K variant in the NS3 gene was the most prevalent mutation, being found in 44.66% of subtype 1a and 0.25% of subtype 1b. Other frequent mutations observed in more than 2% of the NS3 sequences were: I170V(3.21%) in genotype 1a, and Y56F(15.93%), V132I(23.28%) and I170V(65.20%) in genotype 1b. For the NS5 A, 2.21% of the genotype 1a sequences have the P58 S mutation, 5.95% of genotype 1b sequences have the R30 Q mutation, 15.79% of subtypes 2a sequences have the Q30 R mutation, 23.08% of subtype 2b sequences have a L31 M mutation, and in subtype 3a sequences, 23.08% have the M31 L resistant variants. For the NS5 B, the V321 L RAV was identified in 0.60% of genotype 1a and in 0.32% of genotype 1b sequences, and the N142 T variant was observed in 0.32% of subtype 1b sequences. The C316 Y, S556 G, D559 N RAV were identified in 0.33%, 7.82% and 0.32% of genotype 1b sequences, respectively, and were not observed in other genotypes.CONCLUSION HCV mutants resistant to DAAs are found in low frequency, nevertheless they could be selected and therapy could fail due resistance substitutions in HCV genome.

Albumin administration in patients with cirrhosis: Current role and novel perspectives

Mortality in cirrhosis is mostly associated with the development of clinical decompensation,characterized by ascites,hepatic encephalopathy,variceal bleeding,or jaundice.Therefore,it is important to prevent and manage such complications.Traditionally,the pathophysiology of decompensated cirrhosis was explained by the peripheral arterial vasodilation hypothesis,but it is currently understood that decompensation might also be driven by a systemic inflammatory state(the systemic inflammation hypothesis).Considering its oncotic and nononcotic properties,albumin has been thoroughly evaluated in the prevention and management of several of these decompensating events.There are formal evidence-based recommendations from international medical societies proposing that albumin be administered in individuals with cirrhosis undergoing large-volume paracentesis,patients with spontaneous bacterial peritonitis,those with acute kidney injury(even before the etiological diagnosis),and those with hepatorenal syndrome.Moreover,there are a few randomized controlled trials and meta-analyses suggesting a possible role for albumin infusion in patients with cirrhosis and ascites(long-term albumin administration),individuals with hepatic encephalopathy,and those with acute-on-chronic liver failure undergoing modest-volume paracentesis.Further studies are necessary to elucidate whether albumin administration also benefits patients with cirrhosis and other complications,such as individuals with extraperitoneal infections,those hospitalized with decompensated cirrhosis and hypoalbuminemia,and patients with hyponatremia.

Hepatocellular carcinoma in nonalcoholic fatty liver disease:A growing challenge

Nonalcoholic fatty liver disease(NAFLD)is the most common cause of liver disease worldwide,and its prevalence increases continuously.As it predisposes to hepatocellular carcinoma both in the presence and in the absence of cirrhosis,it is not surprising that the incidence of NAFLD-related hepatocellular carcinoma would also rise.Some of the mechanisms involved in hepatocarcinogenesis are particular to individuals with fatty liver,and they help explain why liver cancer develops even in patients without cirrhosis.Genetic and immune-mediated mechanisms seem to play an important role in the development of hepatocellular carcinoma in this population.Currently,it is consensual that patients with NAFLD-related cirrhosis should be surveilled with ultrasonography every 6 mo(with or without alpha-fetoprotein),but it is known that they are less likely to follow this recommendation than individuals with other kinds of liver disease.Moreover,the performance of the methods of surveillance are lower in NAFLD than they are in other liver diseases.Furthermore,it is not clear which subgroups of patients without cirrhosis should undergo surveillance.Understanding the mechanisms of hepatocarcinogenesis in NAFLD could hopefully lead to the identification of biomarkers to be used in the surveillance for liver cancer in these individuals.By improving surveillance,tumors could be detected in earlier stages,amenable to curative treatments.

Auditory Health and Risk Factors in Rural Workers Exposed to Pesticides in Piedade de Caratinga County-Minas Gerais

In Brazil, the amount of pesticides consumed doubled in the last 10 years. Thus, in 2008 it assumed the lead position in the world. However, its indiscriminate application in agriculture without the use of the necessary care has contributed to environmental degradation and increased occupational exposures, making it a serious health problem in the country. The recent study looked to evaluate the auditory health and risk factors in rural workers exposed to pesticides in Piedade de Caratinga County—MG, and chart their socioeconomic profile and lifestyle while identifying the types of crops and the use and management of pesticides. Developed, then, a descriptive and exploratory study involving 23 men, rural workers, exposed to pesticides, with no history of exposure to noise, with changes in meatoscopy and aged ≤50 years of age. The results show the sample consisted of 23 men with a mean age of 36.7 ± 9.3, whom have low education, with a monthly income of 1 minimum wage, working in the fields for over 15 years. There was a predominance of horticulture using organophosphate pesticides and pyrethroids. Part of the sample shows auditory loss, the most common sensorineural conductive loss. It is essential that the population exposed to this type of risk is informed and receives guidance from educational campaigns developed by the multidisciplinary team of basic health units.

Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant

BACKGROUND Cholangiocarcinoma(CC)is a rare tumor that arises from the epithelium of the bile ducts.It is classified according to anatomic location as intrahepatic,perihilar,and distal.Intrahepatic CC(ICC)is rare in patients with cirrhosis due to causes other than primary sclerosing cholangitis.Mixed hepatocellular carcinoma-CC(HCC-CC)is a rare neoplasm that shows histologic findings of both HCC and ICC within the same tumor mass.Due to the difficulties in arriving at the correct diagnosis,patients eventually undergo liver transplantation(LT)with a presumptive diagnosis of HCC on imaging when,in fact,they have ICC or HCC-CC.AIM To evaluate the outcomes of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma on pathological examination after liver transplant.METHODS Propensity score matching was used to analyze tumor recurrence(TR),overall mortality(OM),and recurrence-free survival(RFS)in LT recipients with pathologically confirmed ICC or HCC-CC matched 1:8 to those with HCC.Progression-free survival and overall mortality rates were computed with the Kaplan-Meier method using Cox regression for comparison.RESULTS Of 475 HCC LT recipients,1.7%had the diagnosis of ICC and 1.5%of HCC-CC on pathological examination of the explant.LT recipients with ICC had higher TR(46%vs 11%;P=0.006),higher OM(63%vs 23%;P=0.002),and lower RFS(38%vs 89%;P=0.002)than those with HCC when matched for pretransplant tumor characteristics,as well as higher TR(46%vs 23%;P=0.083),higher OM(63%vs 35%;P=0.026),and lower RFS(38%vs 59%;P=0.037)when matched for posttransplant tumor characteristics.Two pairings were performed to compare the outcomes of LT recipients with HCC-CC vs HCC.There was no significant difference between the outcomes in either pairing.CONCLUSION Patients with ICC had worse outcomes than patients undergoing LT for HCC.The outcomes of patients with HCC-CC did not differ significantly from those of patients with HCC.

Effects of Gaseous Drinks in Wistar Rats Esophagus

The consumption of beverages and processed foods, mainly soft drinks, has been incorporated into the usual diet of children, adolescents and adults frequently in recent years. The present study aimed to study the effects of carbonated drinks on Wistar rats, based on the macroscopic and histological morphology of the esophagus. Fifteen Wistar rats were divided into three groups: control group;group fed with ration and cola-type refrigerant ad libitum and group fed with ration and gas industrialized water ad libitum, for a trial period of 90 days. For histopathology and morphology, the esophagus was removed, prepared in slides and stained with hematoxylineosin. Images of the sections were captured for analysis and classification of the inflammatory infiltrate. For morphometry, ten grid fields of 100 points were evaluated in the 40x eyepiece, totaling 3000 points per animal. The results demonstrate that the refrigerant treatment induced the following structural changes in the rats: significant reduction of weight in relation to the control group;inflammatory infiltrate predominantly diffuse mild to moderate and tissue edema. The rats treated with carbonated water had similar results to the control, besides signs of healing and tissue repair.

Cardiac Complications in Maroteaux-Lamy Syndrome： Case Report

MLS （Maroteaux-Lamy syndrome） or MPS VI （mucopolysaccharidosis VI） is an autosomal recessive pathology in which there is absence or low activity of the enzyme N-Acetylgalactosamine-4-Sulfatase, which hydrolyzes GAGs （glycosaminoglycans） in the body （mainly dermatan sulfate）. Consequently, there occurs lysosomal deposition of GAGs in connective tissue multisystemic. Myocardium and heart valves are frequently affected structures, presenting a direct correlation with the reports of complications and deaths. Case report： RGS, male, 3 years and 2 months, diagnosed with MPS VI from the first month of life, in weekly ERT （enzyme replacement therapy） since 4 months of age （inconstant）. At physical examination： normotensive, with holosystolic heart murmur 3＋/6＋ in mitral focus. Complementary tests： normal electrocardiogram, echocardiogram with pronounced mitral regurgitation, concentric left ventricular hypertrophy of moderate degree and mild aortic insufficiency. Discussion： Mitral valve disease is common in patients with MLS. Conditions such as cardiomyopathy, fibroelastosis, aneurysm and pulmonary hypertension may occur in these patients, indicative of morbidity and mortality. Early and constant ERT may be useful in slowing a progression of heart disease. Conclusions： follow-up with a cardiologist is important to evaluate the progression of cardiac complications in MPS VI. Constant and early ERT provides better prognosis for these patients.

Methods Used for Determining Nurse Downsizing: An Integrative Review

The study aimed to look for available evidence in the literature regarding tools and methods used for determining nurse staffing levels. It is an integrative literature review whose data search was performed electronically between September and October 2013. The integrative review consisted of 13 articles that responded to the inclusion criteria proposed in the study. Several tools and methods were identified that determine staffing numbers, however, implementation of the calculated required workforce is not yet effective in the institutions surveyed.

Evaluation of Cytotoxicity of <i>Gossypium barbadense</i>L. Extract in Bone Cord Cells through the Micronucleus Test

The cotton plant is a plant belonging to the family Malvaceae and its leaves are often used in folk medicine. The present study aimed to evaluate the mutagenic or antimutagenic activity of the ethanolic extract of Gossypium barbadense L. (EEG) and to analyze its capacity to prevent or repair mutagenic lesions caused by cyclophosphamide (CP). For the Micronucleus test, Swiss mice were divided into 5 groups: negative control;Positive control: treated with 50 mg/kg cyclophosphamide (CP), group receiving EEG 500 mg/kg for 7 days;Group receiving EEG 500 mg/kg for 7 days associated with CP24h before euthanasia;Group who received CP and EEG 500 mg/kg for 7 days. After the treatment period, the animals were euthanized, the bone marrow removed and the blood smear prepared. From this analysis, it was observed that the EEG caused a significant increase in the number of micronucleated erythrocytes, indicating mutagenic activity of the extract. In addition, it was verified that the extract did not present the capacity to prevent, but it presented the capacity of repair of the chromosomal damages caused by CP.

Non-alcoholic fatty liver disease-related hepatocellular carcinoma:Is there a role for immunotherapy?

Hepatocellular carcinoma(HCC)is among the most common cancers and it is a major cause of cancer-related deaths.Non-alcoholic fatty liver disease(NAFLD)affects approximately one fourth of individuals worldwide and it is becoming one of the most important causes of HCC.The pathogenic mechanisms leading to NAFLD-related HCC are complex and not completely understood.However,metabolic,fibrogenic,oncogenic,inflammatory and immunological pathways seem to be involved.First-line therapy of advanced HCC has recently undergone major changes,since the combination of atezolizumab and bevacizumab was proven to increase survival when compared to sorafenib.Other immune-oncology drugs are also demonstrating promising results in patients with advanced HCC when compared to traditional systemic therapy.However,initial studies raised concerns that the advantages of immunotherapy might depend on the underlying liver disease,which seems to be particularly important in NAFLD-related HCC,as these tumors might not benefit from it.This article will review the mechanisms of NAFLD-related hepatocarcinogenesis,with an emphasis on its immune aspects,the efficacy of traditional systemic therapy for advanced NAFLD-related HCC,and the most recent data on the role of immunotherapy for this specific group of patients,showing that the management of this condition should be individualized and that a general recommendation cannot be made at this time.