Gut epithelial barrier dysfunction in humanimmunodeficiency virus-hepatitis C virus coinfectedpatients:Influence on innate and acquired immunity

Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus(HIV)-infected patients have several non-acquired immunodeficiency syndrome(AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus(HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.

Coagulase Negative Staphylococcus Causes Catheter Associated Bacteriemia in a Patient with Esophagus Adenocarcinome

We report a case of a man suffering esophagus adenocarcinome who acquired catheter associated bacteriemia caused by a coagulase negative Staphylococcus. This CoNS was sensible to linezolid, teicoplanine, vancomycin and rifampicin. This information was relevant for antibiotherapy planning. The patient was successfully treated with teicoplanin together with the catheter exchange. In conclusion, infections should be treated with adequate doses and duration of antibiotics together with catheter exchange. Pre-emptive measurements in the cancer patient and establishing the most adequate treatment are imperative for obtaining good results.

Alcoholism: A systemic proinflammatory condition

Excessive ethanol consumption affects virtually any organ,both by indirect and direct mechanisms.Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism.These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria,which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability.Reactive oxygen species(ROS)that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol.The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage.In addition to the classic consequences of endotoxemia associated with liver cirrhosis that weredescribed several decades ago,important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain,bone,muscle,heart,lung,gonads,peripheral nerve,and pancreas.These effects are even seen in alcoholics without significant liver disease.Therefore,alcoholism can be viewed as an inflammatory condition,a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease.In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.

Thrombin activation and liver inflammation in advanced hepatitis C virus infection

Hepatitis C virus(HCV) infection is associated with increased thrombotic risk. Several mechanisms are involved including direct endothelial damage by the HCV virus, with activation of tissue factor, altered fibrinolysis and increased platelet aggregation and activation. In advanced stages, chronic HCV infection may evolve to liver cirrhosis, a condition in which alterations in the portal microcirculation may also ultimately lead to thrombin activation, platelet aggregation, and clot formation. Therefore in advanced HCV liver disease there is an increased prevalence of thrombotic phenomena in portal vein radicles. Increased thrombin formation may activate hepatic stellate cells and promote liver fibrosis. In addition, ischemic changes derived from vascular occlusion by microthrombi favor the so called parenchymal extinction, a process that promotes collapse of hepatocytes and the formation of gross fibrous tracts. These reasons may explain why advanced HCV infection may evolve more rapidly to end-stage liver disease than other forms of cirrhosis.

Timing of surgery in Crohn’s disease: A key issue in the management

The timing of the decision for operation in Crohn’s disease is based on an evaluation of the several factors such as the failure of medical treatment, complications due to the Crohn’s disease or to the farmacological therapy, development of dysplasia or cancer and growth retardation. A complete evaluation of these factors should result in operation timed to the patient’s best advantage, achieving maximal relief of symptoms with improvement of quality of life. Given the complexity and heterogeneity of the disease and the different options for treatment, is difficult to systematize when the optimal moment for the surgery is arrived. A very important factor in the management of Crohn’s disease is the multidisciplinary approach and the patient preference should be a significant factor in determining the choice of therapy. The surgery should be considered such another option in the sequential treatment of Crohn’s disease. We have analyzed the factors that are involved in the decision taking of the surgical treatment regarding to the experience and the published literature. When did the medical therapy fail? when is the appropriate moment to operate on the patient? Or which complications of Crohn’s disease need a surgery? These are some of the questions we will try to answer.

Liver steatosis in hepatitis C patients

There is controversy regarding some aspects of hepatitis C virus(HCV) infection-associated liver steatosis,and their relationship with body fat stores. It has classically been found that HCV,especially genotype 3,exerts direct metabolic effects which lead to liver steatosis. This supports the existence of a so called viral steatosis and a metabolic steatosis,whichwould affect HCV patients who are also obese or diabetics. In fact,several genotypes exert metabolic effects which overlap with some of those observed in the metabolic syndrome. In this review we will analyse the pathogenic pathways involved in the development of steatosis in HCV patients. Several cytokines and adipokines also become activated and are involved in "pure" steatosic effects,in addition to inflammation. They are probably responsible for the evolution of simple steatosis to steatohepatitis,making it difficult to explain why such alterations only affect a proportion of steatosic patients.

Bone changes in alcoholic liver disease

Alcoholism has been associated with growth impairment, osteomalacia, delayed fracture healing, and aseptic necrosis(primarily necrosis of the femoral head), but the main alterations observed in the bones of alcoholic patients are osteoporosis and an increased risk of fractures. Decreased bone mass is a hallmark of osteoporosis, and it may be due either to decreased bone synthesis and/or to increased bone breakdown. Ethanol may affect both mechanisms. It is generally accepted that ethanol decreases bone synthesis, and most authors have reported decreased osteocalcin levels(a "marker" of bone synthesis), but some controversy exists regarding the effect of alcohol on bone breakdown, and, indeed, disparate results have been reported for telopeptide and other biochemical markers of bone resorption. In addition to the direct effect of ethanol, systemic alterations such as malnutrition, malabsorption, liver disease, increased levels of proinflammatory cytokines, alcoholic myopathy and neuropathy, low testosterone levels, and an increased risk of trauma, play contributory roles. The treatment of alcoholic bone disease should be aimed towards increasing bone formation and decreasing bone degradation. In this sense, vitamin D and calcium supplementation, together with biphosphonates are essential, but alcohol abstinence and nutritional improvement are equally important. In this review we study the pathogenesis of bone changes in alcoholic liver disease and discuss potential therapies.

Adipokines,cytokines and body fat stores in hepatitis Cvirus liver steatosis

AIM: To identify patients with or without liver steatosis and its severity in treatment-na?ve patients affected by hepatitis C virus(HCV) infection.METHODS: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body(by densitometry), hormones [insulin, homeostatic model assessment(HOMA)], adipokines(resistin, adiponectin, leptin), and cytokines(tumor necrosis factor α, interleukin-6).RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunkfat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin.CONCLUSION: Steatosis in HCV infection is common(67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

Disseminated infection due to Mycobacterium bovis after intravesical BCG instillation

Intravesical bacillus Calmette-Guerin(BCG) instillation has been adopted for the treatment of patients with superficial bladder cancer. Severe adverse events due to local instillation of BCG are uncommon, with an overall rate of serious complications of less than 5%. We report the case of an immunocompetent adult patient with multi-system effects, namely pneumonitis, granulomatous hepatitis and meningitis, who responded well to standard treatment for Mycobacterium bovis. This case highlights the importance of a thorough assessment of this type of patient.

Management of betablocked patients after sustained virological response in hepatitis C cirrhosis

BACKGROUND Current guidelines do not address the post–sustained virological response management of patients with baseline hepatitis C virus (HCV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option. AIM To assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population. METHODS Inclusion criteria were age > 18 years, HCV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after directacting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was < 12 mmHg, at the discretion of the attending physician. RESULTS Sample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, Child-Pugh score A 77%, median platelets 77.000 × 103/μL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was < 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was ≥ 12 mmHg in 12/19 patients. The elastography area under receiver operating characteristic for HVPG ≥ 12 mmHg was 0.62. Betablockers were stopped permanently in 10/13 patients with gradient < 12 mmHg, with no bleeding episodes after a median follow-up of 68 wk. CONCLUSION Portal hypertension dropped below the bleeding threshold in 39% of patients more than one year after antiviral treatment. Endoscopy and transient elastography are inaccurate for reliable detection of this change. Stopping betablockers permanently seems uneventful in patients with a gradient < 12 mmHg.

Effectiveness of sacubitril-varsartan versus angiotensin converting enzyme inhibitors in patients hospitalized for acute heart failure:a retrospective cohort study of the RICA registry

BACKGROUND Sacubitril-valsartan has been shown to reduce hospitalizations and mortality in patients with heart failure(HF)and reduced ejection fraction.The PIONEER-HF trial demonstrated that initiation of the drug during acute HF hospitalization reduced NT-proBNP levels and a post-hoc analysis of the trial found a reduction in HF hospitalizations and deaths.Real-life studies in the elderly population are scarce.The aim of our study was to assess the effectiveness of sacubitril-valsartan versus angiotensin converting enzyme inhibitors(ACEI)in elderly patients who initiate this treatment during hospitalization for acute HF.METHODS We conducted a retrospective cohort study using the Spanish acute heart failure registry(RICA)comparing rehospitalizations and deaths at 3 months and 1 year among patients aged 70 years or older who had initiated treatment with sacubitrilvalsartan during hospitalization for acute HF versus those treated with ACEI.RESULTS One hundred and ninety-nine patients hospitalized between October 2016 and November 2020 were included,with a median age of 82 years and high rate of comorbidity.Of these,107 were treated with sacubitril-valsartan and 92 with ACEI.The adjusted OR for readmission for HF at 3 months was 0.906(95%CI:0.241-3.404)and for the combined variable readmission for HF or death at 3 months was 0.696(95%CI:0.224-2.167).The adjusted OR for HF readmission at one year was 0.696(95%CI:0.224-2.167).and for the combined variable HF readmission or death at one year 0.724(95%CI:0.325-1.612).CONCLUSION Treatment with sacubitril-valsartan initiated early in hospitalization for HF in elderly patients with high comorbidity was associated with a trend towards a reduction in readmissions and death due to HF compared to treatment with ACEI,which did not reach statistical significance either at 3 months or 1 year of follow-up.

Machine learning insights concerning inflammatory and liver-related risk comorbidities in non-communicable and viral diseases

The liver is a key organ involved in a wide range of functions,whose damage can lead to chronic liver disease(CLD).CLD accounts for more than two million deaths worldwide,becoming a social and economic burden for most countries.Among the different factors that can cause CLD,alcohol abuse,viruses,drug treatments,and unhealthy dietary patterns top the list.These conditions prompt and perpetuate an inflammatory environment and oxidative stress imbalance that favor the development of hepatic fibrogenesis.High stages of fibrosis can eventually lead to cirrhosis or hepatocellular carcinoma(HCC).Despite the advances achieved in this field,new approaches are needed for the prevention,diagnosis,treatment,and prognosis of CLD.In this context,the scientific community is using machine learning(ML)algorithms to integrate and process vast amounts of data with unprecedented performance.ML techniques allow the integration of anthropometric,genetic,clinical,biochemical,dietary,lifestyle and omics data,giving new insights to tackle CLD and bringing personalized medicine a step closer.This review summarizes the investigations where ML techniques have been applied to study new approaches that could be used in inflammatoryrelated,hepatitis viruses-induced,and coronavirus disease 2019-induced liver damage and enlighten the factors involved in CLD development.

A Case Report of Hypothyroidism and Pericardial Effusion

The pericardial sac is made of two layers: the visceral and parietal pericardium. Located between these two layers, the pericardial cavity is found. It contains around 15 to 50 mL of a liquid secreted by mesothelial cells. Pericardial effusion is described as the accumulation of liquid within the pericardial cavity, exceeding the previous mentioned quantity. It has multiple causes, such as malignancy, infectious origins, inflammation, and others, such as hypothyroidism. One of the multiple clinical manifestations associated with hypothyroidism is pericardial effusion. It is related to the severity and duration of the disease, being more frequent in congenital hypothyroidism or cases of a long history of hypothyroidism, as well as clinical hypothyroidism. It can present a clinical challenge mainly due to the discordance between the total volume of the effusion and the clinical symptoms shown by the patient. The main objective of this work is to present a case of a forty-two-year-old male with hypothyroidism-associated pericardial effusion which resolved satisfactorily with hormone replacement therapy.

HCV与HIV协同感染可缩短HCV相关性失代偿期肝硬化患者的存活期

The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95%CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]);Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model for end-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compar- ed with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.

肺结核病人心包渗液的发生率

结核病是导致心包疾病的病因之一,为了解肺结核病人结核性心包渗液(TPE)的发生率及HIV感染对其的影响因素,作者进行了超声心动图检查,以确定有无心包渗液,并分析了各种相关的参数。TPE的发生率为14.1％,胸腔渗液常与TPE有关(比值比为24.39)。本文未发现HIV病人的TPE发生率增高,与免疫抑制状态也无关。因此,肺结核病人。

Loiasis in sub-Saharan migrants living in Spain with emphasis of cases from Equatorial Guinea

Background:Loiasis is an uncommon and poorly understood parasitic disease outside endemic areas of Africa.The aim of this study was to describe the clinical and biological patterns and treatment of imported loiasis by sub-Saharan migrants diagnosed in Madrid,Spain.Methods:A retrospective study was conducted with sub-Saharan immigrants seen at the Tropical Medicine Unit of the Carlos III Hospital in Madrid,Spain,a reference center,over 19 years.Categorical variables were expressed as frequency counts and percentages.Continuous variables were expressed as the mean and standard deviation(SD)or median and interquartile range(IQR:Q3–Q1).Chi-square tests were used to assess the association between categorical variables.The measured outcomes were expressed as the odds ratio(OR)with a 95%confidential interval.Continuous variables were compared by Student’s t-tests or Mann-Whitney U tests.Binary logistic regression models were used.P<0.05 was considered a statistically significant difference.Results:One hundred thirty-one migrants from tropical and subtropical areas with loiasis were identified.Forty-nine patients were male(37.4%).The migrants’mean age(±SD)was 42.3±17.3 years,and 124(94.7%)were from Equatorial Guinea.The median time(IQR)between arrival in Spain and the first consultation was 2(1–7)months.One hundred fifteen migrants had eosinophilia,and one hundred thirteen had hyper-IgE syndrome.Fifty-seven patients had pruritus(43.5%),and thirty patients had Calabar swelling(22.9%).Seventy-three patients had coinfections with other filarial nematodes(54.2%),and 58 migrants had only Loa loa infections(45.8%).One hundred two patients(77.9%)were treated;45.1%(46/102)patients were treated with one drug,and 54.9%(56/102)patients were treated with combined therapy.Adverse reactions were described in 14(10.7%)migrants.Conclusions:Our patients presented early clinical manifestations and few atypical features.Thus,physicians should systematically consider loiasis in migrants with a typical presentation.However,considering that 72.5%of the patients had only positive microfilaremia without any symptoms,we suggest searching for microfilaremia in every migrant from endemic countries for loiasis presenting with eosinophilia.

Imported Mansonella perstans infection in Spain

Background Mansonella perstans infection can be considered one of the most neglected tropical infectious diseases.Very few studies have reported on the clinical picture caused by infection with this nematode.Therefore,our study was aimed to describe the clinical patterns and treatment of imported M.perstans infection by migrants from Africa.Methods The present study evaluated a large cohort of migrants who have been diagnosed,examined and treated for imported M.perstans infection at a Spanish reference center(Hospital Carlos III Tropical Medicine Unit,Madrid,Spain)over a 19-year period.Most patients voluntarily attend the emergency unit or are referred from primary care or general hospitals in Madrid.Chi-square test was used to compare the association between categorical variables.The continuous variables were compared by Student’s t-test or the Mann–Whitney test.The corresponding regression models were used for multivariate analysis.Results Five hundred three cases of migrants from tropical and subtropical areas with M.perstans infection were identified.Two hundred sixty-four patients were female(52.5%).The mean age(±SD)was 44.6±18.2 years(range:16–93 years).The mean time(±SD)between the arrival in Spain and the first consultation was 8.6±18.0 months.The major origin of the patients was Equatorial Guinea(97.6%).Regarding the clinical picture,257 patients were asymptomatic(54.7%)and 228 were symptomatic(45.3%);190 patients had pruritus(37.8%),50(9.9%)had arthralgia,18 patients had Calabar-like swelling(3.6%),and 15(3%)had abdominal pain.Four hundred forty-two(87.9%)migrants had hyper-IgE,and 340(67.6%)had eosinophilia.One hundred ninety-five patients had coinfections with other filarial nematodes(38.8%),and 308 migrants had only M.perstans infection(61.2%).Four hundred thirty-seven cases(86.9%)had been treated with anti-filarial drugs;292 cases were treated with one anti-filarial drug,and 145 cases were treated with combined anti-filarial therapy.Additionally,20(4%)cases received steroids and 38(7.6%)cases received antihistamines.Conclusions A long series of M.perstans infections is presented in sub-Saharan immigrants whose data indicate that it should be included in the differential diagnosis in patients with pruritus or analytical alterations such as eosinophilia or hyper-IgE presentation,and they also have a high number of coinfections with other microorganisms whose treatment needs to be protocolized.