The impact of stressors and overload on informal caregivers of patients with cirrhosis: The first use of the Burden Scale for Family Caregivers in Brazil.

INTRODUCTION: Cirrhosis affects liver functions and compromises much of the body's organs. The significant increase in chronic diseases, including cirrhosis, has led to changes in medical practice and health systems, leading the informal caregiver to play a major role because of family ties or some level of proximity to the patient, assuming daily care function. However, the burden generated by informal caregivers for uninterrupted care is present at different levels (physical, mental, social, professional, and financial) and even in the prognosis of the patient. OBJECTIVE: The present study aims to evaluate the impact of stressors and overload on informal caregivers of cirrhosis patients. METHOD: Cross-sectional study, conducted with 54 informal caregivers of cirrhosis patients, followed up at the Liver Transplant Service Outpatient Clinic of the University of São Paulo School of Medicine Hospital das Clínicas, where they had access to a sociodemographic questionnaire, history of the patient's disease and the scale Burden Scale for Family Caregivers. RESULTS: It was observed that higher levels of education and income of the caregiver correlates with a lower degree of stress. In addition, there is a significant difference found in the caregiver's age variable, which indicates that the youngest are those who have the highest degree of stress. The variable Na mEg/l of the patient also presents a statistically significant difference. CONCLUSION: Our study was a precursor using the BSFC scale of worldwide coverage and that had not yet been applied in any study in Brazil, thus allowing a look at the various aspects that affect the quality of life of caregivers of patients with cirrhosis. Our results and the literature corroborate the importance not only of the patient, but also the informal caregiver's health.

Instrument to evaluate the knowledge of patient with cirrhosis on his disease: construction and validity.

BACKGROUND: The application of measurement instruments is a strategy to evaluate the patient's knowledge about the disease. This study aims to build an instrument that evaluates the patient's knowledge about liver cirrhosis. METHOD: This study includes three phases. The first one was the construction of the instrument based on a literature review. In the second phase, five experts were participated in the evaluation of the instrument, to check the validity of the content. Quantitative and qualitative analyzes were made. The tool used was the CVI (Content Validity Index) and it was used the semantic study of the questions. The third phase was the process of the restructuring the instrument. RESULTS: The final version of the instrument consisted of 36 questions. The instrument was evaluated in 91.7 by the average CVI and 94.4% by the universal CVI. CONCLUSIONS: The questions are properly structured and clear, therefore, understandable. Thus, the final instrument presented satisfactory content validity, so that, it reached the aim of this study.

Treating incarcerated inguinal hernias with TEP is a viable option for experienced surgeons.

Despite inguinal hernias being a common problem in public health, there is still scarce information about the epidemiology of the complications, especially incarceration, and their influence on the laparoscopic surgical methods considering the role of the learning process of the surgeon. Compare laparoscopic totally extraperitoneal (TEP) approach in the repair of incarcerated and non-incarcerated inguinal hernias from the perspective of technical difficulty for trained surgeons. We obtained data about sex, age, location and type of hernia, surgery duration, ASA score, postoperative complications, previous surgeries and BMI. Groups were descriptively analyzed and statistically compared to verify how similar the samples were. 265 (90.1%) patients had non-incarcerated hernias and 29 (9.9%) incarcerated. We observed that there was no significant difference in the pattern of location (right, left or bilateral), sex, ASA, previous or complications between the two groups. Unilateral incarcerated hernias had longer operative times compared to non-incarcerated. No difference was found between bilateral hernias. We didn´t find significant epidemiological differences between incarcerated and non-incarcerated hernias. In our experience, with the limitation of a single-surgeon series, laparoscopic hernia repair achieved satisfactory results in terms of feasibility (especially for bilateral hernias) and safety.

Survival curve identifies critical period for postoperative mortality in cardiac patients undergoing emergency general surgery.

The number of non-cardiac major surgeries carried out has significantly increased in recent years to around 200 million procedures carried out annually. Approximately 30% of patients submitted to non-cardiac surgery present some form of cardiovascular comorbidity. In emergency situations, with less surgery planning time and greater clinical severity, the risks become even more significant. The aim of this study is to determine the incidence and clinical outcomes in patients with cardiovascular disease submitted to non-cardiac surgical procedures in a single cardiovascular referral center. This is a prospective cohort study of patients with cardiovascular disease submitted to non-cardiovascular surgery. All procedures were carried out by the same surgeon, between January 2006 and January 2018. 240 patients included were elderly, 154 were male (64%), 8 patients presented two diagnoses. Of the resulting 248 procedures carried out, 230 were emergency (92.8%). From the data obtained it was possible to estimate the day from which the occurrence of mortality is less probable in the postoperative phase. Our research evaluated the epidemiological profile of the surgeries and we were able to estimate the survival and delimit the period of greatest risk of mortality in these patients. The high rate of acute mesenteric ischemia was notable, a serious and frequently fatal condition.

Survival curve identifes critical period for postoperative mortality in cardiac patients undergoing emergency general surgery

The number of non-cardiac major surgeries carried out has signifcantly increased in recent years to around 200 million procedures carried out annually. Approximately 30% of patients submitted to non-cardiac surgery present some form of cardiovascular comorbidity. In emergency situations, with less surgery planning time and greater clinical severity, the risks become even more signifcant. The aim of this study is to determine the incidence and clinical outcomes in patients with cardiovascular disease submitted to non-cardiac surgical procedures in a single cardiovascular referral center. This is a prospective cohort study of patients with cardiovascular disease submitted to non-cardiovascular surgery. All procedures were carried out by the same surgeon, between January 2006 and January 2018. 240 patients included were elderly, 154 were male (64%), 8 patients presented two diagnoses. Of the resulting 248 procedures carried out, 230 were emergency (92.8%). From the data obtained it was possible to estimate the day from which the occurrence of mortality is less probable in the postoperative phase. Our research evaluated the epidemiological profle of the surgeries and we were able to estimate the survival and delimit the period of greatest risk of mortality in these patients. The high rate of acute mesenteric ischemia was notable, a serious and frequently fatal condition.

The impact of properly diagnosed sarcopenia on postoperative outcomes after gastrointestinal surgery: A systematic review and meta-analysis.

BACKGROUND: Sarcopenia is defined as the loss of muscle mass combined with loss of muscle strength, with or without loss of muscle performance. The use of this parameter as a risk factor for complications after surgery is not currently used. This meta-analysis aims to assess the impact of sarcopenia defined by radiologically and clinically criteria and its relationship with complications after gastrointestinal surgeries. MATERIALS AND METHODS: A review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO registration number: CRD42019132221). Articles were selected from the PUBMED and EMBASE databases that adequately assessed sarcopenia and its impact on postoperative complications in gastrointestinal surgery patients. Pooled estimates of pre-operative outcome data were calculated using the odds ratio (OR) and 95% confidence interval (CI). Subgroup analysis were performed to assess each type of surgery. RESULTS: The search strategy returned 1323, with 11 studies meeting the inclusion criteria. A total of 4265 patients were analysed. The prevalence of sarcopenia between studies ranged from 6.8% to 35.9%. The meta-analysis showed an OR for complications after surgery of 3.01 (95% CI 2.55-3.55) and an OR of 2.2 (95% CI 1.44-3.36) for hospital readmission (30 days). CONCLUSION: Sarcopenia, when properly diagnosed, is associated with an increase in late postoperative complications, as well as an increase in the number of postoperative hospital readmissions for various types of gastrointestinal surgery. We believe that any preoperative evaluation should include, in a patient at risk, tests for the diagnosis of sarcopenia and appropriate procedures to reduce its impact on the patient's health.

Laparoscopically excised retroperitoneal presacral Schwannoma: atypical pre and postoperative manifestations - case report.

BACKGROUND: We are a reporting a rare case of retroperitoneal schwanomma with atypical pre and postoperative manifestations. Retroperitoneal schwannomas are rare tumors that are difficult to preoperatively diagnose. CASE PRESENTATION: This is a case report of a male patient, 41 years old, with symptoms of hipogastric and lower right member pain, as well as a history of a papilliferous thyroid tumor. Computerized tomography exams were inconclusive, showing a mass in the presacral region with dimensions of 4.4 × 3.9 × 3.4 cm. Removal was carried out by laparoscopic surgery, with self-limited postoperative complications. Diagnosis was carried out by anatomopathological examination, and syndromic hypotheses were discarded. CONCLUSIONS: The postoperative complications of schwanomma are little reported in the literature. In the simultaneous occurrence of schwanomma and other endocrine tumors, further studies are warranted to better differentiate the cases that need investigation of syndromic causes.

Intussusception reveals MUTYH-associated polyposis syndrome and colorectal cancer: a case report.

BACKGROUND: We are reporting a rare case of MUTYH-associated polyposis, a colorectal cancer hereditary syndrome, diagnosticated after an intussusception. Colorectal cancer is an important cause of cancer related mortality that can be manifested by an intussusception, a rare occurrence in adults and almost always related to tumors. Approximately 5% of colorectal cancers can be attributed to syndromes known to cause hereditary colorectal cancer, such as MUTYH-associated polyposis, autosomal genetic syndrome associated with this disease. CASE PRESENTATION: We present the case of a 44 years old male, that sought medical consultation with a complaint of abdominal discomfort, that after five days changed its characteristics. The patient was sent to the emergency department were a CT-scan revealed intestinal sub-occlusion by ileocolic invagination. Right colectomy was carried out. The anatomic-pathological examination revealed a moderately differentiated mucinous adenocarcinoma and multiples sessile polyps, which led to the suspicion of a genetic syndrome. In the genetics analysis two mutations were observed in the MUTYH gene, and MUTYH-associated polyposis was diagnosticated. CONCLUSION: This case demonstrates the importance of meticulous analysis of the patient examinations results to identify possible discrete alterations that can lead to improved understanding of disease.

Antiviral activity of bone morphogenetic proteins and activins.

Understanding the control of viral infections is of broad importance. Chronic hepatitis C virus (HCV) infection causes decreased expression of the iron hormone hepcidin, which is regulated by hepatic bone morphogenetic protein (BMP)/SMAD signalling. We found that HCV infection and the BMP/SMAD pathway are mutually antagonistic. HCV blunted induction of hepcidin expression by BMP6, probably via tumour necrosis factor (TNF)-mediated downregulation of the BMP co-receptor haemojuvelin. In HCV-infected patients, disruption of the BMP6/hepcidin axis and genetic variation associated with the BMP/SMAD pathway predicted the outcome of infection, suggesting that BMP/SMAD activity influences antiviral immunity. Correspondingly, BMP6 regulated a gene repertoire reminiscent of type I interferon (IFN) signalling, including upregulating interferon regulatory factors (IRFs) and downregulating an inhibitor of IFN signalling, USP18. Moreover, in BMP-stimulated cells, SMAD1 occupied loci across the genome, similar to those bound by IRF1 in IFN-stimulated cells. Functionally, BMP6 enhanced the transcriptional and antiviral response to IFN, but BMP6 and related activin proteins also potently blocked HCV replication independently of IFN. Furthermore, BMP6 and activin A suppressed growth of HBV in cell culture, and activin A inhibited Zika virus replication alone and in combination with IFN. The data establish an unappreciated important role for BMPs and activins in cellular antiviral immunity, which acts independently of, and modulates, IFN.

Large primary hepatic gastrinoma in young patient treated with trisegmentectomy: A case report and review of the literature.

Primary hepatic gastrinoma is a rare disease, with fewer than 40 cases reported in the medical literature. Because it is located in an organ in which metastases are common, its diagnosis is difficult. We report a case of a 19 years old male patient with a history of gastric ulcers since the age of nine. Following gastric surgery, an antrectomy and a vagotomy, there was some alleviation of symptoms. Subsequently, the patient reported various intermittent episodes of diarrhea, diffuse abdominal pain, and vomiting. The patient underwent tomography, which revealed the presence of a hepatic mass measuring 19.5 cm × 12.5 cm × 17 cm. Primary hepatic gastrinoma was diagnosed based on laboratory examinations that indicated hypergastrinemia and a positron emission tomography/magnetic resonance study with somatostatin analogue that confirmed the liver as the primary site. After hepatic trisegmentectomy (II, III, IV, V, VIII), the patient's symptoms improved. The case is notable for the presence of a rare tumor with uncommon dimensions.

Component separation of abdominal wall with intraoperative botulinum A presents satisfactory outcomes in large incisional hernias: a case report.

PURPOSE: Transplantation patients have a series of associated risk factors that make appearance of incisional hernia (IH) more likely. A number of aspects of the closure of large defects remain controversial. In this manuscript, we present the repair of a large IH following liver transplantation through the technique of posterior components separation combined with the anterior, together with the intraoperative use of botulinum toxin A and the placement of mesh. As a secondary objective, we analyze the incidence of IH following liver transplantation in our service. METHODS: Between the years 2013 and 2016, 247 patients underwent liver transplantation in the Liver Transplantation Service at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. We analyzed the incidence of IH in these patients. One of these cases operated in March 2017 presented a defect in the abdominal wall of 22×16.6×6.4cm in the median and paramedian regions. We present the details of this innovative surgical technique. RESULTS: The total operating time was 470min. During the postoperative phase the patient presented ileus paralysis, without systemic repercussions. Resumption of an oral diet on the fifth postoperative day, without incident. Hospital discharge occurred on the 12th postoperative day, with outpatient follow up. CONCLUSION: In our service, the incidence of incisional hernias following liver transplantation is 14.5%. We described a successful approach for selected patient group for whom there is no established standard treatment. Given the complexity of such cases, however, more studies are necessary.

TAK1 is a key modulator of the profibrogenic phenotype of human ileal myofibroblasts in Crohn's disease.

Transforming growth factor (TGF)-ß-activated kinase 1 (TAK1) signaling can mediate inflammatory responses as well as tissue remodeling. Intestinal mucosal myofibroblast (IMF) activation drives gut fibrosis in Crohn's disease (CD); however, the molecular pathways involved are largely unknown. Thus we investigated the yet-unknown expression and function of TAK1 in human CD-associated fibrosis. Ileal surgical specimens, ileal biopsies, and IMF isolated from controls and CD patients were analyzed for TAK1 and its active phosphorylated form (pTAK1) by Western blotting, immunohistochemistry, and real-time quantitative PCR. TAK1 pharmacological inhibition and silencing were used to assess its role in collagen and inflammatory cytokine synthesis in IMF. TAK1 and pTAK1 levels increased in ileum specimens from CD patients compared with controls and correlated to tissue fibrosis. Similarly, TAK1 mRNA in ileal biopsies of CD patients correlated with fibrogenic marker expression but not inflammatory cytokines. CD-derived IMF showed higher TAK1 and pTAK1 expression associated with increased collagen1(α)1 mRNA levels compared with control IMF. TGF-ß1 promoted pTAK1 nuclear translocation and collagen synthesis. TAK1 inhibition or silencing significantly reduced TGF-ß1-stimulated collagen production and normalized the profibrogenic phenotype of CD-derived IMF. Taken together, these data suggest that TAK1 activation and nuclear translocation induce and maintain a fibrogenic phenotype in the IMF. Thus the TAK1 signaling pathway may represent a suitable target to design new, antifibrotic therapies.

A cost-consequence analysis of hepatitis B screening in an immigrant population.

OBJECTIVE: Screening for HBV among groups at risk, such as migrant populations, has proved to be a cost-effective strategy. With a view to advising local policy-makers, the cost-consequences of HBV screening was assessed using a modeling approach. METHODS: This cost-consequence analysis of an HBV screening strategy was conducted in a cohort of adult migrants in the province of Padua, northern Italy. RESULTS: The population targeted for screening consisted of 65 405 migrants, among whom the weighted rate for the prevalence of HBV was 0.04972, with 3251 people infected. Over a period of 5 years, the screening strategy prevented 565 cases/year of chronic hepatitis, 141 of compensated cirrhosis, 9 of decompensated cirrhosis, 14 hepatocellular carcinomas and 12 deaths. The above data revealed that the incremental cost of the screening strategy compared to no screening strategy was € 7 974 959 over the five year period. The cost per life saved amounted to € 676 709. CONCLUSIONS: The present study provides useful information to policy-makers at local and regional levels.

Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system.

BACKGROUND & AIMS: In the intestines, Toll-like receptor 2 (TLR2) mediates immune responses to pathogens and regulates epithelial barrier function; polymorphisms in TLR2 have been associated with inflammatory bowel disease phenotype. We assessed the effects of TLR2 signaling on the enteric nervous system (ENS) in mice. METHODS: TLR2 distribution and function in the ileal neuromuscular layer of mice were determined by immunofluorescence, cytofluorimetric analysis, immunoprecipitation, and immunoblot analyses. We assessed morphology and function of the ENS in Tlr2(-/-) mice and in mice with wild-type Tlr2 (wild-type mice) depleted of intestinal microbiota, using immunofluorescence, immunoblot, and gastrointestinal motility assays. Levels and signaling of glial cell line-derived neurotrophic factor (GDNF) were determined using quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry, and immunoprecipitation analyses. Colitis was induced by administration of dextran sulfate sodium or 2,4 dinitrobenzensulfonic acid to Tlr2(-/-) mice after termination of GDNF administration. RESULTS: TLR2 was expressed in enteric neurons, glia, and smooth muscle cells of the intestinal wall. Tlr2(-/-) mice had alterations in ENS architecture and neurochemical profile, intestinal dysmotility, abnormal mucosal secretion, reduced levels of GDNF in smooth muscle cells, and impaired signaling via Ret-GFRα1. ENS structural and functional anomalies were completely corrected by administration of GDNF to Tlr2(-/-) mice. Wild-type mice depleted of intestinal microbiota had ENS defects and GDNF deficiency, similar to Tlr2(-/-) mice; these defects were partially restored by administration of a TLR2 agonist. Tlr2(-/-) mice developed more severe colitis than wild-type mice after administration of dextran sulfate sodium or 2,4 dinitrobenzensulfonic acid; colitis was not more severe if Tlr2(-/-) mice were given GDNF before dextran sulfate sodium or 2,4 dinitrobenzensulfonic acid. CONCLUSIONS: In mice, TLR2 signaling regulates intestinal inflammation by controlling ENS structure and neurochemical coding, along with intestinal neuromuscular function. These findings provide information as to how defective TLR2 signaling in the ENS affects inflammatory bowel disease phenotype in humans.

Effects of coffee consumption in chronic hepatitis C: a randomized controlled trial.

BACKGROUND: Coffee is associated with a reduced risk of hepatocellular carcinoma in patients with chronic C hepatitis. This prospective trial was aimed at assessing the mechanisms underlying coffee-related protective effects. METHODS: Forty patients with chronic hepatitis C were randomized into two groups: the first consumed 4 cups of coffee/day for 30 days, while the second remained coffee "abstinent". At day 30, the groups were switched over for a second month. RESULTS: At baseline, aspartate aminotransferase and alanine aminotransferase were lower in patients drinking 3-5 (Group B) than 0-2 cups/day (Group A) (56 ± 6 vs 74 ± 11/60 ± 3 vs 73 ± 7 U/L p=0.05/p=0.04, respectively). HCV-RNA levels were significantly higher in Group B [(6.2 ± 1.5) × 10(5)vs (3.9 ± 1.0) × 10(5)UI/mL, p=0.05]. During coffee intake, 8-hydroxydeoxyguanosine and collagen levels were significantly lower than during abstinence (15 ± 3 vs 44 ± 16 8-hydroxydeoxyguanosine/10(5)deoxyguanosine, p=0.05 and 56 ± 9 vs 86 ± 21 ng/mL, p=0.04). Telomere length was significantly higher in patients during coffee intake (0.68 ± 0.06 vs 0.48 ± 0.04 Arbitrary Units, p=0.006). Telomere length and 8-hydroxydeoxyguanosine were inversely correlated. CONCLUSION: In chronic hepatitis C coffee consumption induces a reduction in oxidative damage, correlated with increased telomere length and apoptosis, with lower collagen synthesis, factors that probably mediate the protection exerted by coffee with respect to disease progression.

Cingulin is dispensable for epithelial barrier function and tight junction structure, and plays a role in the control of claudin-2 expression and response to duodenal mucosa injury.

Cingulin (CGN) is a 140 kDa protein, which is localized to the cytoplasmic region of vertebrate tight junctions (TJ), and regulates gene expression and RhoA signaling in cultured cells. To investigate the function of CGN at the organism level, we generated CGN knockout (CGN(-/-)) mice by homologous recombination. CGN(-/-) mice are viable and fertile, and are born at the expected mendelian ratios. Immunohistochemistry, immunofluorescence, electron microscopy and permeability assays of epithelial tissues of CGN(-/-) mice show no cingulin labeling at junctions, a normal localization of TJ proteins, and normal TJ structure and barrier function. Microarray analysis of intestinal cells does not show significant changes in gene expression between CGN(-/-) and CGN(+/+) mice, whereas immunoblotting analysis shows a twofold increase in the levels of claudin-2 protein in the duodenum and the kidney of CGN(-/-) mice, compared to CGN(+/+) littermates. Furthermore, CGN(-/-) mice show an exacerbated response to the ulcerogenic action of cysteamine, whereas acute injury of the colon by dextran sodium sulfate elicits undistinguishable responses in CGN(-/-) and CGN(+/+) mice. We conclude that at the organism level cingulin is dispensable for the structure and barrier function of TJ, and is embedded in signaling networks that control the expression of claudin-2, and the mucosal response to acute injury in the duodenum.

Performance and utility of transient elastography and noninvasive markers of liver fibrosis in primary biliary cirrhosis.

BACKGROUND: The performance of transient elastography in primary biliary cirrhosis has yet to be fully established. AIM: To assess: (1) the performance of transient elastography in identifying significant fibrosis in primary biliary cirrhosis by comparison with surrogate markers (AST platelet ratio index (APRI), FIB-4, Fibroindex, Forns, aspartate aminotransferase/alanine aminotransferase ratio); (2) the correlation between liver stiffness and Mayo score prognostic index. METHODS: One hundred and twenty patients with primary biliary cirrhosis were consecutively enrolled. The performance of each marker and of liver stiffness was compared with histological staging and METAVIR at time of liver biopsy. RESULTS: The area under receiver operating characteristic (ROC) of liver stiffness were 0.87, 0.88, 0.99 for histological stage ≥II, ≥III and =IV and 0.89, 0.92, 0.99 for METAVIR ≥2, ≥3 and =4. Transient elastography alone proved better able in identifying any grade of fibrosis or cirrhosis than noninvasive markers. Combining each surrogate marker with transient elastography did not improve the area under ROC. Transient elastography correlated positively with the Mayo score (P<0.001). Logistic regression analysis showed that transient elastography was associated with an advanced fibrosis (P<0.001). CONCLUSIONS: Transient elastography proved a simple, reliable and useful method for assessing liver fibrosis in primary biliary cirrhosis, whereas noninvasive surrogate markers proved unsatisfactory in predicting significant fibrosis.

Snail1 transcription factor is a critical mediator of hepatic stellate cell activation following hepatic injury.

Following liver injury, the wound-healing process is characterized by hepatic stellate cell (HSC) activation from the quiescent fat-storing phenotype to a highly proliferative myofibroblast-like phenotype. Snail1 is a transcription factor best known for its ability to trigger epithelial-mesenchymal transition, to influence mesoderm formation during embryonic development, and to favor cell survival. In this study, we evaluated the expression of Snail1 in experimental and human liver fibrosis and analyzed its role in the HSC transdifferentiation process. Liver samples from patients with liver fibrosis and from mice treated by either carbon tetrachloride (CCl(4)) or thioacetamide (TAA) were evaluated for mRNA expression of Snail1. The transcription factor expression was investigated by immunostaining and real-time quantitative RT-PCR (qRT-PCR) on in vitro and in vivo activated murine HSC. Snail1 knockdown studies on cultured HSC and on CCl(4)-treated mice were performed by adenoviral delivery of short-hairpin RNA; activation-related genes were quantitated by real-time qRT-PCR and Western blotting. Snail1 mRNA expression resulted upregulated in murine experimental models of liver injury and in human hepatic fibrosis. In vitro studies showed that Snail1 is expressed by HSC and that its transcription is augmented in in vitro and in vivo activated HSC compared with quiescent HSC. At the protein level, we could observe the nuclear translocation of Snail1 in activated HSC. Snail1 knockdown resulted in the downregulation of activation-related genes both in vitro and in vivo. Our data support a role for Snail1 transcription factor in the hepatic wound-healing response and its involvement in the HSC transdifferentiation process.