Acute myocardial infarction (AMI) is the main cause of morbidity and mortality worldwide and is characterized by severe and fatal arrhythmias induced by cardiac ischemia/reperfusion (CIR). However, the molecular mechanisms involved in these arrhythmias are still little understood. To investigate the cardioprotective role of the cardiac Ca2+/cAMP/adenosine signaling pathway in AMI, L-type Ca2+ channels (LTCC) were blocked with either nifedipine (NIF) or verapamil (VER), with or without A1-adenosine (ADO), receptors (A1R), antagonist (DPCPX), or cAMP efflux blocker probenecid (PROB), and the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET) induced by CIR in rats was evaluated. VA, AVB and LET incidences were evaluated by ECG analysis and compared between control (CIR group) and intravenously treated 5 min before CIR with NIF 1, 10, and 30 mg/kg and VER 1 mg/kg in the presence or absence of PROB 100 mg/kg or DPCPX 100 µg/kg. The serum levels of cardiac injury biomarkers total creatine kinase (CK) and CK-MB were quantified. Both NIF and VER treatment were able to attenuate cardiac arrhythmias caused by CIR; however, these antiarrhythmic effects were abolished by pretreatment with PROB and DPCPX. The total serum CK and CK-MB were similar in all groups. These results indicate that the pharmacological modulation of Ca2+/cAMP/ADO in cardiac cells by means of attenuation of Ca2+ influx via LTCC and the activation of A1R by endogenous ADO could be a promising therapeutic strategy to reduce the incidence of severe and fatal arrhythmias caused by AMI in humans.

Brazil is a country with expressiveness and relevance in the organ and tissue donation and transplantation scenarios.Numerical indicators regarding the rate of transplants demonstrated this importance.During 2021, 23,929 cells, tissues, and organs transplants were performed 1 .However, despite this numerical indicator, the waiting list for transplantation is still lengthy.During the first semester of 2022, 51,674 people were registered waiting for the treatment, which often means a chance for continue living 2 .Due to the difference between the number of transplants and the number of people on the waiting list, strategies are developed to look for problems and failures in the cells, tissues, and organs donation and transplantation processes, as well as improvement opportunities.Regarding these strategies, it was identified that organs and tissues were lost ofdue to logistical problems.According to the Brazilian Association of Organ Transplantation (Associação Brasileira de Transplantes de Órgãos -ABTO), in 2022, 15% of the organs offered were not transplanted for various reasons.Some of these reasons were related to fragilities during the packaging for transport 2 .Currently, the organs are packaged in three primary packages and then in a thermal box filled with ice for transport 3 .Identification is done with labels standardized in current legislation 4 , and the internal temperature is not controlled.Furthermore, the packaging route is not shared.The problems with this type of transport are related to the lack of temperature control, causing the organs to freeze when in contact with the ice or, due to the thawing of the ice, the temperature increase.Both situations result in tissue death and, thus, there is not control over the quality of the transplanted organ.

Background. To evaluate the capacity of BARS to predict 90-day, 1-year, 3-year, and 5-year survival after liver transplantation (LTx). The Balance of Risk Score (BARS), proposed by the Swiss Hepato-pancreato-biliary and Transplant Center, University Hospital Zurich, Switzerland, was conceptualized to determine survival after LTx preemptively.Sample and Methods. This was a retrospective observational study on 866 cases of LTx among adults (>18 years) performed within the transplantation program at Hospital Israelita Albert Einstein between January 1, 2010, and December 31, 2015. Cases of loss from follow-up, split-liver transplantation, transplantation from a live donor, and combinations of LTx with transplantation of other organs were excluded. BARS was calculated for each transplantation performed. The survival estimates were accompanied by 95% CIs, and the associations between the variables of interest and the patients' overall survival were evaluated using Cox proportional risk models. Receiver operating characteristic curves and the estimated area under the curve were used with 95% CIs and P values for the equality test on the area at .5.Results. The area under the curve for the 90-day period was 0.725, with a 95% CI from 0.670 to 0.81 and a P value < .001 for the equality test at 0.5. In the stratified analysis, the score of 18 presented the highest sensitivity, taking a minimum specificity of 90%. The BARS >18 gave rise to a significant decline in survival, from 89.7% to 60.4% over the first 90 days, from 83.3% to 56.2% over a 1-year period, from 75.7% to 49.5% over 3 years, and from 72.2% to 43.4% over 5 years.Conclusion. The BARS was shown to be reproducible and can be used as a tool for estimating survival among LTx patients. LTx performed on patients with BARS >18 significantly predicts lower survival for such patients.

Background: Iodine is essential for thyroid hormone biosynthesis. We investigated the prevalence of iodine deficiency (ID) and hypothyroidism in children with intestinal failure (IF) followed up longitudinally, considering selenium status, which is also essential for thyroid gland function. Methods: Children admitted to an intestinal rehabilitation program and receiving home PN were regularly followed-up for urine iodine concentration (UIC), selenium, and thyroid function tests from April 2019 to June 2022. The outcome variable ID was defined as a UIC value < 100 μg/L. Generalized estimating equations were used to assess the effects of potential variables associated with UIC. The study was approved by the hospital’s ethics committee. Results: Twenty-four patients aged 62.7 (39.1; 79.7) months receiving PN for 46.5 (21.5) months were included. The average energy supply was 81.2 kcal/kg/day, 77.6% of which was provided by PN. An average of 5.2 UIC measurements per patient were performed. The prevalence of ID decreased from the first assessment (83.3 %) to the last (45.8%). Three patients developed hypothyroidism secondary to iodine and selenium combined severe deficiency. In the adjusted analysis, iodine intake from oral or enteral nutritional formulas was associated with UIC (β= 0.71 [0.35, 1.07]; p < 0.001). Normal UIC values were observed in patients who reached ≥ 80% of the recommended iodine intake from nutritional formula.Figure 1.: Adjusted linear prediction of iodine intake adequacy from oral or enteral nutritional formulas on urinary iodine concentration (µg/L). The dotted line represents the lower limit of UIC (urinary iodine concentration).Conclusion: ID is highly prevalent in children with IF who receive long-term PN, and its frequency decreases with iodine intake by nutritional formula. Patients who developed hypothyroidism had severe combined iodine and selenium deficiency. Iodine and selenium status, thyroid function, and iodine intake should be monitored in children with IF.

BACKGROUND:Intestinal transplantation (IT) and multivisceral transplantation (MVT) are curative therapies for patients with intestinal failure and severe complications associated with total parenteral nutrition. High levels of immunosuppression are required to prevent acute cellular rejection (ACR) from the bowel. Studies regarding pre-treatment, induction, and post-transplant therapy have improved graft acceptance, reducing immunosuppression doses and infectious complications. However, the low rate of IT and MVT and the small number of specialized centers have resulted in a limited number of evidence-based immunosuppression protocols. We reviewed immunosuppression in IT and MVT to draw useful conclusions regarding the best protocol strategies for the induction, maintenance, and management of ACR.METHODS:A review was performed using the PubMed database. Articles on immunosuppression protocols in IT and MVT that addressed graft rejection, infection, or survival, published between 2006 and 2022, were selected.RESULTS:A total of 690 articles were selected. Two researchers applied the inclusion and exclusion criteria and selected 14 articles independently. For induction, thymoglobulin, alemtuzumab, and basiliximab are the most frequently used immunosuppressants for induction. Classic maintenance therapy consists of a combination of corticosteroids and tacrolimus. Methylprednisolone with an increased tacrolimus dose is used most frequently to manage ACR. Depending on the receptor response, such as thymoglobulin, infliximab, adalimumab, or bortezomib, other immunosuppressants should be considered.CONCLUSIONS:There have been great advances in IT and TMV immunosuppression. We conclude that the gold standard immunosuppressive protocol is triple therapy, comprising induction with thymoglobulin, maintenance with steroids for a few months, and tacrolimus and mycophenolate therapy. Innovative approaches for treating intestinal rejection episodes with more appropriate drugs, such as infliximab, adalimumab, or bortezomib, are necessary.

O sarcoma embrionário indiferenciado de fígado (SEIF) consiste em uma neoplasia maligna rara com etiopatogenia ainda pouco conhecida, acometendo em sua maioria crianças na faixa etária entre 6 e 10 anos. Corresponde a 7% dos tumores primários de fígado, e é a quarta neoplasia hepática mais frequente na pediatria. O diagnóstico do SEIF se dá em um conjunto de achados de imagem, idade e nível de alfa-fetoproteína (AF), que geralmente está normal, assim como as provas de função hepática. O diagnóstico precoce é prejudicado pelos sintomas inespecíficos, como dor abdominal, massa abdominal palpável de rápido crescimento, febre, perda de peso e sintomas gastrintestinais. O achado de imagem mais característico é o de massa grande, única e bem-delimitada. A ultrassonografia mostra massa predominantemente sólida e ecogênica. Já a tomografia computadorizada evidencia uma massa que assume característica principalmente cística. Histologicamente é evidenciado tecido mixoide com células neoplásicas fusiformes. Alguns estudos imuno-histoquímicos indicam origem mesenquimal do SEIF. O aspecto macroscópico do tumor se apresenta como grande massa hepática, de componente sólido predominantemente, com algumas áreas císticas, hemorragia e necrose em até 80% de sua superfície. Ainda não é bem-definida a melhor abordagem para o tratamento do sarcoma primário de fígado. As opções terapêuticas incluem ressecção cirúrgica, quimioterapia, radioterapia e transplante hepático (TH). Porém, nos casos de tumores irressecáveis, o TH é uma opção que deve ser considerada, uma vez que nesse tipo histológico tanto quimioterapia como radioterapia têm benefício questionável. Este artigo tem por objetivo relatar um caso de SEIF gigante, com invasão vascular, submetido a TH com boa evolução pós-operatória e sem sinais de recidiva após nove meses de TH.

Abstract Background Mucinous cyst neoplasm of the liver (MCN-L) comprise less than 5% of all cystic liver lesions and is characterized by the presence of ovarian stroma and absence of bile duct communication. Case presentation Here, we discuss a 45-year-old woman who presented with symptomatic liver mass. Diagnostic workup detected a 4.2 × 3.6 cm septate cyst located in segments I, V, and VIII of the liver in communication with the right hepatic duct. An open right liver resection with total bile duct excision and hilar lymphadenectomy was performed. Pathology revealed a multiloculated cyst with lined mucinous epithelium and ovarian-like stroma, consistent with low-grade MCN-L. Conclusions This case shows that unusual location and bile duct communication can be present in MCN-L.

AbstractPancreatic duct stones are direct sequelae of chronic pancreatitis (CP) and can occur in ∼50% of patients. Selection of the appropriate treatment method for pancreatic duct stones depends on location, size and number of stones. We present a patient with upper abdominal pain and weight loss for the previous 3 months. Diagnostic workup detected a chronic inflammation of the pancreas with stone in the main pancreatic duct and a nodular lesion in the head of the pancreas. Endoscopic retrograde cholangiopancreatography was performed without success. Given the rise in incidence and prevalence of CP, the potential complications and high mortality rate, it is imperative that physicians understand the risk factors, disease process and management of this disease. Pancreaticoduodenectomy in patients with CP is a feasible option for the treatment of focal cystic lesions to the head of the pancreas associated to pancreatic stone in selected cases.

Encapsulating Peritoneal Sclerosis (EPS) is a severe and rare condition frequently associated with peritoneal dialysis, characterized by bowel obstruction, with lethal consequences in 20% of the patients. The disease presents as a mass of fibrous tissue encapsulating visceral organs that may potentially compromise digestive tract function. This report describes the case of a patient under peritoneal dialysis (PD) due to chronic kidney disease secondary to focal segmental glomerulosclerosis diagnosed with EPS. The patient had undergone two living-donor kidney transplant procedures. Surgical techniques and clinical measures employed to unravel bowel obstruction are described, which have been shown to ameliorate EPS secondary complications. Parenteral nutrition has significantly contributed to afford adequate nutrition, improving tissue healing as well as serum protein levels, vitamins and electrolytes. Therapy with tamoxifen and sodium thiosulfate effectively delayed the development of EPS.

Introduction:Copper is necessary for normal function of hematopoietic, cardiovascular, connective/skeletal and the central nervous systems. A >50% prevalence of copper deficiency has been reported in retrospective case series of children with intestinal failure (IF) during transition from parenteral to enteral nutrition (Yang CJ et al, 2011; Namjoshi SS et al, 2017). We sought to determine the frequency and factors associated with copper deficiency in children with IF who had their copper plasma levels monitored according to a standard protocol. Methods:Prospective cohort study in children with IF followed-up at an intestinal rehabilitation center between July 2015 and November 2018 and who were receiving home parenteral nutrition (PN). Patient’s micronutrient status was routinely monitored at 3-month intervals or once a month when deficiency was detected. Copper was given at a standard dose of 20 mcg/kg as part of a trace-element solution, and was omitted in the PN if the patient developed intestinal failure liver associated disease. The outcome variable was copper plasma level during the follow-up period. The effect of the exposure variables (length of time on PN, prematurity, serum direct bilirubin levels, C-reactive protein, length of remnant small bowel and ostomy) on the outcome was analyzed by generalized estimating equations. Results:Thirteen patients aged 34.2 months (IQR: 25.3; 41.1) were included; median time on PN was 26.4 months (IQR: 15.2 to 32.9). An average of 7 (range 2 to 15) copper measurements/patient were performed; 53.8% of patients had at least 1 copper measurement below normal during the follow-up. Eight patients who had cholestasis had trace elements of PN discontinued for 4 months (IQR: 1.6 to 12.2); from June 2017 these patients began to receive copper solution separately in doses to achieve basal requirements or to correct deficiency. Direct bilirubin levels (β coeff. -5.9, 95% CI: -9.0;-2.7, p=0.04), time on PN without copper (β coeff. -1.7, 95% CI: -3.2;-0.2, p<0.001) and ostomy (β coeff. -20.3, 95% CI: -37.6;-2.9, p=0.02) were associated with decreased copper levels in multivariable analysis. The figure shows adjusted predictions and marginal effects of the length of time without copper on copper serum levels. Conclusion:Direct bilirubin levels, length of time on PN without copper and ostomy are independently associated with the high frequency of decreased copper plasma levels in patients with IF receiving long term PN.

Introduction: The use of central venous catheters (CVC) for parenteral nutrition (PN) administration has increased survival rates and allowed patients with short bowel syndrome who are dependent on long-term PN to be discharged for home care. However, catheter related bloodstream infection (CRBSI) remains as a major complication of long-term PN and is associated to increased morbidity, mortality, length of stay and hospital costs. Several lock solutions have been used to prevent CVC contamination. Among them, the citrate-taurolidine solution (composed of 2% taurolidine and 4% citrate), which is unique by reducing the biofilm formation of bacterial cells and avoiding bacterial adhesion and clotting in the catheter. We aimed to identify the rates of CRBSI before and after the use of the citrate-taurolidine solution in de-hospitalized children receiving home PN. Methods: This was a prospective cohort study in 11 children with intestinal failure (IF), mean age 35.4 months (12.7), receiving home PN and followed-up at a center for intestinal rehabilitation between July 2015 and November 2018. The rate of CRBSI was calculated for each patient by the incidence density ratio, defined as number of infections per 1,000 catheter-days. The citrate-taurolidine solution began to be used from March 2017 onward. The primary outcome was the variation in the rate of CRBSI before and after use of citrate-taurolidine lock solution. Results: The median time on PN was 26.4 months (interquartile range 15.2 - 32.9). The mean number of catheter days per patient before and after taurolidine were 178 (interquartile range 32 - 85.5) and 238 (interquartile range 203 - 386) days, respectively. There were 13 episodes of CRBSI before and only one episode after the use of citrate-taurolidine line locks. The incidence density of pre-taurolidine CRBSI was 5.7 and of post-taurolidine was 0.3 per 1000 catheter days. The main microorganism identified was Staphylococcus epidermidis. Conclusion: The rate of CRBSI was greatly reduced after the citrate-taurolidine use; this lock solution should be the first choice in reducing CRBSI in children with IF receiving home PN.

Introduction: Regular and frequent monitoring of the patient’s nutritional status is necessary for optimizing nutritional support in children with intestinal failure (IF). We aimed at examining the changes in anthropometric nutritional status and identifying factors associated with this outcome in children with IF followed at a pediatric intestinal rehabilitation center. Methods: Prospective cohort study in 13 children with IF (8 males and 5 females), mean current age of 32.9 (16.7) months. Patients were followed-up at an intestinal rehabilitation center between July 2015 and December 2018; all were receiving long-term parenteral nutrition (PN). The main primary cause of IF was necrotizing enterocolitis (6/13) and 7 patients had ultrashort bowel syndrome. Z scores of weight, height, and body mass index for age were routinely monitored at two-week intervals and compared with the WHO reference standards. Data were collected regarding the energy and protein supplied by PN and by oral/tube feeding route. Age, sex, time of follow-up, prematurity, length of the remnant small bowel, ostomy and the diagnosis of intestinal failure associated liver disease were the main explanatory variables for the outcome (Z scores of weight/age and height/age). The effect of the exposure variables on the outcomes was analyzed by generalized estimating equations. Results: The median time of follow up was 16.5 months, with interquartile range (IQR) of 8.9 to 32.4 months. The Z scores of the anthropometric parameters increased significantly during the follow-up. Median weight/age Z score increased from -3.68 (IQR: -4.97 to -2.66) to 0.45 (IQR: -2.0 to 0.44) and mean height/age Z score increased from -3.93 (IQR: -4.66 to -2.63) to -1.12 (IQR -4.18 to -0.28). Malnutrition (based on weight for age Z score) decreased from 77% to 23% by the last assessment. Mean (SD) total energy and protein supply were 88 (23.4) kcal/kg/day and 2.3 (0.7) g/kg/day, respectively, and both decreased significantly along the follow-up period (p< 0.001). Mean energy and protein supply by PN were 67.6 (SD 17.5) kcal/kg/d and 1.8 (0.5) g/kg/d respectively. The increase in the anthropometric z scores was not associated with any of the clinical and demographic factors considered in the analysis. Conclusion: There was a significant improvement in the nutritional status of children during the follow-up period. This improvement seems to occur independently of demographic factors and comorbidities.

Introduction: Hematological cytopenias have been reported in copper-deficient children with intestinal failure (IF) and receiving parenteral nutrition (PN). However, no cohort study has investigated a possible association between copper deficiency and low blood cell count in patients who had their copper plasma levels monitored according to a standard protocol. We investigated how much copper plasma levels influence anemia, neutropenia and thrombocytopenia in children receiving long-term home PN. Methods: Children with IF admitted to a pediatric intestinal rehabilitation program and who were receiving home PN were followed-up prospectively from July 2015 to November 2018. Outcome variables were hemoglobin (Hb, g/ dL), neutrophils and platelet counts (mm3); plasma copper levels during the follow-up were considered as the main explanatory variable. Patient’s micronutrient status was routinely monitored at 3-month intervals or once a month when deficiency was detected. All patients were receiving a fixed dose of vitamins, and multi-trace element solution including copper (at a standard dose of 20mcg/kg). Complete blood counts were performed bi-weekly. Generalized estimating equations models were adjusted for vitamin B12, iron and folate plasma levels. Results: Thirteen patients aged 34.2 months (IQR: 25.3; 41.1) were included; median time on PN was months 26.4 (15.2 to 32.9). An average of 7 (range 2 to 15) copper measurements/patient were performed; 53.8% of patients had at least 1 copper measurement below normal. Eight patients who had cholestasis had trace elements of PN discontinued. All but one patient had anemia; neutropenia was seen in 11 patients (among them 8 had < 1000 neutrophils/mm3), and 8 patients had thrombocytopenia. Copper deficiency (plasma level <72μg/dL) was associated with lower Hb and lower neutrophils and platelet counts. The decrease of 10 μg/dL in plasma copper resulted in decreases in Hb level (β coeff.: -0.08 (95% CI: -0.02;-0.14, p=0.009), in neutrophil (β coeff. -201.6, 95% CI:-134.8;-268, p<0.001) and in platelet counts (β coeff. -6278, 95% CI: -2026;-10529, p=0.004). The figure shows predictions and marginal effects of copper serum levels on neutrophils count. Conclusion: Copper deficiency is associated with lower blood cell counts and higher risk of anemia, neutropenia and thrombocytopenia. This effect was more pronounced for neutropenia. Copper status should be routinely monitored in children with IF receiving long term PN.

Introduction: Selenium is essential in the protection against oxidative stress, for optimum immune response and for thyroid hormone biosynthesis and metabolism. We describe a case of chronic selenium deficiency with severe hypothyroidism and metabolic encephalopathy in a child with ultra-short bowel syndrome receiving long-term home parenteral nutrition (PN) without selenium supplementation. Methods: The patient is a 4-year-old girl, born prematurely at 26 weeks of gestation, birth weight 670g. At the 13th day of life she was diagnosed with necrotizing enterocolitis and required exploratory laparotomy. There was necrosis of the small bowel and need of extensive resection, with 3 cm of small bowel and half of colon remaining. After the surgery, she was started on exclusive PN containing a fixed dose of multi-trace element solution but lacking selenium, probably due to drug shortage. After a one-year hospitalization, she was discharged and continued to receive PN at home. At 3 years old she presented with converging strabismus and regression of motor development. Initially she had inability to ambulate, which worsened until she couldn’t walk, sit and talk. At that time, she was diagnosed with decompensated hypothyroidism, requiring T3 and T4 replacement therapy. Results: At the age of 3 years 8 months, she was referred to our intestinal rehabilitation center for investigation. On examination she had an edematous face, muscle weakness, irritability and depigmented hair. Plasma selenium levels were undetectable. The diagnosis of encephalopathy and myxedema secondary to severe selenium deficiency was made. Intravenous selenium repletion therapy was initiated (4 µg/kg/day), followed by 2 µg/kg/day as maintenance and, as selenium plasma levels normalized, the need of T3 replacement was reduced until it was discontinued and maintenance treatment with levothyroxine isolated was initiated. She was discharged from hospital to home care four months later at the age of 4. After selenium levels restored to normal, neurological signs improved progressively and growing hair was repigmented. She continues to receive physio, speech and occupational therapy and she is progressing well. Conclusion: Chronic selenium deficiency caused severe hypothyroidism and metabolic encephalopathy in a child receiving exclusive long-term home PN without selenium. Patients on long-term PN need selenium supplementation to avoid serious clinical manifestations of deficiency.

AMM, sexo feminino, 40 anos, portadora de leucemia mieloide crônica (LMC), em uso de Imanitibe 400 mg/dia desde o diagnóstico da doença, em 13/06/2016; foi internada no dia 21/01/2018 para investigação, com história de icterícia, náuseas e vômitos em grande quantidade há uma semana da data da internação. Após seis dias, a paciente foi diagnosticada com insuficiência hepática aguda grave, apresentava-se ictérica 4+/4+ e com bilirrubina de 5,41 g/dL, albumina de 2,8, INR de 4,1, ascite moderada, creatina s rica de 0,7mg/dL. O transplante foi realizado 13 dias após a internação com fígado de doador falecido, com morte encefálica. Procedimento foi realizado sem intercorrências. Imatinibe é um inibidor seletivo da BCR-ABL tirosina quinase, uma enzima que tem atividade na Leucemia Mieloide Crônica (LMC) e tumores estromais gastrointestinais. A droga é metabolizada no fígado pelo sistema de enzimas CYP3A4, e gera muitos metabólitos ativos. Reportamos um caso de uma mulher de 40 anos, em uso de Imatinibe por um ano e sete meses até o reconhecimento de sua hepatoxicidade. Na literatura, recomenda-se que sejam feitos testes de função hepática antes do início do tratamento de LMC, e que tais parâmetros sejam monitorizados mensalmente ou segundo recomendações clínicas. Além disso, é possível observar que há boa recuperação da hepatotoxicidade de alguns pacientes apenas com a parada da droga, se as alterações hepáticas forem diagnosticadas a tempo. O manejo mais eficiente da LMC após o transplante ainda não foi estabelecido. No caso reportado, o uso de PRISMA antes, durante e após o transplante pode ter sido responsável pelo bom prognóstico.