Beware: Gastrointestinal symptoms can be a manifestation of COVID-19. / Alerta: los síntomas gastrointestinales podrían ser una manifestación de la COVID-19.

BACKGROUND: There is an increasing number of reports on the presentation of gastrointestinal symptoms in cases of COVID-19. AIM: To review the studies reporting gastrointestinal symptoms in COVID-19. RESULTS: Fifteen articles (2,800 patients) were identified. Gastrointestinal symptom frequency varied from 3.0% to 39.6% and included diarrhea (7.5%), náusea (4.5%), anorexia (4.4%), vomiting (1.3%), abdominal pain (0.5%), and belching/reflux (0.3%). Those symptoms can be the first manifestation of COVID-19, but whether they reflect a better or worse prognosis, is controversial. The potential relation of the angiotensin converting enzyme 2 receptor in the digestive tract as an entry route for the virus is discussed. CONCLUSION: Gastrointestinal symptoms may be common in COVID-19, in some cases appearing as the first manifestation, even before fever and respiratory symptoms. Therefore, clinicians and gastroenterologists must be aware of those atypical cases during the current pandemic, as well as of the fecal-oral route and corresponding preventive measures.

PPAR Agonists Promote the Differentiation of Porcine Bone Marrow Mesenchymal Stem Cells into the Adipogenic and Myogenic Lineages.

PURPOSE: The aim of this work was to evaluate the effect of PPAR agonists on the differentiation and metabolic features of porcine mesenchymal stem cells induced to the adipogenic or myogenic lineages. METHODS: Bone marrow MSCs from neonate pigs were isolated and identified by cell proliferation, cell surface markers or the gene expression of stem cells (CD44, CD90, CD105 or Oct4 and Nanog, respectively). Cells were differentiated into adipose or muscle cells and treated with the PPAR agonists; adipogenic and myogenic differentiation was promoted by adding these compounds. The expression of PPARγ (an adipose marker) and MyoD1 and MyHC (muscle markers), metabolic changes and expression levels of metabolic enzymes involved in glycolysis, lipogenesis, lipolysis and the pentose phosphate pathway were tested by qPCR. RESULTS: MSCs from neonate pigs exhibited high proliferation and were positive for CD44, CD90 and CD105 markers and Oct4 and Nanog expression. The treatment that promoted the highest expression of PPARγ was 50 µM of conjugated linoleic acid (CLA) c9 t11 (6.44 ± 0.69-fold, p ≤ 0.0001) in the adipose differentiation, and upregulation of HX2, ACCAα, ATGL, LPL and G6DP (p ≤ 0.0001) and downregulation of PFK and ACCAß (p ≤ 0.0001) were found. For muscle differentiation, the best treatment was 50 µM of CLA c10 t12 (59.72 ± 4.72-fold, p ≤ 0.0001), and metabolic changes were upregulation of PFK, ACCAß, G6DP, CPT1 and PPARß/δ (p ≤ 0.0001), but no effect was observed with HX2 and ACCAα (p ≥ 0.05). CONCLUSIONS: Our results suggest that differentiated cells exhibit a typical cell lineage metabolism and higher efficiencies both in anabolism and catabolism.

Belatacept and Eculizumab for Treatment of Calcineurin Inhibitor-induced Thrombotic Microangiopathy After Kidney Transplantation: Case Report.

Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome. Belatacept, an inhibitor of T cell costimulatory protein CTLA-4 has been used in immunosuppression strategies aimed at minimization of CNI. Here we report the first case of treatment of CNI-associated TMA/hemolytic uremic syndrome with withdrawal of tacrolimus and initiation of both belatacept and eculizumab. The case describes a favorable clinical course for both graft and patient, and is accompanied by a review of the literature.

Retransplantation of the liver: review of current literature for decision making and technical considerations.

Liver transplantation (LTx) is an established treatment modality for patients with end-stage liver disease, metabolic disorders, and patients with acute liver failure. When a graft fails after primary LTx, retransplantation of the liver (reLTx) is the only potential cure. ReLTx accounts for 7%-10% of all LTx in the United States. Early causes of graft failure for which reLTx may be indicated include primary graft nonfunction and vascular inflow thrombosis. ReLTx in such cases in the early postoperative period is usually straightforward as long as an appropriate secondary allograft is secured in a timely fashion. Late indications may include ischemic cholangiopathy, chronic rejection, and recurrence of the primary liver disease. ReLTx performed in the late period is often more complex and selection criteria are more stringent due to the persistent shortage of organs. The question of whether to retransplant patients with recurrent hepatitis C remains controversial, but these practices are likely to change as the epidemic progresses and new treatments evolve. We also present recent results with reLTx from Yale-New Haven Transplant Center and early results with the use of living donors for reLTx.

Cefazolina vs. ciprofloxacino en la profilaxis de infecciones en pacientes cirróticos con sangrado digestivo / Ciprofloxacin vs cefazolin in the prevention of infection in cirrhotic patients with gastrointestional bleeding

OBJETIVO: Determinar si el uso de Cefazolina como profilaxis antibiótica produce una disminución significativa de las infecciones en pacientes cirróticos con sangrado digestivo, comparado con Ciprofloxacino. Material y MétodoS: Ensayo Clínico aleatorizado. Se incluyeron a pacientes cirróticos mayores de 18 años, con sangrado digestivo, que ingresaron entre Julio del 2008 a julio del 2010 a la Unidad de hemorragia Digestiva del HNERM, sin evidencia clínica ni de laboratorio de infección al momento del ingreso y que no hubieran recibido tratamiento antibióticolas últimas 2 semanas. A un grupo se le administró Ciprofloxacino 200 mg bid EV y al otro Cefazolina 1 g tid EV.x 7 dias. RESULTADOS: Fueron incluidos 98 pacientes, 53 pacientes en el grupo de Cefazolina y 45 en el grupo de Ciprofloxacino. El promedio de edad fue 66 +/- 10 años, 61 % varones; 59,2 % tuvieron ascitis, la frecuencia de infecciones en la población total fue de 14,3% (14/98). El resangrado fue 8,1% y la mortalidad general 4,1%. No hubo diferencias significativas entre los grupos en relación a edad, sexo, estadio Child, ascitis, encefalopatía, ni en promedio de Bilirrubina, TP, Creatinina y niveles de Albúmina. El grupo que usó Cefazolina tuvo 11,3 % de infecciones, comparado con el 17,8% de infecciones en el grupo que recibió Ciprofloxacino (p= 0,398) IC 95%. Cuando se excluyó del análisis los pacientes cirróticos Child A y aquellos sin ascitis, se encontró: 22,2 % de infecciones en el grupo de cefazolina y 26,9 % en el grupo de Ciprofloxacino (p=0,757 IC 95%).

AIM: To determine if prophylaxis with cefazolin produces a significant reduction in infections in cirrhotic patients with gastrointestinal bleeding when compared with ciprofloxacin. METHODS: Randomized clinical trial. Patients 18 years or older with diagnosis of cirrhosis, gastrointestinal bleeding and no clinical or laboratory evidence of infection who were admitted to the gastrointestinal bleeding unit of HNERM between July 2008 and July 2010 were included. Patients were allocated to receive either i.v. ciprofloxacin 200 mg bid or i.v. cefazolin 1 gm tid for 7 days. RESULTS: 98 patients were included, 53 in the cefazolin group and 45 in the ciprofloxacinone. Age average was 66 +/- 10 years, 61% were male, 59,2% had ascites. Overall rate of infections was 14,3% (14/98). Rebleeding rate was 8,1% and mortality 4,1%. There were nodifferences in age, sex, Child Pugh score, ascites, hepatic encephalopathy nor in billirubin, albumin, PT and creatinine levels between the study groups. Infection rate in the cefazolin groups was 11,3% while in the ciprofloxacin one 17,8% (p=0,398). When Child-Pugh A and patients without ascites were excluded of the analysis, the cefalozin group had 22,2% of infections and 26,9% in the ciprofloxacin one (p=0,757).

[Ciprofloxacin vs cefazolin in the prevention of infection in cirrhotic patients with gastrointestinal bleeding]. / Cefazolina vs. Ciprofloxacino en la Profilaxis de Infecciones en Pacientes Cirróticos con Sangrado Digestivo.

AIM: To determine if prophylaxis with cefazolin produces a significant reduction in infections in cirrhotic patients with gastrointestinal bleeding when compared with ciprofloxacin. METHODS: Randomized clinical trial. Patients 18 years or older with diagnosis of cirrhosis, gastrointestinal bleeding and no clinical or laboratory evidence of infection who were admitted to the gastrointestinal bleeding unit of HNERM between July 2008 and July 2010 were included. Patients were allocated to receive either i.v. ciprofloxacin 200 mg bid or i.v. cefazolin 1 gm tid for 7 days. RESULTS: 98 patients were included, 53 in the cefazolin group and 45 in the ciprofloxacin one. Age average was 66 +/- 10 years, 61% were male, 59,2% had ascites. Overall rate of infections was 14,3% (14/98). Rebleeding rate was 8,1% and mortality 4,1%. There were no differences in age, sex, Child Pugh score, ascites, hepatic encephalopathy nor in billirubin, albumin, PT and creatinine levels between the study groups. Infection rate in the cefazolin groups was 11,3% while in the ciprofloxacin one 17,8% (p=0,398).When Child-Pugh A and patients without ascites were excluded of the analysis, the cefalozin group had 22,2% of infections and 26,9% in the ciprofloxacin one (p=0,757). CONCLUSION: there were no differences in infection rates between patients with prophylaxis with cefazolin and ciprofloxacin after an episode of gastrointestinal bleeding.

Conversion to sirolimus allows preservation of renal function in kidney and kidney-pancreas allograft recipients.

The major causes of graft failure are chronic allograft nephropathy (CAN) and patient mortality. Sirolimus (SRL) is a powerful immunosuppressant with a less nephrotoxic profile as well as a lower incidence of cancer. The aim of this study was to evaluate the impact of conversion to SRL from calcineurin inhibitor (CNI)-based therapy in kidney (KT) and kidney-pancreas (SPK) allograft recipients. We analyzed renal function, allograft and patient survival, and SRL-associated adverse effects in 93 adult patients (86 KT and 7 SPK), who were converted to SRL between January 2001 and November 2008. The main reason for conversion was CAN (76; 9%) and 52 (7%) were receiving tacrolimus. Conversion occurred at a median 26.2 months. There was a significant improvement in creatinine clearance (CCr) at 6 months after conversion (CCr(baseline) 51.4 vs CCr(6m) 60.4 mL/min; P < .0001), without changes at 12 and 24 months. However, proteinuria increased significantly at 6 months compared with the baseline: 150 mg/24 hours (0-453) versus 0 mg/24 hours (range, 0-309), respectively (P < .0001), but did not progress at 12 or 24 months. At the same time we observed more extensive use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 60/5%; 65/3% and 70/2% at 6, 12, and 24 months. There were no changes in blood pressure control. Cholesterol significantly increased at 6 months (218.2 +/- 37 vs. 186.6 +/- 44 mg/dL; P < .0001). Graft and patient survivals at 4 years were 88% and 95%, respectively. Our experience suggested that conversion to SRL constituted a safe alternative with excellent results in patient and graft survival.

Preservation of recipient middle hepatic vein for drainage of anterior sector veins in adult-to-adult living-donor liver transplantation.

The inclusion of donor middle hepatic vein (MHV) in right-lobe living-donor grafts and the need for reconstruction of the MHV tributaries have long been controversial areas in living-donor liver transplantation. We report technical details in restoration of venous drainage of the anterior sector (segments V and VIII) of the right lobe of the liver graft using a preserved MHV from the recipient liver, and address the issue of reconstruction of donor MHV tributaries without use of an interposition graft. We review clinical situations in which restoration of outflow drainage of the anterior segment of the liver graft should be considered.

Open abdomen management with human acellular dermal matrix in liver transplant recipients.

BACKGROUND: Abdominal wall closure after liver transplantation is not always feasible and may result in increased intra-abdominal pressure along with associated complications. Various temporary closure techniques as well as open wound management have been used to address this complex problem. The aim of this series was to describe an approach to definitive wound closure of the open abdomen in liver transplant patients. METHODS: We performed a retrospective review of all liver transplant patients at our institution from September 2005 to November 2007. The management of the open abdomen in 10 liver transplant patients was reviewed, and a novel approach described to manage these defects. RESULTS: Ten patients with open wounds were closed during the study period using human acellular dermal matrix (HADM). There were 7 men and 3 women of median age 55 years. Average size of HADM was 235 cm(2). The median follow-up is 10 months with no incidence of evisceration or hernia. In 1 patient, the graft failed along the lateral side due to infection; it dislodged during vacuum-assisted closure dressing change in another patient at 5 months after closure. Fascial closure was not possible due to organ edema (n = 3), a large liver (n = 4) or wound infection with dehiscence (n = 3). CONCLUSIONS: HADM can be used for primary wound closure in both clean and contaminated wounds as an alternative to an open abdomen post-liver transplantation.

[Clinical and epidemiological profile of cirrhosis in the liver unit at Edgardo Rebagliati Martins National Hospital]. / Caracteristicas epidemiológicas y clínicas de la cirrosis hepática en la unidad de hígado del HNERM ES-SALUD.

BACKGROUND: Liver cirrhosis is an important cause of morbidity and mortality all around the world. In Peru it is the 5th cause of general mortality and the 2nd one between all those related to gastrointestinal and hepatobiliary diseases. At HNERM it is the principal etiology between all the cases that need hospitalization in gastroenterology. It is clear that we need to know all the clinical and epidemiologic characteristics to propose national actions to try to control and prevent this disease. MATERIAL AND METHODS: The present is a descriptive, transversal and observational study to clarify the clinical and epidemiological profile of patients with cirrhosis hospitalized in the Liver unit at the Edgardo Rebagliati Martins National Hospital between january 2001 and june 2004. RESULTS: 475 patients were included, 45.1% were female, medium age was 63.4 years (r =26-93). The most frequent causes of cirrhosis were alcoholism (28%), chronic hepatitis B (15.2%), and chronic hepatitis C (11.8%). According to Child-Pugh score 42.3% was in stage B, and 42.5% en C. The main cause for hospitalization was upper gastrointestinal bleeding related to portal hypertension, followed by ascitis and encephalopathy. The principal infections were urinary, pulmonar and spontaneous bacterial peritonitis. Hepatocellullar carcinoma was found in 7.9% of the cases. CONCLUSIONS: Liver cirrhosis affects principally males. The principal causes are alcoholism and chronic viral hepatitis. The principal cause of hospitalization is upper gastrointestinal bleeding. Most of the patients have an advanced disease at the moment of diagnosis. Principal infections are urinary, Pneumonia and SBP.

Hepatocellular carcinoma in renal transplant patients.

INTRODUCTION: Chronic liver diseases, especially those related to hepatitis B (HBV) and C viruses (HCV), are a common problem in renal transplant patients. Hepatocellular carcinoma (HCC) is a complication of chronic liver diseases, incidence in the renal transplant cohort is higher than in the general population (1.4% to 4% vs 0.005% to 0.015%). METHODS: We retrospectively evaluated the incidence of HCC, its clinical presentation, the treatments, and the relation to chronic viral hepatitis among the population transplanted at our center between January 1980 and December 1998 and followed to August 2003. RESULTS: During the study period, six recipients among 534 renal transplants displayed HCC (incidence 1.12% of the entire population and 2.29% of patients with chronic viral hepatitis). Among the cohort five were men, and all had chronic viral hepatitis: three HBV, one HCV, and 2, a coinfection. HCC was diagnosed 124.1 (range 45 to 244) months after transplantation. All patients presented with abnormal liver function tests and tumors larger than 5 cm. Four had more than three tumors and three had an alpha-fetoprotein level higher than 400 IU/mL. Three patients received no treatment (survivals 1, 1, and 4 months); two patients, chemoembolization (survival 6 and 12 months); and one, surgical ethanol injections (survival 4 months). The overall survival was 4.5 months. CONCLUSION: HCC in renal transplant recipients is a common complication among patients with chronic viral hepatitis. The outcome was poor because HCC was detected at an advanced stage. Screening strategies for early diagnosis must be prospectively evaluated.

Hepatotoxicidad y pancreatitis por sales de oro: reporte de caso / Hepatotoxicity and pancreatitis by gold salts: case report

Se reporta el caso de una paciente de 37 años, natural y procedente de Lima, portadora de Artritis Reumatoide quien estuvo en tratamiento con prednisona, metotrexate y cloroquina. Esta terapia fue remplazada por sales de oro un mes antes de su ingreso, presentando luego de la aplicación de la tercera dosis dolor abdominal, diarrea, prurito e ictericia, asociado a astenia y sensación de alza térmica no cuantificada. Los exámenes auxiliares mostraron incremento de las transaminasas, bilirrubinas, fosfatasa alcalina, eosinofilia e inversión de la relación albúmina globulina, con incremento predominante de la inmunoglobulina G, así como de amilasa y lipasa. El estudio Anatomopatológico demostró: colestasis, balonamiento de hepatocitos y necrosis unifocal, a predominio de la zona 3 del lobulillo hepático, lo cual se encontró consistente con reacción tóxica.

The case of a patient, 37 years old, born and resident of Lima, suffering rheumatoid arthritis who underwent treatment with Prednisone, Methotrexate, and Chloroquine is reported. This therapy was substituted for gold salts one month before her admission. After the third dose she presented symptoms of abdominal pain and diarrhea, itching, and jaundice, associated with asthenia and a feverish sensation. Liver biochemistry demonstrated elevated transaminase, bilirubin, alkaline phosphatase, eosinophilia, inversion of the rate albumin / globulin, higher titer of immunoglobulin G, as well as an elevation of amylase and lipase. The anatomopathological study showed cholestasis, hepatocyte ballooning, spotty necrosis, predominantly in zone 3 of the acinus. These findings where found consistent with a toxic reaction.

The systemic inflammatory response syndrome in acute liver failure.

The systemic inflammatory response syndrome (SIRS) in acute liver failure (ALF), in which infection is common, has not been studied. In this study, SIRS components were recorded on admission and during episodes of infection, in 887 ALF patients admitted to a single center during an 11-year period. Overall, 504 (56.8%) patients manifested a SIRS during their illness, with a maximum of 1, 2, and 3 concurrent SIRS components in 166, 238, and 100 patients, respectively. In 353 (39.8%) patients who did not become infected, a SIRS on admission was associated with a more critical illness, subsequent worsening of encephalopathy, and death. Infected patients more often developed a SIRS and one of greater magnitude. The magnitude of the SIRS in 273 patients with bacterial infection correlated with mortality, being 16.7%, 28.4%, 41.2%, and 64.7% in patients with 0, 1, 2, and 3 maximum concurrent SIRS components, respectively. Similar correlations with mortality were seen for SIRS associated with fungal infection, bacteremia, and bacterial chest infection. Fifty-nine percent of patients with severe sepsis died, as did 98% of those with septic shock. A significant association was found between progressive encephalopathy and infection. Infected patients with progressive encephalopathy manifested more SIRS components than other infected patients. For patients with a SIRS, the proportions of infected and noninfected patients manifesting worsening encephalopathy were similar. In ALF, the SIRS, whether or not precipitated by infection, appears to be implicated in the progression of encephalopathy, reducing the chances of transplantation and conferring a poorer prognosis.

[Neurological complications of renal transplant]. / Complicaciones neurológicas del trasplante renal.

Advances in surgical procedures and new immunosuppressor therapies have improved the outcome of renal grafts. However, these changes have been accompanied by infectious, neoplastic and neurologic complications. The purpose of this study was to determine the incidence of neurologic complications among 542 patients receiving a renal transplant (from living or cadaveric donors) at CEMIC between 1970 and 1996. Neurologic complications occurred in 43 patients (8%) as follows: 8 meningitis (1.5%), 8 acute confusional syndrome (1.5%), 7 encephalitis (1.3%), 7 cerebrovascular accidents (1.3%), 6 convulsions (1.1%), 3 tumors (0.5%), 3 femoral nerve lesion (0.5%), and 1 epidural lipomatosis (0.1%). Etiologic agents most commonly observed in meningitis were: Cryptococcus neoformans, Listeria monocytogenes and Mycobacterium tuberculosis. Major difficulties arose in the diagnosis of encephalitis. Diagnosis of the above complications required clinical astuteness and repeated bacteriologic, serologic and imaging studies.

Right frontal EEG asymmetry and lack of empathy in preschool children of depressed mothers.

EEG activity, empathic reactions to emotion-inducing stimuli, and the ability to complete a teaching task were examined in preschool children of depressed and non-depressed mothers. EEG activity from frontal and parietal regions was recorded. Repeated measures MANOVAs indicated that the children of depressed mothers had greater relative right frontal EEG asymmetry, a pattern that typically accompanies greater negative affect and showed less empathic responses to a crying infant as well as to their own mothers' simulated distress. Children of depressed mothers were slower in completing the teaching task (involving mutual cooperation with their mother) and they spent more time asking for help than children of non-depressed mothers. Further, the depressed mothers stated their approval less often and spent less time helping their child complete the task.

Complicaciones neurológicas del trasplante renal. / [Neurological complications of renal transplant]

Advances in surgical procedures and new immunosuppressor therapies have improved the outcome of renal grafts. However, these changes have been accompanied by infectious, neoplastic and neurologic complications. The purpose of this study was to determine the incidence of neurologic complications among 542 patients receiving a renal transplant (from living or cadaveric donors) at CEMIC between 1970 and 1996. Neurologic complications occurred in 43 patients (8

) as follows: 8 meningitis (1.5

), 8 acute confusional syndrome (1.5

), 7 encephalitis (1.3

), 7 cerebrovascular accidents (1.3

), 6 convulsions (1.1

), 3 tumors (0.5

), 3 femoral nerve lesion (0.5

), and 1 epidural lipomatosis (0.1

). Etiologic agents most commonly observed in meningitis were: Cryptococcus neoformans, Listeria monocytogenes and Mycobacterium tuberculosis. Major difficulties arose in the diagnosis of encephalitis. Diagnosis of the above complications required clinical astuteness and repeated bacteriologic, serologic and imaging studies.

The DeltaF508 mutation in Ecuador, South America.

There are few reports about the incidence of the DeltaF508 mutation in Latin American countries. We show the study of the DeltaF508 mutation and the seven most common "European" mutations in 10 Ecuadorian CF affecteds. The incidence of DeltaF508 mutation found was 25% and none of the other seven was detected in our population, which indicates that at least 60% of the mutations in the studied population are different from most common in Europe. Similar data have been reported in other Amerindian populations, therefore it is suggested that Cystic Fibrosis in Ecuador-and other Amerindian countries in Latin America-have a different ethiology than that of Caucasian populations.