HCV Infection in Egyptian Patients with Acute Hepatitis

The diagnostics of community-acquired acute HCVhepatitis in an endemic area was studied in 110 Egyptianpatients with acute jaundice. In the first week of thejaundiced period 30 of 110 patients (27.3%) had anti-HCVantibodies. The majority already showed high levels ofanti-HCV IgG (25/30), associated with anti-HCV IgM innine of them. Five patients showed only an HCV IgMreactivity. Seven had also anti-HEV and/or anti-HBV: their jaundice couldthen be related to an acute infection caused by thoseviruses. All patients were infected with genotype 4a, inthree associated with the 3a. During the follow-up five patients seroconverted for IgG, whiletheir anti-HCV IgM did not show a uniform pattern ofreactivity. Patients with positive serology suspected ofan acute HCV infection were older than the patients with other acute hepatitis and showed a lowerpeak of ALT level. Seroconversion during acute hepatitisstrongly indicated HCV as the etiologic agent. However,the detection of anti-HCV IgG antibodies in the jaundiced period showed that the majorityof patients had already seroconverted to anti-HCVantibodies; in most of them it is possible tohypothesize a reactivation of a chronic HCVinfection.     

Concomitant Use of Levothyroxine and Proton Pump Inhibitors in Patients with Primary Hypothyroidism: a Systematic Review

BackgroundThe aim of this study was to assess the effect of concomitant use of levothyroxine (LT4) and proton pump inhibitors (PPIs) on thyroid-stimulating hormone (TSH) levels in patients with primary hypothyroidism.MethodsA systematic review of interventional and observational studies that compared the TSH levels before and after concomitant use of LT4 and PPI was performed. Articles published in English up to September 1, 2019, were included. PubMed, EMBASE, and Cochrane Library databases. Gray literature was also searched in repositories, websites OpenGrey and Google Scholar, and abstracts of major international congresses. Study quality was assessed with the Newcastle–Ottawa quality assessment scale for observational studies and the Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I) tool was used.ResultsFive thousand twelve discrete articles were identified. Following assessment and application of eligibility criteria, seven studies were included. There was a considerable heterogeneity among the included studies in design, sample size, inclusion and exclusion criteria, treatment regimen, and baseline demographics. Each of the included studies showed an increase in TSH levels following LT4 and PPI consumption, and in the majority of these, the increase was statistically significant.DiscussionThe concomitant use of LT4 and PPI showed a significant increase in TSH concentration. However, given the small number of studies, further research is needed to clarify the interfering role of PPI on LT4 intestinal absorption.PROSPERO Registration NumberCRD42020047084.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06403-y.KEY WORDS: hypothyroidism, drug interaction, levothyroxine     

Detection of Epstein-Barr virus in children and adolescents with Burkitt's lymphoma by in situ hybridization using tissue microarrays

In this retrospective study, we evaluated 53 patients diagnosed with Burkitt's lymphoma (BL). Patients were admitted to the Pediatric Department of Santa Casa de S?o Paulo, Brazil from August 1988 to September 2006. The male gender was found more frequently in the proportion of three males to one female. At the time of the diagnosis, the mean age was 6 years. The most frequent clinical presentation was abdominal (extra nodal) in 42 (79.2%) cases. The patients were treated with chemotherapy using two different treatment methods, 30 cases until September 1994 with BGLTI -87 and the other 23 until September of 2006 with BGLTI -96. According to Murphy's classification, 90.2% of the patients were diagnosed as stages III and VI showing an advanced disease at time of diagnosis. Using Tissue Microarrays (TMA); we searched for the expression of the Epstein-Barr virus (EBV) RNA in 50 patients. The presence of EBV using in situ hybridization was found in 33/50 (66%) and there was no association between the presence of the virus in the tumor cells or patient age, as well as the survival rate. There was 74.5% global survival rate until September, 2005 of 12 years and 8 months. The disease free survival rate was 86.5%. The frequency of the EBV association with this neoplasia in Brazil is intermediate between the endemic and sporadic forms of disease.     

Lymph node micrometastasis in stage II distal rectal cancer following neoadjuvant chemoradiation therapy

Objective The objective was to determine the presence and frequency of micrometastasis in lymph nodes of patients with rectal cancer treated by preoperative chemoradiation followed by curative resection.Patients and methods All 56 patients included were treated with 5-FU and leucovorin plus 5,040 cGy, followed by radical surgery and were diagnosed with stage II distal rectal adenocarcinoma after complete pathological examination (ypT3-4N0M0). Immunohistochemistry was assessed with cytokeratin monoclonal antibody AE1/AE3. Three 4-m paraffin sections were obtained from each lymph node, cut at 50 m apart from each other. The results were reviewed by two independent pathologists.Results Mean number of lymph nodes was 9.6 per patient. Four patients (7%) and seven lymph nodes (1.35%) were positive for micrometastasis. Three patients had pT3 and one a pT4 tumor. One of the patients had positive micrometastasis and the presence of mucinous deposits. One other patient had mucinous deposits without any micrometastasis. All four patients are alive with no evidence of recurrent disease. Fourteen patients negative for micrometastasis had recurrent disease (25%), eight systemic (14.7%) and six locoregional (10.3%). There were two cancer-related deaths. The mean follow-up period was 39 months.Conclusion Patients with rectal cancer treated by preoperative chemoradiation showed a surprisingly low rate of micrometastasis detection (7%), even in high-risk patients (T3 and T4 tumors). Lymph node micrometastasis was not associated with decreased overall or disease-free survival. The identification of mucinous deposits on lymph nodes with no viable tumor cells may be direct evidence of lymph node downstaging. The downstaging effect of preoperative chemoradiation therapy may be significant in reducing even micrometastasis detection in low rectal cancer managed by this treatment strategy.     

Urokinase-type plasminogen activator is a preferred substrate of the human epithelium serine protease tryptase epsilon/PRSS22

Tryptase epsilon is a member of the chromosome 16p13.3 family of human serine proteases that is preferentially expressed by epithelial cells. Recombinant pro-tryptase epsilon was generated to understand how the exocytosed zymogen might be activated outside of the epithelial cell, as well as to address its possible role in normal and diseased states. Using expression/site-directed mutagenesis approaches, we now show that Lys20, Cys90, and Asp92 in the protease's substrate-binding cleft regulate its enzymatic activity. We also show that Arg(-1) in the propeptide domain controls its ability to autoactivate. In vitro studies revealed that recombinant tryptase epsilon possesses a restricted substrate specificity. Once activated, tryptase epsilon cannot be inhibited effectively by the diverse array of protease inhibitors present in normal human plasma. Moreover, this epithelium protease is not highly susceptible to alpha1-antitrypsin or secretory leukocyte protease inhibitor, which are present in the lung. Recombinant tryptase epsilon could not cleave fibronectin, vitronectin, laminin, single-chain tissue-type plasminogen activator, plasminogen, or any prominent serum protein. Nevertheless, tryptase epsilon readily converted single-chain pro-urokinase-type plasminogen activator (pro-uPA/scuPA) into its mature, enzymatically active protease. Tryptase epsilon also was able to induce pro-uPA-expressing smooth muscle cells to increase their migration through a basement membrane-like extracellular matrix. The ability to activate uPA in the presence of varied protease inhibitors suggests that tryptase epsilon plays a prominent role in fibrinolysis and other uPA-dependent reactions in the lung.     

Factors affecting left ventricular remodelling and mechanics in the long-term follow-up after successful repair of aortic coarctation

AIMS: To identify factors predisposing to abnormal left ventricular geometry and mechanics in 52 patients after successful repair of aortic coarctation. METHODS AND RESULTS: We evaluated left ventricular remodelling, systolic midwall mechanics, and isthmic gradient by echo-Doppler, systemic blood pressure at rest/exercise and by ambulatory blood pressure monitoring, and the aortic arch by magnetic resonance imaging. Echocardiographic findings were compared with those of 142 controls. The patients with aortic coarctation showed an increased indexed left ventricular end-diastolic volume, increased mass index, increased ratio of mass to volume and systolic chamber function. The contractility, estimated at midwall level, was increased in 21 percent of the patients. In 26 (50 percent) of the patients, we found abnormal left ventricular geometry, with 9 percent showing concentric remodelling, 33 percent eccentric hypertrophy, and 8 percent concentric hypertrophy. These patients were found to be older, underwent a later surgical repair, and to have higher systolic blood pressures at rest and exercise as well as during ambulatory monitoring. The relative mural thickness and mass index of the left ventricle showed a significant correlation with different variables on uni- and multivariate analysis. Age and diastolic blood pressure at rest are the only factors associated with abnormal left ventricular remodelling. CONCLUSIONS: Patients who have undergone a seemingly successful surgical repair of aortic coarctation may have persistently abnormal geometry with a hyperdynamic state of the left ventricle. This is more frequent in older patients, and in those with higher diastolic blood pressures.     

A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma

We conducted a phase 1/2 trial of high-dose 90Y-ibritumomab tiuxetan in combination with high-dose etoposide (VP-16) 40 to 60 mg/kg (day -4) and cyclophosphamide 100 mg/kg (day -2) followed by autologous stem cell transplantation (ASCT) in 31 patients with CD20+ non-Hodgkin lymphoma (NHL). Patients underwent dosimetry (day -21) with 5 mCi (185 MBq) 111In-ibritumomab tiuxetan following 250 mg/m2 rituximab, followed a week later by 90Y-ibritumomab tiuxetan to deliver a target dose of 1000 cGy to highest normal organ. Bone marrow biopsy was done on day -7 to estimate radiation dose and stem cells were reinfused when the radiation dose was estimated to be less than 5 cGy. The median 90Y-ibritumomab tiuxetan dose was 71.6 mCi (2649.2 MBq; range, 36.6-105 mCi; range, 1354.2-3885 MBq). Histology included follicular lymphoma (n = 12), diffuse large B-cell (n = 14), and mantle cell (n = 5). The median number of prior chemo-therapy treatments was 2. The treatment was well tolerated. The median times to reach an absolute neutrophil count greater than 500/microL and platelet count more than 20,000/microL were 10 days and 12 days, respectively. There were 2 deaths and 5 relapses. At a median follow-up of 22 months, the 2-year estimated overall survival and relapse-free survival rates are 92% and 78%, respectively. We conclude that high-dose 90Y-ibritumomab tiuxetan can be combined safely with high-dose etoposide and cyclophosphamide without an increase in transplant-related toxicity or delayed engraftment.