Low-dose Thymoglobulin vs Basiliximab Induction Therapy in Low-Risk Living Related Kidney Transplant Recipients: A Prospective Randomized Trial

ContextThymoglobulin is used effectively as induction agent in kidney transplantation but the optimal dose is not well established.ObjectiveDemonstrate that low-dose thymoglobulin (3 mg/kg) has similar efficacy and safety compared to basiliximab induction in low-risk kidney transplantation under standard maintenance immunosuppressionDesign, Setting, ParticipantsProspective randomized study in kidney transplant patients (12/2016-05/2018). Inclusion criteria: Recipients > 18 years, first living donor transplant. Exclusion criteria: Second and multiorgan transplant, ABO incompatibility, positive cross-match, panel reactive antibodies (PRA) > 30%, positive donor-specific antibody, human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus positive, white blood cells < 2000 cells/mm³, platelets < 75,000 cells/mm³ and malignancy.InterventionGroup A: basiliximab (20 mg D0 and D4). Group B: thymoglobulin (3 mg/kg total). Maintenance immunosuppression: tacrolimus, mycophenolate mofetil, and steroids.Main Outcome MeasuresBiopsy-proven acute rejection (BPAR), delayed graft function, slow graft function, leukopenia, infections, adverse events, graft loss, estimated glomerular filtration rate, and death within 12 months.Results100 patients (basiliximab, n = 53) (thymoglobulin, n = 47) were included. Donor and recipient characteristics were similar except for longer dialysis (basiliximab), PRA class I (1.2% basiliximab, 4.5% thymoglobulin), HLA match (basiliximab 2.8, thymoglobulin 2.2), and cytomegalovirus status. BPAR rate was basiliximab 3.8% and thymoglobulin 6.4% (P = ns). Delayed graft function (basiliximab 3.8%; thymoglobulin 4.3%), slow graft function, and 12-month leukopenia (basiliximab 11.3%, thymoglobulin 21.3%) were similar between groups (P = ns). There was no difference in infections and adverse events between groups. Patient and graft survival were as follows: basiliximab 98.1% and 92.5%, thymoglobulin 100% and 93.6% (P = ns).ConclusionLow-dose thymoglobulin induction (3 mg/kg) can be used effectively and safely in low-risk kidney transplantation with good results during the first year post-transplant.     

Donor Choriocarcinoma Transmission From Solid Organ Transplantation: A Case Report

Transplantation of any organ has some inherent risk of disease transmission, such as infection and malignancy. The present study aims to describe 2 cases of choriocarcinoma transmission after kidney and liver transplantation originating from the same patient. The donor was a 17-year-old woman who died of cerebral hemorrhage. Both organ recipients died of metastatic choriocarcinoma few months after the transplantation, within days after starting chemotherapy. Retrospective hCG (human chorionic gonadotropin hormone) analysis in donor's blood stored at the time of donation had a result of 9324 mIU/mL. Despite its rarity, clinicians should be aware of the risk of transplant-related choriocarcinoma from female donors in childbearing age. In some cases, hCG dosage should be performed before donation.     

Special surgical approaches during peri-COVID-19 pandemic: Robotic and transanal minimally invasive surgery

During the peri-coronavirus disease 2019 pandemic, the need of special care has raised, not only for our patients but also for health care workers. These needs are different regarding the procedure and the approach performed. This is a dynamic review in the use of robotics and transanal approaches for colorectal diseases. We searched PubMed and KSREvidence.com for studies related to coronavirus disease and robotic surgery/transanal mesorectal excision/transanal surgery(primary and systematic reviews). From 147 results in PubMed, 11 were selected for full text screening, and 11 were included in this paper. From 3 results in KSREvidence, no relevant systematic reviews were identified. We also checked the references in identified papers for further relevant studies. European Society of Coloproctology guidelines were including as part of the recommendations available. Robotic and transanal MIS can be performed safely during the pandemic, but particular characteristics of these procedure need to be taken into consideration.     

Changes in retinoblastoma gene expression during cervical cancer progression

The role of tumour suppressor genes in the development of human cancers has been studied extensively. In viral carcinogenesis, the inactivation of suppressor proteins such as retinoblastoma (pRb) and p53, and cellular oncogenes overexpression, such as c-myc, has been the subject of a number of investigations. In uterine-cervix carcinomas, where high-risk human papillomavirus (HPV) plays an important role, pRb and p53 are inactivated by E7 and E6 viral oncoproteins, respectively. However, little is known about the in situ expression of some of these proteins in pre-malignant and malignant cervical tissues. On the other hand, it has also been demonstrated that c-myc is involved in cervical carcinogenesis, and that pRb participates in the control of c-myc gene expression. By using immunostaining techniques, we investigated pRb immunodetection pattern in normal tissues, squamous intraepithelial lesions (SILs) and invasive carcinomas from the uterine cervix. Our data show low pRb detection in both normal cervical tissue and invasive lesions, but a higher expression in SILs. C-Myc protein was observed in most of the cellular nuclei of the invasive lesions, while in SILs was low. These findings indicate a heterogeneous pRb immunostaining during the different stages of cervical carcinogenesis, and suggest that this staining pattern could be a common feature implicated in the pathogenesis of uterine-cervix carcinoma.     

Mulibrey nanism: Three additional patients and a review of 39 patients

We report on 3 patients with Mulibrey nanism (MN), or Perheentupa syndrome: the first 2 sibs from Argentina and a new patient from Spain. All 3 patients had growth failure, short stature, abnormal pigmentary retinal changes, and a J-shaped sella turcica. These findings are considered major criteria of MN. Two had pericardial constriction, which is a frequent and lifethreatening abnormality in this syndrome. MN is a rare autosomal recessive condition. Reviewing the 39 patients described so far, we have classified the anomalies into the very frequent (present in more than 66%), frequent (in at least 25%), and not frequent. Identifying the anomalies specific to MN should help its early diagnosis and treatment. © 1995 Wiley-Liss, Inc.     

Morphometry of terminal hepatic veins

Summary In the present study, hepatic venous distribution per unit of liver surface area on normal wedge biopsies from man (n=11) and baboon (n=8) were analysed and compared. Terminal hepatic veins (THV - man:n=100; baboon:n=200) morphometric size variables were obtained with a Leitz ASM 68K morphometric equipment. THV, defined as hepatic veins up to 150 m in internal diameter (ID), in the centrolobular position and with sinusoidal openings, represented 84% and 74% of hepatic veins of man and baboon, respectively. Four or more THV were generally found on 8 mm² of liver surface. Transversely sectioned THV selected by the ratio IDminimum/IDmaximum >0.67, was found to be only 25% of the total THV. In baboon, THV merge with other terminal veins and the interlobular veins present sinusoidal inlets. The baboon THV wall surface (WS) and wall thickness (WT) values were higher than in man. Positive correlations between the number of mesenchymal cells (Mc) in the vein wall and wall surface of terminal hepatic veins (man: r= 0.79; baboon: r=0.83) and between wall surface and internal surface (IS) (man: r=0.80; baboon: r=0.72) were found. Two ratios were selected as the most reliable parameters: (1) for the THV wall rim, wall surface/internal surface (WS/IS - man: 0.43±0.16; baboon: 0.63±0.23), regarding transversely sectioned THV; and (2) for the evaluation of wall cell density (WS/Mc-man: 550±231; baboon: 558±183 m²/cell) as they did not depend on THV caliber.Dr. Porto was supported by a fellowship from MEC-CAPES, Brazil. A grant for morphometric equipment was obtained from the Fondation pour la Recherche Médicale and from the Societé d'Hépatologie Expérimentale, 77 rue Pasteur, Lyon, France     

Morphometry of terminal hepatic veins

Summary Alcohol induced perivenular fibrosis of terminal hepatic veins (THV) is claimed to be a precursor lesion leading to fibrosis development in man and baboon. The nature and significance of the THV lesions found in four baboons chronically fed with alcohol were studied in liver biopsies obtained during a three year period. The surface of THV wall and the number of mesenchymal cells were assessed with a semi-automatic image analyser. Histologically, THV were characterized as (a) phlebitic, in the presence of an inflammatory cell infiltrate involving the venous wall; (b) oedematous, when the connective tissue of the THV wall was disrupted or dissociated and (c) fibrotic, when perivenular scarring appeared as an increased rim. These lesions were present simultaneously and their intensity and distribution were independent of the duration of alcohol intoxication. Morphometric data obtained from these THV confirmed the thickening of the THV wall (WS/IS in: oedematous 1.05±0.36; phlebitic 1.65±1.04; fibrotic 1.47±0.36); and revealed an increased number of mesenchymal cells in fibrotic (439 m²/cell;p<0.01) and in phlebitic THV (510 m²/cell;p<0.05). A constant relationship was found between phlebitis and the presence of inflammatory infiltrate within the hepatic acini. Fibrotic THV was a less frequent finding and the lesion disappeared in the sequential biopsies of one of the baboons. In conclusion, THV lesions were heterogeneous and the collagen deposition in the THV wall was potentially reversible during the three year alcohol intoxication period, regardless the inflammatory reaction and, thus, did not indicate early irreversible hapatic fibrosis.Dr. Porto was supported by a fellowship from MEC-CAPES, Brazil. A grant for morphometric equipment was obtained from the Fondation pour la Recherche Médicale and from the Societé d'Hépatologie Expérimentale, 77 rue Pasteur, Lyon, France     

Pharmacological characterization of mediators and vagal influence in the acute allergic bronchoconstriction in guinea pigs

Summary The allergic bronchoconstriction in guinea pigs has been attributed mainly to the release of mast cell mediators. Histamine has been involved in the first minutes of the anaphylactic reaction and new-formed compounds in the subsequent response. In this asthma model the vagal influence has been sparsely investigated. In the present work we evaluated the pharmacological modification of the acute allergic bronchoconstrictor response in guinea pigs sensitized to ovalbumin through aerosol exposure. Pyrilamine (20 g/kg), diethylcarbamazine (a lipoxygenase inhibitor, 10 mg/kg) and dexamethasone (4 mg/kg) each reduced the antigen-induced bronchoconstriction throughout the 30 min studied. Indomethacin (3.1 mg/kg) did not modify the response to the antigen. Atropine (2 mg/kg) plus bilateral vagotomy also diminished this response from 5 min onward. On the other hand, from 5 min ahead pyrilamine-resistant bronchoconstriction was partially inhibited by dexamethasone, and it was almost completely blocked during all of the response when atropine plus bilateral vagotomy were added to dexamethasone. Dipyridamole (an inhibitor of the adenosine uptake, 0.4 mg/kg) enhanced the bronchoconstriction, though this was significant only in the 2–5 min time-interval of the response. These results suggest that histamine and vagal influence play an important role in the whole response to antigen, that other mediators, probably leukotrienes, participate in this response from 5 min onward, and that adenosine could exert a potentiation effect on this response. Send offprint requests to L. M. Montaño at the Instituto Nacional de Enfermedades Respiratorias