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.     

The PROMIS Upper Extremity Computer Adaptive Test Correlates With Previously Validated Metrics in Patients With Carpal Tunnel Syndrome

Background: The Patient-Reported Outcomes Measurement Information System Upper Extremity (PROMIS UE) computer adaptive test was developed to improve precision and reduce question burden. We hypothesized that in patients with carpal tunnel syndrome (CTS): (1) PROMIS UE would correlate with established patient-reported outcome measures (PROs); (2) the time and number of questions required would be lower than current metrics; (3) there would be no floor or ceiling effects; and (4) PROMIS UE would not correlate with disease severity. Methods: Patients undergoing electrodiagnostic evaluation found to have a primary diagnosis of unilateral CTS prospectively completed PROMIS UE, Quick Disabilities of the Arm, Shoulder and Hand (qDASH), and Boston Carpal Tunnel Syndrome Questionnaire (BCTQ). Electrophysiologic and clinical severity was recorded. The relationships among PROs were described with Spearman coefficients. A floor or ceiling effect was confirmed if >15% of patients achieved the lowest or highest possible score, respectively. Results: Fifty-one patients (average, 53.9 years) were enrolled. An excellent correlation was identified between PROMIS UE and qDASH (R = −0.76, P < .001). There was a good correlation between PROMIS UE and BCTQ (R = −0.58, P < 0.001). The PROMIS UE required less time and fewer questions than qDASH and BCTQ (P = .02 and P < .001). There were no floor or ceiling effects. Neither neurophysiologic nor clinical severity correlated with PROMIS UE (R = 0.24, P > .05 and R = −0.18, P > .05). Conclusions: The PROMIS UE has an excellent correlation with qDASH and a good correlation with BCTQ in patients with CTS. Furthermore, PROMIS UE required less time and fewer questions than established PROs. Used as a single PRO, PROMIS UE represents a practical alternative to current metrics in patients with CTS.     

Comprehensive dietary evaluation of Italian primary school children: food consumption and intake of energy,nutrients and phenolic compounds

Abstract

Information on children’s diet including bioactive compounds is quite scarce. This observational study investigated the composition of the diet of children living in Parma (Italy; n?=?172, 8–10?years) using 3-day food records completed in winter and spring. Mean daily intakes of food groups, energy and nutrients were obtained using the national food database, while (poly)phenol contents were estimated from Phenol-Explorer or by specific literature searches. Food consumption, energy and nutrient intakes decreased in spring and were partially in line with national data. Adherence to the nutritional recommendations was not satisfied for the majority of nutrients. Main contributors to the phenolic intake were flavonoids (flavan-3-ols) and phenolic acids (hydroxycinnamic acids), while main dietary sources were fruit, chocolate-based products, vegetables, and tea & coffee (decaffeinated). This study provided the first comprehensive analysis of the nutritional composition of children’s diet. Future research should look at the health implications of dietary choices in children.     

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.     

Clonal proliferation of cyclin D1-positive mantle lymphocytes in an asymptomatic patient: an early-stage event in the development or an indolent form of a mantle cell lymphoma?

Mantle cell lymphoma (MCL) is a B-cell neoplasm with a relatively aggressive clinical course. There is a very small subgroup of patients who present with atypical lymphocytes in peripheral blood, with or without lymphocytosis, lymphadenopathy, or splenomegaly, and with an indolent clinical course. They frequently show mutated IgV(H) genes and CD5 negativity. We report an asymptomatic elderly patient who presented with a single submandibular lymphadenopathy. The biopsy showed immunophenotype and t(11;14)(q13;q32) consistent with MCL. The abnormal lymphoid population was also detected in peripheral blood and bone marrow. The patient has remained asymptomatic for 5 years without receiving any therapy. It is uncertain whether these cases represent an early-stage event in the development or an indolent form of MCL. The existence of such asymptomatic patients with an indolent clinical course should induce a strict clinical judgment in terms of therapeutic decisions.     

Influence of renal nerves on renal function during development

The present review summarizes recent studies describing the role of renal sympathetic innervation in the regulation of renal function during development. The afferent renal innervation appears early during fetal life and probably precedes the development of efferent renal nerves. There is suggestive evidence that renal nerves are required for the proper development of the kidney and that neurotrophic growth factors play an important role in renal embryogenesis and in renal tubular differentiation. Renal sympathetic innervation modulates renal hemodynamics early during development. Renal nerve stimulation during -adrenoceptor blockade produces renal vasodilation in fetal and newborn animals but not in adults. Unlike the effect of renal nerves on fetal renal hemodynamics which is observed in the young fetus, the role of renal sympathetic nerves in modulating fluid and electrolyte homeostasis seems to develop during late gestation. Recent studies have also shown that renal nerves play an important role in regulating renin secretion during the transition from fetal to newborn life. For example, renal denervation during fetal life suppressed the physiological rise in plasma renin activity associated with delivery and decreased renal renin mRNA levels after birth. Taken together, these studies suggest that renal nerves influence fetal renal development and that the influence of renal sympathetic innervation on renal hemodynamics and function changes with maturation.     

Partial epiglottectomy as a possible treatment for globus pharyngeus?

Globus pharyngeus is a relatively common complaint in an ear, nose, and throat consulting room and may account for 3–4% of outpatient referrals. The cause is still unknown, although a number of hypotheses have been suggested. Between 40% and 75% of the patients remain symptomatic despite any treatment regimen. Thirteen patients from a group of 124 with the diagnosis of globus pharyngeus and no response to medical treatment were treated with partial epiglottectomies. One year after the surgery all but one patient were free of symptoms. Our experience indicates that partial epiglottectomy can be a good treatment for those patients with globus pharyngeus in whom no cause is found after all studies are performed or when medical treatment fails. Received: 19 October 1999 / Accepted: 16 December 1999     

Potent induction of human colon cancer cell uptake of chemotherapeutic drugs by N-myristoylated protein kinase C-α (PKC-α) pseudosubstrate peptides through a P-glycoprotein-independent mechanism

Phorbol ester protein kinase C (PKC) activators and PKC isozyme over-expression have been shown to significantly reduce intracellular accumulation of chemotherapeutic drugs, in association with the induction of multidrug resistance (MDR) in drug-sensitive cancer cells and enhancement of drug resistance in MDR cancer cells. These observations constitute solid evidence that PKC plays a significant role in the MDR phenotype of cancer cells. PKC-catalyzed phosphorylation of the drug-efflux pump P-glycoprotein was recently ruled out as a contributing factor in MDR. At present, the sole drug transport-related event that has been identified as a component of the role of PKC in MDR is PKC-induced expression of the P-glycoprotein-encoding gene mdr1. The objective of this study was to test the hypothesis that PKC can modulate the uptake of chemotherapeutic drugs in cancer cells independently of P-glycoprotein. We analyzed the effects of selective PKC activators/inhibitors on the uptake of radiolabelled cytotoxic drugs by cultured human colon cancer cells that lacked P-glycoprotein activity and did not express the drug efflux pump at the level of message (mdr1) or protein. We found that the selective PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) significantly reduced uptake of [¹⁴C] Adriamycin and [³H] vincristine in human colon cancer cells devoid of P-glycoprotein activity, and that PKC-inhibitory N-myristoylated PKC- pseudosubstrate synthetic peptides potently and selectively induced uptake of the cytotoxic drugs in the phorbol ester-treated and non-treated colon cancer cells. TPA treatment of the cells did not induce expression of either P-glycoprotein or its message mdr1. In contrast with [¹⁴C]Adriamycin and [³H] vincristine uptake, [³H] 5-fluorouracil uptake by the cells was unaffected by TPA and reduced by the PKC-inhibitory peptides. These results indicate that PKC activation can significantly reduce the uptake of multiple cytotoxic drugs by cancer cells independently of P-glycoprotein, and that N-myristoylated PKC- pseudosubstrate peptides potently and selectively induce uptake of multiple cytotoxic drugs in cultured human colon cancer cells by a novel mechanism that does not involve P-glycoprotein and may involve PKC isozyme inhibition. Thus, N-myristoylated PKC- pseudosubstrate peptides may offer a basis for the development of agents that reverse intrinsic drug resistance in human colon cancer.