Cec and You Shall Find: Cecal Perforation in a Patient with COVID-19

Digestive Diseases and Sciences -     

Treatment of dyskeratosis congenita with Granulocyte Colony-Stimulating Factor and Erythropoietin

Aplastic anaemia is both frequent and difficult to manage in patients with dyskeratosis congenita (DC). We recently treated a 23-year-old male for a year with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Ep), with an excellent neutrophil response, and a transient effect on haemoglobin levels. G-CSF alone or combined with other cytokines may provide at least a partial effect in pancytopenic patients with DC.     

Improved Late Graft Survival and Half-Lives in Pediatric Kidney Transplantation: A Single Center Experience

We evaluated variables associated with improved late graft survival in 290 children transplanted between 11/1/1984 and 12/31/1997, and who had > 1 year graft survival. We studied the following variables: age, gender, race, primary disease (diseases prone to recurrence, i.e. hemolytic uremic syndrome, focal segmental glomerulosclerosis or oxalosis vs. others), primary vs. retransplant; donor source, acute tubular necrosis, acute rejection episodes in the first year, transplant era and discharge serum creatinine. Graft half-life was defined as the time taken for 1/2 of the grafts functioning at 1 year to fail. There were 205 living donor and 85 cadaveric transplant. The cumulative graft survival at 5 and 10 years was 88% and 75% for living donor, and 72% and 46% for cadaveric, respectively. Multivariate analyses showed a higher late graft survival to be associated with: no acute rejection episodes (risk ratio 0.16, p = 0.0001), age 2-5 years (risk ratio 0.24, p = 0.0007), living donor (risk ratio 0.46, p = 0.017), primary nonrecurrent disease (risk ratio 0.29, p = 0.001), Caucasian race (risk ratio 0.40, p = 0.006). A high half-life was seen with living donor transplant (21.3 years) and the age group 2-5 years (27.5 years). Further, living donor patients with no acute rejection episodes had the best half-life of 37.6 years, while children with hemolytic uremic syndrome, focal segmental glomerulosclerosis or oxalosis had the lowest overall half-life of 5.6 years. This study finds that living donor, no acute rejection episodes, age 2-5 years, Caucasian race and having a disease not prone to recurrence are strong predictors of late graft survival. Hence, preferential use of living donor and prevention of acute rejection episodes in the first year are key variables that can improve long-term renal graft survival in children.     

Cytokine expression and endothelial cell and lymphocyte activation in human cardiac allograft rejection: an immunohistochemical study of endomyocardial biopsy samples.

We used monoclonal antibodies and immunohistochemical staining of frozen tissue sections to study the expression of cytokines in human cardiac allograft rejection. The 113 endomyocardial biopsy samples were stained for interleukin (IL)-2, IL-6, and interferon-gamma. The findings were compared to expression of the endothelial cell adhesion molecule ICAM-1, and the lymphocyte receptor for the adhesion molecule VCAM-1, VLA-4. Four biopsy samples from patients with idiopathic cardiomyopathy served as controls. IL-2 was not expressed in lymphocytes of controls and only occasionally in mild or moderate cellular rejection, humoral rejection, and Quilty lesions. IL-2 expression was prominent in severe cellular rejection. Interferon-gamma expression increased in proportion to the severity of cellular rejection and was not expressed in other conditions. IL-6 staining, which was only observed in occasional cases, was mild. Cytokine and adhesion molecule expression tended to increase with the severity of cellular rejection. This study shows that cytokine expression can be documented in human allograft endomyocardial biopsy samples with immunohistochemical techniques. The findings support the concept of an important role for cytokines in human cardiac allograft rejection.     

Balancing the bipotential gonad between alternative organ fates: a new perspective on an old problem.

The embryonic gonads give rise to one of two morphologically and functionally different organs, a testis or an ovary. Sex determination is the embryonic process that determines the developmental fate of the gonad. In mammals, sex determination is regulated by a DNA binding protein encoded on the Y chromosome, Sry, and it's downstream mediator, Sox9, which trigger testis determination in the bipotential gonad. However, evidence suggests that the extracellular signals. Fgf9 and Wnt4, are also required to establish divergent organogenesis of the gonad. In this review, we discuss how these extracellular signals interface with cell-autonomous factors to determine the fate of the mammalian gonad, and we derive a model that could provide a molecular explanation for testis determination in vertebrates where Sry is absent.     

Prospective study of the occurrence of monoclonal gammapathies following bone marrow transplantation in young children

We have prospectively studied the occurrence of monoclonal serum immunoglobulins in 38 recipients of BMT. Patients were young children with primary immunodeficiencies (n = 31), other inherited diseases (n = 4), leukemia (n = 2), or aplastic anemia (n = 1). Twenty-nine received an HLA-nonidentical marrow and nine an HLA-identical marrow. Serum monoclonal immunoglobulins were detected by the immunofixation method. Monoclonal immunoglobulins were found in 26 patients. Monoclonal components were more frequently detected in patients with primary severe T cell deficiencies (21/25) rather than in the other patients (6/13). In 7 of 29 recipients of HLA-nonidentical transplants, versus 0 out of 9 recipients of HLA-identical transplants, serum monoclonal immunoglobulins were found associated with a B lymphocyte proliferation syndrome due to an Epstein-Barr virus infection. In this group, monoclonal immunoglobulins were detected early, prior to the onset of the clinical syndrome. The simultaneous occurrence of several monoclonal immunoglobulins was more frequent in these patients, while monoclonal immunoglobulin concentrations increased faster, especially those of IgM isotype. These characteristics may allow in patients at risk (recipients with primary T cell immunodeficiencies and receiving HLA-nonidentical transplantation) an earlier diagnosis of B lymphocyte proliferative syndrome that may eventually lead to early and more efficient therapy.     

Predictive factors of virologic success in HIV-1-infected children treated with lopinavir/ritonavir

Predictive factors of the virologic success of the use of lopinavir/ritonavir (LPV/r) in HIV-infected children are unknown, especially in children who have been pretreated with protease inhibitors (PIs). This longitudinal, single-center, observational study included 69 children (21 PI-naive and 48 PI-experienced) who had received LPV/r for at least 3 months. The mean (+/- SD) age was 10.3 +/- 4.8 years, and the mean baseline of CD4 percentage and HIV-1 RNA was 14.9% +/- 9.8% and 4.8 +/- 1.05 log10 copies/mL, respectively. The mean duration of follow-up was 16.5 +/- 8.3 months. At 6, 12, and 18 months, 52%, 57%, and 49% of all children, respectively, had a viral load less than 50 copies/mL. The risk of virologic failure, defined as 2 consecutive viral loads greater than 1000 copies/mL, was significantly higher when the children were previously treated with PIs and when the baseline LPV mutation score exceeded 3 mutations. In the pretreated children, the ratio of the plasma LPV maximal concentration to the baseline LPV score mutation was also associated with failure, independently of resistance score. Finally, in children failing an LPV-containing regimen, accumulation of additional PI-associated resistance mutations was evidenced in viral isolates from children with prior PI treatment, even with viral replication levels less than 10,000 copies/mL. In pretreated children, LPV plasma levels should be optimized in an attempt to achieve sufficient drug concentrations to overcome the resistance level.