Successful low-dose immunotherapy after kidney transplantation in a 10-year-old girl with Schimke immuno-osseous dysplasia

Background

This case report highlights a successful steroid-free, low-dose immunosuppressive protocol for renal transplantation in a pediatric patient with Schimke immuno-osseous dysplasia with excellent 7-year patient and graft survival. Schimke immuno-osseous dysplasia is a rare multisystem disorder involving the kidney. Renal transplantation is a therapeutic option, but posttransplant mortality is high due to severe infections and posttransplant lymphoproliferative disease.

Methods

A 10-year-old girl diagnosed with Schimke immuno-osseous dysplasia and end-stage renal disease underwent an AB0-compatible living-related kidney transplantation, with no donor-specific antibodies. Our standard immunosuppression protocol was modified due to the risk of infection. Basiliximab was used as induction therapy, and a reduced dose of mycophenolate mofetil and tacrolimus was initiated following transplantation, maintaining the patient on a low tacrolimus target (3–5 μg/L). Mycophenolate mofetil was discontinued after 8 weeks due to neutropenia and the patient was kept on tacrolimus as monotherapy. Five years posttransplant the patient developed acute onset of neurological symptoms, consisting of ataxia, lack of voluntary coordination, balance, aphasia and dysphagia, and diplopia. She recovered without neurological deficits within 6 weeks. Extensive evaluation revealed no pathology. To avoid a possible a component of tacrolimus-induced cerebral vasoconstriction, the immunosuppressive therapy was changed to everolimus.

Results

Seven years posttransplant, the patient has experienced no serious infections, no rejections, and had excellent graft function, and no de novo donor-specific antibodies.

Conclusions

The present results indicate that low-dose immunosuppressive therapy after renal transplantation with low immunological risk should be considered for patients with Schimke immuno-osseous dysplasia.     

Associations between biomarkers at discharge and co-morbidities and risk of readmission after community-acquired pneumonia: a retrospective cohort study

To investigate whether hemoglobin, white blood cell count (WBC), urea, sodium, albumin, and C-reactive protein at discharge in patients hospitalized for community-acquired pneumonia (CAP) are associated with 30-day readmission. This study is a retrospective cohort study, which included all adult patients discharged after hospitalization for CAP from three Danish hospitals between January 2011 and July 2012. The outcome was all-cause, unplanned, 30-day readmission. Biomarker concentrations at discharge were transformed into binary variables by using either upper or lower quartiles as cut-off; the upper quartile was used for WBC, urea, and C-reactive protein, and the lower quartile was used for hemoglobin, sodium, and albumin. The study population consisted of 1149 patients. One hundred eighty-four (16.0%) patients were readmitted. Independent risk factors of readmission were WBC?≥?10.6 cells?×?10⁹/L (hazard ratio 1.50; 95% CI, 1.07–2.11) and albumin <32 g/L (hazard ratio 1.78; 95% CI, 1.24–2.54) at discharge and the presence of ≥?2 co-morbidities (hazard ratio 1.74; 95% CI, 1.15–2.64). When WBC, albumin, and co-morbidities were combined into a risk-stratification tool, there was a step-wise increase in risk of readmission for patients with 1, 2, or 3 risk factors with hazard ratios of 1.76 (95% CI, 1.25–2.49), 2.59 (95% CI, 1.71–3.93), and 6.15 (95% CI 3.33–11.38), respectively. WBC?≥?10.6 cells?×?10⁹/L and albumin <?32 g/L at discharge and the presence of ≥?2 co-morbidities were independently associated with increased risk of 30-day readmission.     

Are maternal and sonographic factors associated with the detection of a fetal echogenic cardiac focus?

OBJECTIVE: To evaluate the influence of maternal weight and the orientation of the fetal 4-chamber heart view on the detection of a fetal echogenic cardiac focus. METHODS: In this nested case-control study, 103 women undergoing anatomic surveys at 15 to 22 weeks between January 1, 1997, and June 15, 1999, were identified as having an echogenic cardiac focus via our computerized database. A control group was selected from among the same group of patients. Data were collected from the sonography reports, prenatal records, and sonographic images of 4-chamber heart views; maternal characteristics and sonographic details were recorded, including the orientation of the 4-chamber view (apical, basilar, and right and left lateral). RESULTS: Gravidas in the echogenic cardiac focus group were more likely to be of lower weight (68.0 +/- 14.4 versus 72.9 +/- 18.3 kg; P = .04), of lower body mass index (25.5 +/- 5.3 versus 27.3 +/- 6.2 kg/m2; P = .03), of younger age (24.4 +/- 6.5 versus 26.9 +/- 6.9 years; P = .01), and African American or Asian (37.9% versus 27.2% and 9.7% versus 2%; P = .01). Cases were scanned at earlier gestational ages (18.9 +/- 1.6 versus 19.5 +/- 1.7 weeks; P = .01). The focus group was more likely to have had an apical view of the fetal heart taken (80.8% versus 51.4%; P = .0001). Controls were more likely to have had a right lateral view taken (44.6% versus 20.8%; P = .002). No significant difference was found between groups in terms of any other maternal or sonographic variable studied. CONCLUSIONS: The echogenic cardiac focus group was more likely to have a lower body mass index and to be scanned with the apical fetal heart view. The orientation of the fetal 4-chamber heart view exerted the most statistically significant influence on detection rates for the echogenic cardiac focus, implying that the more technically facile the sonographic study, the more likely an echogenic cardiac focus will be found.     

Electrochemical study of self-assembled monolayers of a β-cyclodextrin methyl sulfide covalently linked to anthraquinone

Self-assembled monolayers of a β-cyclodextrin with methyl sulfides on the primary sites of the molecule and mono-functionalized with anthraquinone on a secondary site have been formed on gold electrodes. The surface coverages obtained by electrochemistry are consistent with values reported previously or calculated for similar non-electroactive β-CD derivatives. The electron transfer rate constants vary markedly with pH, increasing rapidly between pH 7 and 9 to values of approximately 700–900 s^?1. These values are faster than reported previously for thiol derivatives of anthraquinone dispersed in an alkylthiol SAM matrix. Near pH 6, slow electron transfer is observed with a splitting into individual one-electron steps. Lowering the pH further results in very sluggish kinetics and indistinguishable peaks. Inclusion of naphthalene into the β-CD cavity appears to affect the anodic rate constant, and a small potential shift occurs. The efficient electron transfer of the anthraquinone spaced from the gold surface by a β-CD unit suggests promise for use of such molecules as ‘immobilized artificial enzymes’.     

Cisplatin inhibits bone healing during distraction osteogenesis

Osteosarcoma (OS) is the most common malignant bone tumor affecting children and adolescents. Many patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. Surgical reconstructions after tumor resection include structural allografts, non‐cemented endoprostheses, and distraction osteogenesis (DO), which require direct bone formation. Although cisplatin (CDP) is extensively used for OS chemotherapy, the effects on bone regeneration are not well studied. The effects of CDP on direct bone formation in DO were compared using two dosing regimens and both C57BL/6 (B6) and tumor necrosis factor receptor 1 knockout (TNFR1KO) mice, as CDP toxicity is associated with elevated TNF levels. Detailed evaluation of the five‐dose CDP regimen (2 mg/kg/day), demonstrated significant decreases in new bone formation in the DO gaps of CDP treated versus vehicle treated mice (p < 0.001). Further, no significant inhibitory effects from the five‐dose CDP regimen were observed in TNFR1KO mice. The two‐dose regimen significantly inhibited new bone formation in B6 mice. These results demonstrate that CDP has profound short term negative effects on the process of bone repair in DO. These data provide the mechanistic basis for modeling peri‐operative chemotherapy doses and schedules and may provide new opportunities to identify molecules that spare normal cells from the inhibitory effects of CDP. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:464–470, 2014.     

A threshold concentration of FSH is needed during IVM of ex vivo collected human oocytes

Journal of Assisted Reproduction and Genetics - To investigate the effect of different FSH concentrations on human oocyte maturation in vitro and its impact on gene expression of key factors in the...     

Effect of prosthetic gel liner thickness on gait biomechanics and pressure distribution within the transtibial socket

Prosthetic gel liners are often prescribed for persons with lower-limb amputations to make the prosthetic socket more comfortable. However, their effects on residual limb pressures and gait characteristics have not been thoroughly explored. This study investigated the effects of gel liner thickness on peak socket pressures and gait patterns of persons with unilateral transtibial amputations. Pressure and quantitative gait data were acquired while subjects walked on liners of two different uniform thicknesses. Fibular head peak pressures were reduced (p = 0.04) with the thicker liner by an average of 26 +/- 21%, while the vertical ground reaction force (GRF) loading peak increased 3 +/- 3% (p = 0.02). Most subjects perceived increased comfort within the prosthetic socket with the thicker liner, which may be associated with the reduced fibular head peak pressures. Additionally, while the thicker liner presumably increased comfort by providing a more compliant limb-socket interface, the higher compliance may have reduced force and vibration feedback to the residual limb and contributed to the larger vertical GRF loading peaks. We conclude that determining optimal gel liner thickness for a particular individual will require further investigations to better identify and understand the compromises that occur between user perception, residual-limb pressure distribution, and gait biomechanics.