To study the function and maturation of the human hematopoietic and immune system without endangering individuals, translational human-like animal models are needed. We compare the efficiency of CD34+ stem cells isolated from cryopreserved cord blood from a blood bank (CCB) and fresh cord blood (FCB) in generating highly engrafted humanized mice in NOD-SCID IL2Rγnull (NSG) rodents. Interestingly, the isolation of CD34+ cells from CCB results in a lower yield and purity compared to FCB. The purity of CD34+ isolation from CCB decreases with an increasing number of mononuclear cells that is not evident in FCB. Despite the lower yield and purity of CD34+ stem cell isolation from CCB compared to FCB, the overall reconstitution with human immune cells (CD45) and the differentiation of its subpopulations e.g., B cells, T cells or monocytes is comparable between both sources. In addition, independent of the cord blood origin, human B cells are able to produce high amounts of human IgM antibodies and human T cells are able to proliferate after stimulation with anti-CD3 antibodies. Nevertheless, T cells generated from FCB showed increased response to restimulation with anti-CD3. Our study reveals that the application of CCB samples for the engraftment of humanized mice does not result in less engraftment or a loss of differentiation and function of its subpopulations. Therefore, CCB is a reasonable alternative to FCB and allows the selection of specific genotypes (or any other criteria), which allows scientists to be independent from the daily changing birth rate.
A case of lytic lesion of the pelvis in a 23-year-old woman is presented. A biopsy led to the diagnosis aneurysmal bone cyst (ABC). Due to the histologically very aggressive growth of the tumor, a low malignant osteosarcoma could not be excluded. In an initial operation the tumour, affecting the sacrum, the iliac crest and the lower lumbar spine was resected. Temporary restabilisation of the pelvic ring was achieved by a titanium plate. The histological examination of the entire tumour confirmed the diagnosis ABC. After 6 months, the MRI showed no recurrence. The observed tilt of the spine to the operated side on the sacral base prompted a second surgical procedure: a transpedicular fixation of L5 and L4 was connected via bent titanium stems to the ischium, where the fixation was achieved by two screws. This construction allowed the correction of the base angle and yielded a stable closure of the pelvic ring. The patient has now been followed for 6 years: the bone grafts have been incorporated and, in spite of radiological signs of screw loosening in the ischium, the patient is fully rehabilitated and free of symptoms. Pedicle screws in the lower spine can be recommended for fixation of a pelvic ring discontinuity.Key Words: aneurysmal bone cyst, pelvic reconstruction, spino ischial spondylodesils, pelvic tumor A 23-year-old woman presented with a low back pain (LBP) history of 2 years. Plain film radiographs and an MRI of the lumbar spine had not shown any pathologies. The patient had been treated with drugs and physical therapy. The patient was referred to our hospital since the pain increased, especially during the night with referral to the legs. A new X-ray examination of the spine showed a cystic structure in the sacral bone. Immediately following this discovery, images of the whole pelvis were taken, revealing a lytic lesion of the left pelvis involving the ilium near the acetabular roof, the sacrum near the spinal canal, and also the left L5-lamina (Fig. 1). An open biopsy was performed. The histological examination revealed multiple communicating vascular spaces separated by fibrous septa. Some areas showed suspicious bone lesions. The histological diagnosis was aneurysmal bone cyst (ABC) but, due to the very aggressive growth of the tumour, a low malignant osteosarcoma could not be excluded.Therefore the strategy of operative treatment was an initial wide tumour resection and temporary stabilisation of the pelvic ring. After histological examination of the entire lesion, a subsequent operation was planned to reconstruct the pelvic ring with custom-made implants and graft material.A combined anterior and posterior approach in a lateral decubitus position was used to carry out the wide tumour resection. The tumour had spread into the L5-lamina, the left part of the sacrum, the iliac crest, and the ileum down to the level of the back side of the articular cartilage of the acetabulum. Primary stabilisation of the pelvic ring was achieved by mounting a 12-hole titanium osteosynthetic plate between t...
Kidney transplant (KTx) recipients are a high-risk population for osteoporotic fractures. We herein aim to identify the role of pre-transplant parathyroidectomy (PTX) and other modifiable factors associated with osteoporotic fractures in KTx recipients. We conducted a retrospective study involving 711 adult patients (4608 patient-years) who were transplanted at our center between January 2007 and June 2015. Clinical data were extracted from patients’ electronic medical records. Different laboratory and clinical parameters for mineral bone disease (MBD) and osteoporosis, including medication, were evaluated. We chose fracture events unrelated to malignancies or adequate trauma as the primary endpoint. Osteoporotic fractures occurred in 47 (6.6%) patients (median 36.7 months, IQR 45.9) after KTx (fracture incidence of 10 per 1000 person-years). Prior to KTx, subtotal PTX was performed in 116 patients (16.3%, median time 4.2 years before KTx, IQR 5.0). Of the patients with fracture (n = 47), only one (2.2%) patient had previously undergone PTX. After adjusting for the known fracture risk factors MBD and osteoporosis, PTX remained a protective factor against fractures (HR 0.134, CI 0.018–0.991, p = 0.049). We observed a reduced risk for pathological fractures in KTx patients who underwent PTX, independent from elevated parathyroid hormone at the time of KTx or afterwards.
Background and Aims The organ shortage especially in blood group 0 forces transplant professionals to discuss new approaches to expand the donor pool. Recently, the successful therapy of HCV with direct antiviral agents in kidney transplanted patients has made the transplantation of HCV-infected kidneys to uninfected patients possible. Furthermore, these organs promise an above-average organ function as HCV-infected donors are usually young and have fewer comorbidities. Since there is no standard procedure for the treatment of kidney recipients with HCV grafts, we compared a preemptive and a prophylactic approach using direct antiviral drugs after kidney transplantation of two patients. Method We report the transplantation of two HCV-positive kidneys. One recipient was a 49-year-old female patient, who suffered from ESRD caused by an atypical hemolytic uremic syndrome. The other recipient had autosomal dominant polycystic kidney disease. Since the genotype of the HCV donor was unknown at the time of transplantation, we decided to use the pangenotypic, fixed-dose combinations Glecaprevir/Pibrentasvir and Sofosbuvir/Velpatasvir. Results Both patients had blood group 0 and received an AB0-compatible kidney transplant. The initial immunosuppressive therapy consisted of prednisolone, mycophenolate sodium, and tacrolimus. Furthermore, an induction therapy with Basiliximab was given. The first patient received Glecaprevir/Pibrentasvir immediately post-surgery. Treatment was carried on for eight weeks as a prophylactic approach. Frequent HCV-PCRs showed negative results over six months. However, the patient developed anti-HCV antibodies within six days after transplantation. The graft started working on postoperative day four, and the serum creatinine decreased to 1.33 mg/dl on the discharge day and stabilized on this level during further follow-up. Following a preemptive approach, our second patient was treated with Sofosbuvir/Velpatasvir after detection of HCV RNA and rising levels of transaminases on post-transplant day 7. This patient also received Entecavir because of a previous HBV-infection of the donor (non-viremic on the day of transplantation). The graft started working on day two, and the serum creatinine decreased to 1.28 mg/dl on the discharge day and stabilized on this level. Further HCV-PCRs also showed negative results. Conclusion We conclude that kidneys from HCV-viremic donors can be transplanted with precaution. Both therapeutic strategies showed equally good results and can easily be implemented into kidney transplantation. Especially, the combination of Glecaprevir/Pibrentasvir offers a safe HCV prophylaxis without the need of adaptions to the renal function or HCV genotype. In case of a permanent absence of a HCV infection, the preemptive approach offers a chance to avoid the HCV-therapy. On the other hand, causing an iatrogenic infection of HCV in a patient with immunosuppression brings up ethical issues due to the risk of HCV-related liver diseases. Therefore, we favor the prophylactic approach. Further studies are needed to identify the optimal time frame for direct antiviral agents in HCV (D+/R-) transplantations.
Kidney transplant (KTx) recipients are a high-risk population for pathologic fractures. We herein aim to identify modifiable factors associated with pathological fractures and bone disease in KTx recipients. We conducted a retrospective study involving 711 adult patients (4608 patient-years) who were transplanted at our center between January 2007 and June 2015. Clinical data was extracted from patients’ electronic medical records. Different laboratory and clinical parameters for mineral bone disease (MBD) and osteoporosis including medication were evaluated. We chose fracture events unrelated to malignancies or adequate trauma as the primary endpoint. Pathologic fractures occurred in 47 (6.6%) patients (median 36.7 months, IQR 45.9) after KTx, fracture incidence of 10 per 1000 person-years). Prior to KTx, (subtotal) parathyroidectomy (PTX) was performed in 116 patients (16.3%) (median time 4.2 years before KTx, IQR 5.0). Of the patients with fracture (n= 47), only one (2.2%) patient was parathyroidectomized. After adjusting for known fracture risk factors for MBD and osteoporosis, PTX remained a protective factor against fractures (HR 0.134, CI 0.018 – 0.991, p=0.049). We observe a reduced risk for pathological fractures in parathyroidectomized KTx patients independent from elevated parathyroid hormone at the time of KTx or afterwards.
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