Who will care for tomorrow's children with benign hematological conditions?

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56165/1/21254_ftp.pd

We all can contribute to training the new generation of pediatric hematologists

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58088/1/21468_ftp.pd

Accuracy Assessment of Pedicle and Lateral Mass Screw Insertion Assisted by Customized 3D-Printed Drill Guides:A Human Cadaver Study

BACKGROUND: Accurate cervical screw insertion is of paramount importance considering the risk of damage to adjacent vital structures. Recent research in 3-dimensional (3D) technology describes the advantage of patient-specific drill guides for accurate screw positioning, but consensus about the optimal guide design and the accuracy is lacking. OBJECTIVE: To find the optimal design and to evaluate the accuracy of individualized 3D-printed drill guides for lateral mass and pedicle screw placement in the cervical and upper thoracic spine. METHODS: Five Thiel-embalmed human cadavers were used for individualized drill-guide planning of 86 screw trajectories in the cervical and upper thoracic spine. Using 3D bone models reconstructed from acquired computed tomography scans, the drill guides were produced for both pedicle and lateral mass screw trajectories. During the study, the initial minimalistic design was refined, resulting in the advanced guide design. Screw trajectories were drilled and the realized trajectories were compared to the planned trajectories using 3D deviation analysis. RESULTS: The overall entry point and 3D angular accuracy were 0.76 +/- 0.52 mm and 3.22 +/- 2.34 degrees, respectively. Average measurements for the minimalistic guides were 1.20 mm for entry points, 5.61 degrees for the 3D angulation, 2.38 degrees for the 2D axial angulation, and 4.80 degrees for the 2D sagittal angulation. For the advanced guides, the respective measurements were 0.66 mm, 2.72 degrees, 1.26 degrees, and 2.12 degrees, respectively. CONCLUSION: The study ultimately resulted in an advanced guide design including caudally positioned hooks, crosslink support structure, and metal inlays. The novel advanced drill guide design yields excellent drilling accuracy

Operative treatment of anterior thoracic spinal cord herniation:three new cases and an individual patient data meta-analysis of 126 case reports

OBJECTIVE: Anterior thoracic spinal cord herniation is a rare cause of progressive myelopathy. Much has been speculated about the best operative treatment. However, no evidence in favor of any of the promoted techniques is available to date. Therefore, we decided to analyze treatment procedures and treatment outcomes of anterior thoracic spinal cord herniation to identify those factors that determine postoperative outcome. METHODS: An individual patient data meta-analysis was conducted, focusing on age, gender, vertebral segment of herniation, preoperative neurological status, operative interval, operative findings, operative techniques, intraoperative neurophysiological monitoring, postoperative imaging, neurological outcome and follow-up. Three cases from our own institution were added to the material collected. Bivariate analysis tests and multivariate logistic regression tests were used so as to define which variables were associated with outcome after surgical treatment of anterior thoracic spinal cord herniation. RESULTS: Brown-Séquard syndrome and release of the herniated spinal cord appeared to be strong independent factors, associated with favorable postoperative outcome. Widening of the dura defect is associated with the highest prevalence of postoperative motor function improvement when compared with the application of an anterior dura patch (P < 0.036). CONCLUSION: Most patients with anterior thoracic spinal cord herniation require operative treatment because of progressive myelopathy. Patients with Brown-Séquard syndrome have a better prognosis with respect to postoperative motor function improvement. In this review, spinal cord release and subsequent widening of the dura defect were associated with the highest prevalence of motor function improvement. D-wave recording can be a very useful tool for the surgeon during operative treatment of this disorder

Clinical outcome in decompression alone versus decompression and instrumented fusion in patients with isthmic spondylolisthesis:A prospective cohort study

OBJECTIVE In the surgical treatment of isthmic spondylolisthesis, it is debatable whether instrumented fusion is mandatory in addition to decompression. The objective of this prospective cohort study was to assess the long-term effect of decompression alone compared with decompression and instrumented fusion in patients who underwent the intervention of their own preference. The results were compared with those in patients who underwent randomly assigned treatment. METHODS The authors performed a prospective observational multicenter cohort study, including 91 patients with isthmic spondylolisthesis assigned to undergo either decompression alone (n = 44) or decompression and fusion (n = 47). The main outcomes were the Roland-Morris Disability Questionnaire (RDQ) scores and the patient's perceived recovery at the 2-year follow-up. Secondary outcomes were visual analog scale (VAS) leg pain and back pain scores and the reoperation rate. A meta-analysis was performed for data from this cohort study (n = 91) and from a randomized controlled trial (RCT) previously reported by the authors (n = 84). Subgroup analyses were performed on these combined data for age, sex, weight, smoking, and Meyerding grade. RESULTS At the 12-week follow-up, improvements of RDQ scores were comparable for the two procedures (decompression alone [D group] 4.4, 95% CI 2.3-6.5; decompression and fusion [DF group] 5.8, 95% CI −4.3 to 1.4; p = 0.31). Likewise, VAS leg pain scores (D group 35.0, 95% CI 24.5-45.6; DF group 47.5, 95% CI 37.4-57.5; p = 0.09) and VAS back pain scores (D group 23.5, 95% CI 13.3-33.7; DF group 34.0, 95% CI 24.1-43.8; p = 0.15) were comparable. At the 2-year follow-up, there were no significant differences between the two groups in terms of scores for RDQ (difference −3.1, 95% CI −6.4 to 0.3, p = 0.07), VAS leg pain (difference −7.4, 95% CI −22.1 to 7.2, p = 0.31), and VAS back pain (difference −11.4, 95% CI −25.7 to 2.9, p = 0.12). In contrast, patient-perceived recovery from leg pain was significantly higher in the DF group (79% vs 51%, p = 0.02). Subgroup analyses did not demonstrate a superior outcome for decompression alone compared with decompression and fusion. Nine patients (20.5%) underwent reoperation in total, all in the D group. The meta-analysis including both the cohort and RCT populations yielded an estimated pooled mean difference in RDQ of −3.7 (95% CI −5.94 to −1.55, p = 0.0008) in favor of decompression and fusion at the 2-year follow-up. CONCLUSIONS In patients with isthmic spondylolisthesis, at the 2-year follow-up, patients who underwent decompression and fusion showed superior functional outcome and perceived recovery compared with those who underwent decompression alone. No subgroups benefited from decompression alone. Therefore, decompression and fusion is recommended over decompression alone as a primary surgical treatment option in isthmic spondylolisthesis.</p

Accuracy of Patient-Specific 3D-Printed Drill Guides for Pedicle and Lateral Mass Screw Insertion:An Analysis of 76 Cervical and Thoracic Screw Trajectories

STUDY DESIGN: Single-center retrospective case series. OBJECTIVE: The purpose of this study was to assess the safety and accuracy of 3D-printed individualized drill guides for pedicle and lateral mass screw insertion in the cervical and upper-thoracic region, by comparing the pre-operative 3D-surgical plan with the postoperative results. SUMMARY OF BACKGROUND DATA: Posterior spinal fusion surgery can provide rigid intervertebral fixation but screw misplacement involves a high risk of neurovascular injury. However, modern spine surgeons now have tools such as virtual surgical planning and 3D-printed drill guides to facilitate spinal screw insertion. METHODS: A total of 15 patients who underwent posterior spinal fusion surgery involving patient-specific 3D-printed drill guides were included in this study. After segmentation of bone and screws, the post-operative models were superimposed onto the preoperative surgical plan. The accuracy of the realized screw trajectories was quantified by measuring the entry point and angular deviation. RESULTS: The 3D deviation analysis showed that the entry point and angular deviation over all 76 screw trajectories were 1.40 ± 0.81 mm and 6.70 ± 3.77°, respectively. Angular deviation was significantly higher in the sagittal plane than in the axial plane (P = 0.02). All screw positions were classified as 'safe' (100%), showing no neurovascular injury, facet joint violation, or violation of the pedicle wall. CONCLUSIONS: 3D virtual planning and 3D-printed patient-specific drill guides appear to be safe and accurate for pedicle and lateral mass screw insertion in the cervical and upper-thoracic spine. The quantitative 3D deviation analyses confirmed that screw positions were accurate with respect to the 3D-surgical plan. LEVEL OF EVIDENCE: 4

Patient-Derived Papillary Thyroid Cancer Organoids for Radioactive Iodine Refractory Screening

Simple Summary Over the past three decades, the incidence of thyroid cancer has been rising, with 90% being the well-differentiated thyroid cancer subtype. After diagnosis and surgical removal of the thyroid gland, radioactive iodine is administered to induce a localized post-operative radiation treatment. However, in 15-33% of papillary thyroid cancer cases, the cells are unable to take up radioactive iodine, resulting in an ineffective treatment which sometimes has severe side effects. Pre-treatment diagnosis of non-responding patients would prevent ineffective and toxic iodine treatment. Therefore, in this study, we developed a patient-derived papillary thyroid cancer organoid model. Patient-derived organoids responding or not responding to radioactive iodine clearly resembled the tumor of origin, but showed clear differences in sodium/iodide symporter expression. Our results indicate that thyroid cancer organoids might be a suitable tool for the early diagnosis of non-responding patients, in order to eventually reduce radioactive iodine overtreatment and its many side effects for thyroid cancer patients. Patients with well-differentiated thyroid cancer, especially papillary thyroid cancer (PTC), are treated with surgical resection of the thyroid gland. This is followed by post-operative radioactive iodine (I-131), resulting in total thyroid ablation. Unfortunately, about 15-33% of PTC patients are unable to take up I-131, limiting further treatment options. The aim of our study was to develop a cancer organoid model with the potential for pre-treatment diagnosis of these I-131-resistant patients. PTC tissue from thirteen patients was used to establish a long-term organoid model. These organoids showed a self-renewal potential for at least five passages, suggesting the presence of cancer stem cells. We demonstrated that thyroid specific markers, a PTC marker, and transporters/receptors necessary for iodine uptake and thyroid hormone production were expressed on a gene and protein level. Additionally, we cultured organoids from I-131-resistant PTC material from three patients. When comparing PTC organoids to radioactive iodine (RAI)-refractory disease (RAIRD) organoids, a substantial discordance on both a protein and gene expression level was observed, indicating a treatment prediction potential. We showed that patient-derived PTC organoids recapitulate PTC tissue and a RAIRD phenotype. Patient-specific PTC organoids may enable the early identification of I-131-resistant patients, in order to reduce RAI overtreatment and its many side effects for thyroid cancer patients

Defects in muscarinic receptor-coupled signal transduction in isolated parotid gland cells after in vivo irradiation: evidence for a non-DNA target of radiation

Radiation-induced dysfunction of normal tissue, an unwanted side effect of radiotherapeutic treatment of cancer, is usually considered to be caused by impaired loss of cell renewal due to sterilisation of stem cells. This implies that the onset of normal tissue damage is usually determined by tissue turnover rate. Salivary glands are a clear exception to this rule: they have slow turnover rates (>60 days), yet develop radiation-induced dysfunction within hours to days. We showed that this could not be explained by a hypersensitivity to radiation-induced apoptosis or necrosis of the differentiated cells. In fact, salivary cells are still capable of amylase secretion shortly after irradiation while at the same time water secretion seems specifically and severely impaired. Here, we demonstrate that salivary gland cells isolated after in vivo irradiation are impaired in their ability to mobilise calcium from intracellular stores (Ca2+i), the driving force for water secretion, after exposure to muscarinic acetylcholine receptor agonists. Using radioligand-receptor-binding assays it is shown that radiation caused no changes in receptor density, receptor affinity nor in receptor-G-protein coupling. However, muscarinic acetylcholine agonist-induced activation of protein kinase C alpha (PKCα), measured as translocation to the plasma membrane, was severely affected in irradiated cells. Also, the phorbol ester PMA could no longer induce PKCα translocation in irradiated cells. Our data hence indicate that irradiation specifically interferes with PKCα association with membranes, leading to impairment of intracellular signalling. To the best of our knowledge, these data for the first time suggest that, the cells' capacity to respond to a receptor agonist is impaired after irradiation