Magnetic resonance imaging for three-dimensional printing of the bony orbit: is clinical use imminent?

The aim of this study was to examine the accuracy of three dimensionally (3D) printed models of the bony orbit derived from magnetic resonance imaging (MRI) for the purpose of preoperative plate bending in the setting of orbital blowout fracture. Retrospective computed tomography (CT) and MRI data from patients with suspected orbital fractures were used. Virtual models were manually generated and analysed for spatial accuracy of the fracture margins. 3D-printed models were produced and orbital fan plates bent by a single operator. The plates were then digitized and analysed for spatial discrepancy using reverse engineering software. Seven orbital blowout fractures were evident in six orbits. Analysis of the virtual models revealed high congruence between blowout fracture margins on CT and MRI (n=7, average deviation 0.85mm). Three zygomaticomaxillary complex fractures were seen, for which MRI did not demonstrate the same accuracy. For plates bent to the 3D-printed models of blowout fractures (n=6), no significant difference was found between those bent to CT versus those bent to MRI when compared for average surface and average border deviation (Wilcoxon signed rank test). Orbital blowout fractures can be defined on MRI with clinically acceptable accuracy. 3D printing of orbital biomodels from MRI for bending reconstructive plates is an acceptable and accurate technique.

Effectiveness of irrigation with chlorhexidine after removal of mandibular third molars: a randomised controlled trial.

To evaluate the effect of postoperative irrigation with chlorhexidine on inflammatory complications after the extraction of lower third molars under local anaesthesia, we recruited 100 patients to participate in a controlled, single-blind, randomised clinical trial. They were assigned to one of two groups: the intervention group (postoperative irrigation of the surgical site with chlorhexidine for seven days) or the control group (postoperative chlorhexidine mouth rinse for seven days). The primary outcome variables were pain, swelling, trismus, infection, and alveolar osteitis. The secondary outcome variables were wound dehiscence and food impaction. A total of 95 participants completed the study (47 in the irrigation group and 48 in the rinse group). In the irrigation group, alveolar osteitis and facial swelling had reduced significantly at seven days postoperatively (both p<0.01). Pain scores had also reduced significantly at seven days (p<0.01), but not at 48hours, and patients had lower levels of food impaction (p<0.01) and less severe symptoms (p=0.02). Routine irrigation with chlorhexidine after the extraction of third molars helps to reduce pain and lowers the incidence of alveolar osteitis.

Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL/SLL.

In the phase 3 RESONATE study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%) and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared with patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations.

Postoperative interventions to reduce inflammatory complications after third molar surgery: review of the current evidence.

Inflammatory complications such as pain, swelling, trismus, infection and alveolar osteitis have an adverse affect on the quality of life of patients after third molar removal. This review presents the current evidence on postoperative strategies to reduce these complications. A literature search was performed to identify articles published in English between 2000 to 2016 using the following keywords: third molar(s), wisdom tooth/teeth, pain, swelling, trismus, infection, alveolar osteitis and dry socket. In total, 221 papers were reviewed. Methods published included analgesics, antibiotics, corticosteroids, mouthwashes, topical gels, cryotherapy and ozone therapy. This review highlights the variability in evidence available and summarizes the findings from best-quality evidence. In conclusion, paracetamol and ibuprofen are efficacious in managing postoperative pain. Corticosteroids and antibiotics should only be used in selected cases. Chlorhexidine reduces alveolar osteitis. The benefits of cryotherapy, postoperative irrigation and ozone gel are yet to be established.

Cancer Moonshot Data and Technology Team: Enabling a National Learning Healthcare System for Cancer to Unleash the Power of Data.

The Cancer Moonshot emphasizes the need to learn from the experiences of cancer patients to positively impact their outcomes, experiences, and qualities of life. To realize this vision, there has been a concerted effort to identify the fundamental building blocks required to establish a National Learning Healthcare System for Cancer, such that relevant data on all cancer patients is accessible, shareable, and contributing to the current state of knowledge of cancer care and outcomes.

Epidural adhesiolysis: an evidence-based review.

First described over 25 years ago, epidural lysis of adhesions (LOA) involves the mechanical dissolution of epidural scar tissue, which may directly alleviate pain and facilitate the spread of analgesic substances to area(s) of pain generation. Although it most commonly performed for lumbar failed back surgery syndrome, there is a growing body of evidence that suggests it may be effective for spinal stenosis and radicular pain stemming from a herniated disc. There is weak positive evidence that LOA is more effective than conventional caudal epidural steroid injections for failed back surgery syndrome and spinal stenosis, and that LOA is more effective than sham adhesiolysis and conservative management for lumbosacral radiculopathy. For cervical disc herniation and spinal stenosis, there is only anecdotal evidence suggesting effectiveness and safety. Factors that may contribute to the enhanced efficacy compared to traditional epidural steroid administration include the high volume administered, the use of hypertonic saline, and to a lesser extent the use of hyaluronidase and a navigable catheter to mechanically disrupt scar tissue and guide medication administration. Although LOA is widely considered a safe intervention, the complication rates are higher than for conventional epidural steroid injection.

Leptin resistance following over-expression of protein tyrosine phosphatase 1B in liver.

Obesity is typically associated with resistance to leptin, yet the mechanism by which leptin signaling becomes impaired is poorly understood. Here we sought to determine if the development of obesity and leptin resistance correlates with increased expression of protein tyrosine phosphatase 1B (PTP1B) in peripheral tissues and whether over-expression of this phosphatase, specifically in liver, could alter the leptin-mediated effects on feeding and glucose metabolism. Obesity was induced in mice through a high-fat diet that resulted in hyperglycemia, hyperinsulinemia and hyperleptinemia. Resistance to leptin was confirmed as exogenous leptin administration reduced food intake in animals on low-fat, but not high-fat diets. Diet-induced resistance to leptin and insulin was associated with increased hepatic levels of PTP1B. Intriguingly, hepatic adenoviral over-expression of PTP1B in ob/ob mice attenuated the ability of exogenous leptin to reduce both plasma glucose levels and food intake. These findings suggest that leptin reduces both plasma glucose and food intake in part through actions on the liver, and hepatic leptin resistance resulting from over-expression of PTP1B may contribute to the development of both diabetes and obesity.

Improved detection of CFTR mutations in Southern California Hispanic CF patients.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), a common autosomal recessive disease in Caucasians. The broad mutation spectrum varies among different patient groups. Current molecular diagnoses are designed to detect 80-97% of CF chromosomes in Caucasians and Ashkenazi Jews but have a much lower detection rate in Hispanic CF patients. Grebe et al. [1994] reported a 58% detection rate in Hispanic patients. Since then, there has been no large-scale, complete mutational analysis of Hispanic CF patients. In this study, the mutations in 62 Hispanic patients from southern California were investigated. The entire coding and flanking intronic regions of the CFTR gene were analyzed by temporal temperature gradient gel electrophoresis (TTGE) followed by sequencing to identify the mutations. Eleven novel mutations were discovered in this patient group: 3876delA, 406-1G>A, 935delA, 663delT, 3271delGG, 2105-2117del13insAGAAA, 3199del6, Q179K, 2108delA, 3171delC, and 3500-2A>T. Among the mutations, seven were out-of-frame insertions and deletions that result in truncated proteins, two were splice-site mutations, one was an in-frame 6 bp deletion, and one was a missense mutation that involved the non-conservative change of glutamine-179 to lysine. All patients presented severe classical clinical course with pancreatic insufficiency and poor growth, consistent with the nature of truncation mutation. The results indicate that TTGE screening following the analysis of recurrent mutations will substantially improve the mutation detection rate for Hispanic CF patients from southern California.

CDw150(SLAM) is a receptor for a lymphotropic strain of measles virus and may account for the immunosuppressive properties of this virus.

Natural isolates of measles virus readily infect several lymphocyte cell lines. These viruses appear to use a receptor other than CD46, the molecule to which most laboratory strains of virus bind. Methods used to identify and characterize this lymphocyte receptor for measles virus are described in this study. A binding assay with a soluble form of measles virus H protein demonstrated that B-cell lines, activated with Epstein-Barr virus, or T cells, transformed with human T-cell leukemia virus, exhibit this receptor on their cell surfaces. On the other hand, resting lymphocytes, monocytes, or immature leukocytes either failed to express or possessed reduced levels of this receptor. A cDNA library derived from B95-8 marmoset B-cell lines was used to identify this receptor through expression cloning. This molecule was shown to be CDw150, which is also known as the signaling lymphocytic activation molecule (SLAM). When the lymphocyte receptor was expressed in Chinese hamster ovary (CHOP) or human embryonic kidney (293T) cells, these cells became susceptible to lymphotropic as well as laboratory strains of measles virus. Binding assays confirmed that either lymphotropic or laboratory strains of measles virus could adhere to human or marmoset CDw150, but interaction with the mouse homolog was weak. These infections were independent of the presence of CD46 on the host cell surface. Interaction of measles virus with CDw150(SLAM) could explain the immunosuppressive properties of this virus.

X protein of hepatitis B virus inhibits Fas-mediated apoptosis and is associated with up-regulation of the SAPK/JNK pathway.

The X protein from a chronic strain of hepatitis B virus (HBx) was determined to inhibit Fas-mediated apoptosis and promote cell survival. Fas-mediated apoptosis is the major cause of hepatocyte damage during liver disease. Experiments demonstrated that cell death caused by anti-Fas antibodies was blocked by the expression of HBx in human primary hepatocytes and mouse embryo fibroblasts. This effect was also observed in mouse erythroleukemia cells that lacked p53, indicating that protection against Fas-mediated apoptosis was independent of p53. Components of the signal transduction pathways involved in this protection were studied. The SAPK/JNK pathway has previously been suggested to be a survival pathway for some cells undergoing Fas-mediated apoptosis, and kinase assays showed that SAPK activity was highly up-regulated in cells expressing the HBx protein. Normal mouse fibroblasts expressing HBx were protected from death, whereas identical fibroblasts lacking the SEK1 component from the SAPK pathway succumbed to Fas-mediated apoptosis, whether HBx was present or not. Assays showed that caspase 3 and 8 activities and the release of cytochrome c from mitochondria were inhibited, in the presence of HBx, following stimulation with anti-Fas antibodies. Coprecipitation and confocal immunofluorescence microscopy experiments demonstrated that HBx localizes with a cytoplasmic complex containing MEKK1, SEK1, SAPK, and 14-3-3 proteins. Finally, mutational analysis of HBx demonstrated that a potential binding region for 14-3-3 proteins was essential for induction of SAPK/JNK activity and protection from Fas-mediated apoptosis.

A novel mutation detected by temporal temperature gradient gel electrophoresis led to the confirmative prenatal diagnosis of a Hispanic CF family.

Mutational analysis of 30 recurrent known mutations detects only about 58% of Hispanic cystic fibrosis (CF) chromosomes. The low mutation detection rate has greatly hindered prenatal diagnosis and carrier testing of Hispanic families who have multiple affected children with unidentified cystic fibrosis transmembrane conductance regulator (CFTR) mutations. We recently employed a temporal temperature gradient gel electrophoresis (TTGE) method to effectively scan unknown mutations in the entire CFTR gene. A novel mutation, 2105-2117 del13insAGAAA was identified in a Hispanic family heterozygous for delta F508. The discovery of the devastating mutation facilitated the prenatal diagnosis for this family who already had two severely affected children. The fetus was found to be a compound heterozygote of delta F508/2105-2117 del13insAGAAA. This case emphasizes the importance of whole gene mutational analysis in patients with a clinical diagnosis of CF, but without the identifiable DNA mutations by routine mutation analysis. Finding of CF mutations in the patient would allow proper genetic counselling and prenatal and carrier detection of at-risk family members.

Medulloblastoma in children--the Ottawa experience.

A retrospective review of 36 children diagnosed with medulloblastoma in the Ottawa area between 1974 and 1997 was completed (mean age 7.8+/-4.2 years, range 1.2-15.3 years). Via a suboccipital approach, complete tumor resection was achieved in 75% and subtotal resection (>90%) in 25%, without any operative mortality. The tumor was located in the vermis in 39% and in the cerebellar hemisphere in 11%; it occupied both locations in 50%. In 47% of the children a ventriculoperitoneal shunt was required. Postoperatively, craniospinal radiation at 3600 cGy with a boost to the posterior fossa was administered. Chemotherapy was used in 56%. The 1-year survival rate was 92%, and survival plateaued at 54% at 5 years. Children less than 3 years of age fared worse than those over 3 years old. While the male-to-female ratio was 1.6:1, there was no gender difference in survival. Chang's classification was used to grade the tumors. T stage did not have an impact on survival, but M stage did. No statistically significant difference in survival was found between the patients who had a total resection and those who had a subtotal resection. There was no difference in survival in terms of tumor location, hydrocephalus or ventriculoperitoneal shunt. Chemotherapy showed no survival benefit. The recurrence rate was 26%, and its timing followed Collin's law. Recurrence led to death within 1-9 months. GH deficiency was diagnosed in 5 patients and hypothyroidism in 4 patients. The mean follow-up time was 4.4+/-3.7 years, with a range of 2.5 months to 16.5 years. Fourteen patients died, 5 were lost to follow-up, and 7 were transferred to adult care without persistent disease. Ten children are presently being followed up by the Neuro-oncology Clinic. Four children continue to be followed through psychology services. Our results are comparable to those in larger series, and are similar to those of the Montreal Children's Hospital.

Brain tumors in childhood and adolescence.

Brain tumors are the second most common neoplasm in childhood and adolescence. With the recent advances in technology, changes in tumor incidence have been reported. This study examines this statement. A 19-year retrospective case review of primary brain tumors in persons younger than 18 years of age at time of diagnosis, who had permanent residence in our catchment area, was performed. Data were examined for changes in presenting symptoms and signs and incidence rates for tumors on the basis of anatomic location and histologic tumor type. An incidence rate of 2.76 per 100,000 people younger than 18 years of age was found. During the period of this study a small, but significant, trend toward increasing incidence was evident. No changes in patterns of presentation or duration of symptoms before diagnosis was observed. The incidence rate based on histologic tumor diagnosis remained fairly constant during the study period.

MRI diagnosis of gliomatosis cerebri.

Until recently the diagnosis of gliomatosis cerebri has been made on postmortem examination. This article reviews the use of serial magnetic resonance imaging studies to suggest premorbid diagnosis of this condition. The following is a case report of a 14-year-old female who had a subtotal cortical resection of tumor and several years later developed a progressive dementia. At postmortem examination the diagnosis of gliomatosis cerebri was made. Diffuse progressive white matter changes involving both hemispheres and brainstem, with increased thickness of the corpus callosum and without changes in cortical markings on T2-weighted magnetic resonance images, in this patient were highly suggestive of the diagnosis of gliomatosis cerebri.

3849 + 10 kb C --> T splicing mutation in Hispanic CF patients.

Seven patients compound heterozygous for the 3849 + 10kb C --> T mutation in the CFTR gene were found among the 152 patients attending the CHLA CF Clinic. The frequency of this mutation accounts for 2.3 and 3.9% of thetotal and Hispanic CF alleles of CHLA patients. These are significantly higher than the 0.6% of the general CF population. The average age of diagnosis of this group of Hispanics is 3.1 years, which is much younger than that reported for CF patients of other ethnicities with the same mutation. Both pancreatic sufficient and pancreatic insufficient patients were observed. It is concluded that the 3849 + 10kb C --> T mutation is associated with a variable but potentially mild type of CF.

Bone marrow metastasis in astrocytic gliomata.

With the increasing survival time of many pediatric patients with malignancies, unexpected symptoms or signs require diligent search for rare complications or second cancers related to the disease or treatment. We recently encountered a patient with extensive glioblastoma multiforme who developed pancytopenia six months after completion of treatment with craniospinal radiation and chemotherapy with etoposide and cyclophosphamide. Bone marrow aspirate and biopsy confirmed bone marrow metastasis from the brain tumor. He showed good partial remission with chemotherapy with carmustine and cis-platinum as demonstrated by serial bone marrow aspirate for cytology and cytogenetics and enjoyed good quality of life for eight months. 14 other patients with astrocytic glioma, two of whom are children, are reported in the literature to have diffuse bone marrow metastasis. Therefore, in patients with malignant astrocytic tumor, bone marrow metastasis, though not common, should be considered when bone pain or cytopenias occur, especially when prolonged.