Does virtual reality simulation have a role in training trauma and orthopaedic surgeons?

Aims: The aim of this study was to assess the current evidence relating to the benefits of virtual reality (VR) simulation in orthopaedic surgical training, and to identify areas of future research. Materials and Methods: A literature search using the MEDLINE, Embase, and Google Scholar databases was performed. The results' titles, abstracts, and references were examined for relevance. Results: A total of 31 articles published between 2004 and 2016 and relating to the objective validity and efficacy of specific virtual reality orthopaedic surgical simulators were identified. We found 18 studies demonstrating the construct validity of 16 different orthopaedic virtual reality simulators by comparing expert and novice performance. Eight studies have demonstrated skill acquisition on a simulator by showing improvements in performance with repeated use. A further five studies have demonstrated measurable improvements in operating theatre performance following a period of virtual reality simulator training. Conclusion: The demonstration of 'real-world' benefits from the use of VR simulation in knee and shoulder arthroscopy is promising. However, evidence supporting its utility in other forms of orthopaedic surgery is lacking. Further studies of validity and utility should be combined with robust analyses of the cost efficiency of validated simulators to justify the financial investment required for their use in orthopaedic training. Cite this article: Bone Joint J 2018;100-B:559-65.

Complications following arthroscopic surgery of the hip: a systematic review of 36 761 cases.

AIMS: The number of patients undergoing arthroscopic surgery of the hip has increased significantly during the past decade. It has now become an established technique for the treatment of many intra- and extra-articular conditions affecting the hip. However, it has a steep learning curve and is not without the risk of complications. The purpose of this systematic review was to determine the prevalence of complications during and following this procedure. MATERIALS AND METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in designing this study. Two reviewers systematically searched the literature for complications related to arthroscopy of the hip. The research question and eligibility criteria were established a priori. Pertinent data were abstracted and analysed. RESULTS: We found 276 relevant studies with a total of 36 761 arthroscopies that met the inclusion criteria. The mean age of the patients was 36.7 years (1.7 to 70) and the mean body mass index was 25.7 kg/m2 (20.2 to 29.2). Femoroacetabular impingement and labral tears were the most common indications for the procedure. The total number of complications was 1222 (3.3%). Nerve injury (0.9%), mainly involving the pudendal and lateral femoral cutaneous nerves, and iatrogenic chondral and labral injury (0.7%), were the two most common complications. There were 58 major complications (0.2%), the most common being intra-abdominal extravasation of fluid, which was found in 13 cases (0.04%). There were three deaths (0.008%). CONCLUSION: Arthroscopic surgery of the hip is a procedure with a relatively low rate of complications, although some may be significant in this young cohort of patients. This study relied on the reported complications only and the results should be interpreted with caution. Cite this article: Bone Joint J 2017;99-B:1577-83.

CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients.

Although the introduction of tyrosine kinase inhibitors (TKIs) has improved overall survival of patients with chronic myeloid leukemia (CML), about half of the patients eventually relapse after cessation of TKIs. In contrast, the remainder of the patients maintain molecular remission without TKIs, indicating that the patients' immune system could control proliferation of TKI-resistant leukemic stem cells (LSCs). However, the precise mechanism of immunity against CML-LSCs is not fully understood. We have identified a novel immune target, CXorf48, expressed in LSCs of CML patients. Cytotoxic T cells (CTLs) induced by the epitope peptide derived from CXorf48 recognized CD34+CD38- cells obtained from the bone marrow of CML patients. We detected CXorf48-specific CTLs in the peripheral blood mononuclear cells from CML patients who have discontinued imatinib after maintaining complete molecular remission for more than 2 years. Significantly, the relapse rate of CXorf48-specific CTL-negative patients was 63.6%, compared to 0% in CXorf48-specific CTL-positive patients. These results indicate that CXorf48 could be a promising therapeutic target of LSCs for immunotherapy to obtain durable treatment-free remission in CML patients.

Early application of related SCT might improve clinical outcome in adult T-cell leukemia/lymphoma.

Allogeneic hematopoietic SCT (allo-HSCT) is a curative treatment for aggressive adult T-cell leukemia/lymphoma (ATLL). Considering the dismal prognosis associated with conventional chemotherapies, early application of allo-HSCT might be beneficial for patients with ATLL. However, no previous study has addressed the optimal timing of allo-HSCT from related donors. Hence, to evaluate the impact of timing of allo-HSCT for patients with ATLL, we retrospectively analyzed data from patients with ATLL who received an allo-HSCT from a related donor. The median age was 52 years. Patients were grouped according to the interval from diagnosis to allo-HSCT: early transplant group, <100 days, n=72; late transplant group, ⩾100 days, n=428. The corresponding constituents of disease status were not statistically different between the two groups (P=0.11). The probability of OS in the early transplant group was significantly higher than that in the late transplant group (4-year OS, 49.3% vs 31.2%). Multivariate analysis revealed that late allo-HSCT was an unfavorable prognostic factor for OS (hazard ratio, 1.46; 95% confidence interval (CI), 1.01-2.11; P=0.04). Despite the limitations of a retrospective study, it might be acceptable to consider early application of allo-HSCT for ATLL.

A radiographic analysis of alignment of the lower extremities--initiation and progression of varus-type knee osteoarthritis.

OBJECTIVE: This study aimed to investigate alignment based on age in normal knees and alignment based on deformity in osteoarthritis (OA) knees using detailed radiographic parameters. DESIGN: Various parameters were measured from weight-bearing long leg radiographs of 1251 legs (797 normal and 454 OA knees) as a cross-sectional study. Normal knees were classified by age (young, middle aged, aged, and elderly) and symptomatic OA knees on the basis of the alignment (femorotibial angle (FTA): mild, moderate, severe and profound). The mean measurements in each group were calculated and compared within each group. RESULTS: The femoral shaft showed medially bowed curvature (femoral bowing) of approximately 2° in the young normal group, which shifted to lateral bowing with age. However, OA knees showed larger lateral bowing with OA grade, which might reduce the condylar-shaft angle and subsequently shifted the mechanical axis medially. Progression of mild to moderate OA might be associated with a decreasing condylar-shaft angle (femoral condylar orientation) and widening condylar-plateau angle (joint space narrowing) rather than decreasing tibial plateau flattering. Steeping of the tibial plateau inclination due to increasing tibial plateau shift (tibial plateau compression) rather than medial tibial bowing might be the main contributor to worsening of varus deformity in knees with severe and profound OA. CONCLUSIONS: This cross-sectional study might provide the possibility of OA initiation and progression. The lateral curvature of the femoral shaft associated with aging may contribute to the initiation of varus-type OA of the knee. These changes in the femur may be followed by secondary signs of OA progression including varus femoral condylar orientation, medial joint space narrowing, and tibial plateau compression.

Cyclooxygenase-2 inhibition restores ultraviolet B-induced downregulation of ATP2A2/SERCA2 in keratinocytes: possible therapeutic approach of cyclooxygenase-2 inhibition for treatment of Darier disease.

BACKGROUND: ATP2A2 encoding the sarcoplasmic/endoplasmic reticulum Ca(2+) -ATPase2 (SERCA2) is a Darier disease (DD)-related gene. Ultraviolet (UV) B irradiation downregulates ATP2A2/SERCA2 expression in keratinocytes, whereas cyclooxygenase-2 (COX-2) expression is dramatically upregulated by UVB. OBJECTIVES: To analyse the involvement of COX-2 in ATP2A2/SERCA2 expression. METHODS: Keratinocytes were transfected with COX-2 siRNA or treated with COX-2 inhibitor, celecoxib, to evaluate the effect of COX-2 on ATP2A2/SERCA2 expression. Quantitative real-time polymerase chain reaction, Western blotting analysis and reporter assay were used to determine the amount of mRNA, protein level and transcription activity, respectively. RESULTS: COX-2 knockdown by siRNA resulted in upregulation of ATP2A2 transcription. Treatment by celecoxib rescued UVB-mediated suppression of the ATP2A2 transcription and SERCA2 protein expression. Simple addition of prostaglandin (PG) E(2) , which is a product of COX-2 enzyme, reduced the amounts of ATP2A2 mRNA and SERCA2 protein in keratinocytes. CONCLUSIONS: UVB downregulates ATP2A2/SERCA2 expression via induction of COX-2 expression and subsequent increase of PGE(2) production in keratinocytes. Considering that DD is caused by the decreased function of SERCA2 due to the reduced expression of the ATP2A2 gene, this finding shows the possibility that COX-2 inhibition may be useful to prevent and/or treat DD.

Rapidly progressive fatal hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in hematologic malignancy.

BACKGROUND: Pneumonia caused by Stenotrophomonas maltophilia is rare, but can be lethal in severely immunocompromised patients. However, its clinical course remains unclear. PATIENTS AND METHODS: Patients with pneumonia caused by S. maltophilia in Toranomon Hospital (890 beds, Tokyo, Japan) were reviewed retrospectively between April 2006 and March 2010. RESULTS: During the study period, 10 cases of S. maltophilia pneumonia were identified. Seven patients had acute myeloid leukemia, 2 had myelodysplastic syndrome, and 1 had malignant lymphoma. All patients developed symptoms after allogeneic hematopoietic stem cell transplantation (HSCT). Five patients received first cord blood transplantation (CBT), 4 patients received second CBT, and 1 patient received first peripheral blood stem cell transplantation (PBSCT). The overall incidence of S. maltophilia pneumonia among 508 patients who received HSCT during the period was 2.0%. The incidence was 0% (0/95) in patients after bone marrow transplantation, 0.8% (1/133) after PBSCT, and 3.2% (9/279) after CBT. Pneumonia developed a median of 13.5 days (range, 6-40) after transplantation. At onset, the median white blood cell count was 10/µL (range, 10-1900), and the median neutrophil count was 0/µL (range, 0-1720). In all patients, S. maltophilia bacteremia developed with bloody sputum or hemoptysis. The 28-day mortality rate was 100%; the median survival after onset of pneumonia was 2 days (range, 1-10). CONCLUSIONS: Hemorrhagic S. maltophilia pneumonia rapidly progresses and is fatal in patients with hematologic malignancy. Attention should be particularly paid to the neutropenic phase early after HSCT or prolonged neutropenia due to engraftment failure. A prompt trimethoprim-sulfamethoxazole-based multidrug combination regimen should be considered to rescue suspected cases of S. maltophilia pneumonia in these severely immunosuppressed patients.

Interaction of functional FCER2 promoter polymorphism and phenotype-associated haplotypes.

Low-affinity IgE receptor gene (FCER2) rs3760687 polymorphism was found to be associated with differential binding affinity of transcription factors Sp1 and Sp3 leading to altered transcriptional activity. Haplotypic interaction of functional FCER2 polymorphisms (rs28364072, rs2228137 and rs3760687) might potentially provide a background for genotype-phenotype associations previously observed for some rather non-functional FCER2 variants.

Role of Msx2 as a promoting factor for Runx2 at the periodontal tension sides elicited by mechanical stress.

Early changes of Runx2 and Msx2 expressions were examined by immunohistochemistry in mouse periodontal ligament exposed to mechanical stress. 8-week-old ddY mouse was used as experimental animal. To provide a continuous mechanical stress on periodontal ligament, rubber dam sheet was placed between upper molars of the mouse. At 20 minutes, 1 hour, 3 hours, 9 hours and 24 hours after insertion of the sheet, relevant parts of the mouse tissues were excised and fixed in 4% paraformaldehyde/0.05M phosphate buffered fixative solution. Then serial paraffin sections were prepared and histopathological evaluation as well as examination of Runx2, Msx2 and alkaline phosphatase (ALP) expressions by immunohistochemistry were performed. Control animals were not subjected to mechanical stress. In the experimental group, strong expressions of Runx2 and Msx2 were seen in periodontal fibroblasts of the tension side at 20 minutes after mechanical stress. Expressions of Runx2 and Msx2 became stronger in parallel with time, and at 24 hours after mechanical stress, the periodontal fibroblasts, cementoblasts as well as osteoblasts showed strong expression. Moreover, ALP has also demonstrated similar strong expression. On the other hand, in the control group, although expressions of Runx2, Msx2 and ALP were detected at all the experiment times, the expressions were weak. All these results strongly suggested that Runx2 promoted differentiation of osteoblasts at early stage and Msx2 worked as an activator of Runx2 function.

Granulomatous prostatitis due to Cryptococcus neoformans: diagnostic usefulness of special stains and molecular analysis of 18S rDNA.

A 57-year-old Japanese man complained of pain on micturition. The prostate was of normal size but hard. Transrectal needle biopsy demonstrated granulomatous prostatitis with small focal abscesses. Staining with periodic acid-Schiff, Grocott's methenamine silver and Fontana-Masson revealed yeast-form fungus in the granulomas. The mucoid capsule of the fungus stained with mucicarmine. PCR specific for cryptococcal 18S rDNA using DNA extracted from the pathological specimen was positive, and the sequence was homologous to Cryptococcus neoformans. A diagnosis of cryptococcal granulomatous prostatitis was made. The patient was then found to suffer from meningitis and lung abscess, and was treated with amphotericin B and flucytosine. Careful histological and molecular studies are beneficial to reach the correct diagnosis and to prevent an unfavorable outcome of disseminated cryptococcosis.

CDK5 regulates cell-cell and cell-matrix adhesion in human keratinocytes.

BACKGROUND: CDK5 is a member of proline-directed serine/threonine kinases. Although its cDNA was originally cloned as a homologue to those for the other members of the cyclin-dependent kinase (CDK) family, CDK5 has been shown to function differently from other CDKs. CDK5 is activated by non-cyclin partners, p35 and p39, and important during brain development by influencing adhesion, migration and differentiation of neurones. OBJECTIVES: We sought to investigate the expression and functions of CDK5 in human keratinocytes. METHODS: Expression of CDK5/p35, interaction of CDK5/p35 with adhesion molecules, and its roles in cell-cell and cell-matrix adhesion were studied by reverse transcriptase-polymerase chain reaction, immunoblotting and aggregation/adhesion assays in primary cultured normal human keratinocytes from infant foreskins and a human keratinocyte HaCaT cell line. Localization of CDK5 and p35 in normal human epidermis and psoriatic epidermis was studied by immunohistochemistry. RESULTS: Both CDK5 and p35 were expressed in primary cultured keratinocytes, HaCaT cells and normal human epidermis. Roscovitine, an inhibitor of CDK5, enhanced Ca2+-dependent (cadherin-dependent) aggregation of HaCaT cells whereas it inhibited adhesion of HaCaT cells to fibronectin associated with reduced active states of beta1 integrin. Interestingly, psoriatic skin showed reduced CDK5 and p35 expression in the lower half of the epidermis, which might be associated with decreased amount of activated beta1 integrin in the epidermis of psoriatic skin. CONCLUSIONS: CDK5/p35 may be involved in cell-cell and cell-matrix adhesion in human keratinocytes by differently regulating cadherins and integrins. Furthermore, reduced expression of CDK5/p35 in the epidermis might be involved in the pathogenesis of psoriasis.

[Lung cancer associated with the right aortic arch; report of a case].

We report a rare case of lung cancer associated with the right aortic arch. A 72-year-old male was admitted to our hospital for surgical treatment of squamous cell carcinoma arising from left B3. The patient had a right aortic arch with the type of mirror-image branching. He underwent a left upper lobectomy and lymph node dissection. We easily resected the lymph nodes in the left side of the upper mediastinum without rotating aortic arch because the aortic arch was positioned on the other side.

Hypercytokinemia in hemiconvulsions-hemiplegia syndrome associated with dual infection with varicella zoster and Epstein-Barr viruses.

Hemiconvulsions-hemiplegia (HH) syndrome is an acquired condition in which hemiplegia develops after a preceding febrile unilateral status epilepticus in a previously healthy child. Although viral encephalitis or vascular diseases may be the underlying etiology, the pathogenesis remains unknown in the majority of cases. We measured both plasma and cerebrospinal fluid cytokine levels in a girl with HH syndrome, and found elevated plasma concentrations of soluble interleukin-2 receptor and tumor necrosis factor-alpha, and a slightly increased plasma level of interleukin-6. Furthermore, she had a high serum concentration of soluble E-selectin, which is a marker of inflammatory endothelial activation. These findings suggest that proinflammatory cytokine-induced cerebrovascular endothelial injury could play a role in the pathogenesis of HH syndrome.