Significant association of increased PD-L1 and PD-1 expression with nodal metastasis and a poor prognosis in oral squamous cell carcinoma.

Programmed cell death ligand 1 (PD-L1) and its receptor PD-1 are immune checkpoint molecules that attenuate the immune response. Blockade of PD-L1 enhances the immune response in a variety of tumours and thus serves as an effective anti-cancer treatment. However, the biological and prognostic roles of PD-L1/PD-1 signalling in oral squamous cell carcinoma (OSCC) remain to be elucidated. The purpose of this study was to examine the correlation of PD-L1/PD-1 signalling with the prognosis of OSCC patients to assess its potential therapeutic relevance. The expression of PD-L1 and of PD-1 was determined immunohistochemically in 97 patients with OSCC and the association of this expression with clinicopathological characteristics was examined. Increased expression of PD-L1 was found in 64.9% of OSCC cases and increased expression of PD-1 was found in 61.9%. Univariate and multivariate analysis revealed that increased expression of PD-L1 and PD-1 positively correlated with cervical lymph node metastasis. The expression of CD25, an activated T-cell marker, was negatively correlated with the labelling index of PD-L1 and PD-1. Moreover, the patient group with PD-L1-positive and PD-1-positive expression showed a more unfavourable prognosis than the group with PD-L1-negative and PD-1-negative expression. These data suggest that increased PD-L1 and PD-1 expression is predictive of nodal metastasis and a poor prognosis and is possibly involved in cancer progression via attenuating the immune response.

Do screws and screw holes affect osteolysis in cementless cups using highly crosslinked polyethylene? A 7 to 10-year follow-up case-control study.

BACKGROUND: The use of screws and the presence of screw holes may cause acetabular osteolysis and implant loosening in cementless total hip arthroplasty (THA) using conventional polyethylene. In contrast, this issue is not fully understood using highly crosslinked polyethylene (HXLPE), particularly in large comparative study. Therefore, we performed a case-control study to assess the influence of screw usage and screw holes on: (1) implant fixation and osteolysis and (2) polyethylene steady-state wear rate, using cases with HXLPE liners followed up for 7-10 years postoperatively. HYPOTHESIS: The screw usage and screw holes adversely affect the implant fixation and incidence of wear-related osteolysis in THA with HXLPE. PATIENTS AND METHODS: We reviewed 209 primary cementless THAs performed with 26-mm cobalt-chromium heads on HXLPE liners. To compare the effects of the use of screws and the presence of screw holes, the following groups were established: (1) with-screw (n=140); (2) without-screw (n=69); (3) no-hole (n=27) and (4) group in which a cup with screw holes, but no screw was used (n=42). Two adjunct groups (no-hole cups excluded) were established to compare the differences in the two types of HXLPE: (5) remelted group (n=100) and (6) annealed group (n=82). Implant stability and osteolysis were evaluated by plain radiography and computed tomography. The wear rate from 1 year to the final evaluation was measured using plain X-rays and PolyWare Digital software. RESULTS: All cups and stems achieved bony fixation. On CT-scan, no acetabular osteolysis was found, but there were 3 cases with a small area of femoral osteolysis. The mean steady-state wear rate of each group was (1) 0.031±0.022, (2) 0.033±0.035, (3) 0.031±0.024, (4) 0.029±0.018, (5) 0.030±0.018 and (6) 0.034±0.023mm/year, respectively. A comparison of the effects of screw usage or screw holes found no significant between-group differences in the implant stability, prevalence of osteolysis [no acetabular osteolysis and 3/209 at femoral side (1.4%)] and steady-state wear rate. DISCUSSION: This study suggests that there are no adverse effects on the results of THA with HXLPE from the use of cups with screw holes and the use of screws for cup fixation. LEVEL OF EVIDENCE: Level III retrospective case-control study.

Comparison of wear rate and osteolysis between second-generation annealed and first-generation remelted highly cross-linked polyethylene in total hip arthroplasty. A case control study at a minimum of five years.

BACKGROUND: There is no previous report that directly compared wear resistance of second-generation annealed highly cross-linked polyethylene with that of first-generation remelted highly cross-linked polyethylene. We therefore performed a retrospective study at a minimum of 5-year follow-up comparing second-generation annealed and first-generation remelted highly cross-linked polyethylene in order to: (1) assess wear rates and (2) compare the incidence of osteolysis between, (3) identify the frequency of complication related to the two types of highly cross-linked polyethylene. HYPOTHESIS: There is a difference in the linear wear rate and the incidence of osteolysis between the two types of highly cross-linked polyethylene in total hip arthroplasty. MATERIALS AND METHODS: In a single centre study, we reviewed 123 primary cementless total hip arthroplasties between 2010 and 2011 that were performed with 32mm alumina ceramic on second-generation annealed (X3) or first-generation remelted (Longevity) highly cross-linked polyethylene liner. There was no specific reason for the choice of the type of highly cross-linked polyethylene. There were no significant differences between the two groups in respect of gender, diagnosis, body mass index, pre- and post-operative functional and activity score, cup size, and cup orientation except the younger age in the X3 group. The mean wear rate and the incidence of osteolysis were evaluated at the latest follow-up. RESULTS: One hundred nine cases followed over 5 years post-operatively (88.6% in all consecutive cases) were evaluated. X3 and Longevity were used in 54 and 55 cases, respectively. The mean follow-up was 5.3 years in both groups. The mean linear wear rate of X3 and Longevity group was 0.045±0.023mm/year and 0.076±0.031mm/year, respectively (P<0.001). No osteolysis was found on plain X-rays in both groups and no specific complication was related to these highly cross-linked components. DISCUSSION: Excellent wear resistance of both types of highly cross-linked polyethylene liner was revealed in our study. The difference of wear rate between two materials should be monitored in a longer follow-up. LEVEL OF EVIDENCE: Level III retrospective case control study.

Comparison of wear rate and osteolysis between annealed and remelted highly cross-linked polyethylene in total hip arthroplasty. A case control study at 7 to 10 years follow-up.

BACKGROUND: Low polyethylene wear rate and low incidence of osteolysis after total hip arthroplasty using annealed and remelted highly cross-linked polyethylene have been reported. However, there is no previous report that directly compared both types of highly cross-linked polyethylene. We therefore performed a retrospective study on a series of highly cross-linked polyethylene, in order to: (1) compare wear rates and the incidence of osteolysis between annealed and remelted highly cross-linked polyethylene at 7-10 years; (2) identify the frequency of complication related to annealed and remelted highly cross-linked polyethylene. HYPOTHESIS: There is no difference in the linear wear rate and the incidence of osteolysis between the annealed and remelted highly cross-linked polyethylene in total hip arthroplasty. PATIENTS AND METHODS: Two hundred and sixteen cases of cementless total hip arthroplasties with annealed or remelted highly cross-linked polyethylene, which were performed between January 2003 and December 2006 in one institution, were followed for 7-10 years and received computed tomography scan, in addition to radiography at the latest follow-up. Annealed and remelted highly cross-linked polyethylene was used in 91 cases and 125 cases, respectively. A 26-mm cobalt-chromium head was used in all cases. Penetration rates from 1 year to the last evaluation were used to estimate the yearly linear wear rate. Existence of osteolysis was evaluated by plain radiography and computed tomography. RESULTS: There were no significant differences in patients' background between the two groups. The linear wear rate of annealed and remelted group was 0.031±0.022mm/year and 0.032±0.020mm/year, respectively (P=0.91). Two cases of small femoral osteolysis were found in the annealed group. Any complication related to highly cross-linked polyethylene was not found in both groups. DISCUSSION: There was no significant difference in the linear wear rate and the incidence of osteolysis between the annealed and remelted group at postoperative 7 to 10 years. Excellent results of both types of highly cross-linked polyethylene were revealed by this study. LEVEL OF EVIDENCE: Level III retrospective case control study.

Cementless total hip replacement after previous intertrochanteric valgus osteotomy for advanced osteoarthritis.

We present a series of 30 uncemented total hip replacements performed between June 1985 and January 2002 with a mean follow-up of seven years (5 to 20) in 27 patients who had previously undergone a valgus intertrochanteric osteotomy. No further osteotomy was undertaken to enable hip replacement. We used a number of uncemented modular or monoblock femoral components, acetabular components and bearings. The patients were followed up clinically and radiologically. We report 100% survival of the femoral component. One acetabular component was revised at five years post-implantation for aseptic loosening. We noted cortical hypertrophy around the tip of the monoblock stems in six patients. We believe that modular femoral components should be used when undertaking total hip replacement in patients who have previously undergone valgus femoral osteotomy.

[One-staged operation for multiple aortic aneurysms of the descending thoracic aorta and abdominal aorta; report of a case].

A 66-year-old man underwent successfully on one-staged operation for aneurysms of the descending thoracic aorta and abdominal aorta. For the operation of descending thoracic aortic aneurysm, a temporary bypass was used from the proximal side of aneurysm to the distal one. The sacculer aneurismal wall of the descending thoracic aorta was repaired by patch formation using a knitted graft. Abdominal aortic aneurysm was replaced using a Gelsoft graft. The operation time was 7 hours and 35 minutes. Blood transfusion was not needed. The postoperative course was uneventful. It is suggested that one-staged operation for descending thoracic aortic aneurysm under the assist of temporary bypass and abdominal aortic aneurysm is possible.

Amended biochemical characteristics and phylogenetic position of Treponema medium.

Umemoto et al. (1997, Int J Syst Bacteriol 47, pp. 67-72) proposed spirochete strain G7201, isolated from the periodontal pocket of an adult patient, as a new species, Treponema medium. They deposited this strain in the American Type Culture Collection (ATCC) as type strain ATCC 700293T. Recently, ATCC suggested that there is a discrepancy between the previous report and the results obtained by ATCC in biochemical tests on T. medium ATCC 700293T. In this study, we re-examined and verified the biochemical characteristics of T. medium. The fermentation pattern of carbohydrates of T. medium resembled that of Treponema vincentii and Treponema denticola, but T. medium was clearly differentiated from T. vincentii in the production of indole, and from T. denticola in the hydrolysis of esculin. Also, sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) protein profile analysis and phylogenetic comparison of 16S rDNA sequences revealed that T. medium is clearly differentiated from any established treponemal species, which supports the validity of the proposal of Treponema medium as a new species.

[DeBakey IIIb type dissecting aneurysm with adrenal myelolipoma; report of a case].

We report a case of DeBakey IIIb type dissecting aneurysm with adrenal myelo-lipoma in a 50-year-old woman. The patient was referred to our hospital for severe back pain with severe hypertension. The chest computed tomography (CT) scans and aortography showed the DeBakey IIIb type dissecting aneurysm. And the round-shaped masses on her both side adrenal glands were detected by abdominal CT scans. First, the thoracic aneurysm was replaced with a 26 mm woven dacron graft under cardiopulmonary bypass. Six months later a right adrenal tumor was removed under a postero lateral approach. Her postoperative course was uneventful. And her blood pressure control was good with no antihypertensive drug. Pathological findings for the resected tumor was diagnosed as myelolipoma. To our knowledge, a dissecting aneurysm with adrenal myelolipoma has not been previously reported.

[Aneurysm of the diverticulum of the ductus arteriosus in the adult with left pneumonectomy; report of a case].

A 51-year-old man with dyspnea was admitted to our hospital. Chest computed tomography (CT) scan and aortogram indicated a diagnosis of aneurysm of diverticulum of the ductus arteriosus. Aneurysm of the diverticulum of the ductus arteriosus in the adult is rare. To our knowledge, 34 cases have been reported in the Japanese literature. Operation was performed through standard left postero-lateral thoracotomy. Initially left pneumonectomy was performed because of severe left lung collapse. And subsequently graft replacement of distal aortic arch was performed with hypothermic retrograde cerebral perfusion. The aneurysmal wall directly penetrated into the trachea with occluded orifice by thrombus. The penetrating wall of the trachea was closed by mattress suture with pericardial pledget. And an omental graft was placed. Five weeks after surgery, high fever and pus discharge from the wound of the thoracotomy developed. The debridement of the thoracic cavity was performed, and the cavity was intermittently irrigated with an electrolyzed strong acid solution. The infection successfully subsided gradually and the patient has been well for 9 months after the initial surgery.

Chemotaxis of oral treponemes toward sera and albumin of rabbit.

The motility and chemotaxis of human oral spirochetes Treponema denticola ATCC 35404, T. medium ATCC 700293, and T. vincentii ATCC 35580 were examined by a capillary assay method. Of five sera three human oral treponemes were dominantly chemoattractant to the rabbit serum. The checkerboard analysis of chemotaxis toward rabbit serum clearly showed that the motile T. denticola cells swam toward the culture media containing higher concentrations of the rabbit serum. T. denticola chemotaxis to the rabbit serum was clearly reduced by heating serum, and rabbit albumin contributed by 60 to 70% to its chemotaxis to the rabbit serum. Western blotting analysis demonstrated that these treponemes possessed rabbit albumin-binding polypeptides with approximate molecular sizes of 65 kDa and 70 kDa. Immunoelectron microscopy demonstrated that a 65 kDa rabbit albumin-binding polypeptide was located on the outer envelopes, suggesting that the rabbit albumin-binding polypeptide is responsible for chemotaxis toward rabbit serum.

Rapid repair of titanium particle-induced osteolysis is dramatically reduced in aged mice.

Aseptic loosening is the most common cause of orthopaedic implant failure. This process is thought to be due to osteolysis induced by implant-derived wear particles. Teitelbaum and colleagues have recently developed a promising murine calvarial model of wear particle-induced osteolysis. However, prior to this study, this model had only been assessed qualitatively. We now report a reproducible, quantitative version of the calvarial model of wear particle-induced osteolysis, in which the extent of osteolysis (and repair) of entire parietal bones is assessed by histomorphometry of contact microradiographs. Using this model, we found that the osteolytic response is transient and rapidly repaired in one month old mice. The extent of osteolysis peaks 7 days after particle implantation and returns to baseline levels by 13 days. A similar amount of osteolysis and even more extensive repair is observed when particles are implanted repeatedly. In contrast, aged mice develop progressive osteolysis with no detectable repair. As a result, 26 month old mice have approximately 17-fold more osteolysis than one month old mice 21 days after particle implantation. Skeletally mature, adult mice (4-16 months old) show an intermediate pattern of response. Osteolysis in these mice peaks at 7 days after particle implantation but it is repaired more slowly than in the one month old mice. Taken together, these results underscore the role of an imbalance between bone resorption and bone formation in the development of aseptic loosening and suggest that agents that stimulate bone formation maybe useful in prevention or treatment of aseptic loosening.

[Case of thoracoabdominal aortic aneurysm complicated with Buerger's disease].

We report a rare case of 65-year-old man who developed thoracoabdominal aortic aneurysm of Crawford type III complicated with Buerger's disease. He was admitted to our hospital with chief complaints of upper abdominal and back pain. CT showed that the aneurysm extended from the descending thoracic aorta to the aortic bifurcation and its had a maximum width of 95 mm. Angiogram (IA-DSA) revealed that both popliteal arteries were occluded slightly above the level of the knee joint, although collateral vessels were visualized. He underwent preliminary graft replacement of the abdominal aorta with the end-to-side supplemental branch for cannulation. Subsequently we performed graft replacement of the thoracoabdominal aorta with reconstruction of the celiac and superior mesenteric arteries and intercostal arteries on under partial cardiopulmonary bypass. This supplemental branch of abdominal aortic graft was useful in preventing ipsilateral leg ischemia. During the reconstruction of the major visceral branches, the branches were perfused selectively via partial extracorporeal circulation. Post operative courses were uneventful without paraplegia and leg ischemia. Angiographic examination revealed excellent hemodynamic results.

Soft tissue cephalometric norms in Japanese adults.

Lateral soft tissue cephalometric standards of Japanese normal adults were developed with the use of Ricketts, Epker, Holdaway, and Legan cephalometric analyses. Cephalometric radiographs of 211 Japanese normal adults were analyzed, and the soft tissue measurements were compared with those of an esthetically pleasant Japanese subgroup and white adult sample. Statistically significant differences were found in the Japanese sample when compared with the white norms. On the other hand, the soft tissue mean values of the Japanese supernormal group were similar to the white norms, with the exception of the nasolabial angle and the lip prominence. Soft tissue cephalometric norms are specific for ethnic groups, but these values should not be interpreted as treatment goals. Normative data represent an aid for the diagnosis and planning of orthodontic treatment and orthognathic surgery.

Immunobiological activities of a chemically synthesized lipid A of Porphyromonas gingivalis.

A synthetic lipid A of Porphyromonas gingivalis strain 381 (compound PG-381), which is similar to its natural lipid A, demonstrated no or very low endotoxic activities as compared to Escherichia coli-type synthetic lipid A (compound 506). On the other hand, compound PG-381 had stronger hemagglutinating activities on rabbit erythrocytes than compound 506. Compound PG-381 also induced mitogenic responses in spleen cells from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, as well as LPS-responsive C3H/HeN mice. The addition of polymyxin B resulted in the inhibition of mitogenic activities, however, compound 506 did not show these capacities. Additionally, compound PG-381 showed a lower level of activity in inducing cytokine production in peritoneal macrophages and gingival fibroblasts from C3H/HeN mice, but not C3H/HeJ mice, in comparison to compound 506. Thus, this study demonstrates that the chemical synthesis of lipid A, mimicking the natural lipid A portion of LPS from P. gingivalis, confirms its low endotoxic potency and immunobiological activity.

The effects of processing and low dose irradiation on cortical bone grafts.

The authors studied the effects of standard processing and preprocessing low dose gamma irradiation (1.5 Mrad) on the strength and incorporation of syngeneic and allogeneic cortical bone grafts. Bilateral femoral middiaphyseal 8-mm segmental defects in 120 male Fisher rats were stabilized with internal fixation. Each defect received one of six types of grafts: fresh syngeneic, processed syngeneic, irradiated processed syngeneic, fresh allogeneic, processed allogeneic, and irradiated processed allogeneic grafts. Graft processing included soaking in 70% ethanol and deep freezing for preservation. Irradiation was performed by 60Co source immediately before processing. Grafts were evaluated by histologic analysis, histomorphometric analysis, and biomechanical testing at 4 and 6 months after surgery. Graft treatment, either processing or irradiation processing, did not affect consistently or significantly the incorporation of syngeneic or allogeneic grafts. Graft allogenicity was the major determinant of the revascularization and the histologic pattern of graft incorporation. Processed and irradiated processed allogeneic grafts gained compressive strength with time and were as strong as syngeneic grafts at 6 months. Biomechanical and histologic data from this study suggest that standard processing and preprocessing low dose irradiation do not compromise the natural course of allogeneic cortical bone graft incorporation.

Prevention of endotoxin-induced lethality in mice by calmodulin kinase activator.

Porphyromonas gingivalis strain 381 lipid A showed lower activity in inducing interleukin (IL)-1alpha and IL-1beta production and cytokine mRNA expression than synthetic Escherichia coli lipid A (compound 506) in alveolar macrophages of C57BL/6 mice. Both the lipid As induced tumor necrosis factor alpha in alveolar macrophages and IL-6 in peritoneal macrophages. A calmodulin (CaM) antagonist, W-7, inhibited IL-1beta production and its mRNA expression induced by P. gingivalis lipid A but not compound 506 in alveolar macrophages. A CaM kinase activator reduced the induction of IL-1beta in the serum of mice when administered with compound 506, and protected the mice against the lethal toxicity. The modulation of a variety of intracellular enzymes including the CaM kinase may result in clinical control of endotoxic sepsis.

The bone-implant interface: a dynamic surface.

This study quantifies and compares bone formation on and around roughened titanium implants with roughened cobalt chromium, polished solid implants, and titanium fibermetal implants. Cylindrical rods were implanted into the medullary canal of the distal femur of rabbits. The bone-implant interface was studied 3, 6, and 12 weeks after surgery using histomorphometric methods. Roughened surface implants demonstrated significantly more bone directly apposed to the surfaces when compared to the polished or fiber/metal implants at 6 and 12 weeks after surgery. New bone formation and remodeling of bone occurred directly on roughened surfaces as late as 12 weeks after implantation, but not on the unroughened implants. These results suggest that roughening of the surfaces of both titanium and cobalt chromium implants can enhance osseointegration and may be useful clinically for the fixation of prosthetic components.

[Two cases of coronary artery bypass grafting associated with antiphospholipid syndrome in systemic lupus erythematosus].

We report two cases of coronary artery bypass grafting (CABG) associated with antiphospholipid syndrome (APS) in systemic lupus erythematosus (SLE). Patient 1, 65-year-old female, who had been treated for SLE with prednisolone for 11 years was transferred to our hospital due to unstable angina caused by stenosis of the left main trunk (LMT) and the left anterior descending artery (LAD). She underwent emergency CABG of the LAD using left internal thoracic artery (LITA). Post operative doppler study demonstrated patent LITA to the LAD. Patient 2, 67-year-old female who had been treated for SLE with prednisolone for 8 years was transferred to our hospital due to acute myocardial infarction caused by stenosis of the LMT and the left circumflex artery (LCX). She underwent emergency CABG of the LAD and the LCX using saphenous vein grafts (SVGs). Post operative angiography confirmed a patent SVG to the LAD and an occuluded SVG to the LCX. In cases of SLE, the frequency of occurrences of ischemic heart diseases is high. Until now, however, there are few instances reported on performing CABG for patients with SLE. We are reporting here our particular cases of APS with SLE, discussing the involvement of APS as causative factor of ischemic heart diseases and related issue of surgical and post surgical antithrombotic treatments.

Osseointegration of surface-blasted implants made of titanium alloy and cobalt-chromium alloy in a rabbit intramedullary model.

The purpose of this study was to compare the osseointegration of surface-blasted Ti6A14V and CoCr implants in vivo. Ti6A14V and CoCr rods blasted with 710 microm A12O3 particles were bilaterally press-fit into the medullary space of distal femora of 24 rabbits. Evaluation was made radiographically, histologically, histomorphometrically (3, 6, and 12 weeks after implantation), and mechanically (12 weeks). Both Ti6A14V and CoCr implants demonstrated good biocompatibility radiographically and histologically. Toluidine blue-stained sections revealed an osteoconductive effect of the blasted surface, and fluorochrome labeling analysis showed active bone formation at the bone-implant interface at as late as 12 weeks for both specimens. CoCr showed significantly lower interfacial shear strength than Ti6A14V although the bone contact area with the implant surface was comparable and no intervening soft tissue at the bone-implant interface could be seen for either implant by scanning electron microscopy backscatter analysis. Unmineralized tissue (cartilage and osteoid) was observed more frequently on the CoCr surface than on the Ti6A14V surface. These data show less osseointegration of CoCr implants with this blasted surface for this short period, possibly due to a slight difference in surface roughness and some negative effects of CoCr on bone attachment.

Cephalometric norms in Japanese adults.

PURPOSE: Knowledge of the normal dentofacial patterns of adults belonging to various ethnic and age groups is important for clinical and research purposes. Lateral cephalometric standards of normal Japanese adults were developed using the Burstone and Legan comprehensive cephalometric analyses that are specific for orthognathic surgery. PATIENTS AND METHODS: Cephalometric radiographs of 217 Japanese adults were analyzed, and the mean values of their hard and soft tissue measurements were compared with those of white American adults. RESULTS: Statistically significant differences were found in the Japanese sample, who had a shorter maxilla, larger upper anterior face height, and lower posterior dental height than Burstone's white sample. A less prominent chin was observed in the Japanese male group. Soft tissue analysis of the Japanese subjects showed a retrognathic maxilla and mandible in relation to the soft tissue glabella and bilabial protrusion when compared with the white adult standards. CONCLUSION: Lateral cephalometric norms are specific for the racial group, but these values should not be interpreted as treatment goals. Normative data represents an aid for the diagnosis and treatment planning of orthognathic surgery according to the needs and expectations of each individual patient.