Successful reimplantation surgery after extraction of well-fixed cementless stems by femoral longitudinal split procedure.

BACKGROUND: Well-fixed cementless stems sometimes need to be extracted in patients with complications including periprosthetic infection, stem-neck breakage, or trunnionosis. The purpose of this study was to report the clinical outcome in patients undergoing reimplantation surgery after removal of a well-fixed porous-coated cementless stem by the femoral longitudinal split (FLS) procedure. METHODS: We conducted a retrospective study and radiographic review of 16 patients who had undergone reimplantation following the FLS procedure to remove a well-fixed stem due to periprosthetic infection, stem-neck breakage, or trunnionosis. The study group consisted of 2 men and 14 women with an average age of 68.4 years. Mean follow-up was 44.6 months. The Kaplan-Meier method was used to evaluate the longevity of the stem. RESULTS: The average operation time was 272 ± 63 minutes and intraoperative bleeding was 420 ± 170 mL. Although postoperative dislocation occurred in 5 hips and subsidence of the stem was found in 2 hips after surgery, no progressive subsidence was observed and the clinical JOA and JHEQ scores were both improved after reimplantation surgery. Reimplantation surgery with Zweymüller-type stems revealed evidence of osseointegration of the stem without femoral fracture. Kaplan-Meier survival analysis of stem revision for any reason as the end point revealed 70.0% survival at 9 years. CONCLUSIONS: In this study, we experienced some complications in patients with trunnionosis or periprosthetic infections. However, the FLS procedure is expected to confer successful clinical results without loosening of the reimplanted cementless stem, after safe extraction of well-fixed porous-coated cementless stems without fracture.

The proton pump inhibitor, lansoprazole, prevents the development of non-traumatic osteonecrosis of the femoral head: an experimental and prospective clinical trial.

BACKGROUND: An effective prevention strategy for osteonecrosis of the femoral head (ONFH) has yet to be established. We previously reported that the innate immune system via the toll-like receptor (TLR) response induced by corticosteroids leads to the development of ONFH and that repression of IRF7 activity by an inhibitor could interfere with the development of ONFH while maintaining the therapeutic effect of the corticosteroids. OBJECTIVE: In the present study, we hypothesize that lansoprazole has the potential to suppress IRF7 activity and prevent corticosteroid-induced ONFH in rats. Furthermore, we conducted a preliminary clinical trial to prevent corticosteroid-induced ONFH in autoimmune disease patients. METHODS: Male Wistar rats were randomly divided into four groups. On Day 1, each rat was injected with TLR4 ligand (LPS) or TLR7 ligand (imiquimod), followed by methylprednisolone with or without lansoprazole on Day 2. They were killed at 1 or 14 days after the last injection.We prospectively recruited 30 patients requiring primary high-dose corticosteroid treatment for immune diseases. All patients were administered lansoprazole, starting the night before corticosteroid treatment began. MRI was performed before corticosteroid treatment, and at 4, 12 and 24 weeks afterward. RESULTS: In rats, co-treatment of lansoprazole with corticosteroids significantly repressed both IRF7 activity and the development of ONFH. Moreover, in the human patients, the incidence of ONFH was significantly decreased from 53.4 to 13.3%. CONCLUSIONS: Although the present study is preliminary, the results show that co-treatment of lansoprazole with corticosteroids prevents ONFH development. Lansoprazole may be both safe and effective in preventing osteonecrosis of the femoral head in patients needing corticosteroid treatment.

Restoration of proximal periprosthetic bone loss by denosumab in cementless total hip arthroplasty.

Denosumab contributed to the restoration of proximal periprosthetic bone loss around the femoral stem that were measured using a DEXA, especially in zone 7, at 1 year after cementless THA in elderly osteoporotic patients. INTRODUCTION: Although bone quality is an important issue in elderly osteoporotic patients who underwent total hip arthroplasty (THA) with a cementless stem, periprosthetic bone mineral density (BMD) in the proximal femur has been reported to be decreased by 15-40% postoperatively. Some authors have examined the use of several types of bisphosphonates to prevent decreases in BMD in the proximal femur after cementless THA; however, few reports have demonstrated success in restoring BMD in the proximal medial femoral bone, such as zone 7. METHODS: We conducted prospective study comparing patients who underwent cementless THA administered with denosumab (10 patients) and without denosumab (10 patients). BMD around the femoral stem were measured using a DEXA immediately after surgery, and at 6 months and at 1 year after surgery. No difference was found between the two groups referred to the patient's demographic data. RESULTS: We found that denosumab displayed definitive effects in increasing the % change in periprosthetic BMD at zone 7 by an average of 7.3% in patients with cementless THA, compared to control group who were given only vitamin D. CONCLUSION: Denosumab is one of a number of anti-osteoporotic agents to have a definitive effect on the restoration of proximal periprosthetic bone loss, especially in zone 7, after cementless THA. Denosumab contributed to the restoration of decreased periprosthetic BMD to normal levels. As the decrease in BMD in the proximal femur after THA is considered to be apparent at 6-12 months after surgery, it is believed that prevention of the deterioration of bone quality is important in the proximal femur immediately after cementless THA for elderly female patients with osteoporosis.

Antagonists to TRPV1, ASICs and P2X have a potential role to prevent the triggering of regional bone metabolic disorder and pain-like behavior in tail-suspended mice.

Our recent studies demonstrated that regional bone loss in the unloaded hind limbs of tail-suspended mice triggered pain-like behaviors due to the acidic environment in the bone induced by osteoclast activation. The aims of the present study were to examine whether TRPV1, ASIC and P2X (known as nociceptors) are expressed in bone, and whether the antagonists to those receptors affect the expression of osteoblast and osteoclast regulators, and prevent the triggering of not only pain-like behaviors but also high bone turnover conditions in tail-suspension model mice. The hind limb-unloaded mice were subjected to tail suspension with the hind limbs elevated for 14days. The effects of the TRPV1, ASIC3, P2X2/3 antagonists on pain-like behaviors as assessed by the von Frey test, paw flick test and spontaneous pain scale; the expressions of TRPV1, ASICs, and P2X2 in the bone; and the effects of those antagonists on osteoblast and osteoclast regulators were examined. In addition, we evaluated the preventive effect of continuous treatment with a TRPV1 antagonist on the trigger for pain-like behavior and bone loss in tail-suspended mice. Pain-like behaviors were significantly improved by the treatment with TRPV1, ASIC, P2X antagonists; TRPV1, ASICs and P2X were expressed in the bone tissues; and the antagonists to these receptors down-regulated the expression of osteoblast and osteoclast regulators in tail-suspended mice. In addition, continuous treatment with a TRPV1 antagonist during tail-suspension prevented the induction of pain-like behaviors and regional bone loss in the unloaded hind limbs. We, therefore, believe that those receptor antagonists have a potential role in preventing the triggering of skeletal pain with associated regional bone metabolic disorder.

Teriparatide rapidly improves pain-like behavior in ovariectomized mice in association with the downregulation of inflammatory cytokine expression.

Recent studies have indicated that teriparatide, an anti-osteoporosis agent, significantly improves back pain regardless of the presence of vertebral fracture in osteoporosis patients. The aims of this study were to examine whether teriparatide improves pain-like behavior in an ovariectomized (OVX) mouse model, and to evaluate changes in osteoclast marker levels and inflammatory cytokine expression levels induced by teriparatide treatment in bone tissue in association with improvements in pain-like behavior. OVX and sham operations were performed in 8-week-old mice, followed by teriparatide treatment for 2 weeks. Pain-like behavior tests (von Frey, paw flick and spontaneous pain test), and the measurement of serum tartrate-resistant acid phosphatase 5b (TRAP5b) level and inflammatory cytokine (interleukin [IL]-1ß, IL-6 and tumor necrosis factor [TNF]-α) expression levels in the bone tissue were conducted after teriparatide treatment in OVX mice. Pain-like behavior in the von Frey test was significantly improved by teriparatide treatment in OVX mice. With regard to the early phase (within the first 7 days of treatment), teriparatide significantly improved pain-like behavior in the von Frey test, the paw flick test and the spontaneous pain test. Teriparatide significantly inhibited the expression of IL-1ß, IL-6 and TNF-α in OVX mice in the early phase of the treatment, while the TRAP5b level in OVX mice was not significantly affected. We demonstrated that the teriparatide-induced rapid improvement effect on pain-like behavior in OVX mice was associated with the downregulation of inflammatory cytokine expression, including IL-1ß, IL-6 and TNF-α.

Regional osteoporosis due to osteoclast activation as a trigger for the pain-like behaviors in tail-suspended mice.

Pathological conditions with refractory skeletal pain are often characterized by regional osteoporotic changes such as transient osteoporosis of the hip, regional migratory osteoporosis, or complex regional pain syndrome (CRPS). Our previous study demonstrated that the acidic microenvironment created by osteoclast activation under high bone turnover conditions induced pain-like behaviors in ovariectomized mice through the stimulation of acid-sensing nociceptors. The aim of the present study was to examine whether regional transient osteoporotic changes are related to pain-like behaviors in the hind limb using tail-suspended model mice. The hind limbs of tail-suspended mice were unloaded for 2 weeks, during which time the mice revealed significant regional osteoporotic changes in their hind limbs accompanied by osteoclast activation. In addition, these changes were significantly recovered by the resumption of weight bearing on the hind limbs for 4 weeks. Consistent with the pathological changes in the hind limbs, pain-like behaviors in the mice were induced by tail suspension and recovered by the resumption of weight bearing. Moreover, treatment with bisphosphonate significantly prevented the triggering of the regional osteoporosis and pain-like behaviors, and antagonists of the acid-sensing nociceptors, such as transient receptor potential channel vanilloid subfamily member 1 and acid-sensing ion channels, significantly improved the pain-like behaviors in the tail-suspended mice. We, therefore, believe that regional transient osteoporosis due to osteoclast activation might be a trigger for the pain-like behaviors in tail-suspended model mice. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1226-1236, 2017.

Susceptibility of Males, but Not Females to Developing Femoral Head Osteonecrosis in Response to Alcohol Consumption.

BACKGROUND: We previously reported that ethanol-containing liquid diet feeding induces osteonecrosis of the femoral head in male rats. Also, it was reported that a large amount of consumed ethanol and a long-term history of drinking were risk factors for osteonecrosis of the femoral head, and that the frequency of alcohol-induced osteonecrosis of the femoral head in males was much greater than in females. The higher incidence of alcohol-induced osteonecrosis of the femoral head could be due to either higher prevalence of alcohol drinking in males or due to their potential higher sensitivity to alcohol. The aim of the study is to investigate the influence of alcohol consumption and drinking period on the development of osteonecrosis of the femoral head in rats of both sex. METHODS: All the experimental male rats were allocated to the male one-month ethanol drinking group (M1). Female rats were randomly divided into the female one- to five-months ethanol drinking groups (F1-5). All rats were fed a Lieber-DeCarli liquid diet containing 5% ethanol for one to five months. RESULTS: One-month feeding with the ethanol-containing liquid diet resulted in the development of osteonecrosis of the femoral head in seven of twenty in the M1 group, but none in the F1 group, although the mean intake of ethanol per body weight in the M1 group was significantly lower than that in the F1 group. Furthermore, long drinking periods with a large amount of ethanol intake in the F2-5 groups did not induce osteonecrosis of the femoral head. CONCLUSION: The present study shows that lower alcohol consumption over short periods of time that were sufficient to induce osteonecrosis of the femoral head in males had no effect on females. Even with greater alcohol consumption and longer duration, females did not develop osteonecrosis of the femoral head. Therefore, unknown factors related to sex must be responsible for the development of this condition.

Time-related change evaluation of the cerebrospinal fluid using postmortem CT.

PURPOSE: We retrospectively evaluated the cerebro-spinal fluid (CSF) CT density at the lateral ventricle to compare the postmortem intervals in cadavers. MATERIALS AND METHODS: The number of cadavers enrolled in this study was 189 (male 120, female 69). According to the estimated postmortem time, the cadavers were divided into 13 groups (postmortem day 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 7, 10, 14, 21, 30), and were also re-grouped into 3 groups according to the postmortem time-width: group A (postmortem day 0.5-2.5), group B (day 3-7), and group C (day 10-30). Comparisons between the CSF density and estimated postmortem time were also analyzed. RESULTS: The CSF density was around 20HU up to day 2.5, and it increased gradually after day 3. Day 3 and 4 presented higher CSF density than day 1 and 1.5 (p<0.05). Day 7 presented higher CSF density than day 3 (p<0.05). According to the postmortem time-width, the CSF density increased with postmortem time (p<0.05). The simple linear regression equations presented negative correlation between CSF density and estimated postmortem time, and R(2) was 0.119. CONCLUSION: The CSF density increased, but not linearly, according to the postmortem time, and the 3rd postmortem day was the earliest time allowing the difference to be detected. The CSF density needs further evaluation to enable estimation of the postmortem time.

Experimental drowning lung images on postmortem CT - Difference between sea water and fresh water.

PURPOSE: Experimental drowning models were prepared to investigate the time-related course of lung changes using postmortem CT. This study was approved by our institutional animal ethics committee. MATERIALS AND METHODS: Fifteen NZW rabbits (female fifteen, 2.6-4.3 (mean 3.3)kg) were divided into 3 groups: fresh water drowning (FRESH), sea water drowning (SEA), and sea water drowning with anterior chest compression (ACC). All individuals were examined by CT (Aquilion CX, Toshiba, Japan) on postmortem time course. The rabbit's head was submerged in a water bath for a total of 10 min. In ACC, cardiopulmonary resuscitation was performed for 2 min, additionally. The percentage of aerated lung volumes (%ALV=100 (aerated lung volume/total lung volume)) were statistically evaluated and the lung CT image patterns and pleural fluid appearance time were investigated. RESULTS: All lungs had decreased their %ALV within 24h, and there were no statistical differences in and among the 3 groups. After 36 h, %ALV tended to increase in all groups, and only ACC presented a statistical difference between 1h and 36 h (p<0.005). On postmortem lung CT, all lungs presented ground-glass opacity with interstitial thickening spread pattern (100%) and no pattern change during the follow-up period. After presenting pleural space fluid collection, the %ALV tended to increase. CONCLUSION: There were no differences among FRESH, SEA, and ACC in %ALV within 24h. Only ground-glass opacity could be detected on postmortem lung CT, experimentally.

Freezing effect on brain density in postmortem CT.

Two 60-year-old males were found at their homes whose bodies had deteriorated due to putrefaction. To prevent worm invasion and minimize deterioration, dry ice was used prior to the autopsy investigation. Prior to autopsy, postmortem CT demonstrated a decreased density in brain parenchyma at the dry-iced side, and autopsy revealed deteriorated brain parenchyma with frozen effect (presented like sherbet). Moreover, the deteriorated cerebral parenchyma maintained their structure and they were evaluated by cutting. When lower CT density presents in postmortem CT, the freezing effect may need to be considered and the physician should evaluate the cadaver's postmortem condition to prevent misdiagnoses.

TLR4 stimulation and corticosteroid interactively induce osteonecrosis of the femoral head in rat.

We previously reported that a toll-like receptor 4 signaling contributes to the development of osteonecrosis of the femoral head. Also, oxidative stress is suggested to be one of the possible pathogenesis of osteonecrosis of the femoral head. A recent study showed that toll-like receptor 4 signaling leads to oxidative stress. The aim of the present study was to evaluate whether toll-like receptor 4 stimulation and subsequent corticosteroid treatment lead to the development of osteonecrosis of the femoral head in rat, and oxidative stress is associated with it. Male Wistar rats were randomly divided into four treatment groups: Saline + Saline, Saline + Methylprednisolone, Lipopolysaccharide + Saline, Lipopolysaccharide + Methylprednisolone. Osteonecrosis of the femoral head at 14 days after the treatment was observed in 1 of 10 Lipopolysaccharide + Saline, and 5 of 10 Lipopolysaccharide + Methylprednisolone treated rats. However, it was not observed at all in the Saline + Saline and Saline + Methylprednisolone treated groups. Glutathione peroxidase activity in the liver at 1 day after the treatment was significantly increased when treated with lipopolysaccharide. However, methylprednisolone treatment reduced the activity. On the other hand, glutathione peroxidase activity in the femur did not change in any intergroup. In conclusion, the present study showed that toll-like receptor 4 stimulation by lipopolysaccharide administration strengthen incidence of corticosteroid-induced osteonecrosis of the femoral head, however, concomitant oxidative stress via toll-like receptor 4 signaling may not contribute to the development of osteonecrosis of the femoral head in rats.

Acid-sensing ion channel 3 or P2X2/3 is involved in the pain-like behavior under a high bone turnover state in ovariectomized mice.

We have recently demonstrated that pathological changes leading to increased bone resorption by osteoclast activation are related to the induction of pain-like behavior in ovariectomized (OVX) mice. In addition, bisphosphonate and the antagonist of transient receptor potential vanilloid type 1 (TRPV1), an acid-sensing nociceptor, improved the threshold value of pain-like behaviors accompanying an improvement in the acidic environment in the bone tissue based on osteoclast inactivation. The aim of this study was to evaluate the effect of (i) an inhibitor of vacuolar H(+) -ATPase, known as an proton pump, (ii) an antagonist of acid-sensing ion channel (ASIC) 3, as another acid-sensing nociceptor, and (iii) the P2X2/3 receptor, as an ATP-ligand nociceptor, on pain-like behavior in OVX mice. This inhibitor and antagonists were found to improve the threshold value of pain-like behavior in OVX mice. These results indicated that the skeletal pain accompanying osteoporosis is possibly associated with the acidic microenvironment and increased ATP level caused by osteoclast activation under a high bone turnover state.

Postmortem computed tomography findings in the thorax - Experimental evaluation.

OBJECTIVE: Experimental fatal models were prepared to investigate the time-related course of lung changes using postmortem CT (PMCT). This study was approved by our institutional animal ethics committee. MATERIALS AND METHODS: Twenty-four NZW rabbits (female 24, 2.30-4.30 (mean 3.10)kg) were divided into 4 fatal groups; drowning, hypothermia, bag suffocation, and Potassium Chloride intravenous (control) group. All individuals were examined by CT (Aquilion CX, Toshiba, Japan) on postmortem time course until detection of putrefaction air. The percent of aerated lung volume (%ALV=100*(ALV/total lung volume)) was measured and the pleural space fluid was investigated by axial imaging. A paired t-test and Bonferroni/Dunn study were employed for statistical evaluation. RESULTS: In intra-group analysis, the %ALV showed statistically different periods compared with each pre-image: 4-48 h in control, 1-24h in drowning, 5-6h in hypothermia, and 1-4h in bag suffocation. In inter-group comparison (compared with control group), the %ALV increased in suffocation and decreased in drowning within 12h. The %ALV remained significantly high in hypothermia until 24h. The earliest detection times of pleural space fluid collection were different in each group: control (20 h), drowning (18 h), suffocation (36 h), and hypothermia (95 h). CONCLUSION: The lung hypostasis and the appearance of pleural space fluid collection presented differently in individual causes of death and depending on the postmortem time.

Extraction of well-fixed extended porous-coated cementless stems using a femoral longitudinal split procedure.

We present a technique of posterior femoral longitudinal split (FLS) osteotomy. This technique allows the expansion of the metaphyseal-diaphyseal region of the proximal femur facilitating extraction of well-fixed extended porous-coated stems. The extractions were performed using extended transfemoral osteotomy (ETO) and FLS osteotomy between June 2002 and March 2014. The study group, which comprised patients with well-fixed extended porous-coated stems, consisted of two men and ten women with an average age of 63.2 years. The stem was successfully removed using the FLS procedure in 8 of the 10 hips. Reimplantation surgery was performed in 6 of the 12 hips with ARMD, periprosthetic infection, or metallosis. This FLS technique may allow the easy removal of well-fixed extended porous-coated stems and become an alternative method for the removal of all stems.

Classification of hemopericardium on postmortem CT.

Postmortem CT (PMCT) is increasingly used in forensic practice, and knowledge and classification of typical hemopericardium on PMCT would help to assure correct radiological interpretation. The goal of this study was to evaluate the pericardial and pleural space fluid volumetry, and to evaluate the signs on PMCT pointing to cardiac tamponade as the cause of death, and their pitfalls. Fourteen cadavers (eleven male, three female, 49-87 [mean, 70.9] years) were examined by PMCT. The pericardial volume and pericardial findings with/without pleural space fluid collection were compared with autopsy findings. In addition, the appearance of pericardial lesions on PMCT was documented and compared with the autopsy findings. The respective volumes of pericardial space, and right and left pleural space fluid showed as 172.0-711.0 (mean 368.7) ml, 0-1830.0 (266.1) ml, 0-231.0 (75.2) ml on PMCT, and were 136.0-652.0 (311.1) ml, 0-2100 (299.0) ml, and 0-300.0 (61.3) ml on autopsy. In statistical evaluation, the pericardial space volume was significantly greater on PMCT (p<0.05), but there was no significant difference in pleural space fluid volume. The hemopericardium PMCT showed 3 patterns: double band, single band, and horizontal level, and the former two patterns presented as coagulated blood at autopsy. Single band and horizontal level patterns were thought to result from CPR-related causes and/or postmortem manipulation. In conclusion, double and single band patterns on PMCT were indicative findings of cardiac tamponade. An understanding of the pericardial PMCT appearance and its significance can help to avoid misreading, and is important for making correct radiological interpretation.

Time-related course of pleural space fluid collection and pulmonary aeration on postmortem computed tomography (PMCT).

Postmortem CT (PMCT) is increasingly used in forensic practice, and knowledge and classification of typical postmortem imaging findings would facilitate the interpretation of PMCT. The goal of this study was to define the time-related course of postmortem chest findings. Twelve cadavers (eight male, four female, 27-81 [mean, 60.0]years) were examined twice by PMCT within an interval of time (4-164 h [mean, 30.8; median, 17.5]). The pleural-space-fluid volume, pulmonary parenchyma volume, decreased aerated lung volume (DLV), %DLV (=DLV/pulmonary parenchyma volume) and chest cavity volume were compared between the first and second PMCT examinations. To evaluate the volume change rate, the rate of increase in pleural space fluid volume (mL/h) and the DLV rate (mL/h) were plotted according to the postmortem period. On the second PMCT, the volume of pleural space fluid (p=0.0469) and %DLV (p=0.0161) were significantly increased. The increase rate of the pleural space fluid increased at approximately 30 h and the volume continued to increase until approximately 40 h after death. The rate of DLV constantly decreased in the early postmortem period. In conclusion, the pleural-space-fluid collection and the DLV increased over different time-related courses in the postmortem period.

Acute enlargement of subdural hygroma due to subdural hemorrhage in a victim of child abuse.

An 11-month-old female baby was found dead by her mother. Cranial postmortem CT prior to the forensic autopsy showed dilatation of bilateral extra-axial spaces and ventricles. The autopsy revealed a new linear fracture of the left parietal bone and occipital bone, and a healed linear fracture of the right parietal bone and occipital bone like a mirror image of the left one as well. Intracranially, 230ml of subdural fluid were collected, which was mixed with blood. There was a fresh hemorrhage around a bridging vein of the left parietal lobe and the dura mater. Moreover, the outer side of the cerebrum and the inner side of the dura mater were covered by a thin membrane, which mater might have been previously formed because of being positive for Fe-staining and anti-CD68 antibody. A subdural hematoma might have been developed when the right side of the skull was previously fractured, which was transformed into a subdural hygroma. Subsequently, it is likely that, after the left side fracture of the skull occurred, the subdural hygroma rapidly enlarged due to hemorrhaging from the bridging vein, which resulted in intracranial hypertension, because microbleeding was detected in the brain stem. Accordingly, we diagnosed the cause and manner of death as intracranial hypertension due to subdural hemorrhage in subdural hygroma, and homicide, including child abuse, respectively.

CT-guided percutaneous needle placement in forensic medicine.

We have developed a technique of CT-guided needle placement in the destructed human body in forensic practice. A sixty-year-old male was found in a burned car and he was also destructed severely. Although blood was needed for the external examination, it was difficult to approach the vessels because of the severely burned condition of the cadaver. Thus, we attempted to obtain a blood sample from a vessel using a CT-guided technique. Postmortem CT demonstrated the presence of blood-containing vessels in the pelvis. Indeed, CT-guided needle placement had no difficulty with surface markers, table location, or depth measurement from the surface. CT-guide needle placement is a feasible and reliable technique, so that when the tissue/blood sample is at risk of being spoiled, CT-guided needle placement could be a substitute for conventional sampling techniques.

Development of non-traumatic osteonecrosis of the femoral head requires toll-like receptor 7 and 9 stimulations and is boosted by repression on nuclear factor kappa B in rats.

Non-traumatic osteonecrosis of the femoral head (ONFH) often occurs after corticosteroid therapy in patients with inflammatory diseases. Recent studies suggest that toll-like receptor (TLR) signaling may contribute to the pathogenesis of inflammatory diseases, and that the reason for corticosteroid therapy for inflammatory diseases is related to the anti-inflammatory activities of corticosteroids through the reduction of NF-κB. We hypothesized that the administration of TLR ligands in combination with corticosteroid causes ONFH and that transcription factors may contribute to the pathogenesis of ONFH. The aim of the study was to evaluate (1) the incidence of ONFH in rats after the administration of TLR7 or TLR9 ligands together with methylprednisolone (MPSL) and (2) whether transcription factors contribute to the development of ONFH. Male Wistar rats (n=148) were divided into five groups as follows: Group 1: Saline+MPSL, Group 2: Imiquimod+Saline, Group 3: Imiquimod+MPSL, Group 4: CpG-C+MPSL, Group 5: Imiquimod+BAY11-7082+MPSL. As a result, ONFH was observed in 0 of 12 rats in Group 1, in 1 of 10 in Group 2, in 6 of 12 in Group 3, in 4 of 12 in Group 4, in 0 of 9 in Group 5. MPSL treatment did not significantly affect IRF7 activity, whereas NF-κB activity was significantly repressed in Group 2 and Group 3. Furthermore, the repression in interferon regulatory factor 7 (IRF7) activity by BAY11-7082 interfered with the development of ONFH simultaneously with the MPSL treatment-induced repression in NF-κB activity. In conclusion, in the present study, corticosteroid treatment after the administration of TLR7 or TLR9 ligands caused ONFH. Repression in NF-κB activity by corticosteroid treatment boosted the development of ONFH.

New pitfalls of high-density postmortem computed tomography.

An 80-year-old female was transferred to the hospital due to a traffic accident. Multiple cranial bone fractures with intracranial hemorrhage and intracranial air were detected. Despite treatment, the patient died after 6h. Twenty-one hours after the patient died, her whole body was scanned by postmortem CT, and a region of high density was detected within the left putamen. The autopsy revealed a cerebral contusion and multiple skull base fractures. Moreover, superabsorbent polymers (SAPs) were found within the left lateral ventricle and adjacent to the putamen, which appeared as a high-density lesion on postmortem CT at the left putamen, where the SAPs were compacted. Both ante- and postmortem conditions should be considered to prevent misdiagnoses based only on postmortem CT.