A case of emphysematous cystitis caused by mechanical stimulation of pelvic fracture nonunion.

Emphysematous cystitis is a rare condition that develops due to tissue hyperglycemia and urinary tract infection by gas-producing bacteria. We report a case of emphysematous cystitis caused by mechanical stimulation of a pelvic fracture nonunion. An 80-year-old man was injured in a motorcycle accident and diagnosed with pelvic fracture. Seven days later, he had high fever and computed tomography (CT) revealed gas in the hematoma around the pelvic fracture and the abscess. Therefore, infection following the pelvic fracture was diagnosed. Despite multiple operations and antibiotics treatment, malformation and nonunion of the pelvis occurred. One month after starting weight bearing, emphysema of the bladder wall adjacent to the pubic fracture were found and spread throughout the bladder wall. With stopping of weight bearing, antibiotics treatment and a urinary catheter, emphysema disappeared after 2 months. It was considered that the pubic fracture fragment irritated the bladder wall due to weight bearing and emphysematous cystitis consequently developed.

Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus.

Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas.

Ipsilateral Periprosthetic Fractures above and below the Knee Associated with Navigation Tracker Pin and Bone Fragility.

We report a case of ipsilateral periprosthetic fractures above and below the knee that occurred at different times due to navigation tracker pin and bone fragility. A 66-year-old Japanese woman with rheumatoid arthritis (RA) underwent a total knee arthroplasty. Four months post-surgery, a periprosthetic fracture above the knee at the navigation pin hole was detected. She underwent osteosynthesis and could walk independently, but she developed an ipsilateral tibial component fracture. Conservative treatment with a splint was followed by bone union. Patients with RA treated with oral steroids tend to develop ipsilateral periprosthetic fractures around the knee due to bone fragility.

Coronal shear fractures of the femoral neck: a comparison with basicervical fractures.

PURPOSE: We propose coronal shear fracture of the femoral neck (CSFF) as a new type of fracture that differs from a basicervical fracture. This study aimed to present the incidence of CSFF and compare its clinical characteristics and outcomes with those of basicervical fractures. METHODS: In this multicenter retrospective cohort study, 2207 patients with hip fractures were identified using computed tomography (CT), 17 and 27 patients were diagnosed with CSFF (CSFF group) and basicervical fractures (basicervical fracture group), respectively. The primary outcome was reoperation, while the secondary outcomes were postoperative radiographic findings, ambulatory ability, and 1-year mortality rate. These outcomes were compared between the two groups. We also conducted diagnostic reliability tests for these fractures using the Cohen's kappa coefficient. RESULTS: The incidence of CSFF and basicervical fractures in the 2207 patients were 0.77% and 1.22%, respectively. The inter-and intra-observer agreements for the diagnosis were almost perfect. The comorbidity score was significantly higher in the CSFF group than in the basicervical fracture group. No reoperations occurred in both groups. There were no significant intergroup differences in the postoperative radiographic findings. The 1-year mortality rate was higher in the CSFF group than in the basicervical fracture group (38.5% vs. 5.3%; odds ratio: 11.9, 95% CI: 1.2-118.5; p = 0.025). CONCLUSION: This study presents the definition and incidence of CSFF with a high diagnostic reliability. Patients with CSFF had similar reoperation rate postoperative radiographic outcomes to basicervical fractures, while 1-year mortality rate was high.

Late-onset implant-related neuropathy: Three years after proximal humeral fracture.

There are currently no reports of implant-related neuropathy associated with humeral proximal fracture surgery. Herein, we report a case of implant-related late-onset neuropathy that developed 3 years after proximal humeral fracture surgery. A 51-year-old man underwent minimally invasive plate osteosynthesis for a left proximal humeral fracture 3 years prior. Left upper limb pain and reduced angle of elevation of the shoulder were recognized 1 month before the outpatient consultation. Numbness was noted on the ulnar side of the hand, and radiating pain to the ulnar nerve region was noted during shoulder abduction and compression of the medial side of the upper arm. Computed tomography revealed close proximity of the neurovascular bundle to the locking screw along with muscle atrophy around the shoulder. Hence, the patient was diagnosed with neuropathy. After implant removal, the pain in the ulnar nerve region improved, and the upper arm could be elevated. In our case, the cause of muscle atrophy was axillary nerve manipulation and cervical myelopathy caused by the operation. When late-onset neuropathy occurs, implant-related neuropathy with muscle atrophy should be considered.

Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression.

BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and adolescents. The prognosis of chemotherapy-refractory OS patients is poor. We developed a tumor suppressor p53-expressing oncolytic adenovirus (OBP-702) that exhibits antitumor effects against human OS cells. Here, we demonstrate the chemosensitizing effect of OBP-702 in human OS cells. MATERIALS AND METHODS: The in vitro and in vivo antitumor activities of doxorubicin (DOX) and OBP-702 were assessed using parental and DOX-resistant OS cells (U2OS, MNNG/HOS) and a DOX-resistant MNNG/HOS xenograft tumor model. RESULTS: DOX-resistant OS cells exhibited high multidrug resistant 1 (MDR1) expression, which was suppressed by OBP-702 or MDR1 siRNA, resulting in enhanced DOX-induced apoptosis. Compared to monotherapy, OBP-702 and DOX combination therapy significantly suppressed tumor growth in the DOX-resistant MNNG/HOS xenograft tumor model. CONCLUSION: Our results suggest that MDR1 is an attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.

Oncolytic virotherapy promotes radiosensitivity in soft tissue sarcoma by suppressing anti-apoptotic MCL1 expression.

Soft tissue sarcoma (STS) is a rare cancer that develops from soft tissues in any part of the body. Despite major advances in the treatment of STS, patients are often refractory to conventional radiotherapy, leading to poor prognosis. Enhancement of sensitivity to radiotherapy would therefore improve the clinical outcome of STS patients. We previously revealed that the tumor-specific, replication-competent oncolytic adenovirus OBP-301 kills human sarcoma cells. In this study, we investigated the radiosensitizing effect of OBP-301 in human STS cells. The in vitro antitumor effect of OBP-301 and ionizing radiation in monotherapy or combination therapy was assessed using highly radiosensitive (RD-ES and SK-ES-1) and moderately radiosensitive (HT1080 and NMS-2) STS cell lines. The expression of markers for apoptosis and DNA damage were evaluated in STS cells after treatment. The therapeutic potential of combination therapy was further analyzed using SK-ES-1 and HT1080 cells in subcutaneous xenograft tumor models. The combination of OBP-301 and ionizing radiation showed a synergistic antitumor effect in all human STS cell lines tested, including those that show different radiosensitivity. OBP-301 was found to enhance irradiation-induced apoptosis and DNA damage via suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1), which was expressed at higher levels in moderately radiosensitive cell lines. The combination of OBP-301 and ionizing radiation showed a more profound antitumor effect compared to monotherapy in SK-ES-1 (highly radiosensitive) and HT1080 (moderately radiosensitive) subcutaneous xenograft tumors. OBP-301 is a promising antitumor reagent to improve the therapeutic potential of radiotherapy by increasing radiation-induced apoptosis in STS.

The Early Arthroscopic Pullout Repair of Medial Meniscus Posterior Root Tear Is More Effective for Reducing Medial Meniscus Extrusion.

Clinical studies have demonstrated that transtibial pullout repair led to favorable midterm outcomes in patients with medial meniscus posterior root tears (MMPRTs) although medial meniscal extrusion (MME) continued to be present. It has been unclear whether these residual postoperative MMEs existed after the pullout repair or had progressed at the very short-term evaluation after surgery. We sought to determine which characteristics of patients with MMPRTs influence the incidence of postoperative MME. The cases of 23 patients whose date of injury was known were analyzed. All patients underwent MMPRT pullout fixation. Preoperative and 3-month postoperative magnetic resonance imaging (MRI) examinations were performed. MME was retrospectively assessed on the mid-coronal plane of MRI scans. The preoperative and postoperative MME values were 4.2±1.2 mm and 4.3±1.5 mm, respectively (p=0.559). Pullout repair surgery was performed significantly earlier after the MMPRT-specific injury in patients whose postoperative MME improved compared to the patients whose MME did not improve (p<0.001). Our findings demonstrated that an early transtibial pullout repair of an MMPRT was more effective in reducing MME than a late repair. Surgeons should not miss the optimal timing for the pullout repair of an MMPRT, considering the period from the injury and the preoperative MME.

Clinical outcomes of treatment with locking compression plates for distal femoral fractures in a retrospective cohort.

BACKGROUND: Plate fixation is one of the standard surgical treatments for distal femoral fractures. There are few reports on the relationship between the screw position and bone union when fixing by the bridging plate (relative stability) method. METHODS: This retrospective study included 71 distal femoral fractures of 70 patients who were treated with the locking compression plate for distal femur (DePuy Synthes Co., Ltd, New Brunswick, CA, USA). The following measurements were evaluated and analyzed: (1) bone union rate, (2) bridge span length (distance between screws across the fracture), (3) plate span ratio (plate length/bone fracture length), (4) number of empty holes (number of screw holes not inserted around the fracture), and (5) medial fracture distance (bone fracture distance on the medial side of the distal femur). Patient demographics (age), comorbidities (smoking, diabetes, chronic steroid use, dialysis), and injury characteristics (AO type, open fracture, infection) were obtained for all participants. Univariate analysis was performed on them. RESULTS: Of 71 fractures, 26 fractures were simple fractures, 45 fractures were comminuted fractures, and 7 fractures resulted in non-union. Non-union rate was significantly higher in comminuted fractures with bone medial fracture distance exceeding 5 mm. Non-union was founded in simple fractures with bone medial fracture distance exceeding 2 mm, but not significant (p = 0.06). In cases with simple fractures, one non-union case had one empty hole and one non-union case had four empty holes, whereas in cases with comminuted fractures, five non-union cases had two more empty holes. CONCLUSIONS: We concluded that bone fragment distance between fracture fragments is more important than bridge span length of the fracture site and the number of empty holes. Smoking and medial fracture distance are prognostic risk factors of nonunion in distal femoral fractures treated with LCP as bridging plate.

Nonunion fragility fracture of the pelvis with complication from bladder rupture: A case report.

The incidence rate of bladder rupture associated with pelvic ring fractures is reported to be about 5-10%, mostly occurring at the time of injury. Fragility pelvic ring fractures are reported to increase fracture displacement or become nonunion if they are treated inadequately. Few case reports on bladder rupture associated with fragility pelvic ring fracture have been published. We report a rare case of delayed bladder rupture associated with a fragility fracture of the pelvis. A 65-year-old female felt right hip pain without sustaining any trauma. She was diagnosed with a right pubic rami fracture. However, her pain deteriorated, and a sacral fracture was identified one month later. She was prescribed teriparatide, but her pain worsened and she was referred to our hospital. She was diagnosed with fragility fracture of the pelvis (Rommens classification type IVb) and was treated operatively. During the surgery, her thin bladder wall, which was compressed by a displaced pubic fragment, was torn and repaired. This is the first report describing a fragility fracture of the pelvis associated with a bladder rupture. Our treatment led to a successful result.

Minimally Invasive Percutaneous Spinopelvic Fixation for Unstable Pelvic Ring Fracture Performed With the Patient in a Lateral Position.

Spinopelvic fixation provides a strong fixation for unstable pelvic ring fractures. However, the technique is usually performed with the patient in the prone position, with the applied weight on the anterior superior iliac crests aggravating fracture displacement. We developed a novel approach for minimally invasive percutaneous spinopelvic fixation that is performed with the patient in a lateral (side lying) position. We describe the application of our technique for the treatment of a bilateral pelvic ring and acetabulum fracture in a 79-year-old woman injured in a traffic accident. Initial posterior fixation was performed with the patient in the left-side lying position, using bilateral pedicle screws at L3 and L4 and a left sacral-alar iliac screw and 2 right iliac screws inserted under navigation. The lateral and cranial displacement of the right pelvic ring was reduced percutaneously. One week after this initial surgery, we proceeded with an open anterior reduction and internal fixation of the left pelvic ring and acetabulum fracture. The postoperative course was uneventful and clinical outcomes were satisfactory. Reduction of a pelvic ring fracture in a lateral position, with subsequent spinopelvic fixation, is a reasonable option for the treatment of an unstable pelvic ring fracture.

Impact of contrast extravasation on computed tomography of the psoas major muscle in patients with blunt torso trauma.

BACKGROUND: The clinical significance of contrast extravasation (CE) on computed tomography (CT) of the psoas major muscle after blunt torso trauma and the optimal management of patients requiring transcatheter arterial embolization (TAE) of the lumbar artery have not been well elucidated. The aim of this study was to investigate the impact of CE on CT to determine the need for TAE of the lumbar artery. METHODS: We examined a single-center retrospective cohort of blunt torso trauma patients who underwent contrast-enhanced CT from 2008 to 2017. Basic demographics and clinical data were obtained, including the number of lumbar transverse process fractures (LTPFs) and maximum psoas major muscle hematoma (PMMH) size and ratio. Maximum PMMH size was analyzed by measuring the cross-sectional area of hematoma size at the level of CE. Psoas major muscle hematoma size ratio was obtained by dividing maximum PMMH size by psoas major muscle size of the unaffected side at the same slice level. RESULTS: A total of 762 patients were included. One hundred seventeen patients had LTPFs and/or PMMH. Of 117 patients, 25 had CE on CT of the psoas major muscle and had significantly higher rates of older age and severe injury compared with those without CE. Of the 25 patients with CE, 13 required TAE of the lumbar artery. Patients who required TAE had a significantly higher number of LTPFs (4 vs. 2, p = 0.011) and higher PMMH size ratio (2.10 vs. 1.32, p = 0.016). Psoas major muscle hematoma size ratio revealed moderate accuracy (area under the receiver operating characteristic curve, 0.782). CONCLUSIONS: Approximately half of the blunt torso trauma patients with CE on CT of the psoas major muscle will require TAE of the lumbar artery. Higher number of LTPFs and larger PMMH size can be a predictor of the need for TAE of the lumbar artery among patients with CE on CT. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Emphysematous cystitis successfully treated with hyperbaric oxygen therapy: case report.

Emphysematous cystitis is an uncommon acute infection of the underlying bladder musculature and mucosa, caused by gas-producing organisms. Here we describe an 87-year-old woman with diabetes mellitus and emphysematous cystitis who was successfully treated with hyperbaric oxygen (HBO2) therapy. Her predisposition of diabetes and infection with gas-producing bacteria was considered to precede the development of emphysematous cystitis. Computed tomography revealed gas accumulation in the bladder wall and lumen. Antibiotics and HBO2 therapy were administered. HBO2 therapy may be beneficial due to the improvement in oxygenation of the tissues affected by the disease. HBO2 is a useful adjunct therapy for the management of severe emphysematous cystitis.

Venous thromboembolism in major trauma patients: a single-center retrospective cohort study of the epidemiology and utility of D-dimer for screening.

Aim: Venous thromboembolism (VTE) can be a life-threatening complication after major trauma. The aim of this study was to investigate the epidemiology of VTE and to assess the usefulness of D-dimer for screening for VTE in major trauma cases among the Japanese population. Methods: We examined a single-center retrospective cohort of severely injured trauma patients who had been admitted to the emergency intensive care unit at Okayama University Hospital (Okayama, Japan) from April 2013 through to March 2016. Venous thromboembolism was confirmed by computed tomography angiography and computed tomography venography, which was determined based on the attending physician monitoring daily D-dimer levels. Independent risk factors for VTE were determined by multiple logistic regression analysis. D-dimer levels were evaluated using area under the receiver operating characteristic curve (AUROC) to predict VTE. Results: The study cohort consisted of 204 trauma patients (median Injury Severity Score, 20). Of the 204 patients, 65 (32%) developed VTE. The median time from admission to VTE diagnosis was 10 days. In multiple logistic regression analysis, higher Injury Severity Score and the presence of lower extremity fractures were revealed to be a risk factor for VTE. D-dimer levels at day 10 showed moderate accuracy, of which the AUROC was 0.785 (95% confidence interval, 0.704-0.866; P < 0.001). The cut-off that maximized the Youden index was 12.45 µg/mL. Conclusions: At least one of every three major trauma patients had potential development of VTE at a median of 10 days following admission to the intensive care unit. D-dimer levels on day 10 can be a useful predictor of VTE.

Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction.

Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor-specific replicating oncolytic adenovirus OBP-301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with OBP-301 and ZOL against osteosarcomas with bone destruction. The antitumor activity of OBP-301 and ZOL in monotherapy or combination therapy was assessed using three human osteosarcoma cell lines (143B, MNNG/HOS, SaOS-2). The cytotoxic effect of OBP-301 and/or ZOL was measured by assay of cell apoptosis. The effect of OBP-301 and ZOL on osteoclast activation was investigated. The potential of combination therapy against tumor growth and bone destruction was analyzed using an orthotopic 143B osteosarcoma xenograft tumor model. OBP-301 and ZOL decreased the viability of human osteosarcoma cells. Combination therapy with OBP-301 and ZOL displayed a synergistic antitumor effect, in which OBP-301 promoted apoptosis through suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1). Combination therapy significantly inhibited tumor-mediated osteoclast activation, tumor growth and bone destruction compared to monotherapy. These results suggest that combination therapy of OBP-301 and ZOL suppresses osteosarcoma progression via suppression of MCL1 and osteoclast activation.

A case of traumatic cardiopulmonary arrest with good neurological outcome predicted by amplitude-integrated electroencephalogram.

INTRODUCTION: Traumatic cardiopulmonary arrest has a very high mortality, and survival of patients with this condition without neurological disability is rare. PRESENTATION OF CASE: We herein report a case of traumatic cardiopulmonary arrest secondary to accidental amputation of the left lower leg that was successfully treated without any higher brain dysfunction. Although the long duration of cardiopulmonary arrest in this patient suggested hypoxic ischemic encephalopathy, amplitude-integrated electroencephalogram showed normal findings. DISCUSSION: This system may help intensivists evaluate the neurological conditions of patients with suspected hypoxic ischemic encephalopathy in the early stage of the clinical course and may assist in guiding therapeutic interventions. CONCLUSION: Our case supports the usefulness of neurological monitoring using amplitude-integrated electroencephalogram.

Ablation of MCL1 expression by virally induced microRNA-29 reverses chemoresistance in human osteosarcomas.

Osteosarcoma is a rare disease diagnosed as malignant bone tumor. It is generally refractory to chemotherapy, which contributes to its poor prognosis. The reversal of chemoresistance is a major clinical challenge to improve the prognostic outcome of osteosarcoma patients. We developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301 (telomelysin) and assessed its synergistic effects with chemotherapeutic agents (cisplatin and doxorubicin) using human osteosarcoma cell lines and a xenograft tumor model. The molecular mechanism underlying the chemosensitizing effect of OBP-301 was evaluated in aspects of apoptosis induction. OBP-301 inhibits anti-apoptotic myeloid cell leukemia 1 (MCL1) expression, which in turn leads to chemosensitization in human osteosarcoma cells. The siRNA-mediated knockdown of MCL1 expression sensitized human osteosarcoma cells to common chemotherapeutic agents. We also found that upregulation of microRNA-29 targeting MCL1 via virally induced transcriptional factor E2F-1 activation was critical for the enhancement of chemotherapy-induced apoptosis in osteosarcoma cells. Telomerase-specific oncolytic adenovirus synergistically suppressed the viability of human osteosarcoma cells in combination with chemotherapeutic agents. The combination treatment also significantly inhibited tumor growth, as compared to monotherapy, in an osteosarcoma xenograft tumor model. Our data suggest that replicative virus-mediated tumor-specific MCL1 ablation may be a promising strategy to attenuate chemoresistance in osteosarcoma patients.

Dual programmed cell death pathways induced by p53 transactivation overcome resistance to oncolytic adenovirus in human osteosarcoma cells.

Tumor suppressor p53 is a multifunctional transcription factor that regulates diverse cell fates, including apoptosis and autophagy in tumor biology. p53 overexpression enhances the antitumor activity of oncolytic adenoviruses; however, the molecular mechanism of this occurrence remains unclear. We previously developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301, that kills human osteosarcoma cells, but some human osteosarcoma cells were OBP-301-resistant. In this study, we investigated the antitumor activity of a p53-expressing oncolytic adenovirus, OBP-702, and the molecular mechanism of the p53-mediated cell death pathway in OBP-301-resistant human osteosarcoma cells. The cytopathic activity of OBP-702 was examined in OBP-301-sensitive (U2OS and HOS) and OBP-301-resistant (SaOS-2 and MNNG/HOS) human osteosarcoma cells. The molecular mechanism in the OBP-702-mediated induction of two cell death pathways, apoptosis and autophagy, was investigated in OBP-301-resistant osteosarcoma cells. The antitumor effect of OBP-702 was further assessed using an orthotopic OBP-301-resistant MNNG/HOS osteosarcoma xenograft tumor model. OBP-702 suppressed the viability of OBP-301-sensitive and -resistant osteosarcoma cells more efficiently than OBP-301 or a replication-deficient p53-expressing adenovirus (Ad-p53). OBP-702 induced more profound apoptosis and autophagy when compared with OBP-301 or Ad-p53. E1A-mediated miR-93/106b upregulation induced p21 suppression, leading to p53-mediated apoptosis and autophagy in OBP-702-infected cells. p53 overexpression enhanced adenovirus-mediated autophagy through activation of damage-regulated autophagy modulator (DRAM). Moreover, OBP-702 suppressed tumor growth in an orthotopic OBP-301-resistant MNNG/HOS xenograft tumor model. These results suggest that OBP-702-mediated p53 transactivation is a promising antitumor strategy to induce dual apoptotic and autophagic cell death pathways via regulation of miRNA and DRAM in human osteosarcoma cells.