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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. [ABSTRACT FROM AUTHOR]

Anteroposterior (AP) alignment assessment for nondisplaced femoral neck fractures is important for determining the treatment strategy and predicting postoperative outcomes. AP alignment is generally measured using the Garden alignment index (GAI). However, its reliability remains unknown. We compared the reliability of GAI and a new AP alignment measurement (valgus tilt measurement [VTM]) using preoperative AP radiographs of nondisplaced femoral neck fractures. The study was designed as an intra- and inter-rater reliability analysis. The raters were four trauma surgeons who assessed 50 images twice. The main outcome was the intraclass correlation coefficient (ICC). To calculate intra- and inter-rater reliability, we used a mixed-effects model considering rater, patient, and time. The overall ICC (95% CI) of GAI and VTM for intra-rater reliability was 0.92 (0.89–0.94) and 0.86 (0.82–0.89), respectively. The overall ICC of GAI and VTM for inter-rater reliability was 0.92 (0.89–0.95), and 0.85 (0.81–0.88), respectively. The intra- and inter-rater reliability of GAI was higher in patients aged <80 years than in patients aged ≥80 years. Our results showed that GAI is a more reliable measurement method than VTM, although both are reliable. Variations in patient age should be considered in GAI measurements. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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, Sa OS-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: None., (© 2024 The Authors.)

We report a case of a patient with severe pelvic fracture who showed concurrent ST elevation on electrocardiogram. A 70-year-old man incurred an unstable pelvic fracture from a motorcycle accident. On admission, he was hemodynamically unstable, and massive transfusion and noradrenaline were administered immediately. Although ST elevation was present in leads II, III, aVF, V5, and V6, cardiac function was preserved; thus, trans-arterial embolization and external fixation for pelvic fracture were given priority. Four days after the injury, he suffered a cardiac arrest, and coronary angiography revealed that the cause of ST elevation and cardiac arrest was coronary vasospasm. Physicians should be aware that pain-related stress and platelet activation as well as use of noradrenaline in severe trauma cases can induce coronary vasospasm., Competing Interests: No potential conflict of interest relevant to this article was reported.

Although there are some reports highlighting the applicability of double plates in distal femoral fractures, there is no standard approach or fixation method for supracondylar fractures combined with posterior coronal shear fractures. We report a case of distal femoral fracture treated with a lateral locking plate and posterior buttress plate using anterolateral and posterolateral approaches from one incision. A 70-year-old man was hit by a motorcycle and had an intra-articular distal femoral fracture involving a long medial proximal spike and a single lateral condyle fragment, with the lateral condyle fragment posteriorly displaced. A 12-cm lateral skin incision was made, and the joint was developed using a para-patellar approach from the anterior to iliotibial band. Posterior buttress plate fixation was successfully performed from behind the iliotibial band using a posterolateral approach, followed by cannulated cancellous screw and lateral locking plate fixation from the anterolateral window. Combined anterolateral and posterolateral approaches from one incision enable intra-articular exposure and fixation based on fixation principles for lateral condyle fragments combined with supracondylar fracture., Competing Interests: None., (© 2023 The Authors.)

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., Competing Interests: No potential conflict of interest relevant to this article was reported.

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., Competing Interests: None., (© 2022 The Authors. Published by Elsevier Ltd.)

This retrospective study sought to elucidate the incidence rates of roof impaction (RI) and marginal impaction (MI) and radiological and clinical outcomes of open reduction and internal fixation (ORIF) for RI and MI in geriatric acetabular fractures. The cases of 68 patients aged ≥ 65 years (mean 71 years) treated with ORIF were analyzed. MI was present in 12 fractures (67%) and an RI of the weight-bearing surface was present in 24 (46%) of the potential fracture types. Regarding the reduction quality, 54% of the reductions were graded as anatomical, 37% as imperfect, and 9% as poor. In the clinical evaluations of the 45 patients who had > 1-year follow-up (follow-up rate: 66.2%), 18% were graded as excellent, 53% as good, 16% as fair, and 13% as poor. An anatomic reduction was strongly associated with good or excellent clinical and radiological outcomes. CT was superior to radiographs for detecting the residual displacement postoperatively. Postoperative deep infection occurred in four patients. Three patients (6.7%) underwent a total hip arthroplasty conversion due to secondary osteoarthritis of the hip. We recommend ORIF as the preferred surgical treatment option for displaced acetabular fractures in elderly patients., Competing Interests: No potential conflict of interest relevant to this article was reported.

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., Competing Interests: No potential conflict of interest relevant to this article was reported.

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.

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., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

BACKGROUND Subperiosteal hematoma (SPH) of the iliac bone is an extremely uncommon clinical entity that occurs mostly in young patients with a history of a recent fall or sports-related injury. Patients usually complain of severe hip pain after a fall, mimicking femoral neck fracture. CASE REPORT An 18-year-old female was transported to our hospital complaining of pain in her left hip after falling on her buttocks while engaging in martial arts. Ultrasound of her left iliac region revealed a subperiosteal mass on the internal aspect of the iliac bone lifting the iliac muscle. SPH of the iliac bone was suspected, which was also evident on pelvis and hip magnetic resonance imaging. Repetitive ultrasound did not reveal hematoma expansion. She was discharged from the hospital the next day without femoral neuropathy. CONCLUSIONS Physicians should be aware of our report, which highlights a patient with the rare clinical condition of SPH of the iliac bone occurring immediately after a fall. The differential diagnosis of acute hip pain, which mimics femoral neck fracture, should be considered in young patients. Ultrasound of the iliac region may be useful in detection and further management of SPH of the iliac bone.

Worldwide, hemorrhagic shock in major trauma remains a major potentially preventable cause of death. Controlling bleeding and subsequent coagulopathy is a big challenge. Immediate assessment of unidentified bleeding sources is essential in blunt trauma patients with hemorrhagic shock. Chest/pelvic X-ray in conjunction with ultrasonography have been established classically as initial diagnostic imaging modalities to identify the major sources of internal bleeding including intra-thoracic, intra-abdominal, or retroperitoneal hemorrhage related to pelvic fracture. Massive soft tissue injury, regardless of whether isolated or associated with multiple injuries, occasionally causes extensive hemorrhage and acute traumatic coagulopathy. Specific types of injuries, including soft tissue injury or retroperitoneal hemorrhage unrelated to pelvic fracture, can potentially be overlooked or be considered "occult" causes of bleeding because classical diagnostic imaging often cannot exclude such injuries. The purpose of this narrative review article is to describe "occult" or unusual sources of bleeding associated with blunt trauma., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Cushing's reflex usually results from intracranial hypertension. Although Cushing's sign can implicate severe traumatic brain injury (TBI) in injured patients, no major investigations have been made. The purpose of this study was to assess the predictability of life-threatening brain injury requiring immediate neurosurgical intervention (LT-BI) among trauma patients with Cushing's sign in the prehospital setting., Methods: This was a retrospective study using data from the Japan Trauma Data Bank from the period of 2010 to 2014. Patients 16 years old or older with blunt mechanisms of injury who were transported directly from the scene and Glasgow Coma Scale for eye opening of one in the prehospital setting were included. LT-BI was defined as patients requiring burr hole evacuation or craniotomy within 24 h of hospital arrival and patients who were non-survivors due to isolated severe TBI. Prehospital systolic blood pressure (pSBP) and heart rate (pHR) were assessed using area under the receiver operating characteristic curve (AUROC) and multiple logistic regression analysis to predict LT-BI., Results: Of 6332 eligible patients, 1859 (29%) exhibited LT-BI. AUROC of LT-BI using pSBP and pHR was 0.666 (95% confidence interval (CI); 0.652-0.681, P < 0.001), and 0.578 (95% CI; 0.563-0.594, P < 0.001), respectively. AUROC of pSBP was the highest among the 60 ≤ pHR ≤ 99 subgroup, of which AUROC was 0.680 (95% CI; 0.662-0.699, P < 0.001). Multiple logistic regression analysis showed that the higher the pSBP and the lower the pHR, the more likely that the patients had LT-BI. In a group with pSBP ≥ 180 mmHg and pHR ≤ 59 beats/min, the odds ratio and 95% CI of LT-BI after adjusting for age, sex, and severity of injuries to other body regions was 4.77 (2.85-7.97), P < 0.001 was compared with the reference group, which was defined as patients with normal vital signs., Discussion: Our study has found that the combination of hypertension and bradycardia, which are the components of Cushing's sign without eye opening in the prehospital setting was a weak but a significant predictor of LT-BI, or death due to possible isolated severe TBI., Conclusions: Prehospital Cushing's sign with disturbed level of consciousness in trauma patients was a weak but significant predictor of the need for immediate neurosurgical intervention.

In recent years, it has become evident that molecular hydrogen is a particularyl effective treatment for various disease models such as ischemia-reperfusion injury; as a result, research on hydrogen has progressed rapidly. Hydrogen has been shown to be effective not only through intake as a gas, but also as a liquid medication taken orally, intravenously, or locally. Hydrogen's effectiveness is thus multifaceted. Herein we review the recent research on hydrogen-rich water, and we examine the possibilities for its clinical application. Now that hydrogen is in the limelight as a gaseous signaling molecule due to its potential ability to inhibit oxidative stress signaling, new research developments are highly anticipated.

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.

TiO2 nanoparticles-deposited on hydroxyapatite (HAp) have been successfully synthesized by direct (single step) hydrothermal treatments of a CaCO3 suspension in a H3PO4 solution with 10 vol% TAS-FINE (titanium amine complex) at 150 degrees C for 6 h or 120 degrees C for 12-24 h under nearly neutral pH conditions. The obtained products were characterized by XRD, SEM-EDX, visible, Raman, and TEM. The XRD and Raman results showed the formation of HAp and TiO2 anatase phases under these hydrothermal conditions. SEM and TEM observations revealed that anatase TiO2 nanoparticles with the size of about 10 nm were deposited on the surfaces of the HAp crystals.