Risk factors for collisions attributed to microsleep-related behaviors while driving in professional truck drivers.

Sleep-disordered breathing (SDB) is prevalent among professional drivers. Although SDB is a known risk factor for truck collisions attributed to microsleep-related behaviors at the wheel (TC-MRBs), the usefulness of overnight pulse oximetry for predicting TC-MRBs is debatable. This retrospective study assessed the association between overnight pulse oximetry parameters, the Epworth Sleepiness Scale (ESS), and TC-MRBs, confirmed by dashcam footage. This study included 108 matched professional truck drivers (TC-MRBs: N = 54; non-TC-MRBs: N = 54), with a mean age and body mass index of 41.9 ± 11.3 years and 23.0 ± 3.7 kg/m2, respectively. Night-time drivers, 4% oxygen desaturation index (ODI), and nadir oxygen saturation (SpO2) were associated with TC-MRBs (odds ratio [95% confidence interval]: 25.63 [5.88-111.77], p < 0.0001; 2.74 [1.02-7.33], p = 0.045; and 3.87 [1.04-14.39], p = 0.04, respectively). The area under the curve of 4% ODI and nadir SpO2 for TC-MRBs were 0.50 and 0.57, respectively. In conclusion, night-time driving, 4% ODI, and nadir SpO2 were significantly associated with TC-MRBs in professional truck drivers. However, the sensitivity of overnight pulse oximetry parameters to predict TC-MRBs in a real-world application was poor. Therefore, combining subjective and objective assessments such as dashcam video footage may be needed to achieve high accuracy for predicting TC-MRBs among professional truck drivers.

Nuclear morphological atypia in biopsy accurately reflects the prognosis of myxoid liposarcoma.

Currently, it is difficult to predict the prognosis of myxoid liposarcoma (MLS) in biopsy specimens. In this study, we determined whether nuclear morphology may be used to predict the prognosis of MLS in primary biopsy specimens. Two pathologists evaluated nuclear morphology using the modified WHO/ISUP and Fuhrman grades. Survival analyses were performed by grouping nuclear high- and low-grades. We examined 53 MLS cases, which included 29 (54.7%) male and 24 (45.3%) female patients with a median age of 46 years (interquartile range, 37 - 60). In total, 7 (13.2%) and 16 (30.2%) cases were assigned to the high nuclear grade group based on the modified WHO/ISUP and Fuhrman gradings, respectively. Survival analyses revealed a significantly worse disease-free survival in the high-grade group (hazard ratio (HR), 7.51; 95% confidence interval (CI), 2.67-21.1, p < 0.001 by the modified WHO/ISUP grading; HR, 4.45; 95% CI, 1.63-12.1, p = 0.001 by the modified Fuhrman grading). Moreover, the modified WHO/ISUP grade showed a significantly worse overall survival in the high-grade group (HR, 4.39; 95% CI, 1.04-18.6, p = 0.028), and the modified Fuhrman grade exhibited a similar, but not significant, trend. Our results indicate that nuclear morphology grading is a good predictor of patient prognosis at the time of biopsy in MLS. Even when cell density is sparse, treatment strategies should be carefully considered when individual tumor cells exhibit atypical nuclei.

Low-grade central osteosarcoma with extraosseous dedifferentiation: a rare case.

Low-grade central osteosarcoma (LGCOS), which arises from the intramedullary cavity of the metaphysis of long bones, occasionally exhibits extraosseous spread. Approximately 10-30% of patients with LGCOS exhibit dedifferentiation, but it is rare to experience a primary tumor with a dedifferentiated component. A 38-year-old female patient presented with right knee pain for two months. Imaging studies revealed a bone mass with extraosseous involvement. Wide resection was performed, and pathologic examination led to the diagnosis of LGCOS with a dedifferentiated extraosseous lesion. A single defect in the bone cortex constituted the boundary between the low- and high-grade components. The extraosseous high-grade component included more tumor cells with p53 overexpression and more murine double minute 2 (MDM2) copies compared with the low-grade component. These genetic mutations and copy number alterations can be associated with malignant transformation of LGCOS.

DDIT3-amplified or low-polysomic pleomorphic sarcomas without MDM2 amplification: Clinicopathological review and immunohistochemical profile of nine cases.

Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5') and centromeric (3') amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5'-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5'-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5'-predominant amplification, can be reclassified out of the UPS category.

Immune evasion in lung metastasis of leiomyosarcoma: upregulation of EPCAM inhibits CD8+ T cell infiltration.

BACKGROUND: Leiomyosarcomas are among the most common histological types of soft tissue sarcoma (STS), with no effective treatment available for advanced patients. Lung metastasis, the most common site of distant metastasis, is the primary prognostic factor. We analysed the immune environment targeting lung metastasis of STS to explore new targets for immunotherapy. METHODS: We analysed the immune environment of primary and lung metastases in 38 patients with STS using immunohistochemistry. Next, we performed gene expression analyses on primary and lung metastatic tissues from six patients with leiomyosarcoma. Using human leiomyosarcoma cell lines, the effects of the identified genes on immune cells were assessed in vitro. RESULTS: Immunohistochemistry showed a significant decrease in CD8+ cells in the lung metastases of leiomyosarcoma. Among the genes upregulated in lung metastases, epithelial cellular adhesion molecule (EPCAM) showed the strongest negative correlation with the number of CD8+ cells. Transwell assay results showed that the migration of CD8+ T cells was significantly increased in the conditioned media obtained after inhibition or knock down of EPCAM. CONCLUSIONS: EPCAM was upregulated in lung metastases of leiomyosarcoma, suggesting inhibition of CD8+ T cell migration. Our findings suggest that EPCAM could serve as a potential novel therapeutic target for leiomyosarcoma.

Viable tumor cell density after neoadjuvant chemotherapy assessed using deep learning model reflects the prognosis of osteosarcoma.

Prognosis after neoadjuvant chemotherapy (NAC) for osteosarcoma is generally predicted using manual necrosis-rate assessments; however, necrosis rates obtained in these assessments are not reproducible and do not adequately reflect individual cell responses. We aimed to investigate whether viable tumor cell density assessed using a deep-learning model (DLM) reflects the prognosis of osteosarcoma. Seventy-one patients were included in this study. Initially, the DLM was trained to detect viable tumor cells, following which it calculated their density. Patients were stratified into high and low-viable tumor cell density groups based on DLM measurements, and survival analysis was performed to evaluate disease-specific survival and metastasis-free survival (DSS and MFS). The high viable tumor cell density group exhibited worse DSS (p = 0.023) and MFS (p = 0.033). DLM-evaluated viable density showed correct stratification of prognosis groups. Therefore, this evaluation method may enable precise stratification of the prognosis in osteosarcoma patients treated with NAC.

Rare presentation of a primary intraosseous glomus tumor in the humerus of a teenager.

A glomus tumor is a benign mesenchymal tumor comprised of cells that resemble the perivascular modified smooth muscle cells of the glomus body. Glomus tumors typically appear in the superficial lesions of the soft tissue in the extremities, such as the subungual region. However, their occurrence in the bone is rare, with only about 30 cases reported to date. Half of these cases involved the distal phalanges of the fingers or toes, with only three reported cases involving the long bones. Here, we present the first case, a primary glomus tumor in the humerus of a 14-year-old female. An osteolytic and cystic lesion was detected after a pathological fracture occurred during exercise. Despite the tumor's large size, no pathological findings indicated malignancy. The fracture healed through conservative treatment, while the tumor was effectively managed with curettage. Appropriate medical care can be provided to patients by focusing on pathological findings.

A Novel Method for Assessing the 3-dimensional Morphology of Cartilaginous Acetabulum Via Childhood Magnetic Resonance Imaging.

BACKGROUND: Periarticular cartilage is abundant in children, making evaluations of 3-dimensional (D) cartilaginous acetabular morphology using x-ray or computed tomography (CT) difficult. The study aimed to visualize the 3D cartilaginous acetabular morphology in normal children and patients with pediatric developmental dysplasia of the hip (DDH). METHODS: Magnetic resonance imaging (MRI) of 17 female children without acetabular dysplasia at 7.5 years and CT of 33 normal female adolescents with mature bones at 14.6 years were used as controls. Subjects were 26 female patients with unilateral DDH who underwent angulated Salter innominate osteotomy (A-SIO) at 5.5 years. Preoperative and postoperative MRIs were performed at 5.2 and 7.0 years, respectively. The MRI sequence was 3D-MEDIC. The medial intersection (point A) of the line connecting the centers of the bilateral femoral head and the femoral head were defined as point zero. The 3D coordinates (X, Y, Z) of the cartilaginous acetabular edge (point C) from anterior to posterior were calculated. Subsequently, a 3D scatter plot was created using 3D graph software. The subjects were divided into 6 groups, including control MRI, control CT, unaffected DDH before and after A-SIO, and affected DDH before and after A-SIO. The femoral head coverage ratio (FHCR: AC/AB) was used to quantify coverage and was compared in each group. RESULTS: In the control MRI group, the acetabular coverage was small anteriorly, largest anterolaterally, and gradually decreased posteriorly, similar to the bony acetabulum in adolescents. In the affected DDH before A-SIO group, the coverage was significantly lower than that of the control MRI and unaffected DDH groups. After A-SIO, the morphology improved beyond the unaffected DDH and the control MRI group. CONCLUSIONS: The global defect of the cartilaginous acetabulum in the affected DDH group was significantly improved to normal morphology after A-SIO. Evaluating the cartilaginous acetabulum using MRI was useful for assessing hip morphology in childhood. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Truck collisions attributed to falling asleep at the wheel in two commercial drivers prescribed oral appliance therapy for obstructive sleep apnea.

Falling asleep at the wheel is attributed to sleepiness, and obstructive sleep apnea is a significant cause of sleepiness that increases the risk of motor vehicle collisions due to falling asleep at the wheel. Although continuous positive airway pressure therapy for obstructive sleep apnea reduces the risk of motor vehicle collisions, similar evidence for alternatives such as oral appliance therapy is lacking. We discuss two truck collisions attributed to microsleep confirmed with dashcam video footage of commercial drivers with obstructive sleep apnea. Our results highlight the current situation where there is insufficient evidence for the prevention and reduction of the risk of motor vehicle collisions by oral appliance therapy, objective adherence monitoring of oral appliance therapy, and effectiveness confirmation tests. Therefore, it is suggested that for commercial truck drivers who require a high level of driving safety, careful selection for oral appliance therapy, systematic follow-up, and monitoring of the driver and truck status with dashcam video footage are crucial. CITATION: Kumagai H, Tsuda H, Kawaguchi K, et al. Truck collisions attributed to falling asleep at the wheel in two commercial drivers prescribed oral appliance therapy for obstructive sleep apnea. J Clin Sleep Med. 2023;19(12):2117-2122.

Prognostic implications of the immunohistochemical expression of perilipin 1 and adipophilin in high-grade liposarcoma.

AIMS: Liposarcoma is a malignant soft tissue tumour with adipocytic differentiation. Dedifferentiated liposarcoma (DDLS) and myxoid liposarcoma (MLS) are classified as high-grade liposarcomas. Lipid droplet-associated protein (also known as perilipin 1 (PLIN1)) is the predominant perilipin and has utility as a specific marker of adipogenic differentiation. Adipose differentiation-related protein (also known as adipophilin (ADRP)) is ubiquitously expressed in a range of tissues. High ADRP expression is reportedly a poor prognostic factor in several cancer types. However, no previous studies have examined the association between PLIN1 or ADRP expression and prognosis in sarcoma. This study therefore aimed to evaluate the association between PLIN1 or ADRP expression and prognosis in liposarcoma. METHODS: In total, 97 primary resection specimens (53 MLS and 44 DDLS) were examined in this study. PLIN1 and ADRP expression was evaluated by immunohistochemistry. Survival analyses were performed for MLS and DDLS. RESULTS: Of the 53 MLS specimens, 15 (28.3%) exhibited high PLIN1 expression. PLIN1 expression was not observed in DDLS specimens. High PLIN1 expression was significantly associated with increased disease-free survival (DFS) among patients with MLS (p=0.045). Distinct ADRP expression was observed in 13 of 53 (24.5%) MLS specimens and 5 of 44 (11.4%) DDLS specimens. High ADRP expression was associated with shorter overall survival (OS) in MLS (p=0.042) and DFS and shorter OS in DDLS (p=0.024 and p<0.001, respectively). CONCLUSIONS: PLIN1 and ADRP expression is associated with poor prognosis in high-grade liposarcoma.

Dashcam video footage-based analysis of microsleep-related behaviors in truck collisions attributed to falling asleep at the wheel.

OBJECTIVE: With the rapid spread of dashcams, many car accidents have been recorded; however, behavioral approaches using these dashcam video footage have not been sufficiently examined. We employed dashcam video footage to evaluate microsleep-related behaviors immediately prior to real-world truck collisions in professional drivers to explore a new solution to reduce collisions attributed to falling asleep at the wheel. METHODS: In total, 3,120 s of video footage (60 s/case × 52 cases) from real-world truck collisions of 52 professional drivers obtained from interior and exterior dashcams were used and visually analyzed in a second-by-second manner to simultaneously evaluate any eye changes and microsleep-related behaviors (the driver's anti-sleepiness behavior, behavioral signs of microsleep, and abnormal vehicle behavior) during driving. RESULTS: Assessment of the frequency of occurrence of each item of microsleep-related behavior in the 52 collisions revealed that the item "touching" in terms of anti-sleepiness behavior, "absence of body movement" in terms of behavioral signs of microsleep, and "inappropriate line crossing" in terms of abnormal vehicle behavior were observed at the highest rate in all drivers (46.2%, 75.0%, and 78.8%, respectively). Decreases in anti-sleepiness behavior coincided with increases in behavioral signs of microsleep and abnormal vehicle behavior, with collisions occurring within approximately 40 s of these changes. Collisions were more common among young people and in the early morning and evening. CONCLUSION: Our dashcam video footage-based analysis in truck collisions attributed to falling asleep at the wheel revealed the process of changes in microsleep-related driver and vehicle behaviors, classified as anti-sleepiness behavior, behavioral signs of microsleep, and abnormal vehicle behavior. Based on these findings, to prevent collisions caused by falling asleep at the wheel, it is crucial to monitor not only the driver's eyes, but also the driver's whole body and vehicle behavior simultaneously to reliably detect microsleep-related behaviors.

Prognostic value of nuclear morphometry in myxoid liposarcoma.

Myxoid liposarcoma (MLS) accounts for 20%-30% of liposarcoma and the round cell component (RCC) is believed to be a specific poor prognostic factor. However, the RCC assessment criteria are vaguely defined and, therefore, are inconsistently employed by pathologists. In this study, we modified and applied two established grading systems to evaluate nuclear atypia (namely, the World Health Organization/International Society of Urological Pathology and the Fuhrman grading in renal cell carcinoma) in 64 MLS cases. Detailed software-based assessments of the morphology and the cellularity were performed. DNA mutation analysis, comprehensive mRNA expression analysis, and immunohistochemistry were also performed. Our findings revealed that the high-nuclear-grade group according to the modified Fuhrman grading system exhibited a significantly poor disease-free survival (hazard ratio: 4.43; 95% confidence interval: 0.9-22.6; p = 0.047). On the other hand, the cellularity was significantly higher in the modified Fuhrman high-grade group (p = 0.010 at the percentage of the hypercellular area; p = 0.003 at the maximum cell density) but did not qualify per se as a poor prognostic factor in the survival analyses. Furthermore, the modified Fuhrman high-grade group significantly expressed the cell cycle-related genes (such as FOXM1, PLK1, and CDK1). In conclusion, our analyses suggest that an evaluation focusing on nuclear morphology (rather than on cellular density) can be more reliable in predicting the MLS prognosis.

Clinical significance of signal regulatory protein alpha and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain expression in undifferentiated pleomorphic sarcoma.

PURPOSE: Undifferentiated pleomorphic sarcoma (UPS) is associated with poor prognosis. Recently, signal regulatory protein alpha (SIRPα), which is the immune checkpoint of macrophages, and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), which is the immune checkpoint of T cells and natural killer cells, have been considered as potential targets for cancer immunotherapy. This study aimed to assess the value of SIRPα and TIGIT as prognostic factors of UPS. MATERIALS AND METHODS: The cBio Cancer Genomics Portal was used to analyze mRNA expression data of 50 UPS cases in the Cancer Genome Atlas. We retrieved 49 UPS cases and performed immunohistochemistry (IHC) to detect programmed death ligand 1 (PD-L1), SIRPα, CD68, CD163, TIGIT, CD155, and CD8. RESULTS: SIRPα was positively associated with CD163 (Pearson's r = 0.51, p = 0.0002) as per open access data and IHC of the cohort (p = 0.002), which revealed that SIRPα-positive macrophage infiltration was higher in UPS cells with ≥ 1% PD-L1 expression than that in UPS cells with < 1% PD-L1 expression (p = 0.047). TIGIT was positively correlated with PD-L1 (r = 0.54, p < 0.0001) and CD8A (r = 0.98, p < 0.0001). In 35 of 49 cases, IHC revealed high levels of TIGIT expression on tumor cells. Furthermore, TIGIT expression on tumor cells was negatively correlated with CD155-positive (p = 0.0144) and CD8-positive (p = 0.0487) cell infiltration. Survival analysis showed that the high degree of SIRPα-positive macrophage infiltration was associated with poor overall survival and metastasis (p < 0.0001, p = 0.0006, respectively). CONCLUSION: SIRPα-positive macrophages infiltrated UPS cells, which predicted poor prognosis. High TIGIT expression on tumor cells was associated with decreased levels of tumor-infiltrating macrophages in UPS.

Expression of SATB2, RUNX2, and SOX9 and possible osteoblastic and chondroblastic differentiation in chondroblastoma.

Chondroblastoma (CB) is histologically characterized by oval to polygonal-shaped mononuclear neoplastic cells, multinucleated osteoclastic giant cells, and eosinophilic matrix with occasional calcification. Genetically, the majority of CBs harbor H3F3B p.K36M mutation. Despite the historical nomenclature, it has been reported that the matrix of CB is similar to osteoid rather than true cartilage; however, it remains unclear whether neoplastic cells in CB have the potential for osteoblastic differentiation. To clarify this issue, we immunohistochemically examined the expression of osteogenic and chondrogenic markers (SATB2, RUNX2, p63, and SOX9) as well as H3K36M mutant protein in 33 cases of CB. All 33 cases of CB were positive for H3K36M, while SATB2, RUNX2, p63, and SOX9 were expressed in 30/33 (91%), 33/33 (100%), 29/33 (88%), and 31/32 (97%) CB cases, respectively. Our immunohistochemical results suggest that neoplastic cells in CB frequently express both osteogenic and chondrogenic markers and may have an intermediate feature of osteoblastic and chondroblastic nature.

Nocturnal hypoxemia is related to morning negative affectivity in untreated patients with severe obstructive sleep apnea.

The relationship between sleep apnea and morning affectivity remains unclear. We aimed to clarify how sleep disturbance in patients with obstructive sleep apnea (OSA) influences their affectivity. The enrolled participants underwent the Positive and Negative Affect Schedule on their beds immediately before and after overnight polysomnography. Thirty patients with OSA were divided into two groups according to the apnea-hypopnea index (AHI): mild to moderate OSA (5 ≤ AHI < 30/h) and severe OSA (AHI ≥ 30/h) groups. Additionally, 11 healthy participants (AHI < 5/h) were included as the control group. No independent association was found between affectivity and OSA severity markers in the whole population; however, the severe OSA group had a significantly higher cumulative percentage of sleep time at saturations < 90% (CT90) and worsened morning negative affectivity. Multiple regression analysis showed that CT90 was an independent factor for increasing negative affectivity in the severe OSA group (p = 0.0422). In patients with OSA, the receiver operating characteristic curve analysis showed that the best cutoff value for CT90 for predicting no decrease in negative affectivity after sleep was 1.0% (sensitivity = 0.56, specificity = 0.86); the corresponding area under the curve was 0.71. Worsening of negative affectivity in the morning was influenced by nocturnal hypoxemia in patients with severe OSA.

A new scoring system for the grading of conventional chondrosarcoma: Its clinicopathological significance.

BACKGROUND: Chondrosarcoma is the second most common primary malignant bone tumor, which produces cartilaginous matrix without neoplastic osteoid or bone formation. The histological grade in the WHO Classification of Soft Tissue and Bone (2020 edition) is the most important factor in predicting the clinical outcome of conventional chondrosarcoma, but the lack of clarity in its detailed definition is occasionally problematic. Here, we reviewed conventional chondrosarcoma cases and validated the significance of histological findings. Moreover, we proposed a new scoring system of conventional chondrosarcoma. MATERIAL AND METHODS: Clinicopathological features of 60 cases of conventional chondrosarcoma and 21 cases of dedifferentiated chondrosarcoma were reviewed. RESULTS: Moderate to severe nuclear atypia was correlated with distant metastasis. Moderate and severe nuclear atypia, high cellularity, and >1 % myxoid change were correlated with adverse overall survival. On the other hand, cases with mild nuclear atypia showed no tumor-related death and no metastases. Based on the above results, we proposed a new scoring system based on nuclear atypia (mild: 0, moderate: +1, severe: +2), cellularity (no and mildly increased cellularity: 0, moderately and diffusely increased cellularity: +1), necrosis [(-): 0, (+): + 1], and chondromyxoid area [(-): 0, (+): + 1]. Each grade was defined as follows: cases with only mild nuclear atypia as grade 1, cases with total score 1-3 excluding mild nuclear atypia as grade 2, and cases with total score 4 or 5 as grade 3. There were 18 cases (30 %) of grade 1 including 5 cases (28 %) of local recurrence, but no metastasis or tumor-related death; 26 cases (43 %) of grade 2 including 2 cases (8 %) of local recurrence, 3 cases (12 %) of metastasis, and 1 case (4 %) of tumor-related death; and 16 cases (27 %) of grade 3 including 4 cases (25 %) of local recurrence, 6 cases (38 %) of metastasis, and 5 cases (31 %) of tumor-related death. There was no statistically significant association between the histological findings and dedifferentiation. CONCLUSION: From this study, we propose a new histological scoring system for the grading of conventional chondrosarcoma, based on nuclear atypia, cellularity, necrosis, and myxoid change. Using this system, conventional chondrosarcoma may be clearly classified into three grades: grade 1, non-metastasizing; grade 2, metastasizing but rarely life-threatening; and grade 3, frequently metastasizing and life-threatening.

Effects of Continuous Positive Airway Pressure Therapy on Nocturnal Blood Pressure Fluctuation Patterns in Patients with Obstructive Sleep Apnea.

This retrospective study was designed to evaluate the effects of continuous positive airway pressure (CPAP) therapy, a well-established treatment for obstructive sleep apnea (OSA), on nocturnal blood pressure fluctuations (NBPFs) during rapid eye movement (REM) and non-REM sleep, and to evaluate the NBPF patterns in patients with OSA. We included 34 patients with moderate-to-severe OSA who underwent polysomnography using pulse transit time before and at 3−6 months after CPAP therapy. Nocturnal BP and NBPF frequency in REM and non-REM sleep were investigated, as well as NBPF pattern changes after receiving CPAP therapy. CPAP therapy resulted in significant reductions in the apnea−hypopnea index (AHI), arousal index, nocturnal systolic and diastolic BP, and NBPF frequency in REM and non-REM sleep (all p < 0.01). A higher AHI before CPAP resulted in lower nocturnal systolic BP (r = 0.40, p = 0.019) and NBPFs (r = 0.51, p = 0.002) after CPAP. However, 58.8% of patients showed no change in NBPF patterns with CPAP therapy. CPAP therapy significantly improved almost all sleep-related parameters, nocturnal BP, and NBPF frequency in REM and non-REM sleep periods, but NBPF patterns showed various changes post-CPAP therapy. These results suggest that factors other than OSA influence changes in NBPF patterns.

The recent bacterial etiology of childhood osteoarticular infections focusing on the vaccine initiation for Streptococcus pneumoniae and Haemophilus influenzae: A single-center retrospective analysis in Japan.

Background: Pediatric acute osteomyelitis and septic arthritis can destroy growth plate cartilage and joint cartilage, causing permanent deformities and growth disorders. Preventing the contraction of osteoarticular infections is important. Various types of bacteria cause osteoarticular infections in children. Since 2013, when routine vaccination against Streptococcus pneumoniae and Haemophilus influenzae was initiated in Japan, diseases caused by these bacteria (other than osteoarticular infection) are reported to decrease. In this study, we aimed to re-confirm the actual situation including the presence of pathogenic bacteria of pediatric bone and joint infections. Methods: The subjects were patients of 15 years old or younger who had been diagnosed with acute osteomyelitis or septic arthritis and received initial treatment in our hospital from April 1995 to March 2019. We obtained information from the medical records and analyzed them statistically. Results: There were 65 patients with 65 bones with acute osteomyelitis, and 120 patients with 124 joints with septic arthritis. The pathogenic bacteria were identified in 26 (40.0%) osteomyelitis patients and 59 (49.2%) septic arthritis patients. Staphylococcus aureus was the most common pathogenic bacterium, and S. pneumoniae and H. influenzae were identified in four and seven patients respectively, frequently in younger patients. After routine vaccination against S. pneumoniae and H. influenzae, these bacteria were no longer detected in patients under five years old. Conclusions: The efficacy of the S. pneumoniae and H. influenzae vaccine against orthopedic infectious diseases in Japan was indicated.

Myxoid type and non-myxoid type of intimal sarcoma in large vessels and heart: review of histological and genetic profiles of 20 cases.

Intimal sarcoma is one of the most common and well-known primary malignant neoplasms of the aorta and heart. The authors reviewed cases of intimal sarcoma from histological, immunohistochemical and genetic perspectives. Twenty cases of intimal sarcoma were retrieved. Immunohistochemistry and FISH of MDM2 and PDGFRA genes were performed. All 20 tumours were composed of spindle-shaped, stellate, oval or polygonal tumour cells with irregular hyperchromatic nuclei arranged in a haphazard pattern, accompanied by nuclear pleomorphism and frequent mitotic figures. Other histological findings were as follows: abnormal mitosis in 10 cases (50%), necrosis in 15 cases (75%), myxoid stroma in 12 cases (60%), cartilaginous formation in 1 case (5%), haemorrhage in 12 cases (60%) and fibrinous deposition in 14 cases (70%). The tumours were positive for MDM2 in 16 cases (80%), ERG in 4 cases (20%), alpha-smooth muscle actin in 6 cases (30%), desmin in 5 cases (25%) and AE1/AE3 in 4 cases (20%). Immunohistochemical positivity was focal in each case. Loss of H3K27me3 expression was noted in 2 cases (10%). MDM2 and PDGFRA gene amplifications were detected in 11 cases (55%) and 1 case (5%), respectively. Fisher's exact test revealed a significant correlation between MDM2 gene amplification and myxoid stroma (p = 0.0194). No parameters showed any association with the anatomical location of the tumours. It was suggested that myxoid histology of intimal sarcoma may be associated with MDM2 gene amplification and that intimal sarcoma may be divided into myxoid and non-myxoid types.

Histological and immunohistochemical features and genetic alterations in the malignant progression of giant cell tumor of bone: a possible association with TP53 mutation and loss of H3K27 trimethylation.

In rare cases, giant cell tumor of bone (GCTB) can undergo primary or secondary malignant transformation to malignant giant cell tumor of bone (MGCTB), but the details of the molecular alterations are still unclear. The present study aimed to elucidate the clinicopathologic and molecular features of MGCTBs based on immunohistochemistry, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) of nine MGCTBs (five primary and four secondary). Seven (78%) of 9 MGCTBs were immunohistochemically positive for H3.3 G34W. In two (22%) patients, although GCTB components were focally or diffusely positive for H3.3 G34W, their malignant components were entirely negative for H3.3 G34W, which was associated with heterozygous loss of H3F3A by FISH. NGS on four MGCTBs revealed pathogenic mutations in TP53 (n = 3), EZH2 (n = 1) and several other genes. Immunohistochemical analysis of the nine MGCTBs confirmed the p53 nuclear accumulation (n = 5) and loss of H3K27me3 expression (n = 3) and showed that they were mutually exclusive. In addition, four (80%) of five cases of pleomorphic or epithelioid cell-predominant MGCTBs were positive for p53, while three (75%) of four cases of spindle cell-predominant MGCTBs were negative for trimethylation at lysine 27 of histone 3 (H3K27me3). The results suggested that p53 alteration and dysfunction of histone methylation as evidenced by H3K27me3 loss may play an important role in the malignant progression of GCTB, and might contribute to the phenotype-genotype correlation in MGCTB. The combined histologic, immunohistochemical and molecular information may be helpful in part for the diagnosis of challenging cases.