A Histopathologic Image Analysis for the Classification of Endocervical Adenocarcinoma Silva Patterns Depend on Weakly Supervised Deep Learning.

Twenty-five percent of cervical cancers are classified as endocervical adenocarcinomas (EACs), which comprise a highly heterogeneous group of tumors. A histopathologic risk stratification system known as the Silva pattern system was developed based on morphology. However, accurately classifying such patterns can be challenging. The study objective was to develop a deep learning pipeline (Silva3-AI) that automatically analyzes whole slide image-based histopathologic images and identifies Silva patterns with high accuracy. Initially, a total of 202 patients with EACs and histopathologic slides were obtained from Qilu Hospital of Shandong University for developing and internally testing the Silva3-AI model. Subsequently, an additional 161 patients and slides were collected from seven other medical centers for independent testing. The Silva3-AI model was developed using a vision transformer and recurrent neural network architecture, utilizing multi-magnification patches, and its performance was evaluated based on a class-specific area under the receiver-operating characteristic curve. Silva3-AI achieved a class-specific area under the receiver-operating characteristic curve of 0.947 for Silva A, 0.908 for Silva B, and 0.947 for Silva C on the independent test set. Notably, the performance of Silva3-AI was consistent with that of professional pathologists with 10 years' diagnostic experience. Furthermore, the visualization of prediction heatmaps facilitated the identification of tumor microenvironment heterogeneity, which is known to contribute to variations in Silva patterns.

Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19-Related Hospitalization and Mortality: A Systematic Literature Review.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. AREAS OF UNCERTAINTY: As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. DATA SOURCES: We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness. THERAPEUTIC ADVANCES: In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. CONCLUSION: The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

Associations of retinal microvascular alterations with diabetes mellitus: an OCTA-based cross-sectional study.

BACKGROUND: Diabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes. METHODS: The Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed. RESULTS: This study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P < 0.001), longer axial length (AL, mm) (Beta = -0.13, 95%CI = -0.48 to -0.25, P = 0.002), and elevated heart rate (Beta = -0.10, 95%CI = -0.14 to -0.19, P = 0.014), after adjusting for younger age (Beta = -0.18, 95%CI = -0.24 to -0.35, P < 0.001), consistent with VD of the whole macular region. A higher FPG level was significantly correlated with lower SCP density of both PD and VD in the macular and parafoveal region (P < 0.05 for all), as well as increased systolic blood pressure and low-density lipoprotein cholesterol concentration (P < 0.01 for all). CONCLUSIONS: In this large-sample cross-sectional study, OCTA evaluation revealed that high prevalence of diabetes and elevated FPG levels were correlated with reduced retinal VD and PD. Hypertension and hyperlipidemia are important risk factors for the development of atherosclerotic cardiovascular disease but have no significant effect on retinal microvascular abnormalities.

Toward Antifragility: Social Defeat Stress Enhances Learning and Memory in Young Mice Via Hippocampal Synaptosome Associated Protein 25.

Social adversity not only causes severe psychological diseases but also may improve people's ability to learn and grow. However, the beneficial effects of social adversity are often ignored. In this study, we investigated whether and how social adversity affects learning and memory in a mouse social defeat stress (SDS) model. A total of 652 mice were placed in experimental groups of six to 23 mice each. SDS enhanced spatial, novelty, and fear memory with increased synaptosome associated protein 25 (SNAP-25) level and dendritic spine density in hippocampal neurons among young but not middle-aged mice. Chemogenetic inhibition of hippocampal CaMK2A+ neurons blocked SDS-induced enhancement of learning or memory. Knockdown of SNAP-25 or blockade of N-methyl-D-aspartate (NMDA) receptor subunit GluN2B in the hippocampus prevented SDS-induced learning memory enhancement in an emotion-independent manner. These findings suggest that social adversity promotes learning and memory ability in youths and provide a neurobiological foundation for biopsychological antifragility.

Prevalence and associated health and lifestyle factors of myopic maculopathy in northern China: the Kailuan eye study.

BACKGROUND: To evaluate the prevalence and associated health and lifestyle factors of myopic maculopathy (MM) in a northern Chinese industrial city. METHODS: The cross-sectional Kailuan Eye Study included subjects who participated in the longitudinal Kailuan Study in 2016. Ophthalmologic and general examinations were performed on all the participants. MM was graded based on fundus photographs using the International Photographic Classification and Grading System. The prevalence of MM was evaluated. Univariate and multiple logistic regression were adopted to evaluated risk factors of MM. RESULTS: The study included 8330 participants with gradable fundus photographs for MM and ocular biometry data. The prevalence of MM was 1.11% (93/8330; 95% confidence interval [CI] 0.89-1.33%). Diffuse chorioretinal atrophy, patchy chorioretinal atrophy, macular atrophy, and plus lesions were observed in 72 (0.9%), 15 (0.2%), 6 (0.007%), and 32 eyes (0.4%), respectively. MM was more common in eyes with longer axial length (OR 4.517; 95%CI 3.273 to 6.235) and in participants with hypertension (OR 3.460; 95%CI 1.152 to 10.391), and older age (OR 1.084; 95%CI 1.036 to 1.134). CONCLUSIONS: The MM was present in 1.11% of the northern Chinese individuals 21 years or older and the associate factors include longer axial length, older age, and hypertension.

Ferulic Acid Alleviates Hepatic Lipid Accumulation and Inflammation by Improving Proximal and Distal Intestinal Barriers in NAFLD Mice.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with low-grade chronic inflammation which is usually induced by intestinal dysbiosis. As ferulic acid (FA) has been proven effective at improving the intestinal integrity, we aimed to determine the effect of dietary FA on NAFLD development in high-fat dieted (HFD) mice, a well-established model of NAFLD. Male C57BL/6J mice were fed either a normal chow diet (ND) or HFD with or without FA (40 mg/kg) orally for 6 weeks. FA significantly alleviated lipid metabolism disorder and reduced liver inflammation in HFD mice (P < 0.05). As expected, FA improved the ileal intestinal integrity likely via the Nuclear factor E2-related factor 2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling pathway. Importantly, we found that FA also relieved HFD-induced gut microbiota dysbiosis by inhibiting the growth of harmful bacteria such as Helicobacter and increased the abundance of many short-chain fatty acids (SCFAs)-producing bacteria (P < 0.05). Our data indicated that FA not only increased the colonic levels of SCFAs, but also maintained the colonic barrier integrity by up-regulating the expression of the epithelial tight junction protein. These data indicated that FA alleviated NAFLD by reducing circulating lipopolysaccharide levels. These effects may be due to improved proximal and distal intestinal barriers, which presumably mediated through the interaction of FA with the gut microbiota.

Real-world cost-effectiveness of primary prophylaxis with G-CSF biosimilars in patients at intermediate/high risk of febrile neutropenia.

Background: Real-world data suggests superiority of pegfilgrastim (PEG) over filgrastim (FIL) in reducing the incidence of chemotherapy-induced febrile neutropenia (FN), probably attributable to underdosed FIL in practice. We used real-world data to assess the cost-effectiveness of primary prophylaxis with PEG versus FIL in cancer patients at intermediate-to-high risk of FN from a US payer perspective. Methods: A Markov model with lifetime horizon. Results: For the high-risk group, PEG (vs FIL) biosimilars resulted in 0.43 FN events prevented (FNp), 0.27 quality-adjusted life-years gained (QALYg) and a cost saving of USD$5703. For the intermediate-risk group, PEG biosimilar led to 0.18 FNp and 0.12 QALYg, at USD$9674/FNp and USD$14,502/QALYg. Conclusion: PEG biosimilars may provide opportunities to optimize FN management in patients with intermediate-to-high FN risk.

Our results have demonstrated that, by taking the real-world dosing and effectiveness of pegfilgrastim versus filgrastim into account, pegfilgrastim biosimilars have the potential to financially optimize neutropenia management in cancer patients by reducing febrile neutropenia (FN) incidence and FN-related healthcare resource utilization, and to potentially improve health outcomes. Extending primary prophylaxis with pegfilgrastim biosimilars from cancer patients with high-to-intermediate risk of FN resulted in clinical benefits, at acceptable incremental costs. Given the accelerated availability of pegfilgrastim biosimilars, it is important to instigate a rethink of FN management in cancer patients and implement guidelines that maximize the benefits of pegfilgrastim both clinically and economically.

Intercalary frozen autografts for reconstruction of bone defects following meta-/diaphyseal tumor resection at the extremities.

BACKGROUND: For patients with malignant limb tumors, salvage surgery can be achieved using endoprosthesis or biological reconstructions like allograft or autograft. In carefully selected patients, resected bone can be recycled after sterilization using methods like autoclaving, irradiation, pasteurization or freezing with liquid nitrogen. We evaluated the clinical outcome and complications of malignant limb tumors treated with intercalary resection and frozen autograft reconstruction. METHODS: We reviewed 33 patients whose malignant bone tumors were treated by wide resection and reconstruction with recycling liquid nitrogen-treated autografts between 2006 and 2017. Limb function, bone union at the osteotomy site and complications were evaluated. Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) scoring system. RESULTS: The cohort comprised 16 males and 17 females, with a mean age of 35.4 years (14-76 years). The most common tumor was osteosarcoma (7 cases). Tumors were located in the humerus (5), ulna (1), femur (10) and tibia (17). The mean follow-up was 49.9 months (range 12-127 months). Of the 33 patients, 16 remained disease-free, and 3 were alive with disease. The mean size of the defect after tumor resection was 11.6 cm (range 6-25 cm). Bone union was achieved in 32 patients, with a mean union time of 8.8 months (range 4-18 months). Complications included 1 graft nonunion, 2 infections (1 superficial, 1 deep infection), 1 leg length discrepancy, 2 graft fractures and 3 local recurrences. The mean MSTS score was 87.2% (range 70-100%). CONCLUSION: Liquid nitrogen-treated tumor-bearing autograft is an effective option for biological reconstruction after meta-/diaphyseal tumor resection of long bones. This method has excellent clinical outcomes and is especially recommended for patients with no severe osteolytic bone tumors.

Size selection and placement of pedicle screws using robot-assisted versus fluoroscopy-guided techniques for thoracolumbar fractures: possible implications for the screw loosening rate.

BACKGROUND: There has been increased development of robotic technologies for the accuracy of percutaneous pedicle screw placement. However, it remains unclear whether the robot really optimize the selection of screw sizes and enhance screw stability. The purpose of this study is to compare the sizes (diameter and length), placement accuracy and the loosening rate of pedicle screws using robotic-assisted versus conventional fluoroscopy approaches for thoracolumbar fractures. METHODS: A retrospective cohort study was conducted to evaluate 70 consecutive patients [34 cases of robot-assisted percutaneous pedicle screw fixation (RAF) and 36 of conventional fluoroscopy-guided percutaneous pedicle screw fixation (FGF)]. Demographics, clinical characteristics, and radiological features were recorded. Pedicle screw length, diameter, and pedicle screw placement accuracy were assessed. The patients' sagittal kyphosis Cobb angles (KCA), anterior vertebral height ratios (VHA), and screw loosening rate were evaluated by radiographic data 1 year after surgery. RESULTS: There was no significant difference in the mean computed tomography (CT) Hounsfield unit (HU) values, operation duration, or length of hospital stay between the groups. Compared with the FGF group, the RAF group had a lower fluoroscopy frequency [14 (12-18) vs. 21 (16-25), P < 0.001] and a higher "grade A + B" pedicle screw placement rate (96.5% vs. 89.4%, P < 0.05). The mean screw diameter was 6.04 ± 0.55 mm in the RAF group and 5.78 ± 0.50 mm in the FGF group (P < 0.001). The mean screw length was 50.45 ± 4.37 mm in the RAF group and 48.63 ± 3.86 mm in the FGF group (P < 0.001). The correction loss of the KCA and VHR of the RAF group was less than that of the FGT group at the 1-year follow-up [(3.8 ± 1.8° vs. 4.9 ± 4.2°) and (5.5 ± 4.9% vs. 6.4 ± 5.7%)], and screw loosening occurred in 2 out of 34 patients (5.9%) in the RAF group, and 6 out of 36 patients (16.7%) in the FGF group, but there were no significant differences (P > 0.05). CONCLUSION: Compared with the fluoroscopy-guided technique, robotic-assisted spine surgery decreased radiation exposure and optimizes screw trajectories and dimensions intraoperatively. Although not statistically significant, the loosening rate of the RAF group was lower that of than the FGT group.

Baseline Neurocognitive Impairment (NCI) Is Associated With Incident Frailty but Baseline Frailty Does Not Predict Incident NCI in Older Persons With Human Immunodeficiency Virus (HIV).

BACKGROUND: Neurocognitive impairment (NCI) and frailty are more prevalent among persons with human immunodeficiency virus (HIV, PWH) compared to those without HIV. Frailty and NCI often overlap with one another. Whether frailty precedes declines in neurocognitive function among PWH or vice versa has not been well established. METHODS: AIDS Clinical Trials Group (ACTG) A5322 is an observational cohort study of older PWH. Participants undergo annual assessments for NCI and frailty. ACTG A5322 participants who developed NCI as indexed by tests of impaired executive functioning and processing speed during the first 3 years were compared to persons who maintained normal cognitive function; those who demonstrated resolution of NCI were compared to those who had persistent NCI. Participants were similarly compared by frailty trajectory. We fit multinomial logistic regression models to assess associations between baseline covariates (including NCI) and frailty, and associations between baseline covariates (including frailty) and NCI. RESULTS: In total, 929 participants were included with a median age of 51 years (interquartile range [IQR] 46-56). At study entry, 16% had NCI, and 6% were frail. Over 3 years, 6% of participants developed NCI; 5% developed frailty. NCI was associated with development of frailty (odds ratio [OR] = 2.06; 95% confidence interval [CI] = .94, 4.48; P = .07). Further adjustment for confounding strengthened this association (OR = 2.79; 95% CI = 1.21, 6.43; P = .02). Baseline frailty however was not associated with NCI development. CONCLUSIONS: NCI was associated with increased risk of frailty, but frailty was not associated with development of NCI. These findings suggest that the presence of NCI in PWH should prompt monitoring for the development of frailty and interventions to prevent frailty in this population.

LncRNA CTD-3252C9.4 modulates pancreatic cancer cell survival and apoptosis through regulating IFI6 transcription.

BACKGROUND: Pancreatic cancer (PC) is one of the most lethal cancer types with high degree of malignancy and poor prognosis. Recent studies have shown that long non-coding RNAs (lncRNAs) were associated with the initiation and progression of pancreatic cancer. In the current study, we have investigated the expression, biological function and mechanism of a lncRNA CTD-3252C9.4 in pancreatic cancer. METHODS: The expression of CTD-3252C9.4 in pancreatic cancer cells and tissues was measured by qRT-PCR. In vitro and in vivo functional experiments assays were implemented for identifying CTD-3252C9.4 function in pancreatic cancer. Molecular relationships among CTD-3252C9.4, IRF1 and IFI6 were investigated via luciferase reporter assay, pulldown assay and ChIP assays. RESULTS: CTD-3252C9.4 was found remarkably decreased in pancreatic cancer cells and tissues. Overexpression of CTD-3252C9.4 suppressed migration, invasion and proliferation, yet facilitated apoptosis of pancreatic cancer cells both in vitro and in vivo. Then, IFI6 was identified as a downstream target that could be down-regulated by CTD-3252C9.4 and IFI6 overexpression could counteract the effects of CTD-3252C9.4 upregulation on the survival and apoptosis of pancreatic cancer cells. Furthermore, mechanism experiments revealed that IRF1 was a transcriptional factor of IFI6 that can be blocked by CTD-3252C9.4 to inhibit IFI6 transcription. CONCLUSION: Our data indicated that CTD-3252C9.4 could promote pancreatic cancer cell apoptosis and restrain cell growth via binding IRF1 and preventing the transcription of IFI6, which may become a potential therapeutic target for pancreatic cancer.

Real-world use and acceptance of biosimilar monoclonal antibodies of rituximab in oncology practice in the USA.

Aim: To describe treatment patterns and patient and provider characteristics associated with the recently introduced biosimilar rituximab-pvvr. Methods: This retrospective analysis included adult patients with one or more claims for rituximab-pvvr, with an index date of 23 January 2020 and a study period covering 1 January 2019-31 July 2020. Results: Of 249 patients included, the most common rituximab-pvvr indications were non-Hodgkin's lymphoma (77.5%) and chronic lymphocytic leukemia (11.2%). Some patients with non-Hodgkin's lymphoma (42.5%) and chronic lymphocytic leukemia (39.3%) switched to rituximab-pvvr from the reference product or another rituximab biosimilar. Most patients were aged ≥65 years (63.5%) and were male (54.6%). Most (59.0%) rituximab-pvvr prescribers practiced in the south of the USA. Conclusion: Utilization occurred in approved and extrapolated indications. These preliminary findings suggest switching between reference product and rituximab biosimilars; rituximab-pvvr combination regimens are being adopted in real-world oncology practice.

Lay abstract A biosimilar is a biological medication that is highly similar in structure and function to a biological medication already approved by the US FDA ­ the 'original biologic'. The first biosimilars approved to treat certain blood cancers have become available in the USA. This study examined how a recently introduced rituximab biosimilar was being utilized, looking at patient and physician characteristics from a medical and prescription insurance claims database. This study did not examine the safety or effectiveness of this medication. While initial data are limited, the biosimilar, rituximab-pvvr, appears to be utilized to treat the same types of cancer as the original biologic, rituximab. The biosimilar was most frequently prescribed for non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

A comparison of pregnancy outcome of emergency modified transvaginal cervicoisthmic cerclage performed in twin and singleton pregnancies.

PURPOSE: To compare the pregnancy outcome of emergency cerclage performed in twin and singleton pregnancies. METHODS: A retrospective trial was carried out in the Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital in Zhejiang, China, from January 2013 to December 2018. A total of 89 women with acute cervical incompetence underwent the emergency cerclage. Main outcome measures were gestational age at delivery and the fetal outcome. RESULTS: There were 31 twin and 58 singleton pregnancies that underwent emergency cerclage. In singleton pregnancies, gestational age at delivery (31.57 ± 6.11 vs 28.81 ± 4.34, p = 0.016), and prolongation of pregnancy (8.69 ± 6.13 vs 5.41 ± 3.72, p < 0.001) were greater, and the preterm delivery rate before 34 weeks was lower (53.4% vs 80.6%, p = 0.011) compared with twin pregnancies. Fetal weight was greater in singletons than in twins (2377.3 ± 862.1 vs 1630.3 ± 557.6, p < 0.001), but the fetal survival rate was similar. The proportion of twin gestations was significantly higher in the group with preterm delivery before 34 weeks (44.6% vs 18.2%, p = 0.011) and the proportion of previous term delivery was higher in the group with delivery at or after 34 weeks (30.3% vs 12.5%, p = 0.039). The group with preterm delivery before 34 weeks had a significantly larger size of visible membranes at cerclage than the group with delivery at or after 34 weeks (2.23 ± 0.86 vs 1.64 ± 0.80, p = 0.001). In binary logistic regression analysis, twin gestations and a larger size of visible membranes were associated with an increased risk of preterm delivery. CONCLUSION: The pregnancy outcome of emergency cerclage appears to have a better prognosis in singleton pregnancies than in twin pregnancies, and twin pregnancy is a risk factor for preterm delivery.

[Comparison of endogenetic microbial community diversity between wild Cordyceps sinensis,artificial C. sinensis and habitat soil].

To obtain the difference of the fungal and bacterial community diversity between wild Cordyceps sinensis, artificial C. sinensis and their habitat soil, Illmina Hiseq high-throughput sequencing technology was applied. The results show that Proteobacteria was the dominant bacterial phylum in C. sinensis, Actinobacteria was the dominant bacterial phylum in soil microhabitat, Ophiocordyceps sinensis was the predominant dominant fungus of C. sinensis. The α diversity analysis showed that the fungal diversity of stroma was lower than other parts, and the fungal diversity of wild C. sinensis was lower than that of artificial C. sinensis. The ß diversity analysis showed that the fungal and bacterial community diversity of soil microhabitat samples was significantly different from that of C. sinensis. The fungal community diversity was less different between wild and artificial C. sinensis, especially in sclerotia. LEfSe analysis showed a lot of species diversity between wild and artificial C. sinensis. Those different species between wild C. sinensis, artificial C. sinensis and their habitat soil provide ideas for further research on breed and components of C. sinensis.

Patterns of seizure prophylaxis after oncologic neurosurgery.

BACKGROUND: Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely unknown beyond survey data. OBJECTIVE: To describe patterns and predictors of postoperative AED prophylaxis following intracranial tumor surgery. METHODS: The MarketScan Database was used to analyze pharmacy claims data and clinical characteristics in a national sample over a 5-year period. RESULTS: Among 5895 patients in the cohort, levetiracetam was the most widely used AED for prophylaxis (78.5%) followed by phenytoin (20.5%). Prophylaxis was common but highly variable for patients who underwent open resection of supratentorial intraparenchymal tumors (62.5%, reference) or meningiomas (61.9%). In multivariate analysis, biopsies were less likely to receive prophylaxis (44.8%, OR 0.47, 95% CI 0.33-0.67), and there was near consensus against prophylaxis for infratentorial (9.7%, OR 0.07, CI 0.05-0.09) and transsphenoidal procedures (0.4%, OR 0.003, CI 0.001-0.010). Primary malignancies (52.1%, reference) and secondary metastases (42.2%) were more likely to receive prophylaxis than benign tumors (23.0%, OR 0.63, CI 0.48-0.83), as were patients discharged with home services and patients in the Northeast. There was a large spike in duration of AED use at approximately 30 days. CONCLUSIONS: Use of seizure prophylaxis following intracranial biopsies and supratentorial resections is highly variable, consistent with a lack of guidelines or consensus. Current practice patterns do not support a clear standard of care and may be driven in part by geographic variation, availability of post-discharge services, and electronic prescribing defaults rather than evidence. Given uncertainty regarding effectiveness, indications, and appropriate duration of AED prophylaxis, well-powered trials are needed.

Prevalence of osteoporosis and osteopenia diagnosed using quantitative CT in 296 consecutive lumbar fusion patients.

OBJECTIVE: Osteoporosis is a metabolic bone disease that increases the risk for fragility fractures. Screening and diagnosis can be achieved by measuring bone mineral density (BMD) using quantitative CT tomography (QCT) in the lumbar spine. QCT-derived BMD measurements can be used to diagnose osteopenia or osteoporosis based on American College of Radiology (ACR) thresholds. Many reports exist regarding the disease prevalence in asymptomatic and disease-specific populations; however, osteoporosis/osteopenia prevalence rates in lumbar spine fusion patients without fracture have not been reported. The purpose of this study was to define osteoporosis and osteopenia prevalence in lumbar fusion patients using QCT. METHODS: A retrospective review of prospective data was performed. All patients undergoing lumbar fusion surgery who had preoperative fine-cut CT scans were eligible. QCT-derived BMD measurements were performed at L1 and L2. The L1-2 average BMD was used to classify patients as having normal findings, osteopenia, or osteoporosis based on ACR criteria. Disease prevalence was calculated. Subgroup analyses based on age, sex, ethnicity, and history of abnormal BMD were performed. Differences between categorical groups were calculated with Fisher's exact test. RESULTS: Overall, 296 consecutive patients (55.4% female) were studied. The mean age was 63 years (range 21-89 years). There were 248 (83.8%) patients with ages ≥ 50 years. No previous clinical history of abnormal BMD was seen in 212 (71.6%) patients. Osteopenia was present in 129 (43.6%) patients and osteoporosis in 44 (14.9%). There were no prevalence differences between sex or race. Patients ≥ 50 years of age had a significantly higher frequency of osteopenia/osteoporosis than those who were < 50 years of age. CONCLUSIONS: In 296 consecutive patients undergoing lumbar fusion surgery, the prevalence of osteoporosis was 14.9% and that for osteopenia was 43.6% diagnosed by QCT. This is the first report of osteoporosis disease prevalence in lumbar fusion patients without vertebral fragility fractures diagnosed by QCT.

An 11-gene-based prognostic signature for uveal melanoma metastasis based on gene expression and DNA methylation profile.

Uveal melanoma (UM) is the most common intraocular tumor worldwide. We proposed to identify a vital gene signature that has prognostic value for UM metastasis. For this purpose, we obtained a published DNA methylation and gene expression data set associated with UM from the Gene Expression Omnibus. The genes whose aberrant expression significantly associated with UM patients' metastasis-free survival (MFS) were identified by applying a univariate Cox proportional hazards model to the gene expression data set followed by a robust likelihood-based survival analysis to screen the optimal prognostic gene signatures (PGS). A formula for calculating the risk score that represents UM metastasis risk was constructed by including the PGSs' expression values weighted by their regression coefficients, which were obtained by a multivariate Cox regression analysis. As a result, aberrant expression of 2884 genes were found to be significantly associated with UM patients' MFS, which were referred to as MFSGs, and 11 out of those MFSGs, GJC1, TCEA1, MFSD3, FAF2, TLCD1, GPAA1, CYC1, ASAP1, JPH1, LDB3, and KDELR3, were identified as PGSs through which we could accurately separate UM samples with shorter MFS from those with longer MFS. By combining the DNA methylation data set and MFSGs, we further identified 265 MFSGs, which contained CpG sites that significantly hyper- or hypo-methylated in UM samples compared with control samples. Functional enrichment analysis and pathway crosstalk analysis of those genes indicated significant enrichment of cancer-related pathways. In conclusion, we identified an 11-gene-based prognostic signature and several gene biomarkers for UM metastasis, which should be helpful for selecting an appropriate treatment method for specific patients with UM.

Extraperiosteal segmental excision for osteofibrous dysplasia of tibia with reconstruction by liquid nitrogen-treated recycled autograft.

BACKGROUND: Osteofibrous dysplasia usually progresses until ten years of age and occasionally regresses spontaneously after puberty. Patients with osteofibrous dysplasia usually require close observation. Surgery is an option considered only for extensive, deforming lesions and those with pathological fractures and rapid progression prior to puberty. If surgery is indicated, the traditional intra-lesional curettage or subperiosteal resection usually leads to high recurrence. Hence, extraperiosteal wide excision and various methods of reconstruction after resection have been advocated for this lesion. We reviewed the clinical results of patients managed with extraperiosteal segmental excision and reconstruction by liquid nitrogen-treated tumor-bearing autograft combined with allograft. METHODS: From January 2010 to December 2014, twelve patients with final diagnosis of tibial osteofibrous dysplasia were studied retrospectively. All these patients were treated with extraperiosteal segmental excision and reconstruction by liquid nitrogen-treated tumor-bearing autograft combined with allograft. RESULTS: The patient group consisted of 5 males and 7 females, with a median age of 13 years (6-24 years). 3 lesions were located in left tibia and 9 in right. The median length of resected segment was 8 cm (5-11 cm). The patients were followed for 36-84 months (median 52 months). Follow-up radiographs showed that the median time for complete union of the grafted bone was 9 months (6-15 months). There was no evidence of recurrence. All patients had full range of motion in the knee and ankle joints after surgery. CONCLUSIONS: Extraperiosteal segmental excision for osteofibrous dysplasia of tibia with reconstruction by liquid nitrogen-treated recycled autograft and allograft is a good surgical option to prevent recurrence and fill bone defects in this rare lesion.

Inositol polyphosphate-4-phosphatase type II and rucaparib treatment inhibit the growth of osteosarcoma cells dependent on phosphoinositide 3-kinase/protein kinase B pathway.

Osteosarcoma (OS) is an aggressive malignant tumor of bone, which often occurs in children and adolescents. Currently, the effective method for the treatment of OS is still limited. The study aimed to investigate the synergistic antitumor effect of inositol polyphosphate-4-phosphatase, type-II (INPP4B) and rucaparib on OS cells. The expression levels of INPP4B in OS tissues and OS cell lines were examined by quantitative real-time polymerase chain reaction and Western blot analysis. SaOS2 and U2OS cells were then transfected with overexpression vector of INPP4B or were treated with different concentrations of rucaparib, and cell viability, cell cycle, and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry. Western blot assay uncovered the combined effects of INPP4B and rucaparib on cell cycle, apoptosis and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signal pathway. Further, the tumor formation was examined in vivo. Results showed that INPP4B was low expressed in OS tissues and in OS cell lines. INPP4B overexpression significantly decreased cell viability and induced apoptosis in SaOS2 and U2OS cells. Additionally, rucaparib remarkably reduced cell viability in a dose-dependent and time-dependent manner. Meanwhile, rucaparib suppressed cell cycle progression in the S phase and promoted apoptosis in a dose-dependent manner. Further, combination of INPP4B overexpression and rucaparib declined Myc, cyclin E1 and cyclin D1 expressions, enhanced Bad, Bax, and cleaved-caspase-3 expressions, and blocked PI3K/AKT signal pathway in SaOS2 and U2OS cells. Finally, combination of INPP4B overexpression and rucaparib inhibited tumor formation in vivo. The study demonstrated that INPP4B and rucaparib exhibited synergistic antitumor effect by regulating PI3K/AKT pathway in OS cells.

The modified frailty index and 30-day adverse events in oncologic neurosurgery.

The modified frailty index (mFI) is emerging as a leading measure for preoperative risk assessment using routinely available medical record data. Our objective was to determine if mFI predicts morbidity and mortality in the diverse national cohort of patients undergoing neurosurgery for intracranial neoplasms. We identified patients in the National Surgical Quality Improvement Program who underwent oncologic neurosurgery procedures between 2008 and 2012. The mFI, ranging from 0 to 1, was calculated as the proportion of 11 possible risk factors present. We assessed the associations between mFI and 30-day mortality, neurologic and medical complications, prolonged length of stay, and unfavorable discharge in univariate and multivariable analyses and compare the index to established risk stratification techniques. A total of 9149 patients were identified. Mortality, severe medical complications, prolonged length of stay, and unfavorable discharge increased incrementally with increasing levels of frailty. Severe neurologic complications were highest in those with low frailty. In multivariable logistic regression analysis, increased frailty increased the odds of all adverse outcomes, including neurologic complications. The mFI increased the ability to predict all outcomes beyond available indices and was the most reliable predictor of neurologic complications. The mFI can be calculated from routinely collected medical record data and is predictive of 30-day adverse outcomes in a wide variety of neurosurgical oncology patients. The index may be a useful component of preoperative risk assessment with implications for shared decision-making, perioperative planning, and risk adjusted outcomes measurement in national quality registries.