Solid tumor size for prediction of recurrence in large and giant non-functioning pituitary adenomas.

A subset of large non-functioning pituitary adenomas (lNFPA) and giant non-functioning pituitary adenomas (gNFPA) undergoes early progression/recurrence (P/R) after surgery. This study revealed the clinical and image predictors of P/R in lNFPA and gNFPA, with emphasis on solid tumor size. This retrospective study investigated the preoperative MR imaging features for the prediction of P/R in lNFPA (> 3 cm) and gNFPA (> 4 cm). Only the patients with a complete preoperative brain MRI and undergone postoperative MRI follow-ups for more than 1 year were included. From November 2010 to December 2020, a total of 34 patients diagnosed with lNFPA and gNFPA were included (median follow-up time 47.6 months) in this study. A total of twenty-three (23/34, 67.6%) patients had P/R, and the median time to P/R is 25.2 months. Solid tumor diameter (STD), solid tumor volume (STV), and extent of resection are associated with P/R (p < 0.05). Multivariate analysis showed large STV is a risk factor for P/R (p < 0.05) with a hazard ratio of 30.79. The cutoff points of STD and STV for prediction of P/R are 26 mm and 7.6 cm3, with AUCs of 0.78 and 0.79 respectively. Kaplan-Meier analysis of tumor P/R trends showed that patients with larger STD and STV exhibited shorter progression-free survival (p < 0.05). For lNFPA and gNFPA, preoperative STD and STV are significant predictors of P/R. The results offer objective and valuable information for treatment planning in this subgroup.

A novel surgical technique in transforaminal lumbar interbody fusion by the bone graft delivery device: evaluation of therapeutic effect in patients with minimally invasive spine surgery.

BACKGROUND: Transforaminal Lumbar Interbody Fusion (TLIF) is commonly associated with higher complications and longer operative time. This study aims to evaluate the effectiveness, safety, and usability of a novel minimally invasive surgery (MIS) bone graft delivery device. METHODS: 73 consecutive patients with lumbar spondylosis, degenerative disc disease, spondylolisthesis, scoliosis or trauma were enrolled in this randomized controlled trial. Group 1 comprised 39 patients treated with the novel MIS bone graft delivery device. Group 2 consisted of 34 patients treated with the conventional system. The primary objective of the study was the assessment of the amount of bone graft delivery using the device. The secondary objectives were the effect of the device on operative time, pain relief, disability improvement, and bone fusion grade. RESULTS: Bone delivery amount was significantly higher in the MIS device group (6.7 ± 2.9 mL) compared to the conventional group (2.3 ± 0.5 mL), p < 0.001. Regarding the operation time, the MIS device group was associated significantly lower duration than the conventional group (p < 0.001). After a 3-month follow-up, 39.5% of the patients in the MIS device group and 3.5% of the patients in the conventional group were observed to achieve grade I fusion (complete fusion). There was a significant difference in fusion success rates (p < 0.01). CONCLUSION: The novel MIS bone graft delivery device was associated with successful bone delivery. Our MIS device provides promising modality with less operative time and higher bone fusion rates than conventional modalities. Trial Registration This trial was retrospectively registered on ClinicalTrials.gov (Registration date: 11/19/2021; Registration number: NCT05190055).

Ceftriaxone therapy attenuates brain trauma in rats by affecting glutamate transporters and neuroinflammation and not by its antibacterial effects.

BACKGROUND: Ceftriaxone is a ß-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. METHODS: Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn's Gram staining. These parameters above were measured at 72 h after TBI. RESULTS: Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. CONCLUSIONS: The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

Triglyceride is a Good Biomarker of Increased Injury Severity on a High Fat Diet Rat After Traumatic Brain Injury.

Injury severity is correlated with poor prognosis after traumatic brain injury (TBI). It is not known whether triglycerides (TGs) or total cholesterol (TC) is good biomarker of increased injury of neuroinflammation and apoptosis in a high fat diet (HFD)-treated rat after TBI episodes. Five-week-old male Sprague-Dawley (SD) rats were fed a HFD for 8 weeks. The anesthetized male SD rats were divided into three sub-groups: sham-operated and TBI with 1.6 atm or with 2.4 atm fluid percussion injury (FPI). Cell infarction volume (triphenyltetrazolium chloride stain), tumor necrosis factor-alpha (TNF-α) expression in the microglia (OX42 marker) and astrocytes (Glial fibrillary acidic protein marker), TNF-α receptor expression in the neurons (TNFR1 and TNFR2 markers), and the extent of neuronal apoptosis (TUNEL marker) were evaluated by immunofluorescence, and the functional outcome was assessed by an inclined plane test. These tests were performed 72 h after TBI. Serum triglyceride and cholesterol levels were measured at 24, 48 and 72 h after TBI. The FPI with 2.4 atm significantly increased body weight loss, infarction volume, neuronal apoptosis and TNF-α expression in the microglia and astrocytes, and it decreased the maximum grasp degree and TNFR1 and TNFR2 expression in neurons at the 3rd day following TBI. The serum TG level was positively correlated with FPI force, infarction volume, Neu-N-TUNEL, GFAP-TNFα, and OX42-TNFα Simultaneously; the serum TG level was negatively correlated with Neu-N-TNFR1 and Neu-N-TNFR2. TG is a good biomarker of increased injury for neuroinflammation and apoptosis at the 3rd day after TBI in HFD rats.

Effects of a High-Fat Diet on Neuroinflammation and Apoptosis in Acute Stage After Moderate Traumatic Brain Injury in Rats.

BACKGROUND: A high-fat diet (HFD) is correlated with a higher risk of metabolic syndrome. The effect of HFD on neuroinflammation and apoptosis in acute stage after traumatic brain injury (TBI) in rats is not well known. MATERIALS AND METHODS: Five-week-old male Sprague-Dawley (SD) rats were fed a HFD or normal diet (ND) for 8 weeks. Anesthetized male SD rats were divided into two subgroups: sham-operated and TBI. Motor function was measured using an inclined plane. The numbers of apoptotic neurons (markers Neu-N, TUNEL, caspase-3), activated astrocytes (marker GFAP) and microglia (marker OX42), and TNF-α expression in microglia and astrocytes in the ischemic cortex were investigated using an immunofluorescence assay. All of the parameters were measured on the 3rd day after TBI. RESULTS: Rats fed a HFD for 8 weeks had higher body weight, serum cholesterol, and triglycerides. TBI-induced motor deficits, neuronal decrease, neuronal apoptosis, astrocyte and microglia activation, and TNF-α expression in microglia and astrocytes in the ischemia cortex were significantly increased in ND and HFD rats compared to sham rats. However, these parameters were not significantly different between the ND and HFD TBI groups, except motor deficit. CONCLUSIONS: HFD has no significant effects on neuronal apoptosis or neuroinflammation in acute stage compared with ND for 8 weeks after moderate TBI in experimental rats.

The Short-Term Effects of Isolated Traumatic Brain Injury on the Heart in Experimental Healthy Rats.

BACKGROUND: To date, cardiac dysfunction after traumatic brain injury (TBI) has not been consistent. In this study, we hypothesized that TBI may play a role in the development of new-onset cardiac dysfunction in healthy experimental rats. MATERIALS AND METHODS: Anesthetized healthy male Sprague-Dawley rats were divided into two groups: a sham-operated control group and a TBI group. The brain was injured with 2.4 atm percussion via a fluid percussion injury model. During the 120 min after TBI, we continuously measured brain parameters, including intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and cardiac parameters, such as heart rate (HR), inter-ventricular septum dimension (IVSD), left ventricular internal dimension diastole (LVIDd), end-diastolic volume (EDV), ejection fraction (EF), fractional shortening (FS), and LV mass diastole (LVd mass) by cardiac echo. On days 1, 3, 7, and 14 after TBI, the brain damage volume was evaluated with triphenyltetrazolium chloride; the physiological parameters of the heart, including HR, IVSd, LVIDd, EDV, EF, FS, and LVd mass, were evaluated with cardiac echo; the morphology of cardiomyocytes was examined by hematoxylin and eosin (HE) and Masson trichrome staining; and the biomarkers of cardiac injury troponin I and B-type natriuretic peptide (BNP) were also examined. RESULTS: Compared to sham-operated controls, the TBI groups had higher ICP, lower CPP, and higher brain neuronal apoptosis and infarction contusion volume. The impact of TBI on heart function showed hyperdynamic response trends in IVSd, LVIDd, EDV, EF, FS, and LVd mass within 30 min after TBI; however, EF and FS exhibited eventual decreasing trends. Simultaneously, the values of the biomarkers troponin I and BNP were within normal limits, and HE and Mass trichrome staining revealed no significant differences between the sham-operated control group and the TBI group. CONCLUSIONS: Our results suggest that TBI due to 2.4 atm fluid percussion injury in healthy experimental rats may cause significant damage to the brain and affect the heart function as investigated by cardiac echo but not as investigated by HE and Masson trichrome stainings or troponin I and BNP evaluation.

Radiomics approach for prediction of recurrence in skull base meningiomas.

PURPOSE: A subset of skull base meningiomas (SBM) may show early progression/recurrence (P/R) as a result of incomplete resection. The purpose of this study is the implementation of MR radiomics to predict P/R in SBM. METHODS: From October 2006 to December 2017, 60 patients diagnosed with pathologically confirmed SBM (WHO grade I, 56; grade II, 3; grade III, 1) were included in this study. Preoperative MRI including T2WI, diffusion-weighted imaging (DWI), and contrast-enhanced T1WI were analyzed. On each imaging modality, 13 histogram parameters and 20 textural gray level co-occurrence matrix (GLCM) features were extracted. Random forest algorithms were utilized to evaluate the importance of these parameters, and the most significant three parameters were selected to build a decision tree for prediction of P/R in SBM. Furthermore, ADC values obtained from manually placed ROI in tumor were also used to predict P/R in SBM for comparison. RESULTS: Gross-total resection (Simpson Grades I-III) was performed in 33 (33/60, 55%) patients, and 27 patients received subtotal resection. Twenty-one patients had P/R (21/60, 35%) after a postoperative follow-up period of at least 12 months. The three most significant parameters included in the final radiomics model were T1 max probability, T1 cluster shade, and ADC correlation. In the radiomics model, the accuracy for prediction of P/R was 90%; by comparison, the accuracy was 83% using ADC values measured from manually placed tumor ROI. CONCLUSIONS: The results show that the radiomics approach in preoperative MRI offer objective and valuable clinical information for treatment planning in SBM.

Prediction of progression in skull base meningiomas: additional benefits of apparent diffusion coefficient value.

A subset of benign (WHO grade I) skull base meningiomas show early progression/recurrence (P/R) in the first years after surgical resection. Besides, complete surgical resection may be difficult to achieve safely in skull base meningiomas due to complex neurovascular structures. The one main challenge in the treatment of skull base meningiomas is to determine factors that correlate with P/R. We retrospectively investigated the preoperative CT and MR imaging features for the prediction of P/R in skull base meningiomas, with emphasis on quantitative ADC values. Only patients had postoperative MRI follow-ups for more than 1 year (at least every 6 months) were included. From October 2006 to December 2015, total 73 patients diagnosed with benign (WHO grade I) skull base meningiomas were included (median follow-up time 41 months), and 17 (23.3%) patients had P/R (median time to P/R 28 months). Skull base meningiomas with spheno-orbital location, adjacent bone invasion, high DWI, and lower ADC value/ratio were significantly associated with P/R (P < 0.05). The cut-off points of ADC value and ADC ratio for prediction of P/R are 0.83 × 10- 3 mm2/s and 1.09 respectively, with excellent area under curve (AUC) values (0.86 and 0.91) (P < 0.05). In multivariate logistic regression, low ADC values (< 0.83 × 10- 3 mm2/s) and adjacent bone invasion are high-risk factors of P/R (P < 0.05), with odds ratios of 31.53 and 17.59 respectively. The preoperative CT and MRI features for prediction of P/R offered clinically vital information for the planning of treatment in skull base meningiomas.

Simvastatin Therapy in the Acute Stage of Traumatic Brain Injury Attenuates Brain Trauma-Induced Depression-Like Behavior in Rats by Reducing Neuroinflammation in the Hippocampus.

BACKGROUND: The antidepressant-like effects of simvastatin on traumatic brain injury (TBI) remain unclear. The present study aimed to investigate the neuroprotective effects of simvastatin and determine whether simvastatin attenuates TBI-induced depression-like behavior and, more specifically, acts as an antineuroinflammatory. METHODS: Anesthetized male Sprague-Dawley rats were divided into five groups: sham-operated controls, TBI controls, and TBI treatment with simvastatin 4, 10, or 20 mg/kg. Simvastatin was intraperitoneally injected 0, 24, and 48 h after TBI. The motor function was measured using an inclined plane, and depression-like behavior was evaluated using forced swimming tests. Neuronal apoptosis (markers: NeuN, TUNEL, caspase-3), microglia (marker: OX42) and astrocyte (marker: GFAP) activation, and TNF-α expression in the microglia and astrocytes of the hippocampal CA3 area were investigated using immunofluorescence assay. All parameters were measured on the 4th, 8th, and 15th day, or only on the 15th day after TBI. RESULTS: TBI-induced depression-like behavior, which increased duration of immobility, was significantly attenuated by 20 mg simvastatin therapy on day 15 after TBI. TBI-induced neuronal apoptosis, microglia and astrocyte activation, and TNF-α expression in the microglia and astrocytes of the CA3 area of the hippocampus were significantly reduced by simvastatin treatment, particularly when 20 mg/kg was administered for 3 days. CONCLUSIONS: Intraperitoneal injection of simvastatin attenuated TBI in rats during the acute stage by reducing neuronal apoptosis, microglia, and TNF-α expression, thereby resulting in a reduction of depressive-like behavior. Our results suggest that simvastatin may be a promising treatment for TBI-induced depression-like behavior.

Hyperbaric oxygen effects on neuronal apoptosis associations in a traumatic brain injury rat model.

BACKGROUND: The neuroprotective mechanisms of hyperbaric oxygen (HBO) therapy on traumatic brain injury (TBI) remain unclear, especially neuronal apoptosis associations such as the expression of tumor necrosis factor alpha (TNF-α), transforming growth-interacting factor (TGIF), and TGF-ß1 after TBI. The aim of this study was to investigate the neuroprotective effects of HBO therapy in a rat model of TBI. MATERIALS AND METHODS: The experimental rats were randomly divided into three groups as follows: TBI + normobaric air (21% O2 at one absolute atmosphere), TBI + HBO, and sham-operated normobaric air. The TBI + HBO rats received 100% O2 at 2.0 absolute atmosphere for 1 h immediately after TBI. Local and systemic TNF-α expression, neuropathology, levels of the neuronal apoptosis-associated proteins TGIF and TGF-ß1, and functional outcome were evaluated 72 h after the onset of TBI. RESULTS: Compared to the TBI control groups, the running speed of rats on the TreadScan after TBI was significantly attenuated by HBO therapy. The TBI-induced local and systemic TNF-α expression, neuronal damage score, and neuronal apoptosis were also significantly reduced by HBO therapy. Moreover, HBO treatment attenuated the expression of TGIF but increased TGF-ß1 expression in neurons. CONCLUSIONS: We concluded that treatment of TBI with HBO during the acute phase of injury can decrease local and systemic proinflammatory cytokine TNF-α production, resulting in neuroprotective effects. We also suggest that decreased levels of TGIF and increased levels of TGF-ß in the injured cortex leading to decreased neuronal apoptosis is one mechanism by which functional recovery may occur.

Microglial activation induced by traumatic brain injury is suppressed by postinjury treatment with hyperbaric oxygen therapy.

BACKGROUND: The mechanisms underlying the protective effects of hyperbaric oxygen (HBO) therapy on traumatic brain injury (TBI) are unclear. TBI initiates a neuroinflammatory cascade characterized by activation of microglia and increased production of proinflammatory cytokines. In this study, we attempted to ascertain whether the occurrence of neuroinflammation exhibited during TBI can be reduced by HBO. METHODS: TBI was produced by the fluid percussion technique in rats. HBO (100% O2 at 2.0 absolute atmospheres) was then used at 1 h (HBO I) or 8 h (HBO II) after TBI. Neurobehavior was evaluated by the inclined plane test on the 72 h after TBI and then the rats were killed. The infarction area was evaluated by Triphenyltetrazolium chloride. Immunofluorescence staining was used to evaluate neuronal apoptosis (TUNEL + NeuN), microglial cell aggregation count (OX42 + DAPI), and tumor necrosis factor-alpha (TNF-α) expression in microglia cell (OX42 + TNF-α). RESULTS: The maximum grasp angle in the inclined plane test and cerebral infarction of the rats after TBI were significantly attenuated by HBO therapy regardless of whether the rats were treated with HBO 1 or 8 h after TBI compared with the controls. TBI-induced microglial activation, TNF-α expression, and neuronal apoptosis were also significantly reduced by HBO therapy. CONCLUSIONS: Our results demonstrate that treatment of TBI during the acute phase of injury can attenuate microgliosis and proinflammatory cytokine TNF-α expression resulting in a neuroprotective effect. Even treating TBI with HBO after 8 h had a therapeutic effect.

Pretreatment diffusion-weighted imaging for prediction of relapsed and refractory primary central nervous system lymphoma.

Objectives: A subset of primary central nervous system lymphoma (PCNSL) has been shown to undergo an early relapsed/refractory (R/R) period after first-line chemotherapy. This study investigated the pretreatment clinical and MRI features to predict R/R in PCNSL, emphasizing the apparent diffusion coefficient (ADC) values in diffusion-weighted imaging (DWI). Methods: This retrospective study investigated the pretreatment MRI features for predicting R/R in PCNSL. Only patients who had undergone complete preoperative and postoperative MRI follow-up studies were included. From January 2006 to December 2021, 52 patients from two medical institutions with a diagnosis of PCNSL were included (median follow-up time, 26.3 months). Among these, 24 (46.2%) had developed R/R (median time to relapse, 13 months). Cox proportional hazard regression analyses were performed to determine hazard ratios for all parameters. Results: Significant predictors of R/R in PCNSL were female sex, complete response (CR) to first-line chemotherapy, and ADC value/ratio (p < 0.05). Cut-off points of ADC values and ADC ratios for prediction of R/R were 0.68 × 10-3 mm2/s and 0.97, with AUCs of 0.78 and 0.77, respectively (p < 0.05). Multivariate Cox proportional hazards analysis showed that failure of CR to first-line chemotherapy and low ADC values (<0.68 × 10-3 mm2/s) were significant risk factors for R/R, with hazard ratios of 5.22 and 14.45, respectively (p < 0.05). Kaplan-Meier analysis showed that lower ADC values and ratios predicted significantly shorter progression-free survival (p < 0.05). Conclusion: Pretreatment ADC values in DWI offer quantitative valuable information for the treatment planning in PCNSL.

Determinants of cancer incidence and mortality among people with vitamin D deficiency: an epidemiology study using a real-world population database.

Introduction: This study aimed to investigate the determinants of cancer incidence and mortality in patients with vitamin D deficiency using a real-world population database. Methods: We utilized the International Diagnostic Classification Code (ICD9:268 / ICD10: E55) to define patients with vitamin D deficiency. Additionally, the Cox regression model was used to estimate overall mortality and identify potential factors contributing to mortality in cancer patients. Results: In 5242 patients with vitamin D deficiency, the development of new-onset cancer was 229 (4.37%) patients. Colon cancer was the most prevalent cancer type. After considering confounding factors, patients aged 50-65 and more than 65 indicated a 3.10-fold (95% C.I.: 2.12-4.51) and 4.55-fold (95% C.I.: 3.03-6.82) cancer incidence, respectively compared with those aged <50. Moreover, patients with comorbidities of diabetes mellitus (DM) (HR: 1.56; 95% C.I.: 1.01-2.41) and liver disease (HR: 1.62; 95% C.I.: 1.03-2.54) presented a higher cancer incidence rate than those without DM/ liver disease. In addition, vitamin D deficiency patients with cancer and dementia histories indicated a significantly higher mortality risk (HR: 4.04; 95% C.I.: 1.05- 15.56) than those without dementia. Conclusion: In conclusion, our study revealed that vitamin D deficiency patients with liver disease had an increased incidence of cancer, while those with dementia had an increased mortality rate among cancer patients.

Machine Learning for Prediction of Recurrence in Parasagittal and Parafalcine Meningiomas: Combined Clinical and MRI Texture Features.

A subset of parasagittal and parafalcine (PSPF) meningiomas may show early progression/recurrence (P/R) after surgery. This study applied machine learning using combined clinical and texture features to predict P/R in PSPF meningiomas. A total of 57 consecutive patients with pathologically confirmed (WHO grade I) PSPF meningiomas treated in our institution between January 2007 to January 2019 were included. All included patients had complete preoperative magnetic resonance imaging (MRI) and more than one year MRI follow-up after surgery. Preoperative contrast-enhanced T1WI, T2WI, T1WI, and T2 fluid-attenuated inversion recovery (FLAIR) were analyzed retrospectively. The most significant 12 clinical features (extracted by LightGBM) and 73 texture features (extracted by SVM) were combined in random forest to predict P/R, and personalized radiomic scores were calculated. Thirteen patients (13/57, 22.8%) had P/R after surgery. The radiomic score was a high-risk factor for P/R with hazard ratio of 15.73 (p < 0.05) in multivariate hazards analysis. In receiver operating characteristic (ROC) analysis, an AUC of 0.91 with cut-off value of 0.269 was observed in radiomic scores for predicting P/R. Subtotal resection, low apparent diffusion coefficient (ADC) values, and high radiomic scores were associated with shorter progression-free survival (p < 0.05). Among different data input, machine learning using combined clinical and texture features showed the best predictive performance, with an accuracy of 91%, precision of 85%, and AUC of 0.88. Machine learning using combined clinical and texture features may have the potential to predict recurrence in PSPF meningiomas.

The Association between Smoking and Mortality in Women with Breast Cancer: A Real-World Database Analysis.

Smoking increases the cancer-specific and overall mortality risk in women with breast cancer (BC). However, the effect of smoking cessation remains controversial, and detailed research is lacking in Asia. We aimed to investigate the association between smoking status and mortality in women with BC using the population-based cancer registry. The Taiwan Cancer Registry was used to identify women with BC from 2011 to 2017. A total of 54,614 women with BC were enrolled, including 1687 smokers and 52,927 non-smokers. The outcome, mortality, was identified using Taiwan's cause-of-death database. The association between smoking status and mortality was estimated using Cox proportional regression. Women with BC who smoked had a 1.25-fold higher (95% C.I.: 1.08-1.45; p = 0.0022) risk of overall mortality and a 1.22-fold higher (95% C.I.: 1.04-1.44; p = 0.0168) risk of cancer-specific mortality compared with non-smokers. The stratified analysis also indicated that women with BC who smoked showed a significantly higher overall mortality risk (HR: 1.20; 95% CI: 1.01-1.43; p = 0.0408) than women with BC who did not smoke among women without comorbidities. Additionally, current smokers had a 1.57-fold higher risk (95% CI: 1.02-2.42; p = 0.0407) of overall mortality compared with ever smokers among women with BC who smoked. It was shown that a current smoking status is significantly associated with an increase in overall and cancer-specific mortality risk in women with BC. Quitting smoking could reduce one's mortality risk. Our results underscore the importance of smoking cessation for women with BC.

The efficacy of vancomycin-loaded biphasic calcium phosphate bone substitute in the promotion of new bone growth and the prevention of postoperative infection.

Background: Due to the increasing need for suitable alternatives to bone grafts, artificial bones made of biphasic calcium phosphate (BCP) are currently being extensively researched. These porous bone substitutes have also demonstrated considerable incorporation with the host bone, and new bone is able to grow within the porous structure. They therefore offer a potential therapeutic approach for bone defects. Methods: Vancomycin-loaded Bicera™, a BCP bone substitute, was investigated in order to prevent implant-associated osteomyelitis and postoperative infection after orthopedic surgery. The loading capacity of Bicera™ was measured to understand its potential antibiotic adsorption volume. An antibiotic susceptibility test was also carried out to analyze the effect of Bicera™ loaded with different concentrations of vancomycin on the growth inhibition of methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin-loaded Bicera™ was implanted into rabbits with bone defects, and general gross, radiographic, and histological evaluation was undertaken at 4, 12, and 24 weeks after implantation. Results: The maximum loading capacity of vancomycin-loaded Bicera™ was 0.9 ml of liquid regardless of the vancomycin concentration. Antibiotic susceptibility tests showed that vancomycin-loaded Bicera™ inhibited the growth of MRSA for 6 weeks. In addition, animal studies revealed that new bone grew into the vancomycin-loaded Bicera™. The percentage of new bone formation from 4 to 24 weeks after implantation increased from 17% to 36%. Conclusion: Vancomycin-loaded Bicera™ could effectively inhibit the growth of MRSA in vitro. It was found to incorporate into the host bone well, and new bone was able to grow within the bone substitute. The results of this study indicate that vancomycin-loaded Bicera™ is a potential bone substitute that can prevent implant-associated osteomyelitis and postoperative infection.

Deep Learning for Prediction of Progression and Recurrence in Nonfunctioning Pituitary Macroadenomas: Combination of Clinical and MRI Features.

Objectives: A subset of non-functioning pituitary macroadenomas (NFMAs) may exhibit early progression/recurrence (P/R) after tumor resection. The purpose of this study was to apply deep learning (DL) algorithms for prediction of P/R in NFMAs. Methods: From June 2009 to December 2019, 78 patients diagnosed with pathologically confirmed NFMAs, and who had undergone complete preoperative MRI and postoperative MRI follow-up for more than one year, were included. DL classifiers including multi-layer perceptron (MLP) and convolutional neural network (CNN) were used to build predictive models. Categorical and continuous clinical data were fed into the MLP model, and images of preoperative MRI (T2WI and contrast enhanced T1WI) were analyzed by the CNN model. MLP, CNN and multimodal CNN-MLP architectures were performed to predict P/R in NFMAs. Results: Forty-two (42/78, 53.8%) patients exhibited P/R after surgery. The median follow-up time was 42 months, and the median time to P/R was 25 months. As compared with CNN using MRI (accuracy 83%, precision 87%, and AUC 0.84) or MLP using clinical data (accuracy 73%, precision 73%, and AUC 0.73) alone, the multimodal CNN-MLP model using both clinical and MRI features showed the best performance for prediction of P/R in NFMAs, with accuracy 83%, precision 90%, and AUC 0.85. Conclusions: DL architecture incorporating clinical and MRI features performs well to predict P/R in NFMAs. Pending more studies to support the findings, the results of this study may provide valuable information for NFMAs treatment planning.

Allopregnanolone suppresses glioblastoma survival through decreasing DPYSL3 and S100A11 expression.

Allopregnanolone (allo) is a physiological regulator of neuronal activity that treats multiple neurological disorders. Allo penetrates the blood-brain barrier with very high efficiency, implying that allo can treat CNS-related diseases, including glioblastoma (GBM), which always recurs after standard therapy. Hence, this study aimed to determine whether allo has a therapeutic effect on GBM. We found that allo enhanced temozolomide (TMZ)-suppressed cell survival and proliferation of TMZ-resistant cells. In particular, allo enhanced TMZ-inhibited cell migration and TMZ-induced apoptosis. Additionally, allo strongly induced DNA damage characterized by γH2Ax. Furthermore, quantitative proteomic analysis, iTRAQ, showed that allo significantly decreased the levels of DPYSL3, S100A11, and S100A4, reflecting the poor prognosis of patients with GBM confirmed by differential gene expression and survival analysis. Moreover, single-cell RNA-Seq revealed that S100A11, expressed in malignant cells, oligodendrocytes, and macrophages, was significantly associated with immune cell infiltration. Furthermore, overexpression of DPYSL3 or S100A11 prevented allo-induced cell death. In conclusion, allo suppresses GBM cell survival by decreasing DPYSL3/S100A11 expression and inducing DNA damage.

Preoperative Apparent Diffusion Coefficient Values for Differentiation between Low and High Grade Meningiomas: An Updated Systematic Review and Meta-Analysis.

The meta-analysis aimed to compare the preoperative apparent diffusion coefficient (ADC) values between low-grade meningiomas (LGMs) and high-grade meningiomas (HGMs). Medline, Cochrane, Scopus, and Embase databases were screened up to January 2022 for studies investigating the ADC values of meningiomas. The study endpoint was the reported ADC values for LGMs and HGMs. Further subgroup analyses between 1.5T and 3T MRI scanners, ADC threshold values, ADC in different histological LGMs, and correlation coefficients (r) between ADC and Ki-67 were also performed. The quality of studies was evaluated by the quality assessment of diagnostic accuracy studies (QUADAS-2). A χ2-based test of homogeneity was performed using Cochran's Q statistic and inconsistency index (I2). Twenty-five studies with a total of 1552 meningiomas (1102 LGMs and 450 HGMs) were included. The mean ADC values (×10−3 mm2/s) were 0.92 and 0.79 for LGMs and HGMs, respectively. Compared with LGMs, significantly lower mean ADC values for HGMs were observed with a pooled difference of 0.13 (p < 0.00001). The results were consistent in both 1.5T and 3T MRI scanners. For ADC threshold values, pooled sensitivity of 69%, specificity of 82%, and AUC of 0.84 are obtained for differentiation between LGMs and HGMs. The mean ADC (×10−3 mm2/s) in different histological LGMs ranged from 0.87 to 1.22. Correlation coefficients (r) of mean ADC and Ki-67 ranged from −0.29 to −0.61. Preoperative ADC values are a useful tool for differentiating between LGMs and HGMs. Results of this study provide valuable information for planning treatments in meningiomas.