Bone-derived PDGF-BB enhances hippocampal non-specific transcytosis through microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

BACKGROUND: It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. MAIN BODY: Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1ß (IL-1ß) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. CONCLUSION: Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

Does the angle between dynamic hip screw and anti-rotation screw affect the outcome of vertically oriented femoral neck fractures? A biomechanical analysis and clinical results.

OBJECTIVE: To analyze the effects of the angle between dynamic hip screw (DHS) and anti-rotation screw (AS) on vertically oriented femoral neck fractures (VOFNFs) and investigate the clinical results of them. METHODS: Eighteen synthetic femurs were simulated and divided into 3 groups. The angle between DHS and AS in anteroposterior-view was marked as α, and in lateral-view was marked as ß, thus the total angle (TA) was defined as the summation of α and ß. The groups were categorized as group A (TA ≤ 5°), B (5° < TA ≤ 10°), and C (TA > 10°), respectively. All samples were tested under incremental, cyclical loading, and loading to failure. In clinic, 80 consecutive VOFNFs in 78 patients were treated with DHS plus AS. The patients were divided into 2 groups, including 48 fractures in parallel group (TA ≤10°) and 32 in angular group (TA >10°). RESULTS: Group A and B survived during incremental and cyclical loading and endured longer than group C. Axial stiffness and failure loads were not different between group A and B, and greater than group C. Fracture gaps compressive stress was highest in group A, followed by group B and C. Forty-one fractures in parallel group and 23 in angular group healed at final follow-up. Nonunion and osteonecrosis occurred in 3 and 4 of parallel group, and 4 and 5 of angular group. CONCLUSION: The construction with TA ≤10° between DHS and AS showed superior biomechanical performance and clinical results than those with TA >10°.

Lipoteichoic acid restrains macrophage senescence via ß-catenin/FOXO1/REDD1 pathway in age-related osteoporosis.

Osteoporosis and its related fractures are common causes of morbidity and mortality in older adults, but its underlying molecular and cellular mechanisms remain largely unknown. In this study, we found that lipoteichoic acid (LTA) treatment could ameliorate age-related bone degeneration and attenuate intramedullary macrophage senescence. FOXO1 signaling, which was downregulated and deactivated in aging macrophages, played a key role in the process. Blocking FOXO1 signaling caused decreased REDD1 expression and increased phosphorylation level of mTOR, a major driver of aging, as well as aggravated bone loss and deteriorated macrophage senescence. Moreover, LTA elevated FOXO1 signaling through ß-catenin pathway while ß-catenin inhibition significantly suppressed FOXO1 signaling, promoted senescence-related protein expression, and accelerated bone degeneration and macrophage senescence. Our findings indicated that ß-catenin/FOXO1/REDD1 signaling plays a physiologically significant role that protecting macrophages from senescence during aging.

Frog leg lateral view is a reliable predictor of the prognosis in osteonecrosis of the femoral head.

The location and size of necrotic lesions are primary factors that predict the prognosis in osteonecrosis of the femoral head (ONFH). The Japanese Investigation Committee (JIC) classification system, based on the location of the necrotic lesion, has been widely accepted and applied around the world. However, there is no report about whether the location of the necrotic area in lateral view may affect the prognosis predicted initially by the JIC classification. The purpose of this study was to investigate whether the location of the necrotic area in the frog leg lateral (FL) view would affect the prediction of prognosis for patients with ONFH. We retrospectively studied 90 hips in 76 patients with ONFH (Ficat stage I to II) after a mean follow-up of 35.3 months. All patients received standard radiographs including an anteroposterior (AP) and a FL view of the affected hip. The percentage of the necrotic area (necrotic area/whole femoral head area) was measured and compared between AP and FL view. Hips with ONFH were categorized using the JIC classification and the FL view type system, and inter- and intraobserver reliability was compared between them. All patients underwent personalized hip physiotherapy, and the cumulative survival rate with subsequent collapse and/or requirement for further hip surgery as the endpoints was evaluated for the two classification systems. The percentage of the necrotic area was found to be significantly greater in the FL views (47.0 ± 1.5%) than that in the AP views (37.7 ± 1.7%, P < .01). Intraobserver reliability in the JIC classification (mean: 0.91, range: 0.85-0.98) was higher than that in the FL view type (mean: 0.77, range: 0.63-0.89; P < .01), as well as the interobserver reliability in the JIC classification (mean: 0.74, range: 0.38-0.87) was higher than that in the FL view type (mean: 0.58, range: 0.31-0.76; P < .01). Comparisons of survival curves showed that type III in FL view type had the worst prognosis than other two divisions, following the type II. The type I was likely to gain optimal outcomes. These findings provide evidence that the location to which necrosis extended in the FL view is a reliable indicator in predicting the prognosis of ONFH.

Platelet-Rich Plasma-Incorporated Autologous Granular Bone Grafts Improve Outcomes of Post-Traumatic Osteonecrosis of the Femoral Head.

BACKGROUND: To investigate the effects of platelet-rich plasma (PRP)-incorporated autologous granular bone grafts for treatment in the precollapse stages (Association of Research Circulation Osseous stage II-III) of posttraumatic osteonecrosis of the femoral head. METHODS: A total of 46 patients were eligible and enrolled in the study. Twenty-four patients were treated with core decompression and PRP-incorporated autologous granular bone grafting (treatment group), and 22 patients were treated with core decompression and autologous granular bone grafting (control group). During a minimum follow-up duration of 36 months, X-ray and computed tomography were used to evaluate the radiological results, and the Harris hip score (HHS) and visual analog scale were chosen to assess the clinical results. RESULTS: Both the treatment and control groups had a significantly improved HHS (P < .001). The minimum clinically important difference for the HHS was reached in 91.7% of the treatment group and 68.2% of the control group (P < .05). The HHS and visual analog scale in the treatment group were significantly improved than that in the control group at the last follow-up (P < .05). Successful clinical and radiological results were achieved 87.5% and 79.2% in the treatment group compared with 59.1% and 50.0% in the control group (P < .05), respectively. The survival rates based on the requirement for further hip surgery as an endpoint were higher in the treatment group in comparison to those in the control group (P < .05). CONCLUSION: PRP-incorporated autologous granular bone grafting is a safe and effective procedure for treatment in the precollapse stages (Association of Research Circulation Osseous stage II-III) of posttraumatic osteonecrosis of the femoral head.

Salmonella potsdam causing lumbar vertebral osteomyelitis: A case report.

RATIONALE: Salmonella osteomyelitis is an uncommon complication of salmonella infection, especially the salmonella vertebral osteomyelitis (SVO). PATIENT CONCERNS: We reported a case of a 29-year-old female who presented with serious lower back pain and severe limitation of motion for 50 days with no obvious inducements. She once had a fever up to 39.5°C. Physical examination only revealed limited motion of lower back without neurological complications. The laboratory results revealed no specificity. MRI of the lumbar spine revealed a spondylodiscitis at L4-L5. She underwent anterior lateral approach debridement and percutaneous posterior instrumentation. DIAGNOSES: Tissue and abscess culture grew showed Salmonella Potsdam infection. INTERVENTIONS: With susceptibility testing guidance, the patient was treated with intravenous levofloxacin and ceftazidime for a period of 3 weeks and another 3-week oral antibiotics therapy. OUTCOMES: The patient recovered well with no neurological deficits during the follow-up time. LESSONS: SVO is really rare and it alerts us the importance to consider uncommon pathogens in the differential diagnosis in which the etiological evidences are crucial of healthy individuals.

Generalized seizures presurgically in a cohort of children with hemispherectomy: Predictors and a potential link to surgical outcome?

PURPOSE: Generalized seizures were often thought to be contraindications for hemispherectomy. However, few studies had investigated this issue comprehensively, as well as the predictors for generalized seizures in hemispheric lesion. We studied the predictors of generalized seizures and their potential link to seizure outcomes in a cohort of children who underwent hemispherectomy. METHODS: A cohort of 76 children with hemispherectomy were reviewed and dichotomized into two groups with and without generalized seizures confirmed by vEEG presurgically. All preoperative evaluation data correlated to generalized seizures and postoperative prognosis were collected and analysed. RESULTS: Of 76 patients, 11 (14.5%) cases were documented with various generalized seizures, including atypical absence (54.5%, 6/11), myoclonic (45.5%, 5/11), atonic (36.4%, 4/11), myoclonic-atonic (18.2%, 2/11), myoclonic-absence (9.1%, 1/11) and spasms (9.1%). Electrical status epilepticus during sleep (ESES) was recorded in 3 patients (27.3%, 3/11). At last follow-up, 72.7% (8/11) patients remained seizure-free. ESES was a predictor of generalized seizures (χ2 = 4.69, P = 0.043). No correlation was found between generalized seizures and unfavourable postoperative seizure outcome (P = 0.153). For different seizure types, focal to bilateral tonic-clonic seizures (P = 0.020) and myoclonic-atonic seizures (P = 0.002) might correlate with unfavourable outcomes. CONCLUSION: Generalized seizures were not an absolute contraindication for hemispherectomy. Those patients with ESES might experience generalized seizures presurgically. Focal to bilateral tonic-clonic seizures and myoclonic-atonic seizures pre-surgery may indicate unfavourable post-operative seizure outcomes.

[Surgery for pediatric intractable epilepsy due to posterior quadrantic cortical dysplasia].

OBJECTIVE: To investigate the clinical features and surgical strategy for pediatric intractable epilepsy due to posterior quadrantic cortical dysplasia and to assess the surgical outcomes. METHODS: The clinical features and preoperative evaluation results of 14 children with intractable epilepsy due to posterior quadrantic cortical dysplasia were retrospectively analyzed. The localization values of video-electroencephalography and intraoperative monitoring and the indications, advantages and disadvantages of temporoparietooccipital disconnection were evaluated. RESULTS: The 14 children had different seizure types, of which spasm was the most common one. The lesions of cortical dysplasia involved the central cerebral region in 2 cases. After temporoparietooccipital disconnection in 14 patients, 13 cases were seizure-free; only one case still had seizures, but the frequency dropped by more than 50%. CONCLUSIONS: Temporoparietooccipital disconnection is a safe and effective surgical procedure for children with intractable epilepsy due to posterior quadrantic cortical dysplasia.