Diagnostic value of alkaline phosphatase and bone-specific alkaline phosphatase for metastases in breast cancer: a systematic review and meta-analysis.

PURPOSE: Numerous studies had reported the diagnostic value of alkaline phosphatase (ALP) and its bone-specific isoforms (BAP) in the metastases of breast cancer (BC). The purpose of this meta-analysis was to summarize the diagnostic value of serum ALP and BAP in metastatic BC, especially focused on bone metastases. METHODS: We searched comprehensively in the PubMed, Cochrane Library, and EMBASE for studies to explore the diagnostic accuracy of serum ALP/BAP level for metastatic BC. Qualities of including studies were assessed and pooled sensitivity, specificity, and summary receiver operating characteristic curve were calculated. Publication bias was assessed and meta-regression was conducted. RESULTS: We finally included 25 studies with a total of 12,155 BC patients (1681 metastatic cases and 10,474 controls). According to the QUADAS-2 tool to assessment the methodological quality, most of the included studies were judged as high risk of patient selection bias. High serum levels of ALP/BAP in bone metastatic BC patients could be found compared with non-metastatic BC patients. The pooled sensitivity and specificity of ALP for BC bone metastases were 0.62 and 0.86, and the area under the curve (AUC) was 0.80. The pooled sensitivity and specificity of ALP for all site metastases (mainly bone and liver) were 0.56 and 0.91, and the AUC was 0.90. The pooled sensitivity and specificity of BAP for BC bone metastases were 0.66 and 0.92, and the AUC was 0.89. CONCLUSION: Although not promising, serum ALP and BAP could bring useful information for the early detection of BC metastases especially for the bone metastases.

External fixation versus dynamic hip screw in treatment of elderly intertrochanteric hip fractures: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of external fixation compared with dynamic hip screw (DHS) for the treatment of elderly intertrochanteric hip fractures. METHODS: We searched Pubmed, Embase, Cochrane central database (All to December 19th, 2015) for comparative studies relevant to external fixation versus DHS for the management of intertrochanteric hip fractures. Only randomized controlled trial (RCT) were included. We extracted the trial characteristics, intervention details, primary and secondary outcomes. Risk of bias was assessed. Fixed/random effect model was adapted according to the heterogeneity tested by I2 statistic. Sensitivity analysis was conducted and publication bias was assessed. RESULTS: A total of 4 RCTs were retrieved involving 260 patients. Pooled results showed for the primary outcomes of Harris hip score and final mortality, no significant difference was found between external fixation and DHS, however, for the secondary outcomes, external fixation had advantages in the aspects of length of surgery, operative blood loss, blood transfusion and hospital stay while shortcomings in pin-track infection. For other secondary outcomes such as fracture reduction, cut out and varus malunion, no significant difference could be found. CONCLUSIONS: While there was no conclusive evidence, as external fixation with less surgery time, less blood loss and less post-operative pain while no compromise in final functional outcome and mortality compared with DHS, it could be considered as an alternative for the elderly intertrochanteric hip fractures, especially in highrisk patients who could not tolerate routine spinal anesthesia and open surgery.

Spinal gout with intervertebral foramen infiltration: A rare case perfectly mimicking degenerative lumbar disc disease.

Spinal gout is a relatively rare disease characterized by significant clinical symptoms. In the current study, the first case of spinal gout with tophus in the intervertebral foramen, which perfectly mimicked degenerative lumbar disc disorders, was presented. The patient was a 57-year-old man with a medical history of gout who had suffered from progressive neurological deterioration for the last 12 months. Imaging examination revealed bilateral stenosis in the L5/S1 intervertebral foramen, mimicking degenerative lumbar disc disease. Nerve root radiculography and blocking were performed and the neurological symptoms were completely relieved. Open surgery was further performed and unexpectedly, the intra-operative findings were amorphous chalky white lesions. Histopathology confirmed the diagnosis of spinal gout. After surgery, the patient was prescribed a medication and achieved complete remission of clinical symptoms. No deterioration was found at the 1-year follow-up. To the best of our knowledge, this is the first report of spinal gout tophus in intervertebral foramen in the literature. It was concluded that, although intraspinal tophaceous gout is relatively rare, orthopedic surgeons should take it into consideration as a differential diagnosis, particularly if the patient has a medical history of gout. Early diagnosis and timely medical management may possibly be able to avoid neurological compromise and the need for surgery.

Preoperative classification assessment reliability and influence on the length of intertrochanteric fracture operations.

PURPOSE: The accuracy of intertrochanteric fracture classification is important; indeed, the patient outcomes are dependent on their classification. The aim of this study was to use the AO classification system to evaluate the variation in classification between X-ray and computed tomography (CT)/3D CT images. Then, differences in the length of surgery were evaluated based on two examinations. METHODS: Intertrochanteric fractures were reviewed and surgeons were interviewed. The rates of correct discrimination and misclassification (overestimates and underestimates) probabilities were determined. The impact of misclassification on length of surgery was also evaluated. RESULTS: In total, 370 patents and four surgeons were included in the study. All patients had X-ray images and 210 patients had CT/3D CT images. Of them, 214 and 156 patients were treated by intramedullary and extramedullary fixation systems, respectively. The mean length of surgery was 62.1 ± 17.7 min. The overall rate of correct discrimination was 83.8 % and in the classification of A1, A2 and A3 were 80.0, 85.7 and 82.4 %, respectively. The rate of misclassification showed no significant difference between stable and unstable fractures (21.3 vs 13.1 %, P = 0.173). The overall rates of overestimates and underestimates were significantly different (5 vs 11.25 %, P = 0.041). Subtracting the rate of overestimates from underestimates had a positive correlation with prolonged surgery and showed a significant difference with intramedullary fixation (P < 0.001). CONCLUSIONS: Classification based on the AO system was good in terms of consistency. CT/3D CT examination was more reliable and more helpful for preoperative assessment, especially for performance of an intramedullary fixation.

Prognostic value of alkaline phosphatase and bone-specific alkaline phosphatase in breast cancer: A systematic review and meta-analysis.

Numerous studies have reported the clinical value of alkaline phosphatase (ALP) and its bone-specific isoforms (bone-specific alkaline phosphatase (BAP)) in breast cancer. The purpose of this meta-analysis was to summarize the prognostic value of serum ALP and BAP in breast cancer, especially focused on bone metastasis and survival. PRISMA guidelines were followed to conduct this review. Observational studies were searched in PubMed, Cochcrane Library and EMBASE to January 1, 2022. Data were extracted to explore the prognostic value of ALP and BAP. The quality of the included studies was assessed and the outcome effects were evaluated. Subgroup and sensitivity analyses were performed to explore the potential sources of heterogeneity. Publication bias was assessed. There was a total of 53 studies with 22,436 patients included. For the primary outcome of survival, high levels of both ALP and BAP were associated with short survival time. The hazard ratio of high ALP level on overall survival was 1.72 (95% CI 1.37, 2.16, P < 0.001). For the secondary outcomes, a high ALP level (not BAP) was detected in breast cancer compared with healthy controls, and high levels of both ALP and BAP were risk factors for bone metastasis, while ALP (not BAP) was a risk factor for non-bone metastasis. This study showed that high levels of both serum ALP and BAP were associated with metastasis (BAP was associated with bone metastasis) and survival in breast cancer. The biomarkers could provide useful information for the early diagnostic assessment and monitoring in the follow-up of breast cancer patients.

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature.

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

Silencing long noncoding RNA colon cancer-associated transcript-1 upregulates microRNA-34a-5p to promote proliferation and differentiation of osteoblasts in osteoporosis.

Long noncoding RNAs (lncRNAs) have been revealed to be related to multiple physiological and pathology processes such as development, carcinogenesis, and osteogenesis. It is reported that lncRNAs might exert function in osteoblast differentiation and bone formation. Here, we determined this study to clarify whether lncRNA CCAT1 could regulate osteoblast proliferation and differentiation in ovariectomized rats with osteoporosis. The osteoporosis models were established by bilateral ovariectomy and treated with CCAT1 siRNAs to discuss the effect of CCAT1 on pathological changes and osteocyte apoptosis in ovariectomized rats with osteoporosis. The osteoblasts from ovariectomized rats were cultured in vitro, which were then treated with CCAT1 siRNAs to explore the role of CCAT1 in osteoblast proliferation and differentiation. Moreover, the relationships among CCAT1, miR-34a-5p, and SMURF2 were confirmed. CCAT1 and SMURF2 were amplified while miR-34a-5p expression was inhibited in bone tissues and osteoblasts of ovariectomized rats with osteoporosis. Inhibited CCAT1 improved pathology and restricted osteocyte apoptosis of bone tissues in ovariectomized rats with osteoporosis in vivo, and also enhanced differentiation, mineralization abilities, and proliferation, and suppressed apoptosis of osteoblasts from ovariectomized rats in vitro through upregulating miR-34a-5p expression. LncRNA CCAT1 could competitively bind with miR-34a-5p to prevent the degradation of its target gene SMURF2. Results of this research suggested that the CCAT1 inhibits the proliferation and differentiation of osteoblasts in rats with osteoporosis by binding to miR-34a-5p, providing novel biomarkers for osteoporosis treatment.

A novel classification for medial malleolar fracture based on the 3-D reconstruction CT.

BACKGROUND: Fracture of the medial malleolus is one of the most frequent injuries treated surgically; however, the classification of the fracture has not attracted much attention and a good classification system is still lacking. METHODS: Consecutive cases of medial malleolus fractures were prospectively enrolled. Based on the 3-D reconstruction CT morphology and centered on the posterior colliculus of the medial malleolus, we classified the fractures into 4 types: type 1 with no involvement of the posterior colliculus, type 2 with partial involvement of posterior colliculus, type 3 with the entire involvement of posterior colliculus, and type 4 with the fracture line 4 vertically extended from the intercollicular groove to the comminuted fracture of the posterior malleolus. Statistical analyses were performed to evaluate the clinical significance of the classification. RESULTS: There were 273 cases prospectively enrolled. The distribution of the cases was type 1 of 12.1%, type 2 of 41.0%, type 3 of 30.0%, and type 4 of 16.8%. Statistics showed that the new classification had significant associations but did not totally depend on the classical ankle fracture classifications. Results showed that the new classification had implications in the severity of ankle fractures. From type 1 to type 4, the ankle joint was more and more unstable. Furthermore, comminuted medial malleolar fractures could be subdivided, and the new classification could provide useful information for surgical decision-making. CONCLUSIONS: The novel classification was a useful system to describe the 3-D geometry of the fractured medial malleolus.

Pathoanatomy and Injury Mechanism of Typical Maisonneuve Fracture.

OBJECTIVE: Maisonneuve fracture is a special type of injury which are rare in clinic. The manifestation of such fractures is variable. The aim of this study is to describe the pathoanatomical features of typical Maisonneuve fracture on the basis of radiographs, computed tomography (CT) scans, magnetic resonance imaging (MRI), and intraoperative exploration findings, and to investigate the injury mechanism of this variety. METHODS: The data of 41 patients with Maisonneuve fracture from April 2014 to September 2019 were retrospectively analyzed. There were 32 males and nine females, the average age was 37.9 years (range, 18 to 61 years), the fractures occurred on the left side in 20 patients and on the right side in 21 patients. The cause of injuries were traffic accident in five patients, sprain injury in 20 patients, and falling injury from height in 16 patients. All patients underwent posteroanterior and lateral X-ray examinations of the ankle and calf. CT scan of the ankle was performed in 38 patients, including three-dimensional reconstruction in 33 patients. MRI examination of the ankle and calf was performed in 28 and five patients, respectively. Forty patients were treated with open reduction and internal fixation. The features of proximal fibular fracture, injuries of the medial and posterior structures of the ankle, injuries of the anterior inferior tibiofibular ligament and the interosseous membrane were recorded and analyzed. RESULTS: Forty-one patients had proximal one-third fractures of the fibula including six patients with fracture involving the fibular neck, 30 with proximal one-third fractures of the fibular shaft, and five with proximal-medial one-third junction fracture of the fibular shaft. Thirty-five patients (35/41, 85.37%) with injury of posterior structures, 34 patients had posterior malleolar fracture (34/41, 82.93%), and one patient had posterior inferior tibiofibular ligament rupture (1/41, 2.44%). There were 20 patients with type I fracture, four patients with type II fracture, and 10 patients with type III fracture according to the Haraguchi classification of posterior malleolus fracture. The fracture of the medial malleolus was in 30 patients (30/41, 73.17%), rupture of the deltoid ligament was in 10 patients (10/41, 24.39%), and medial structures intact were in one patient (1/41, 2.44%). All 41 patients had injury of the anterior inferior tibiofibular ligament. CONCLUSIONS: Maisonneuve fracture is characterized by fractures of the proximal fibula and the complete rupture of the anterior inferior tibiofibular ligament. Pronation-external rotation is the main injury mechanism. The manifestations of typical Maisonneuve fracture including that the fibular fracture located in proximal one-third diaphysis and the fracture line was from anterosuperior to posteroinferior.

The effectiveness and safety of aminocaproic acid for reducing blood loss in total knee and hip arthroplasty: A meta-analysis.

OBJECTIVE: This meta-analysis aimed to evaluate the safety and efficacy of aminocaproic acid in total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: The electronic databases include PubMed, Medline, Embase, Web of Science and the Cochrane Library from inception to January, 2018. Two reviewers abstracted total blood loss, hemoglobin drop, transfusion requirements, and postoperative complications. Data were using fixed-effects or random-effects models with weighted mean differences and risk difference for continuous and dichotomous variables, respectively. STATA 14.0 was used to perform the meta-analysis. RESULTS: Six studies encompassing 756 participants were retrieved for this meta-analysis. Our study indicated that intravenous aminocaproic acid was associated with a significantly reduction in total blood loss, hemoglobin drop and need for transfusion. Additionally, no increased risk of thromboembolic events were identified. CONCLUSION: Based on the present meta-analysis, intravenous aminocaproic acid is effective and safe in total knee and hip arthroplasty without increasing the incidence of thromboembolic events. Further studies should focus on the comparison of aminocaproic acid and TXA in arthroplasties.

Quantitative ELISA-Like Immunohistochemistry of Fibroblast Growth Factor 23 in Diagnosis of Tumor-Induced Osteomalacia and Clinical Characteristics of the Disease.

Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic disorder and fibroblast growth factor 23 (FGF23) plays a key role in its pathogenesis. This study was conducted to describe a novel FGF23 detecting procedure and describe clinical features of the disease. Fourteen TIO cases were retrieved and FGF23 expression was measured by quantitative ELISA-like immunohistochemistry using formalin-fixed and paraffin-embedded tissues. As summarized from 14 TIO cases, clinical features of TIO were long-standing history of osteomalacia, hypophosphatemia, and urinary phosphate wasting. The associated tumors were mostly benign phosphaturic mesenchymal tumors mixed connective tissue variant (PMTMCT) which could be located anywhere on the body, and most of them could be localized by conventional examinations and octreotide scanning. By quantitative ELISA-like immunohistochemistry, all the 14 TIO cases had high FGF23 expression (median 0.69, 25%-75% interquartile 0.57-1.10, compared with 26 non-TIO tumors of median 0.07, 25%-75% interquartile 0.05-0.11, p < 0.001). The quantitative ELISA-like immunohistochemistry was a feasible and reproducible procedure to detect the high FGF23 expression in formalin-fixed and paraffin-embedded biopsies or specimens. Since TIO was often delay-diagnosed or misdiagnosed, clinicians and pathologists should be aware of TIO and PMTMCT, respectively.

Functional Restriction for the Fear of Falling In Family Caregivers.

Hip fractures often result from falls, and most family caregivers fear another fall. This study aimed to assess this fear in family caregivers and analyze its influence on functional recovery.This study was retrospectively performed by interview at the clinic or through telephone contact. The Falls Efficacy Scale International (FES-I) was used to assess fall-related feelings of patients and their family caregivers.Of the 539 patients studied, hip fracture was caused by a fall in 467 (86.6%). The mean FES-I value of the family caregivers was significantly lower than that of the patients (85.39 versus 99.02, P < 0.001). The mean patient functional recovery score (FRS) was 68.41. A fracture caused by a fall and recurrent fall-related fractures both reduced caregiver FES-I scores. The difference between patient and caregiver FES-I scores showed a significant positive correlation with the FRS (P < 0.001).Family caregivers were more concerned about falls than were patients. Furthermore, a greater difference in the fall-related reaction between caregivers and patients was associated with greater adverse effects on rehabilitation.

Preoperative predictors for mortality following hip fracture surgery: a systematic review and meta-analysis.

BACKGROUND: Hip fractures are always associated with a high postoperative mortality, the preoperative predictors for mortality have neither been well identified or summarised. This systematic review and meta-analysis was performed to identify the preoperative non-interventional predictors for mortality in hip fracture patients, especially focused on 1 year mortality. METHODS: Non-interventional studies were searched in Pubmed, Embase, Cochrane central database (all to February 26th, 2011). Only prospective studies and retrospective studies with prospective collected data were included. Qualities of included studies were assessed by a standardised scale previous reported for observational studies. The effects of individual studies were combined with the study quality score using a previous reported model of best-evidence synthesis. The hazard ratios of strong evidence predictors were combined only by high quality studies. RESULTS: 75 included studies with 94 publications involving 64,316 patients were included and the available observations was a heterogeneous group. The overall inpatient or 1 month mortality was 13.3%, 3-6 months was 15.8%, 1 year 24.5% and 2 years 34.5%. There were strong evidence for 12 predictors, including advanced age, male gender, nursing home or facility residence, poor preoperative walking capacity, poor activities of daily living, higher ASA grading, poor mental state, multiple comorbidities, dementia or cognitive impairment, diabetes, cancer and cardiac disease. We also identified 7 moderate evidence and 12 limited evidence mortality predictors, and only the race was identified as the conflicting evidence predictor. CONCLUSION: Whilst there is no conclusive evidence of the preoperative predictors for mortality following hip fractures, special attention should be paid to the above 12 strong evidence predictors. Future researches were still needed to evaluate the effects of these predictors.

Proximal femoral nail antirotation versus hemiarthroplasty: a study for the treatment of intertrochanteric fractures.

Intertrochanteric fractures in elderly patients are always associated with poor prognosis in the functional outcome as a result of the complications and mortality. A retrospective study was performed in our institution, 303 consecutive patients were followed up with mean age of 81.7 years. 147 were treated with PFNA, and 156 were underwent hemiarthroplasty. The average follow-up period was 39.9 months. The mortality at 1 month, 1 year, 3 years and the total was 6.6%, 18.6%, 27.6% and 30.3%, respectively. There were no significant differences between the groups in terms of demographic data. There were statistical significances in the operative statistics, especially the anaesthesia, operation lasting time, blood loss, blood transfusion and the drainage. There was no significant difference in Harris Hip Score between PFNA and hemiarthroplasty group, but the detail items were quite different. Significant difference was found in the excellent-to-fine rate (PFNA 90.2% and hemiarthroplasty 79.6%). Complications occurred in 34 patients, although incidences of complications were higher in hemiarthroplasty group (14.1% vs. PFNA 8.96%), no statistical difference was found. For elderly patients with intertrochanteric fractures, PFNA was superior to hemiarthroplasty according to the operative statistics, but there were no significant differences in functional outcome.

The tumor suppressor role of Src homology phosphotyrosine phosphatase 2 in hepatocellular carcinoma.

PURPOSE: The human gene PTPN11, which encodes the non-receptor protein tyrosine phosphatase of Src homology phosphotyrosine phosphatase 2 (Shp2), has been previously well interpreted as a proto-oncogene in a variety of malignancies. However, the tumor suppressor role of Shp2 has also been reported. The present study was conducted to investigate the role of Shp2 expression and its associated clinical manifestations in hepatocellular carcinoma (HCC). METHODS: A tissue microarray of 333 pairs of HCC and self-matched adjacent non-tumor tissues was constructed, and the expression of Shp2 was determined by immunohistochemistry. The results were also conformed by Western blotting and quantitative PCR of 31 self-paired fresh HCC specimens. The associations of Shp2 expression with 25 clinicopathologic features were analyzed. Overall survival analysis and multivariate analysis were performed. RESULTS: Significantly decreased Shp2 expression in tumor tissues (T) compared with adjacent non-tumor tissues (NT) could be detected, and the positive rate was 66.1 and 96.7%, respectively. We combined the T and NT Shp2 immunoreactivity by a variable of the decrease in Shp2 expression (ΔShp2) and divided cases into 2 groups: T < NT and T ≥ NT. Survival analysis showed both low Shp2 expression and T < NT group were significantly associated with short overall survival. Multivariate analysis showed ΔShp2 was an independent prognostic marker (P = 0.033; HR: 0.527; 95% CI: 0.293-0.950). CONCLUSION: Shp2 is a tumor suppressor, and the decrease in Shp2 expression was a new prognostic marker in HCC. The oncogenic role of Shp2 was tissue specific, and the therapeutic target of human gene PTPN11 should be reconsidered.

[Effectiveness of AO anatomical locking compression plate in treating type C distal humeral fracture].

OBJECTIVE: To evaluate the effectiveness of the AO anatomical locking compression plate in treating type C distal humeral fracture. METHODS: Between July 2008 and April 2009, 13 cases of type C distal humeral fracture were treated with the AO anatomical locking compression plates. There were 5 males and 8 females with an average age of 52.1 years (range, 24-80 years). Fractures were caused by tumbling in 7 cases, by traffic accident in 4 cases, and by falling from height in 2 cases. According to Association for Osteosynthesis/Orthopaedic Trauma Association (AO/OTA) classification, there were 3 cases of type C1, 6 cases of type C2, and 4 cases of type C3. Two cases complicated by ulnar nerve injuries, 1 by radial nerve injury, 2 by fractures of ulnar olecranon, 3 by fractures of other parts of extremities, and 6 by osteoporosis. The time from injury to hospitalization ranged from 3 hours to 4 days (0.9 day on average). RESULTS: All the incisions achieved healing by first intention. Thirteen cases were followed up 12 to 21 months with an average of 15.9 months. According to the X-ray films, unions were achieved both at fracture site and the olecranon osteotomy site with a healing time of 8 to 13 weeks (10 weeks on average). The function of elbows recovered from 3 to 32 weeks (10 weeks on average). No fixation failure, myositis ossificans, delayed union, or malunion occurred during the follow-up. The Mayo Elbow Performance score ranged from 75 to 100 with an average score of 95.8; the results were excellent in 9 cases, good in 3 cases, and fair in 1 case with an excellent and good rate of 92.3%. CONCLUSION: The AO anatomical locking compression plate has a good fixation in treating type C distal humeral fracture. Through the approach of olecranon osteotomy, it is easy to get anatomical reduction, stable fixation, and early exercise.