The Time-Effect Relationship between Time to Surgery and In-Hospital Postoperative Pneumonia in Older Patients with Hip Fracture.

INTRODUCTION: Pneumonia is a common and devastating complication following hip fracture surgery in older patients. Time to surgery is a potentially modifiable factor associated with improved prognosis, and we aim to quantify the time-effect relationship between time to surgery and in-hospital postoperative pneumonia (IHPOP) and identify the effect of delayed surgery on the risk of IHPOP. METHODS: We analyzed clinical data of older hip fracture patients (≥60 years) undergoing surgical treatments at a tertiary referral trauma center between 2015 and 2020. Restricted cubic spline (RCS) was used to fit the time-effect relationship between time to surgery and IHPOP. Based on the results of RCS, we divided patients into two groups of "early surgery" and "delayed surgery." A 1:1 propensity score matching (PSM) analysis and multivariate conditional logistic regression analysis were performed to minimize the selection bias and determine the association magnitude. Subgroup analysis was conducted to assess potential interaction effects between delayed surgery and common risk factors for IHPOP. RESULTS: 3,118 eligible patients were included. The RCS curve showed an inverse S-shape trend and the relative risk of IHPOP decreased in the range of days 2-3 and increased on day 1 and day 3 or more post-injury, with the lowest point on day 3. PSM yielded 1,870 matched patients and delayed surgery (>3 days) was identified to be independently associated with IHPOP (relative ratio, 1.66; 95% confidence interval, 1.12-2.46; p value, 0.011). We observed positive interaction effects between delayed surgery and age of 80 years or more, female gender, COPD, heart disease, ASA score ≥3, anemia, and hypoproteinemia. CONCLUSION: The relative risk of IHPOP decreased in the range of 2-3 days and increased on day 1 and day 3 or more post-injury. Delayed surgery (>3 days) was identified to be independently associated with a 1.66-fold increased risk of IHPOP.

Association of preoperative nutritional status evaluated by the controlling nutritional status score with walking independence at 180 days postoperatively: a prospective cohort study in Chinese older patients with hip fracture.

BACKGROUND: Malnutrition is significantly associated with unfavorable outcomes, but there is little high-level evidence to elucidate the association of malnutrition with losing walking independence (LWI) after hip fracture surgery. This study aimed to assess the association between preoperative nutritional status evaluated by the Controlling Nutritional Status (CONUT) score and walking independence at 180 days postoperatively in Chinese older hip fracture patients. METHODS: This prospective cohort study included 1958 eligible cases from the SSIOS database. The restricted cubic spline was used to assess the dose-effect relationship between the CONUT score and the recovery of walking independence. Propensity score matching was performed to balance potential preoperative confounders, and multivariate logistic regression analysis was applied to assess the association between malnutrition and LWI with perioperative factors for further adjustment. Furthermore, inverse probability treatment weighting and sensitivity analyses were performed to test the robustness of the results and the Fine and Gray hazard model was applied to adjust the competing risk of death. Subgroup analyses were used to determine potential population heterogeneity. RESULTS: The authors found a negative relationship between the preoperative CONUT score and recovery of walking independence at 180 days postoperatively, and that moderate-to-severe malnutrition evaluated by the CONUT score was independently associated with a 1.42-fold (95% CI, 1.12-1.80; P =0.004) increased risk of LWI. The results were overall robust. And in the Fine and Gray hazard model, the result was still statistically significant despite the apparent decrease in the risk estimate from 1.42 to 1.21. Furthermore, significant heterogeneities were observed in the subgroups of age, BMI, American Society of Anesthesiologists score, Charlson's comorbidity index, and surgical delay ( P for interaction < 0.05). CONCLUSION: Preoperative malnutrition is a significant risk factor for LWI after hip fracture surgery, and nutrition screening on admission would generate potential health benefits.

Preoperative Risk Factor Analysis and Dynamic Online Nomogram Development for Early Infections Following Primary Hip Arthroplasty in Geriatric Patients with Hip Fracture.

Background: Hip arthroplasty is in increasing demand with the aging of the world population, and early infections, such as pneumonia, surgical site infection (SSI), and urinary tract infection (UTI), are uncommon but fatal complications following hip arthroplasty. This study aimed to identify preoperative risk factors independently associated with early infections following primary arthroplasty in geriatric hip fracture patients, and to develop a prediction nomogram. Methods: Univariate and multivariate logistical analyses were performed to identify the independent risk factors for early infections, which were combined and transformed into a nomogram model. The prediction model was evaluated by using the area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow test, concordance index (C-index), 1000 bootstrap replications, decision curve analysis (DCA), and calibration curve. Results: One thousand eighty-four eligible patients got included and 7 preoperative variables were identified to be independently associated with early infections, including heart disease (odds ratio (OR): 2.17; P: 0.026), cerebrovascular disease (OR: 2.25; P: 0.019), liver disease (OR: 8.99; P: <0.001), time to surgery (OR: 1.10; P: 0.012), hematocrit (44.52; OR: 2.73; P: 0.047), and high-sensitivity C-reactive protein (HCRP; >78.64mg/L; OR: 3.71; P: <0.001). For the nomogram model, AUC was 0.807 (95% confidence interval (CI): 0.742-0.873), the Hosmer-Lemeshow test demonstrated no overfitting (P = 0.522), and C-index was 0.807 (95% CI: 0.742-0.872) with corrected value of 0.784 after 1000 bootstrapping validations. Moreover, the calibration curve and DCA exhibited the tools' good prediction consistency and clinical practicability. Conclusion: Heart disease, cerebrovascular disease, liver disease, time to surgery, hematocrit, PMR, and HCRP were significant preoperative predictors for early infections following primary arthroplasty in elderly hip fracture patients, and the converted nomogram model had strong discriminatory ability and translatability to clinical application.

Red Cell Distribution Width-to-High-Density Lipoprotein Cholesterol Ratio (RHR): A Promising Novel Predictor for Preoperative Deep Vein Thrombosis in Geriatric Patients with Hip Fracture.

Background: Deep vein thrombosis (DVT) is a devastating complication in geriatric patients before hip fracture surgery, and the predictive value of red cell distribution width (RDW) and high-density lipoprotein cholesterol (HDL-C) for DVTs after hip fracture remains to be established. This study aimed to assess the predictive value of RDW, HDL-C, and RDW-to-HDL-C ratio (RHR) in preoperative DVTs screening. Methods: We retrospectively analyzed the data of geriatric patients (≥65 years old) admitted for hip fracture surgery between 2015 and 2020. The receiver operating characteristic (ROC) curve and related parameters were used to evaluate the predictive value of the biomarkers. Patients were divided into two groups according to the cutoff value of RHR, and propensity score matching (PSM) and subgroup analyses were performed to assess the true correlations between RHR and DVT. Results: Among 2566 eligible patients included, we identified RDW with the area under ROC curve (AUC) of 0.532, cut-off value of 15.89, specificity of 88.2%, sensitivity of 18.2%, HDL-C with AUC of 0.574, cut-off value of 1.20, specificity of 55.6%, sensitivity of 59.3%, and RHR with AUC of 0.578, cut-off value of 13.45, specificity of 71.3%, sensitivity of 43.4%. RHR (>13.45) was independently associated with 1.54-fold risk (95% CI: 1.11-2.14, P=0.011) of DVTs among the post-PSM cohort. And compared with the counterparts, the relative risk of RHR associated with DVT was higher in the subgroups of aged 65-79 years (1.61 vs 1.45), non-hypoproteinemia (2.70 vs 1.29), non-diabetic (1.58 vs 1.41), non-hypertension (2.40 vs 1.06), ASA score I-II (2.38 vs 1.04), and femoral neck fracture (1.70 vs 1.50). Conclusion: RDW, HDL-C and RHR were valuable biomarkers in predicting preoperative DVTs in geriatric patients with hip fracture, and RHR would be more efficient in the subgroups of younger age, better medical condition or femoral neck fracture.

Development and validation of a predictive nomogram for preoperative deep vein thrombosis (DVT) in isolated calcaneal fracture.

The fact that most of the patients with preoperative DVTs after calcaneal fractures are asymptomatic brought challenges to the early intervention, and periodic imaging examinations aggravated the financial burden of the patients in preoperative detumescence period. This study aimed to use routine clinical data, obtained from the database of Surgical Site Infection in Orthopaedic Surgery (SSIOS), to construct and validate a nomogram for predicting preoperative DVT risk in patients with isolated calcaneal fracture. The nomogram was established base on 7 predictors independently related to preoperative DVT. The performance of the model was tested by concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), and the results were furtherly verified internally and externally. 952 patients were enrolled in this study, of which 711 were used as the training set. The AUC of the nomogram was 0.870 in the training set and 0.905 in the validation set. After internal verification, the modified C-index was 0.846. Calibration curve and decision curve analysis both performed well in the training set and validation set. In short, we constructed a nomogram for predicting preoperative DVT risk in patients with isolated calcaneal fracture and verified its accuracy and clinical practicability.

Clinical application of the sinus tarsi approach in the treatment of intra-articular calcaneal fracture.

To observe the clinical outcome of the sinus tarsi approach in the operative treatment of intra-articular calcaneal fractures.Forty-nine intra-articular calcaneal fractures in 45 patients were managed surgically with sinus tarsi approach. The anatomical plate and compression bolts were applied in 14 feet. The anatomical plate and screws were applied in 35 feet. Maryland foot score system was used to evaluate the function of the hindfoot at the followup.The reduction of the posterior facet was graded as nearly anatomical (less than 2 mm articular displacement) in 46 feet (93.9%). The width, height, and Böhler angle were significantly improved in all patients (P < .01). After a mean follow-up period of 18.7 months (14.5-29 months), the Maryland foot scores were: 34 feet scored 90-100 points (excellent), 6 feet scored 80-90 points (good), 6 feet scored 70-80 points (fair), and 3 feet scored 60-70 points (poor). Incision-edge necrosis occurred in 2 cases. One case suffered from incomplete medial plantar nerve injury. One case suffered from heel pad branch of the tibial nerve injury. Six cases suffered from sural nerve injury, and 4 cases sustained a lateral wound dehiscence due to a hematoma. No case suffered from lateral impingement syndrome. Up to now, no patient had to accept subtalar arthrodesis.Sinus tarsi approach provides good exposure to the subtalar joint. Open reduction and internal fixation of calcaneus fractures through a sinus tarsi approach allows adequate reduction with low risk of wound-healing complications.

[Value of preventive tracheotomy in patients with acute cervical spinal cord injury].

OBJECTIVE: To evaluate the value of preventive tracheotomy in patients with acute cervical spinal cord injury. METHODS: A retrospective analysis was performed on 54 cases of severe C4-C8 cervical spinal cord injury patients undergoing anterior fixation. They were classified as A and B according to the criteria of American Spinal Injury Association. And no tracheotomy was performed preoperatively. The patients with a high risk of dyspnea and with an indication for preventive tracheotomy received a preventive tracheotomy right after anterior fixation. 11 cases were classified into tracheotomy group and 43 cases were in non-tracheotomy group. The preoperative and hospital stays, incidence of hypoxemia and pulmonary infection, incidence of surgical incision site infection and mortality were analyzed between two groups. RESULTS: The preoperative and hospital stays of tracheotomy group were shorter than those of non-tracheotomy group (2.9 ± 1.2 vs 5.7 ± 4.4 days, 10.3 ± 4.0 vs 16.5 ± 9.2 days). The incidence of hypoxemia was lower in tracheotomy group (9.1% vs 44.2%). There was difference existed between two groups. 44.2% patients in the non-tracheotomy group underwent tracheotomy or endotracheal intubation for dyspnea and hypoxemia. There was no significant difference between two groups in the incidence of pulmonary infection (9.1% vs 7.0%) or surgical incision site infection (0 vs 2.3%). The mortality of non-tracheotomy group was 3.07 folds of that of tracheotomy group (9.1% vs 27.9%). But there was no significant statistical difference. CONCLUSION: The preventive tracheotomy is an effective solution for the patients with respiratory compromises, a high risk of dyspnea and with an indication for preventive tracheotomy. The preventive tracheotomy for severe cervical spinal cord can improve respiratory function effectively and fixation may be performed earlier. And there are lower rates of mortality and infection.

Multiple increased osteoclast functions in individuals with neurofibromatosis type 1.

Skeletal abnormalities including scoliosis, tibial dysplasia, sphenoid wing dysplasia, and decreased bone mineral density (BMD) are associated with neurofibromatosis type 1 (NF1). We report the cellular phenotype of NF1 human-derived osteoclasts and compare the in vitro findings with the clinical phenotype. Functional characteristics (e.g., osteoclast formation, migration, adhesion, resorptive capacity) and cellular mechanistic alterations (e.g., F-actin polymerization, MAPK phosphorylation, RhoGTPase activity) from osteoclasts cultured from peripheral blood of individuals with NF1 (N = 75) were assessed. Osteoclast formation was compared to phenotypic, radiologic, and biochemical data. NF1 osteoprogenitor cells demonstrated increased osteoclast forming capacity. Human NF1-derived osteoclasts demonstrated increased migration, adhesion, and in vitro bone resorption. These activities coincided with increased actin belt formation and hyperactivity in MAPK and RhoGTPase pathways. Although osteoclast formation was increased, no direct correlation of osteoclast formation with BMD, markers of bone resorption, or the clinical skeletal phenotype was observed suggesting that osteoclast formation in vitro cannot directly predict NF1 skeletal phenotypes. While NF1 haploinsufficiency produces a generalized osteoclast gain-in-function and may contribute to increased bone resorption, reduced BMD, and focal skeletal defects associated with NF1, additional and perhaps local modifiers are likely required for the development of skeletal abnormalities in NF1.

Ras dependent paracrine secretion of osteopontin by Nf1+/- osteoblasts promote osteoclast activation in a neurofibromatosis type I murine model.

Neurofibromatosis type 1 (NF1) is a pandemic genetic disorder characterized by malignant and nonmalignant manifestations, including skeletal abnormalities, such as osteoporosis, scoliosis, short stature, and pseudarthrosis. Recent studies in genetically inbred mice and from human patients with NF1 have identified multiple gains in osteoclast (OCL) functions both in vitro and in vivo. Given that osteoblasts secrete cytokines that promote OCL maturation/activation, we sought to identify whether haploinsufficiency of Nf1 (Nf1+/-) osteoblasts and their precursors secrete cytokines that have a central role in this process. Osteoblast conditioned media (OBCM) from Nf1+/- osteoblasts promoted OCL migration and bone resorption compared with WT OBCM. Osteopontin (OPN), a matrix protein found in mineralized tissues and pivotal in modulating OCL functions, was present in increased concentrations in Nf1+/- osteoblasts. Addition of OPN neutralizing antibody to Nf1+/- OBCM diminished the gain in bioactivity on OCL functions, including OCL migration and bone resorption. Our study identifies an important paracrine loop whereby elevated secretion of OPN by osteoblasts activate Nf1+/- OCLs that already have an intrinsic propensity for bone resorption leading to osteopenia and osteoporosis.

The p85alpha subunit of class IA phosphatidylinositol 3-kinase regulates the expression of multiple genes involved in osteoclast maturation and migration.

Intracellular signals involved in the maturation and function of osteoclasts are poorly understood. Here, we demonstrate that osteoclasts express multiple regulatory subunits of class I(A) phosphatidylinositol 3-kinase (PI3-K) although the expression of the full-length form of p85alpha is most abundant. In vivo, deficiency of p85alpha results in a significantly greater number of trabeculae and significantly lower spacing between trabeculae as well as increased bone mass in both males and females compared to their sex-matched wild-type controls. Consistently, p85alpha(-/-) osteoclast progenitors show impaired growth and differentiation, which is associated with reduced activation of Akt and mitogen-activated protein kinase extracellular signal-regulated kinase 1 (Erk1)/Erk2 in vitro. Furthermore, a significant reduction in the ability of p85alpha(-/-) osteoclasts to adhere to as well as to migrate via integrin alphavbeta3 was observed, which was associated with reduced bone resorption. Microarray as well as quantitative real-time PCR analysis of p85alpha(-/-) osteoclasts revealed a significant reduction in the expression of several genes associated with the maturation and migration of osteoclasts, including microphathalmia-associated transcription factor, tartrate-resistant acid phosphatase, cathepsin K, and beta3 integrin. Restoring the expression of the full-length form of p85alpha but not the version with a deletion of the Src homology-3 domain restored the maturation of p85alpha(-/-) osteoclasts to wild-type levels. These results highlight the importance of the full-length version of the p85alpha subunit of class I(A) PI3-K in controlling multiple aspects of osteoclast functions.

Rac1 mediates the osteoclast gains-in-function induced by haploinsufficiency of Nf1.

Neurofibromatosis type I (NF1) is a congenital disorder resulting from loss-of-function of the tumor suppressor gene, NF1, a GTPase-activating protein for p21ras. Fifty percent of NF1 patients have osseous manifestations including a high incidence of osteoporosis. Osteoclasts are specialized macrophage/monocyte lineage-derived cells that resorb bone and NF1 haploinsufficient osteoclasts have abnormal Ras-dependent bone resorption. Ras-regulated functions are in part mediated via the activation of small Rho family of GTPases including the Rac-GTPases. In the present study, we demonstrate that the Rho-GTPase Rac1 is a crucial Ras-mediated effector in Nf1 haploinsufficient (+/-) osteoclasts. Nf1+/- mice were intercrossed with conditional Rac1(flox/flox)Mxcre+ (Rac1-/-) mice to generate Nf1+/-; Rac1-/- mice. Genetic disruption of Rac1 restored the pathological increase in osteoclast progenitor cells in Nf1+/- mice and was sufficient to correct the increased Nf1+/- osteoclast motility and osteoclast belt formation, an f-actin structure observed in mature osteoclasts critical for bone resorption and lytic activity. Finally, we demonstrate that Nf1+/-; Rac1-/- osteoclasts have normalized Erk activation compared with Nf1+/- osteoclasts, a biochemical function critical for osteoclast formation, actin organization and motility. Collectively, these data demonstrate that Rac1 critically contributes to increased osteoclast function induced by haploinsufficiency of Nf1 and implicate Rac1 as a rational therapeutic target for osteoporosis.

Genetic analysis of 17 Y-chromosomal STRs haplotypes of Chinese Tibetan ethnic group residing in Qinghai province of China.

We have co-amplified and analyzed 17 Y-chromosomal STRs loci including European 'extended haplotypes' (DYS19, DYS389 I, DYS389 II, DYS390, DYS391, DYS392, DYS393, DYS385a,b, DYS438, and DYS439) and also six additional loci DYS437, DYS448, DYS456, DYS458, DYS635 and YGATA H4 in a population sample of 167 healthy unrelated autochthonous male individuals of Chinese Tibetan ethnic minority group residing in Qinghai province of China using a multiplex PCR system. The gene diversity values for the Y-STRs loci ranged from a minimum 0.3581 for DYS391 locus to a maximum of 0.8702 for DYS385a,b loci in Tibetan population. A total of 163 haplotypes were identified in the set of Y-STR loci, of which 159 were unique and 4 found in two individuals. The overall haplotype diversity for the set of Y-STRs loci was 0.9998, and the discrimination capacity was 0.9938. Research results will be valuable for human identification and paternity tests in the region and for Chinese population genetic study in the future.

Hyperactivation of p21ras and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions.

Individuals with neurofibromatosis type 1 (NF1) have a high incidence of osteoporosis and osteopenia. However, understanding of the cellular and molecular basis of these sequelae is incomplete. Osteoclasts are specialized myeloid cells that are the principal bone-resorbing cells of the skeleton. We found that Nf1(+/-) mice contain elevated numbers of multinucleated osteoclasts. Both osteoclasts and osteoclast progenitors from Nf1(+/-) mice were hyperresponsive to limiting concentrations of M-CSF and receptor activator of NF-kappaB ligand (RANKL) levels. M-CSF-stimulated p21(ras)-GTP and Akt phosphorylation was elevated in Nf1(+/-) osteoclasts associated with gains of function in survival, proliferation, migration, adhesion, and lytic activity. These gains of function are associated with more severe bone loss following ovariectomy as compared with that in syngeneic WT mice. Intercrossing Nf1(+/-) mice and mice deficient in class 1(A) PI3K (p85alpha) restored elevated PI3K activity and Nf1(+/-) osteoclast functions to WT levels. Furthermore, in vitro-differentiated osteoclasts from NF1 patients also displayed elevated Ras/PI3K activity and increased lytic activity analogous to those in murine Nf1(+/-) osteoclasts. Collectively, our results identify a what we believe to be a novel cellular and biochemical NF1-haploinsufficient phenotype in osteoclasts that has potential implications for the pathogenesis of NF1 bone disease.

[Genetic polymorphism analysis of 6 STR loci on the X chromosome in Xi'an Han population].

OBJECTIVE: To investigate the alleles and genotypes frequency of 6 short tandem repeat (STR) loci (DXS8378, DXS7132, DXS6789, DXS101, HPRTB and DXS7423) on the X chromosome in Han population. METHODS: The six X-chromosome STR loci were analyzed by PCR following polyacylamide gel electrophoresis and silver stain. RESULTS: Among 120 females from Xi'an Han population, the number of alleles in the 6 loci (DXS8378, DXS7132, DXS6789, DXS101, HPRTB and DXS7423) were 5, 6, 11, 10, 8, and 4 respectively; the number of genotypes in the 6 loci were 10, 17, 29, 32, 22, and 7 respectively; Exact tests demonstrated genotype frequencies in females had no departure from Hardy-Weinberg equilibrium. CONCLUSION: The six X-chromosome STR loci are appropriate for individual identification, paternity testing involving a female child and for study on related disease.