Strategies for Treating Traumatic Neuromas with Tissue-Engineered Materials.

Neuroma, a pathological response to peripheral nerve injury, refers to the abnormal growth of nerve tissue characterized by disorganized axonal proliferation. Commonly occurring after nerve injuries, surgeries, or amputations, this condition leads to the formation of painful nodular structures. Traditional treatment options include surgical excision and pharmacological management, aiming to alleviate symptoms. However, these approaches often offer temporary relief without addressing the underlying regenerative challenges, necessitating the exploration of advanced strategies such as tissue-engineered materials for more comprehensive and effective solutions. In this study, we discussed the etiology, molecular mechanisms, and histological morphology of traumatic neuromas after peripheral nerve injury. Subsequently, we summarized and analyzed current nonsurgical and surgical treatment options, along with their advantages and disadvantages. Additionally, we emphasized recent advancements in treating traumatic neuromas with tissue-engineered material strategies. By integrating biomaterials, growth factors, cell-based approaches, and electrical stimulation, tissue engineering offers a comprehensive solution surpassing mere symptomatic relief, striving for the structural and functional restoration of damaged nerves. In conclusion, the utilization of tissue-engineered materials has the potential to significantly reduce the risk of neuroma recurrence after surgical treatment.

Growth factors: Bioactive macromolecular drugs for peripheral nerve injury treatment - Molecular mechanisms and delivery platforms.

Bioactive macromolecular drugs known as Growth Factors (GFs), approved by the Food and Drug Administration (FDA), have found successful application in clinical practice. They hold significant promise for addressing peripheral nerve injuries (PNIs). Peripheral nerve guidance conduits (NGCs) loaded with GFs, in the context of tissue engineering, can ensure sustained and efficient release of these bioactive compounds. This, in turn, maintains a stable, long-term, and effective GF concentration essential for treating damaged peripheral nerves. Peripheral nerve regeneration is a complex process that entails the secretion of various GFs. Following PNI, GFs play a pivotal role in promoting nerve cell growth and survival, axon and myelin sheath regeneration, cell differentiation, and angiogenesis. They also regulate the regenerative microenvironment, stimulate plasticity changes post-nerve injury, and, consequently, expedite nerve structure and function repair. Both exogenous and endogenous GFs, including NGF, BDNF, NT-3, GDNF, IGF-1, bFGF, and VEGF, have been successfully loaded onto NGCs using techniques like physical adsorption, blend doping, chemical covalent binding, and engineered transfection. These approaches have effectively promoted the repair of peripheral nerves. Numerous studies have demonstrated similar tissue functional therapeutic outcomes compared to autologous nerve transplantation. This evidence underscores the substantial clinical application potential of GFs in the domain of peripheral nerve repair. In this article, we provide an overview of GFs in the context of peripheral nerve regeneration and drug delivery systems utilizing NGCs. Looking ahead, commercial materials for peripheral nerve repair hold the potential to facilitate the effective regeneration of damaged peripheral nerves and maintain the functionality of distant target organs through the sustained release of GFs.

The Porous Structure of Peripheral Nerve Guidance Conduits: Features, Fabrication, and Implications for Peripheral Nerve Regeneration.

Porous structure is an important three-dimensional morphological feature of the peripheral nerve guidance conduit (NGC), which permits the infiltration of cells, nutrients, and molecular signals and the discharge of metabolic waste. Porous structures with precisely customized pore sizes, porosities, and connectivities are being used to construct fully permeable, semi-permeable, and asymmetric peripheral NGCs for the replacement of traditional nerve autografts in the treatment of long-segment peripheral nerve injury. In this review, the features of porous structures and the classification of NGCs based on these characteristics are discussed. Common methods for constructing 3D porous NGCs in current research are described, as well as the pore characteristics and the parameters used to tune the pores. The effects of the porous structure on the physical properties of NGCs, including biodegradation, mechanical performance, and permeability, were analyzed. Pore structure affects the biological behavior of Schwann cells, macrophages, fibroblasts, and vascular endothelial cells during peripheral nerve regeneration. The construction of ideal porous structures is a significant advancement in the regeneration of peripheral nerve tissue engineering materials. The purpose of this review is to generalize, summarize, and analyze methods for the preparation of porous NGCs and their biological functions in promoting peripheral nerve regeneration to guide the development of medical nerve repair materials.

Multifunctional wet-adhesive chitosan/acrylic conduit for sutureless repair of peripheral nerve injuries.

The incidence of peripheral nerve injury (PNI) is high worldwide, and a poor prognosis is common. Surgical closure and repair of the affected area are crucial to ensure the effective treatment of peripheral nerve injuries. Despite being the standard treatment approach, reliance on sutures to seal the severed nerve ends introduces several limitations and restrictions. This technique is intricate and time-consuming, and the application of threading and punctate sutures may lead to tissue damage and heightened tension concentrations, thus increasing the risk of fixation failure and local inflammation. This study aimed to develop easily implantable chitosan-based peripheral nerve repair conduits that combine acrylic acid and cleavable N-hydroxysuccinimide to reduce nerve damage during repair. In ex vivo tissue adhesion tests, the conduit achieved maximal interfacial toughness of 705 J m-2 ± 30 J m-2, allowing continuous bridging of the severed nerve ends. Adhesive repair significantly reduces local inflammation caused by conventional sutures, and the positive charge of chitosan disrupts the bacterial cell wall and reduces implant-related infections. This promises to open new avenues for sutureless nerve repair and reliable medical implants.

Micron track chitosan conduit fabricated by 3D-printed model topography provides bionic microenvironment for peripheral nerve regeneration.

The micron track conduit (MTC) and nerve factor provide a physical and biological model for simulating peripheral nerve growth and have potential applications for nerve injury. However, it has rarely been reported that they synergize on peripheral nerves. In this study, we used bioderived chitosan as a substrate to design and construct a neural repair conduit with micron track topography using threedimensional (3D) printing topography. We loaded the MTC with neurotrophin-3 (NT-3) to promote the regeneration of sensory and sympathetic neurons in the peripheral nervous system. We found that the MTC@NT3 composite nerve conduit mimicked the microenvironment of peripheral nerves and promoted axonal regeneration while inducing the targeted growth of Schwann cells, which would promote functional recovery in rats with peripheral nerve injury. Artificial nerve implants with functional properties can be developed using the strategy presented in this study.

Tissue-Engineered Nanomaterials Play Diverse Roles in Bone Injury Repair.

Nanomaterials with bone-mimicking characteristics and easily internalized by the cell could create suitable microenvironments in which to regulate the therapeutic effects of bone regeneration. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone injury repair. First, an overview of the hierarchical architecture from the macroscale to the nanoscale of natural bone is presented, as these bone tissue microstructures and compositions are the basis for constructing bone substitutes. Next, urgent clinical issues associated with bone injury that require resolution and the potential of nanomaterials to overcome them are discussed. Finally, nanomaterials are classified as inorganic or organic based on their chemical properties. Their basic characteristics and the results of related bone engineering studies are described. This review describes theoretical and technical bases for the development of innovative methods for repairing damaged bone and should inspire therapeutic strategies with potential for clinical applications.

An electroencephalography-based human-machine interface combined with contralateral C7 transfer in the treatment of brachial plexus injury.

Transferring the contralateral C7 nerve root to the median or radial nerve has become an important means of repairing brachial plexus nerve injury. However, outcomes have been disappointing. Electroencephalography (EEG)-based human-machine interfaces have achieved promising results in promoting neurological recovery by controlling a distal exoskeleton to perform functional limb exercises early after nerve injury, which maintains target muscle activity and promotes the neurological rehabilitation effect. This review summarizes the progress of research in EEG-based human-machine interface combined with contralateral C7 transfer repair of brachial plexus nerve injury. Nerve transfer may result in loss of nerve function in the donor area, so only nerves with minimal impact on the donor area, such as the C7 nerve, should be selected as the donor. Single tendon transfer does not fully restore optimal joint function, so multiple functions often need to be reestablished simultaneously. Compared with traditional manual rehabilitation, EEG-based human-machine interfaces have the potential to maximize patient initiative and promote nerve regeneration and cortical remodeling, which facilitates neurological recovery. In the early stages of brachial plexus injury treatment, the use of an EEG-based human-machine interface combined with contralateral C7 transfer can facilitate postoperative neurological recovery by making full use of the brain's computational capabilities and actively controlling functional exercise with the aid of external machinery. It can also prevent disuse atrophy of muscles and target organs and maintain neuromuscular junction effectiveness. Promoting cortical remodeling is also particularly important for neurological recovery after contralateral C7 transfer. Future studies are needed to investigate the mechanism by which early movement delays neuromuscular junction damage and promotes cortical remodeling. Understanding this mechanism should help guide the development of neurological rehabilitation strategies for patients with brachial plexus injury.

Polydopamine-modified chitin conduits with sustained release of bioactive peptides enhance peripheral nerve regeneration in rats.

The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve regeneration. However, neurotrophic factors are rapidly degraded in vivo and obstruct axonal regeneration when used at a supraphysiological dose, which limits their clinical benefits. Bioactive mimetic peptides have been developed to be used in place of neurotrophic factors because they have a similar mode of action to the original growth factors and can activate the equivalent receptors but have simplified sequences and structures. In this study, we created polydopamine-modified chitin conduits loaded with brain-derived neurotrophic factor mimetic peptides and vascular endothelial growth factor mimetic peptides (Chi/PDA-Ps). We found that the Chi/PDA-Ps conduits were less cytotoxic in vitro than chitin conduits alone and provided sustained release of functional peptides. In this study, we evaluated the biocompatibility of the Chi/PDA-Ps conduits. Brain-derived neurotrophic factor mimetic peptide and vascular endothelial growth factor mimetic peptide synergistically promoted proliferation of Schwann cells and secretion of neurotrophic factors by Schwann cells and attachment and migration of endothelial cells in vitro. The Chi/PDA-Ps conduits were used to bridge a 2 mm gap between the nerve stumps in rat models of sciatic nerve injury. We found that the application of Chi/PDA-Ps conduits could improve the motor function of rats and reduce gastrocnemius atrophy. The electrophysiological results and the microstructure of regenerative nerves showed that the nerve conduction function and remyelination was further restored. These findings suggest that the Chi/PDA-Ps conduits have great potential in peripheral nerve injury repair.

Sustained release of exosomes loaded into polydopamine-modified chitin conduits promotes peripheral nerve regeneration in rats.

Exosomes derived from mesenchymal stem cells are of therapeutic interest because of their important role in intracellular communication and biological regulation. On the basis of previously studied nerve conduits, we designed a polydopamine-modified chitin conduit loaded with mesenchymal stem cell-derived exosomes that release the exosomes in a sustained and stable manner. In vitro experiments revealed that rat mesenchymal stem cell-derived exosomes enhanced Schwann cell proliferation and secretion of neurotrophic and growth factors, increased the expression of Jun and Sox2 genes, decreased the expression of Mbp and Krox20 genes in Schwann cells, and reprogrammed Schwann cells to a repair phenotype. Furthermore, mesenchymal stem cell-derived exosomes promoted neurite growth of dorsal root ganglia. The polydopamine-modified chitin conduits loaded with mesenchymal stem cell-derived exosomes were used to bridge 2 mm rat sciatic nerve defects. Sustained release of exosomes greatly accelerated nerve healing and improved nerve function. These findings confirm that sustained release of mesenchymal stem cell-derived exosomes loaded into polydopamine-modified chitin conduits promotes the functional recovery of injured peripheral nerves.

The anatomical, electrophysiological and histological observations of muscle contraction units in rabbits: a new perspective on nerve injury and regeneration.

In the conventional view a muscle is composed of intermediate structures before its further division into microscopic muscle fibers. Our experiments in mice have confirmed this intermediate structure is composed of the lamella cluster formed by motor endplates, the innervating nerve branches and the corresponding muscle fibers, which can be viewed as an independent structural and functional unit. In this study, we verified the presence of these muscle construction units in rabbits. The results showed that the muscular branch of the femoral nerve sent out 4-6 nerve branches into the quadriceps and the tibial nerve sent out 4-7 nerve branches into the gastrocnemius. When each nerve branch of the femoral nerve was stimulated from the most lateral to the medial, the contraction of the lateral muscle, intermediate muscle and medial muscle of the quadriceps could be induced by electrically stimulating at least one nerve branch. When stimulating each nerve branch of the tibial nerve from the lateral to the medial, the muscle contraction of the lateral muscle 1, lateral muscle 2, lateral muscle 3 and medial muscle of the gastrocnemius could be induced by electrically stimulating at least one nerve branch. Electrical stimulation of each nerve branch resulted in different electromyographical waves recorded in different muscle subgroups. Hematoxylin-eosin staining showed most of the nerve branches around the neuromuscular junctions consisted of one individual neural tract, a few consisted of two or more neural tracts. The muscles of the lower limb in the rabbit can be subdivided into different muscle subgroups, each innervated by different nerve branches, thereby allowing much more complex muscle activities than traditionally stated. Together, the nerve branches and the innervated muscle subgroups can be viewed as an independent structural and functional unit. This study was approved by the Animal Ethics Committee of Peking University People's Hospital (approval No. 2019PHE027) on October 20, 2019.

Myelin-associated glycoprotein combined with chitin conduit inhibits painful neuroma formation after sciatic nerve transection.

Studies have shown that myelin-associated glycoprotein (MAG) can inhibit axon regeneration after nerve injury. However, the effects of MAG on neuroma formation after peripheral nerve injury remain poorly understood. In this study, local injection of MAG combined with nerve cap made of chitin conduit was used to intervene with the formation of painful neuroma after sciatic nerve transfection in rats. After 8 weeks of combined treatment, the autotomy behaviors were reduced in rats subjected to sciatic nerve transfection, the mRNA expression of nerve growth factor, a pain marker, in the proximal nerve stump was decreased, the density of regenerated axons was decreased, the thickness of the myelin sheath was increased, and the ratio of unmyelinated to myelinated axons was reduced. Moereover, the percentage of collagen fiber area and the percentage of fibrosis marker alpha-smooth muscle actin positive staining area in the proximal nerve stump were decreased. The combined treatment exhibited superior effects in these measures to chitin conduit treatment alone. These findings suggest that MAG combined with chitin conduit synergistically inhibits the formation of painful neuroma after sciatic nerve transection and alleviates neuropathic pain. This study was approved by the Animal Ethics Committee of Peking University People's Hospital (approval No. 2019PHE027) on December 5, 2019.

Brain functional remodeling caused by sciatic nerve transposition repair in rats identified by multiple-model resting-state blood oxygenation level-dependent functional magnetic resonance imaging analysis.

Lower extremity nerve transposition repair has become an important treatment strategy for peripheral nerve injury; however, brain changes caused by this surgical procedure remain unclear. In this study, the distal stump of the right sciatic nerve in a rat model of sciatic nerve injury was connected to the proximal end of the left sciatic nerve using a chitin conduit. Neuroelectrophysiological test showed that the right lower limb displayed nerve conduction, and the structure of myelinated nerve fibers recovered greatly. Muscle wet weight of the anterior tibialis and gastrocnemius recovered as well. Multiple-model resting-state blood oxygenation level-dependent functional magnetic resonance imaging analysis revealed functional remodeling in multiple brain regions and the re-establishment of motor and sensory functions through a new reflex arc. These findings suggest that sciatic nerve transposition repair induces brain functional remodeling. The study was approved by the Ethics Committee of Peking University People's Hospital on December 9, 2015 (approval No. 2015-50).

Chitin Nerve Conduits with Three-Dimensional Spheroids of Mesenchymal Stem Cells from SD Rats Promote Peripheral Nerve Regeneration.

Peripheral nerve injury (PNI) is an unresolved medical problem with limited therapeutic effects. Epineurium neurorrhaphy is an important method for treating PNI in clinical application, but it is accompanied by inevitable complications such as the misconnection of nerve fibers and neuroma formation. Conduits small gap tubulization has been proved to be an effective suture method to replace the epineurium neurorrhaphy. In this study, we demonstrated a method for constructing peripheral nerve conduits based on the principle of chitosan acetylation. In addition, the micromorphology, mechanical properties and biocompatibility of the chitin nerve conduits formed by chitosan acetylation were further tested. The results showed chitin was a high-quality biological material for constructing nerve conduits. Previous reports have demonstrated that mesenchymal stem cells culture as spheroids can improve the therapeutic potential. In the present study, we used a hanging drop protocol to prepare bone marrow mesenchymal stem cell (BMSCs) spheroids. Meanwhile, spherical stem cells could express higher stemness-related genes. In the PNI rat model with small gap tubulization, BMSCs spheres exhibited a higher ability to improve sciatic nerve regeneration than BMSCs suspension. Chitin nerve conduits with BMSCs spheroids provide a promising therapy option for peripheral nerve regeneration.

Enhanced recovery after surgery for hip fractures: a systematic review and meta-analysis.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs have achieved promising results in many surgical specialties. However, uncertainty still remains regarding the effect of ERAS on hip fractures. The objective of this review was to investigate the clinical prognosis of ERAS programs in terms of (1) hospital-related endpoints (time to surgery [TTS], length of stay [LOS]), (2) readmission rate, (3) complications, and (4) mortality. METHODS: Published literature was searched in the PubMed, EMBASE, and Cochrane Library databases. All of the included studies met the inclusion criteria. The primary outcomes were TTS and LOS. The secondary outcomes included the 30-day readmission rate, overall complication rate, specific complication rate (delirium and urinary tract infection), and 30-day and 1-year mortality. Language was restricted to English. The data analysis was carried out by Review Manager 5.3. RESULTS: A total of 7 published studies (9869 patients) were finally included, and these were all cohort studies. The meta-analysis showed that the TTS, LOS, and overall complication rate were significantly reduced in the ERAS group compared with the control group (p < 0.01). Moreover, no significant change was found in the 30-day readmission rate or 30-day and 1-year mortality. CONCLUSIONS: ERAS significantly decreases the TTS, LOS, and complication rate without increasing readmission rate and mortality, which adds to the evidence that the implementation of ERAS is beneficial to patients undergoing hip fracture repair surgeries.

Polymer Scaffolds for Biomedical Applications in Peripheral Nerve Reconstruction.

The nervous system is a significant part of the human body, and peripheral nerve injury caused by trauma can cause various functional disorders. When the broken end defect is large and cannot be repaired by direct suture, small gap sutures of nerve conduits can effectively replace nerve transplantation and avoid the side effect of donor area disorders. There are many choices for nerve conduits, and natural materials and synthetic polymers have their advantages. Among them, the nerve scaffold should meet the requirements of good degradability, biocompatibility, promoting axon growth, supporting axon expansion and regeneration, and higher cell adhesion. Polymer biological scaffolds can change some shortcomings of raw materials by using electrospinning filling technology and surface modification technology to make them more suitable for nerve regeneration. Therefore, polymer scaffolds have a substantial prospect in the field of biomedicine in future. This paper reviews the application of nerve conduits in the field of repairing peripheral nerve injury, and we discuss the latest progress of materials and fabrication techniques of these polymer scaffolds.

Combining chitin biological conduits with small autogenous nerves and platelet-rich plasma for the repair of sciatic nerve defects in rats.

AIMS: Peripheral nerve defects are often difficult to recover from, and there is no optimal repair method. Therefore, it is important to explore new methods of repairing peripheral nerve defects. This study explored the efficacy of nerve grafts constructed from chitin biological conduits combined with small autogenous nerves (SANs) and platelet-rich plasma (PRP) for repairing 10-mm sciatic nerve defects in rats. METHODS: To prepare 10-mm sciatic nerve defects, SANs were first harvested and PRP was extracted. The nerve grafts consisted of chitin biological conduits combined with SAN and PRP, and were used to repair rat sciatic nerve defects. These examinations, including measurements of axon growth efficiency, a gait analysis, electrophysiological tests, counts of regenerated myelinated fibers and observations of their morphology, histological evaluation of the gastrocnemius muscle, retrograde tracing with Fluor-Gold (FG), and motor endplates (MEPs) distribution analysis, were conducted to evaluate the repair status. RESULTS: Two weeks after nerve transplantation, the rate and number of regenerated axons in the PRP-SAN group improved compared with those in the PRP, SAN, and Hollow groups. The PRP-SAN group exhibited better recovery in terms of the sciatic functional index value, composite action potential intensity, myelinated nerve fiber density, myelin sheath thickness, and gastrectomy tissue at 12 weeks after transplantation, compared with the PRP and SAN groups. The results of FG retrograde tracing and MEPs analyses showed that numbers of FG-positive sensory neurons and motor neurons as well as MEPs distribution density were higher in the PRP-SAN group than in the PRP or SAN group. CONCLUSIONS: Nerve grafts comprising chitin biological conduits combined with SANs and PRP significantly improved the repair of 10-mm sciatic nerve defects in rats and may have therapeutic potential for repairing peripheral nerve defects in future applications.

Cortical plasticity and nerve regeneration after peripheral nerve injury.

With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.

Risk factors for cement leakage and nomogram for predicting the intradiscal cement leakage after the vertebra augmented surgery.

BACKGROUND: Vertebral augmentation is the first-line treatment for the osteoporosis vertebral compression fractures. Bone cement leakage is the most common complication of this surgery. This study aims to assess the risk factors for different types of cement leakage and provides a nomogram for predicting the cement intradiscal leakage. METHODS: We retrospectively reviewed 268 patients who underwent vertebral augmentation procedure between January 2015 and March 2019. The cement leakage risk factors were evaluated by univariate analysis. Different types of cement leakage risk factors were identified by the stepwise logistic analysis. We provided a nomogram for predicting the cement intradiscal leakage and used the concordance index to assess the prediction ability. RESULTS: A total of 295 levels of vertebrae were included, with a leakage rate of 32.5%. Univariate analysis showed delayed surgery and lower vertebral compression ratio were the independent risk factors of cement leakage. The stepwise logistic analysis revealed percutaneous vertebroplasty was a risk factor in vein cement leakage; delayed surgery, preoperative compression ratio, and upper endplate disruption were in intradiscal cement leakage; age, preoperative fracture severity, and intravertebral vacuum cleft were in perivertebral soft tissue cement leakage; no factor was in spinal canal cement leakage. The nomogram for intradiscal cement leakage had a precise prediction ability with an original concordance index of 0.75. CONCLUSIONS: Delayed surgery and more vertebral compression increase the risk of cement leakage. Different types of cement leakage have different risk factors. We provided a nomogram for precise predicting the intradiscal cement leakage.

Prognostic Implications of Preoperative Pneumonia for Geriatric Patients Undergoing Hip Fracture Surgery or Arthroplasty.

OBJECTIVE: To report outcomes of geriatric patients undergoing hip fracture surgery or arthroplasty with or without preoperative pneumonia and to evaluate the influence of pneumonia severity on patient prognosis. METHODS: In this single center retrospective study, we included geriatric patients (≥60 years old) who had undergone hip fracture surgery or arthroplasty at Peking University People's Hospital from January 2008 to September 2018. Patients with fractures caused by neoplasms or patients with incomplete clinical data were excluded. Using logistic regression and the CURB-65 (confusion, uremia, respiratory rate, blood pressure, and age ≥65 years) score as a prediction tool of 1-year mortality, the effect of preoperative pneumonia on 1-year mortality was evaluated. Survival of patients with different response to pneumonia-specific therapy and survival of patients with different pneumonia severity (evaluated with CURB-65 score) were analyzed using Cox regression. RESULTS: A total of 1386 patients were included; among them, 109 patients (7.86%) were diagnosed with preoperative pneumonia. Outcomes were evaluated in August 2019 (at least 1 year after surgery for all patients). Compared to patients without preoperative pneumonia, patients with this condition had higher 30-day mortality (11.9% vs 5%, P = 0.002) and 1-year mortality rates (33.9% vs 16.3%, P < 0.001) and higher incidence of acute heart failure (7.3% vs 3.4%, P = 0.034) and acute kidney injury (5.5% vs 1.8%, P = 0.009). In multivariate regression, preoperative pneumonia was identified as an independent predictor of 1-year mortality (odds ratio [OR], 1.45; 95% confidence interval [CI] 1.39-3.52; P = 0.021), with other factors including age (≥84 years, OR, 1.46; 95% CI 1.08-1.60; P = 0.027), body mass index (<18.5 kg/m2 , OR 2.23; 95% CI 1.52-3.17, P < 0.001), anesthesia type (regional, OR 0.87; 95% CI 0.19-0.97, P = 0.042), preoperative pneumonia (OR 1.45; 95% CI 1.39-3.52; P = 0.002), congestive heart failure (OR 2.05, 95% CI 1.57-6.21, P < 0.001), chronic kidney disease (OR 1.73; 95% CI 1.50-2.62; P < 0.001). There was a trend of increased 1-year mortality as the CURB-65 score elevated (P for trend = 0.006). Cox regression reveals a higher risk of mortality in patient with preoperative pneumonia, especially in patients with no radiologic improvements after therapy (log-rank, P = 0.035). Analysis of the impact of pneumonia severity on patient survival using Cox regression reveals that a CURB-65 score ≥3 indicated a lower rate of survival (CURB-65 score of 3: hazard ratio [HR] 3.12, 95% CI 1.39-7.03, P = 0.006; score of 4: HR 3.41, 95% CI 1.69-6.92, P = 0.001; score of 5: HR 6.28, 95% CI 2.95-13.35, P < 0.001). CONCLUSION: In this single center retrospective study, preoperative pneumonia was identified as an independent risk factor of 1-year mortality in geriatric patients undergoing hip fracture surgery or arthroplasty. A CURB-65 score ≥3 indicated a higher risk of mortality.

Author Correction: Repair of bone defects with prefabricated vascularized bone grafts and double-labeled bone marrow-derived mesenchymal stem cells in a rat model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.