SARS-CoV-2-induced Overexpression of miR-4485 Suppresses Osteogenic Differentiation and Impairs Fracture Healing.

The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the cell entry point for SARS-CoV-2. Although ACE2 receptors are present in the bone marrow, the effects of SARS-CoV-2 on the biological activity of bone tissue have not yet been elucidated. In the present study we sought to investigate the impact of SARS-CoV-2 on osteoblastic activity in the context of fracture healing. MicroRNA-4485 (miR-4485), which we found to be upregulated in COVID-19 patients, negatively regulates osteogenic differentiation. We demonstrate this effect both in vitro and in vivo. Moreover, we identified the toll-like receptor 4 (TLR-4) as the potential target gene of miR-4485, and showed that reduction of TLR-4 induced by miR-4485 suppresses osteoblastic differentiation in vitro. Taken together, our findings highlight that up-regulation of miR-4485 is responsible for the suppression of osteogenic differentiation in COVID-19 patients, and TLR-4 is the potential target through which miR-4485 acts, providing a promising target for pro-fracture-healing and anti-osteoporosis therapy in COVID-19 patients.

Delayed surgery versus nonoperative treatment for hip fractures in post-COVID-19 arena: a retrospective study of 145 patients.

Background and purpose - Following the outbreak of COVID-19 in December 2019, in China, many hip fracture patients were unable to gain timely admission and surgery. We assessed whether delayed surgery improves hip joint function and reduces major complications better than nonoperative therapy. Patients and methods - In this retrospective observational study, we collected data from 24 different hospitals from January 1, 2020, to July 20, 2020. 145 patients with hip fractures aged 65 years or older were eligible. Clinical data was extracted from electronic medical records. The primary outcomes were visual analogue scale (VAS) score and Harris Hip Score. Major complications, including deep venous thrombosis (DVT) and pneumonia within 1 month and 3 months, were collected for further analysis. Results - Of the 145 hip fracture patients 108 (median age 72; 70 females) received delayed surgery and 37 (median age 74; 20 females) received nonoperative therapy. The median time from hip fracture injury to surgery was 33 days (IQR 24-48) in the delayed surgery group. Hypertension, in about half of the patients in both groups, and cerebral infarction, in around a quarter of patients in both groups, were the most common comorbidities. Both VAS score and Harris Hip Score were superior in the delayed surgery group. At the 3-month follow-up, the median VAS score was 1 in the delayed surgery group and 2.5 in the nonoperative group (p < 0.001). Also, the percentage of complications was higher in the nonoperative group (p = 0.004 for DVT, p < 0.001 for pulmonary infection). Interpretation - In hip fracture patients, delayed surgery compared with nonoperative therapy significantly improved hip function and reduced various major complications.

ANDC: an early warning score to predict mortality risk for patients with Coronavirus Disease 2019.

BACKGROUND: Patients with severe Coronavirus Disease 2019 (COVID-19) will progress rapidly to acute respiratory failure or death. We aimed to develop a quantitative tool for early predicting mortality risk of patients with COVID-19. METHODS: 301 patients with confirmed COVID-19 admitted to Main District and Tumor Center of the Union Hospital of Huazhong University of Science and Technology (Wuhan, China) between January 1, 2020 to February 15, 2020 were enrolled in this retrospective two-centers study. Data on patient demographic characteristics, laboratory findings and clinical outcomes was analyzed. A nomogram was constructed to predict the death probability of COVID-19 patients. RESULTS: Age, neutrophil-to-lymphocyte ratio, D-dimer and C-reactive protein obtained on admission were identified as predictors of mortality for COVID-19 patients by LASSO. The nomogram demonstrated good calibration and discrimination with the area under the curve (AUC) of 0.921 and 0.975 for the derivation and validation cohort, respectively. An integrated score (named ANDC) with its corresponding death probability was derived. Using ANDC cut-off values of 59 and 101, COVID-19 patients were classified into three subgroups. The death probability of low risk group (ANDC < 59) was less than 5%, moderate risk group (59 ≤ ANDC ≤ 101) was 5% to 50%, and high risk group (ANDC > 101) was more than 50%, respectively. CONCLUSION: The prognostic nomogram exhibited good discrimination power in early identification of COVID-19 patients with high mortality risk, and ANDC score may help physicians to optimize patient stratification management.

ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy Orthopaedic Guidelines for the COVID-19 Post-Outbreak Period: Experience from Wuhan, People's Republic of China

As the outbreak of coronavirus disease 2019 (COVID-19) progresses, prognostic markers for early identification of high-risk individuals are an urgent medical need. Italy has one of the highest numbers of SARS-CoV-2-related deaths and one of the highest mortality rates. Worldwide, a more severe course of COVID-19 is associated with older age, comorbidities, and male sex. Hence, we searched for possible genetic components of COVID-19 severity among Italians by looking at expression levels and variants in ACE2 and TMPRSS2 genes, crucial for viral infection.Exome and SNP-array data from a large Italian cohort were used to compare the rare-variants burden and polymorphisms frequency with Europeans and East Asians. Moreover, we looked into gene expression databases to check for sex-unbalanced expression.While we found no significant evidence that ACE2 is associated with disease severity/sex bias, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, prompting for rapid experimental validations on large patient cohorts. Currently, the coronavirus disease 2019 (COVID-19) crisis has rapidly spread worldwide. As the earliest outbreak area of the pandemic, Wuhan, People's Republic of China, is gradually recovering to its normal state under the effective control of government authorities. Outpatient services in major hospitals are now being restored. An accumulation of asymptomatic infections is a potential risk for medical personnel, especially when there is crowding in hospitals. As the biggest center for orthopaedic patients in Wuhan, our orthopaedic outpatient department admits >300 patients per day. Optimal guidelines on how to handle this huge number of patients during the post-outbreak stage of the COVID-19 pandemic, particularly with regard to potential asymptomatic infection, are urgently needed for orthopaedic surgeons. We have developed and proposed applicable guidelines to fill this knowledge gap, including the necessary protective strategies for medical personnel in orthopaedic outpatient and inpatient wards as well as during surgery. We also have provided mental health recommendations for health-care workers. To the best of our knowledge, these guidelines are the first of their kind for orthopaedic surgeons who are slowly reestablishing medical activity following the pandemic.

COVID-19 Orthopaedic Safe Care Toolset: Guidelines for the Diagnosis and Management of Patients with Fracture and COVID-19.

The SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) was reported in Wuhan, Hubei Province, People's Republic of China, and, subsequently, in other provinces and regions across the People's Republic of China and >212 countries. COVID-19, the disease caused by this coronavirus, was declared a worldwide pandemic by the World Health Organization (WHO). The incidence of patients with fracture who are also positive for COVID-19 is on the rise. The diagnosis and management of such patients can be complicated as their clinical characteristics are heterogeneous. Furthermore, a surgical procedure can be particularly challenging given that the use of high-speed devices results in aerosol generation. In this study, we develop and propose globally applicable guidelines to fill this knowledge gap and we identify and propose the necessary protective strategies for medical personnel in an orthopaedic emergency department and in the inpatient wards. We also introduce diagnostic criteria, surgical complication management, and follow-up strategies for infected patients. These guidelines may be helpful to decrease the infection rate of orthopaedic trauma personnel and to provide diagnosis and treatment therapy for patients with fracture and COVID-19.

Orthopaedic Guidelines for the COVID-19 Post-Outbreak Period: Experience from Wuhan, People's Republic of China.

Currently, the coronavirus disease 2019 (COVID-19) crisis has rapidly spread worldwide. As the earliest outbreak area of the pandemic, Wuhan, People's Republic of China, is gradually recovering to its normal state under the effective control of government authorities. Outpatient services in major hospitals are now being restored. An accumulation of asymptomatic infections is a potential risk for medical personnel, especially when there is crowding in hospitals. As the biggest center for orthopaedic patients in Wuhan, our orthopaedic outpatient department admits >300 patients per day. Optimal guidelines on how to handle this huge number of patients during the post-outbreak stage of the COVID-19 pandemic, particularly with regard to potential asymptomatic infection, are urgently needed for orthopaedic surgeons. We have developed and proposed applicable guidelines to fill this knowledge gap, including the necessary protective strategies for medical personnel in orthopaedic outpatient and inpatient wards as well as during surgery. We also have provided mental health recommendations for health-care workers. To the best of our knowledge, these guidelines are the first of their kind for orthopaedic surgeons who are slowly reestablishing medical activity following the pandemic.

Preventive strategy for the clinical treatment of hip fractures in the elderly during the COVID-19 outbreak: Wuhan's experience.

Hip fractures in the elderly account for more than half of osteoporotic fractures and represent a substantial economic and social burden. Novel coronavirus pneumonia (COVID-19), which began to spread in December 2019, has created challenges in the management of elderly hip fracture patients, not only by influencing the choice of operation and postoperative rehabilitation methods, but also by generating new risks for the medical staff. During this period, our infection and orthopedic treatment unit in the center of the epidemic area effectively treated 82 elderly patients with hip fracture, and no cross-infection occurred. Therefore, our experience in prevention and treatment is worth recommending to frontline anti-epidemic personnel.

Characteristics and Early Prognosis of COVID-19 Infection in Fracture Patients.

BACKGROUND: Studies of the novel coronavirus-induced disease COVID-19 in Wuhan, China, have elucidated the epidemiological and clinical characteristics of this disease in the general population. The present investigation summarizes the clinical characteristics and early prognosis of COVID-19 infection in a cohort of patients with fractures. METHODS: Data on 10 patients with a fracture and COVID-19 were collected from 8 different hospitals located in the Hubei province from January 1, 2020, to February 27, 2020. Analyses of early prognosis were based on clinical outcomes and trends in laboratory results during treatment. RESULTS: All 10 patients presented with limited activity related to the fracture. The most common signs were fever, cough, and fatigue at the time of presentation (7 patients each). Other, less common signs included sore throat (4 patients), dyspnea (5 patients), chest pain (1 patient), nasal congestion (1 patient), headache (1 patient), dizziness (3 patients), abdominal pain (1 patient), and vomiting (1 patient). Lymphopenia (<1.0 × 10 cells/L) was identified in 6 of 10 patients, 9 of 9 patients had a high serum level of D-dimer, and 9 of 9 patients had a high level of C-reactive protein. Three patients underwent surgery, whereas the others were managed nonoperatively because of their compromised status. Four patients died on day 8 (3 patients) or day 14 (1 patient) after admission. The clinical outcomes for the surviving patients are not yet determined. CONCLUSIONS: The clinical characteristics and early prognosis of COVID-19 in patients with fracture tended to be more severe than those reported for adult patients with COVID-19 without fracture. This finding may be related to the duration between the development of symptoms and presentation. Surgical treatment should be carried out cautiously or nonoperative care should be chosen for patients with fracture in COVID-19-affected areas, especially older individuals with intertrochanteric fractures. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.