Mini-subvastus versus medial parapatellar approach for total knee arthroplasty: a prospective randomized controlled study.

PURPOSE: Whether minimally invasive total knee arthroplasty (MIS-TKA) could offer better and faster recovery without the deviation of post-operative prosthesis position and limb alignment is still controversial. This prospective and randomized study was conducted to compare the clinical and radiological outcomes between patients who underwent the mini-subvastus approach of MIS-TKA and those who underwent the medial parapatellar approach of traditional TKA. METHODS: Fifty patients, including 50 knees, who required TKA due to osteoarthritis were randomized to the mini-subvastus group (group I) or the medial parapatellar group (group II). All patients accepted the same method of anaesthesia, equal support therapy and identical rehabilitation exercise after surgery. The evaluation system included operation time, tourniquet time, blood loss, skin incision length in flexion, straight leg raising time, the time of lower limb muscle strength up to grade 4, the time of walking with aid or without aid, the time of walking up and down the stairs, the active flexion angle, range of movement (ROM), the Knee Society Scores (KSS), visual analogue score for pain (VAS), hospital stays and radiographic outcomes. RESULTS: The mini-subvastus approach offered smaller skin incision length in flexion, but at the cost of operation time (P < 0.001). No significant difference was found in tourniquet time and blood loss. The patients in group I could achieve straight leg raising, the lower limb muscle strength up to grade 4, walking with or without aid, and walking up and down the stairs earlier (P < 0.001). The active flexion angle, ROM, VAS and KSS in group I were superior to those in group II until six months post-operatively (P < 0.001), but the differences was not apparent at 12 months post-operatively. More importantly, there was no significant difference between the two groups on radiological outcomes (P > 0.05). CONCLUSIONS: The mini-subvastus approach could offer faster recovery, less pain and shorter hospital stays without compromising the principles of proper prosthesis position and limb alignment compared with the medial parapatellar approach.

[Effect of stump-preserving repair on rotator cuff healing and shoulder function for degenerative total rotator cuff tears].

Objective: To analyze the effect of stump-preserving repair on rotator cuff healing and shoulder function for degenerative total rotator cuff tears. Methods: A clinical data of 152 patients with degenerative total rotator cuff tears, who underwent arthroscopic repair between April 2019 and May 2022, was retrospectively analyzed. There were 76 males and 76 females with an average age of 55.4 years (range, 24-78 years). MRI was performed at 6 months postoperatively to evaluate the rotator cuff healing according to the Sugaya classification. Pre- and intra-operative related factors were included for univariate analysis, including age (≥60 years/<60 years), gender (male/female), passive activity disorder (yes/no), disease duration (≤3 months/>3 months), stump-preserving repair (yes/no), use of suture bridge technique (yes/no), shoulder joint abduction angle at knotting (<45°/≥45°), acromioplasty (yes/no), glucocorticoid injection (yes/no), time for patients to start postoperative passive exercise (≤2 weeks/>2 weeks), and time for patients to start postoperative active exercise (≤3 months/>3 months). The influencing factors of tendon healing were screened; further logistic regression was used to conduct multivariate analysis to screen for risk factors. Two sets of data were balanced by propensity score matching. The American Shoulder and Elbow Surgeons (ASES) score and Constant-Murley score of shoulder joint function at 6 and 12 months postoperatively, as well as rotator cuff healing rate at 6 months postoperatively, were compared between groups based on whether or not stump-preserving repair was used. Results: All patients were followed up 12-33 months (mean, 23.8 months). MRI at 25-31 weeks postoperatively showed the 121 cases of rotator cuff healing and 31 cases of non healing. Univariate analysis showed that the disease duration, stump-preserving repair, shoulder joint abduction angle at knotting, and the time for patients to start postoperative active exercise were the influencing factors of rotator cuff healing ( P<0.05). Multivariate analysis showed that non-stump-preserving repair, shoulder abduction angle more than 45° at knotting, and the time to start active exercise within 3 months postoperatively were risk factors affecting rotator cuff healing ( P<0.05). A total of 51 pairs of cases were matched based on the grouping criteria of whether the disease duration exceeded 3 months, whether the shoulder abduction angle at knotting exceeded 45°, and whether the time to start postoperative active exercise exceeded 3 months. The rotator cuff healing rate, ASES score, and Constant-Murley score of the preserving repair group at 6 months postoperatively were superior to those of the non-preserving repair group, and the differences were significant ( P<0.05). There was no significant difference in ASES score and Constant-Murley score between the two groups at 12 months postoperatively ( P>0.05). Conclusion: For degenerative total rotator cuff tears, the stump-preserving repair can shorten the healing time and promote the shoulder function recovery, but has no significant effect on shoulder function at 1 year postoperatively.

Modified arthroscopic repair of a posterior cruciate ligament tibial avulsion fracture improves IKDC and Lysholm score compared to open reduction.

PURPOSE: The purpose of this study was to analyse the difference between arthroscopic fixation and open reduction internal fixation (ORIF) of posterior cruciate ligament (PCL) tibial avulsion fractures. METHODS: This retrospective study analysed patients with an acute PCL tibial avulsion fracture who underwent surgical treatment at our hospital and follow-up for at least 24 months. Variables based on sex, age, Meyers-McKeever type, surgical method, meniscus tear, external fixation, labour or sports, Lysholm knee score, IKDC score, and KT-1000 value were also recorded. Multifactor unconditional logistic regression and Student's t test with 1:1 propensity score matching (PSM) to remove confounding factors were used for analysis. RESULTS: Sixty-five cases achieved knee function graded as "good" or better, and 9 cases not. Single-factor analysis indicated that Meyers-McKeever type (χ2 = 4.669, P = 0.031) and surgical approach (χ2 = 9.428, P = 0.002) are related to functional outcomes. Multifactorial logistic regression analysis further confirmed that Meyers-McKeever typing (OR = 10.763, P = 0.036, [95% CI 1.174-98.693]) and surgical approach (OR = 9.274, P = 0.008, [95% CI 1.794-47.934]) are independent risk factors affecting prognosis. In addition, PSM verified significant differences in the Lysholm score (t = 3.195, P = 0.006), IKDC score (t = 4.703, P = 0.000) and A-KT/H-KT (t = 2.859, P = 0.012). However, the affected-side KT-1000 value (A-KT, mm, t = 1.225, P = 0.239) and healthy-side KT-1000 value (H-KT, mm, t = 1.436, P = 0.172) did not significantly differ between the two groups. The proportions of cases in which the Lysholm score, IKDC and A-KT/H-KT exceeded the minimal clinically important difference (MCID) were 62.5% (20/32), 62.5% (20/32) and 93.75% (30/32), respectively. CONCLUSION: Compared with ORIF, an arthroscopic approach for PCL tibial avulsion fractures achieves better results. LEVEL OF EVIDENCE: Retrospective cohort study; Level II.

PiRNA hsa_piR_019914 Promoted Chondrocyte Anabolic Metabolism By Inhibiting LDHA-Dependent ROS Production.

OBJECTIVES: Osteoarthritis (OA) is the most common joint disease. The occurrence and progression of OA are regulated by epigenetics. A large number of studies have shown the important regulatory role of noncoding RNAs in joint diseases. As the largest class of noncoding small RNAs, the importance of piRNAs in many diseases, especially cancer, has been increasingly recognized. However, few studies have explored the role of piRNAs in OA. Our study showed that hsa_piR_019914 decreased significantly in OA. This study aimed to demonstrate the role of hsa_piR_019914 as a potential biological target of OA in chondrocytes. DESIGN: The GEO database and bioinformatics analysis were used for a series of screenings, and the OA model using human articular chondrocytes (C28/I2 cells), SW1353 cells under inflammatory factor stimulation was used to determine that hsa_piR_019914 was significantly downregulated in OA. Overexpression or inhibition of hsa_piR_019914 in C28/I2 cells was achieved by transfecting mimics or inhibitors. The effect of hsa_piR_019914 on the biological function of chondrocytes was verified by qPCR, flow cytometry, and colony formation assays in vitro. The target gene of hsa_piR_019914, lactate dehydrogenase A (LDHA), was screened by small RNA sequencing and quantitative polymerase chain reaction (qPCR), LDHA was knocked out in C28/I2 cells by the transfection of siRNA LDHA, and the relationship between hsa_piR_019914, LDHA, and reactive oxygen species (ROS) production was verified by flow cytometry. RESULTS: The piRNA hsa-piR-019914 was significantly downregulated in osteoarthritis (OA). Hsa-piR-019914 reduced inflammation-mediated chondrocyte apoptosis and maintained cell proliferation and clone formation in vitro. Hsa-piR-019914 reduced the production of LDHA-dependent ROS through targeted regulation of LDHA expression, maintained chondrocyte-specific gene expression of ACAN and COL2, and inhibited the gene expression of MMP3 and MMP13. CONCLUSIONS: Collectively, this study showed that hsa_piR_019914 was negatively correlated with the expression of LDHA, which mediates ROS production. Under the stimulation of inflammatory factors, overexpression of hsa_piR_019914 had a protective effect on chondrocytes in vitro, and the absence of hsa_piR_019914 exacerbated the negative effect of inflammation on chondrocytes. Studies on piRNAs provide new therapeutic interventions for OA.

Intermittent cyclic mechanical compression promotes endplate chondrocytes degeneration by disturbing Nrf2/PINK1 signaling pathway-dependent mitophagy.

An abnormal mechanical load is a pivotal inducer of endplate cartilage degeneration, which subsequently promotes intervertebral disc degeneration. Our previous study indicated that intermittent cyclic mechanical compression (ICMC) promotes endplate chondrocyte degeneration, but the mechanism underlying this effect is unclear. In this study, we investigated PTEN-induced kinase 1(PINK1) dependent mitophagy during ICMC-induced endplate chondrocyte degeneration. Furthermore, we determined whether NF-E2-related factor 2 (Nrf2) activation correlated with PINK1-dependent mitophagy regulation and increased oxidation resistance of endplate chondrocytes under ICMC application. First, we generated a mechanical compression-induced endplate chondrocyte degeneration model in vitro and in vivo. ICMC was found to promote endplate chondrocyte extracellular matrix degradation. PINK1-mediated mitophagy was suppressed in the ICMC-stimulated endplate chondrocytes, while increased mitochondrial reactive oxygen species generation suggested that mitophagy is involved in the protective effect of mechanical strain on endplate chondrocytes. Moreover, Nrf2 expression, interaction with Kelch-like ECH-associated protein (Keap1), and nuclear translocation were inhibited by ICMC. Nrf2 overexpression inhibited reactive oxygen species production and reversed ICMC-induced endplate chondrocyte degeneration. Transfection with PINK1 shRNA abolished this effect and partially blocked Nrf2-induced mitophagy. Our findings suggested that ICMC could inhibit the Nrf2/PINK1 signaling pathway to reduce the mitophagy levels which significantly promote oxidative stress and thereby endplate chondrocyte degeneration. Therapeutic regulation of the Nrf2/PINK1 signaling pathway may be an efficient anabolic strategy for inhibiting this process.

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial.

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

[Treatment of intertrochanteric fracture of femur with closed reduction of proximal femoral anti rotation intramedullary nail in supine position].

OBJECTIVE: To investigate the effect and feasibility of closed reduction and internal fixation with PFNA in the treatment of intertrochanteric fracture of femur in the supine position without traction bed. METHODS: From June 2014 to March 2018, 45 patients with intertrochanteric fracture of femur who were treated and followed up were analyzed retrospectively. There were 21 males and 24 females, with an average age of 67.4 years (43 to 92 years);18 cases on the left side and 27 on the right side. According to Evans Jensen classification, there were 7 patients of type Ⅱ, 17 patients of type Ⅲ, 16 patients of type Ⅳ and 5 patients of type Ⅴ. The time from injury to operationwas 2 to 6 days. The operation time, blood loss and fracture healing, closing time, postoperative complications and Harris score of hip joint were recorded. RESULTS: The operation time of 45 patients was 35 to 80 min, with an average of 52.6 min;the intraoperative bleeding volume was 40 to 110 ml, with an average of 68.7 ml;the hospitalization time was 6 to 11 days, with an average of 8.4 days;the follow up time was 12 to 18 months, with an average of 14.7 months;the internal fixation of 2 patients failed, and 43 patients achieved bony healing;the deep vein thrombosis of the lower extremity in the perioperative period was 1 case, and the inferior vena cava filter was inserted;the internal fixation of 2 patients was cut out, and the hip was renovated. The incidence of complications was 8.9%(4 / 45). At the final follow up, Harris score of hip joint was 56 to 95 (81.30±8.40), including excellent 15 cases, good 26 cases, fair 2 cases and poor 2 cases. CONCLUSION: It is safe and feasible to treat intertrochanteric fracture of femur with closed reduction and anti rotation intramedullary nailing under the bed without traction in a supine position. It has the advantages of small trauma and low complications, and the clinical effect is satisfactory. It is worth popularizing and using in basic hospitals.

Asymptomatic patients and asymptomatic phases of Coronavirus Disease 2019 (COVID-19): a population-based surveillance study.

In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129 551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (interquartile range 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Overall, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19 patients. Also, the asymptomatic phase during recovery from COVID-19 implied that negativity in viral RNA is necessary as a de-isolation criterion and follow-up is recommended.

MicroRNA-365 functions as a mechanosensitive microRNA to inhibit end plate chondrocyte degeneration by targeting histone deacetylase 4.

End plate chondrocyte degeneration is a major cause of intervertebral disc degeneration. Mechanical biophysical forces, including intermittent cyclic mechanical tension (ICMT), exacerbate end plate chondrocyte degeneration. However, the underlying molecular mechanism of mechanical stretch-induced end plate chondrocyte degeneration is still unclear. This study sought to determine whether microRNAs (miRNAs) respond to mechanical stretch and play a role in regulating mechanically-induced end plate chondrocyte degeneration. We identified miR-365 as a mechanoresponsive miRNA in primary human end plate chondrocytes after ICMT application by miRNA microarray analysis. The expression of miR-365 was down-regulated in the disc samples obtained from patients with disc degeneration. We also found that the miR-365 stimulates chondrocyte proliferation but does not promote end plate chondrocyte death. Using bioinformatic analyses and subsequent confirmation by real-time RT-PCR, we identified multiple candidate target genes of miR-365 that responded to in vitro mechanical stimulation; among them, HDAC4 was fully characterized. Mutation of putative miR-365 binding sites in HDAC4 mRNA abolished miR-365 mediated repression of HDAC4 3'-untranslated region (3'UTR) luciferase reporter activity, suggesting that miR-365 binds to the HDAC4 3'UTR. Overexpression of miR-365 significantly decreased the HDAC4 protein level, suggesting that miR-365 acts as an endogenous attenuator of HDAC4 in human end plate chondrocytes. Further, perturbation of miR-365 expression also had a significant effect on the expression of COL2A and ACAN and on matrix degeneration. Overexpression of HDAC4 abolished miR-365 rescued end plate chondrocyte degeneration during ICMT application. Furthermore, we found that the wnt/ß-catenin signal pathway was related to HDAC4 and promoted end plate chondrocyte degeneration. Overall, our results suggest that miR-365 is a mechanosensitive miRNA that regulates human chondrocyte degeneration by directly targeting HDAC4. We propose that therapeutic regulation of miR-365 may be an efficient anabolic strategy for inhibiting end plate chondrocyte degeneration.