Two-sample Mendelian randomization analysis reveals causal relationships between blood lipids and venous thromboembolism.

Venous Thromboembolism (VTE) is a complex disease that can be classified into two subtypes: Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). Previous observational studies have shown associations between lipids and VTE, but causality remains unclear. Hence, by utilizing 241 lipid-related traits as exposures and data from the FinnGen consortium on VTE, DVT, and PE as outcomes, we conducted two-sample Mendelian randomization (MR) analysis to investigate causal relationships between lipids and VTE, DVT and PE. The MR results identified that fatty acid (FA) unsaturation traits (Ratio of bis-allylic bonds to double bonds in lipids, and Ratio of bis-allylic bonds to total fatty acids in lipids) were associated with VTE (OR [95% CI]: 1.21 [1.15-1.27]; 1.21 [1.13-1.30]), DVT (OR [95%CI]: 1.24 [1.16-1.33]; 1.26 [1.16-1.36]) and PE (OR [95%CI]: 1.18 [1.08-1.29]; 1.18 [1.09-1.27]). Phosphatidylcholines exhibit potential causal effects on VTE and PE. Phosphatidylcholine acyl-alkyl C40:4 (PC ae C40:4) was negatively associated with VTE (OR [95% CI]: 0.79 [0.73-0.86]), while phosphatidylcholine diacyl C42:6 (PC aa C42:6) and phosphatidylcholine acyl-alkyl C36:4 (PC ae C36:4) were positively associated with PE (OR [95%CI]: 1.44 [1.20-1.72]; 1.22 [1.10-1.35]). Additionally, we found that medium LDL had a protective effect on VTE. Our study indicates that higher FA unsaturation may increase the risk of VTE, DVT, and PE. Different types of phosphatidylcholine have either promotive or inhibitory effects on VTE and PE, contributing to a better understanding of the risk factors for VTE.

Multitissue Integrative Analysis Identifies Susceptibility Genes for Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease with multiple environmental and genetic factors involved in its etiology. Although lots of genetic loci associated with AD have been reported by GWASs, only a small part of phenotypic variations can be explained. To identify additional susceptibility genes on AD, we conducted a large-scale transcriptome-wide association study using a joint-tissue imputation approach in ∼840,000 European individuals combined with six precomputed gene expression weights of four AD-relevant tissues, including skin fibroblast, lymphocyte, and whole blood. The Mendelian randomization causal inference analysis was performed to estimate the causal effect of transcriptome-wide association study‒identified genes. We identified 51 genes significantly associated with AD after Bonferroni corrections, and 19 genes showed putatively causal associations such as an established gene FLG (P = 3.98 × 10‒10) and seven genes that have not been implicated in previous transcriptome-wide association studies, such as AQP3 (P = 4.43 × 10‒7) and PDCD1 (P = 7.66 × 10‒7). Among them, four genes (AQP3, PDCD1, ADCY3, and DOLPP1) were further supported in differential expression analyses or the Mouse Genome Informatics database. Overall, our study identified susceptibility genes associated with AD, providing, to our knowledge, previously unreported clues in revealing the genetic mechanisms in AD.

Bone transport combined with bone graft and internal fixation versus simple bone transport in the treatment of large bone defects of lower limbs after trauma.

BACKGROUND: Bone transport has been successfully applied for the management of large segmental bone defects. However, its main shortcoming is the long-lasting consolidation period, which may cause lots of related complications. To overcome this shortcoming, we developed bone transport combined with bone graft and internal fixation technique. The purpose of this study was to compare the clinical effects of this modified technique with simple bone transport in the treatment of large segmental bone defects of lower limbs after trauma. METHODS: Eighty-four patients with large segmental bone defects treated in our institution from January 2014 to January 2017 were selected for retrospective study. A total of 77 cases were completely followed. Among them, 35 patients were treated by bone transport combined with bone graft and internal fixation technique (Group A), and 42 by simple bone transport technique (Group B). Patients with open injuries were classified according to Gustilo-Anderson (GA) classification. The general data of Group A and B were compared. The time in external fixator, total cure time and operation times of two groups were recorded. Ennecking score was used to evaluate the recovery of limb functions while self-rating anxiety scale (SAS) for the postoperative anxiety evaluation. In addition, the total complication incidence was compared between Group A and B. RESULTS: There was no significant difference in demographic data between Group A and B (p > 0.05). The time in external fixator of Group A and B was (4.8 ± 1.6) and (18.2 ± 3.9) months, respectively (p < 0.05). The total cure time was (17.6 ± 2.2) and (20.4 ± 2.8) months in Group A and B (p < 0.05). The number of operations in Group A and B was (4.9 ± 1.2) and (4.8 ± 1.0) (p > 0.05). Ennecking score of Group A and B was 84.7 and 75.7% (p < 0.05). SAS score and total complication incidence in Group A were significantly lower than those in Group B (p < 0.05). CONCLUSIONS: The clinical effects of bone transport combined with bone graft and internal fixation technique were better than that of simple bone transport technique, including shorter time in external fixator, shorter total cure time, lower anxiety score and better limb functions.

Correlation Between the Fracture Line Plane and Perioperative Deep Vein Thrombosis in Patients with Tibial Fracture.

OBJECTIVE: To explore the correlation between the fracture line inferior plane and perioperative deep venous thrombosis (DVT) in patients with tibial fractures. METHODS: Data was collected from the medical records of 536 consecutive patients with tibial fractures at Xi'an Honghui Hospital. The patients were divided into distal, shaft, and proximal segment groups according to the fracture line inferior plane on radiographs. Multivariate logistic regression models were used to identify the role of the inferior plane of the fracture line in perioperative DVT. RESULTS: A total of 431 patients were included in the study and 226 patients had perioperative DVT in the lower extremities, including 11 proximal and 215 distal DVTs. Univariate regression analysis showed a significant correlation between the proximal segment and perioperative DVT; however, no correlation was found in the shaft segment group. Additionally, age, coronary heart disease, associated injuries, and time to operation ≥6 days were risk factors for perioperative DVT. However, fixation with intramedullary nails may be a protective factor for perioperative DVT compared with plates. After adjusting for potential confounding factors, the proximal segment group had an increased incidence of perioperative DVT compared to the distal segment group. CONCLUSIONS: The proximal segment may be correlated with an increased incidence of perioperative DVT by 7.30-fold in patients with tibial fractures compared to that in the distal segment. In clinical practice, surgeons should be vigilant for DVT formation in these patients.

Nonspecific ST-Segment and T-Wave (NS-STT) on Electrocardiogram is Associated with Increasing the Incidence of Perioperative Deep Vein Thrombosis in Patients with Lower Extremity Fracture Under 75 Years Old.

OBJECTIVE: This study aims to explore the clinical correlation between nonspecific ST-segment or T-wave (NS-STT) changes and perioperative deep vein thrombosis (DVT) in patients with lower extremity fractures. METHODS: One thousand four hundred sixty-nine consecutive patients who suffered lower extremity fractures were screened at Xi'an Honghui Hospital between Feb 2016 and Nov 2018. According to the included and excluded criteria, the patients were included in this retrospective study. After collecting the electrocardiogram baseline, the patients were divided into the NS-STT group and the non-NS-STT group. After comparing the demographic and clinical characteristics, multivariate logistic regression models were used to identify the role of NS-STT changes on perioperative DVT. All analyses were performed with R and EmpowerStats software. RESULTS: Nine hundred and sixty-eight patients were included in the study. Ninety-seven patients (10.02%) had NS-STT changes on the electrocardiogram at admission. A total of 303 patients (31.30%) developed perioperative DVT in lower extremities. The univariate analysis showed that NS-STT segment changes were correlated with perioperative DVT significantly (OR = 3.45, 95% CI: 2.25-5.30, P < 0.0001). In addition, age ≥50 (P < 0.0001), female (OR = 1.50, 95% CI: 1.14-1.97, P = 0.0038), hypertension (OR = 1.54, 95% CI: 1.08-2.20, P = 0.0161), blood transfusion (OR = 1.78, 95% CI: 1.34-2.37, P < 0.0001), joint prosthesis (OR = 3.26, 95% CI: 2.21-4.81, P < 0.0001), and blood loss ≥300 mL (OR = 2.12, 95% CI: 1.50-3.01, P < 0.0001) were associated with perioperative DVT in lower extremities. We identified the confounding factors of age, gender, classification of internal implants, operation time, blood loss, and infusion. After adjustment for potential confounding factors, NS-STT changes were associated with perioperative DVT (OR = 2.13, 95% CI: 1.33-3.42; P = 0.0017). The sensitive analysis showed that the result was stable. CONCLUSION: The NS-STT changes on electrocardiograms are associated with an increase in the incidence of perioperative DVT by 2.13-fold in patients with lower extremity fractures under 75 years old. In clinical practice, surgeons should pay more attention to these patients.

A New Technique for Placement of Blocking Screws and its Mechanical Effect on Stability of Tibia Fractures with Distal Fragments after Insertion of Small-Diameter Intramedullary Nails.

OBJECTIVE: To design a novel blocking screws (BSs) geometry and insertion method to treat distal tibia fracture with nailing and comparison of mechanical properties of novel and traditional screws. METHODS: Twenty-one synthetic left tibiae were sectioned to obtain 21 distal segments measuring 55 mm. Intramedullary (IM) 9-mm tibial nails were advanced to 6 mm from the ankle joint. Two transverse and one anterior-posterior (AP) locking screws were inserted. Both medial-lateral (ML) BSs were placed 10 mm from the topmost interlocking screw. A custom-made jig assisted in placing the novel and traditional BSs. The time spent in placing each BS was recorded. All the samples were repaired with an IM nail and without BSs, with two traditional BSs, and with two novel BSs. An initial loading from -150 to +150 N was applied to specimens in the ML direction at 185 mm from the nail end, followed by cyclic loading of the same for 10,000 cycles with failure-to-test loading of 350 N in the ML direction. The maximum displacement was measured at 80 mm from the nail end and recorded under initial loading. The damage of two kinds of BSs to the nail was recorded. RESULTS: Compared with average 5.21 min of the time of placing a traditional BS, the time spent in positioning a novel BS on the fracture model was 2.53 min. In the distal bone-implant constructs (BICs), the addition of traditional BSs decreased the maximum displacement of the BICs by 26.2%. The addition of the novel BSs decreased the displacement by 28.9%. All constructs survived 10,000 cycles without hardware deformation. The failure rate of the control group was significantly greater than that of the traditional group; however, the novel group was similar to the traditional group. The damage of the traditional BS to the nail was greater than that of the novel one. CONCLUSIONS: The novel and traditional BSs are comparably effective for increasing the primary mechanical stability of distal metaphyseal fractures after nailin. However, compared to the placement of a traditional BS, implanting a novel BS took more less time and caused less damage to the nail. Additionally, the most obvious advantage of the novel BS design and insertion technology was that the pressure and distance between it and the IM nail could be controlled by rotating the screw. These advantages of the novel BS will be beneficial for clinical application.

Causal Associations Between Blood Lipids and COVID-19 Risk: A Two-Sample Mendelian Randomization Study.

[Figure: see text].

Anterolateral approach with two incisions versus posterior median approach in the treatment of middle- and distal-third humeral shaft fractures.

BACKGROUND: The surgical approaches remain controversial for the treatment of middle and distal-third humeral shaft (MDTHS) fractures. This study compared clinical effects of the anterolateral approach with two incisions (AATI) and the posterior median approach (PMA) in the treatment of MDTHS fractures. METHODS: A retrospective analysis was carried out. One hundred sixty-six patients with MDTHS fractures were selected from January 2015 to January 2017 in Xi'an Hong Hui Hospital. According to surgical approaches, patients were divided into AATI (86 cases) and PMA group (80 cases). All patients were treated with open reduction and plate fixation. Operation indexes were compared, including incision length, operation time, and bleeding. Bryan-Morrey score was used to evaluate elbow joint function. Complication incidence was compared, such as incision infection, iatrogenic radial nerve injury, and nonunion. RESULTS: The AATI group showed smaller incision length, less bleeding, lower iatrogenic radial nerve injury rate, and better elbow function than that of PMA group (P<0.05). CONCLUSIONS: The middle and distal-third humeral shaft fractures can be successfully cured by both approaches. Compared with the posterior median approach, it has better clinical effects of the anterolateral approach with two incisions, which is worthy of clinical application and promotion.

Prying reduction with mosquito forceps versus limited open reduction for irreducible distal radius-ulna fractures in older children: a retrospective study.

BACKGROUND: There are disputes about which reduction technique should be adopted in treatment of distal radius-ulna fractures in older children who failed to achieve manual reduction. This study compared clinical effects between prying reduction with mosquito forceps (PRMF) and limited open reduction (LOR) of treating irreducible distal radius-ulna fractures in older children. METHODS: One hundred ten children with irreducible distal radius-ulna fractures were selected from January 2015 to December 2017 in Xi'an Hong Hui hospital. Retrospective analysis was performed. According to different reduction techniques, these children were divided into PRMF group (59 cases) and LOR group (51 cases). All children were treated with percutaneous Kirschner wire fixation and external fixation with plaster. Operation indexes, complications and wrist joint functions were compared between the two groups. RESULTS: Operation time of PRMF group was shorter than that of LOR group (P < 0.05). Incision length in PRMF group was less than that in LOR group (P < 0.05). Bleeding volume of PRMF group was less than that of LOR group (P < 0.05). Incidence of complications in PRMF group was lower than that in LOR group. CONCLUSIONS: Compared with limited open reduction, it has better clinical effects of prying reduction with mosquito forceps in treatment of irreducible distal radius-ulna fractures in older children. This technique has the advantages of simple operation, less trauma, less bleeding and fewer complications, which is worthy of clinical promotion.

Clinical Efficacy of Vertical or Parallel Technique of a Micro-Locking Plate for Treatment of Dubberley B-Type Capitellar Fractures.

OBJECTIVE: To evaluate the clinical efficacy of micro-locking plate through vertical or parallel technique for treatment of Dubberley B-type capitellar fractures. METHODS: A retrospective analysis was performed in 24 patients (17 males and seven females, with an average age of 44.9 years, range from 19 to 75 years) with capitellar fractures that were treated with micro-locking plate using vertical or parallel technique between January 2016 to January 2019. The inclusion criteria include closed capitellar fracture, normal anterior elbow joint movement before injury, and recent capitellar fracture with injury within past 3 weeks. Fractures classified according to Dubberley included four cases of type IB, eight cases of type IIB, and 12 cases of type IIIB. Radiographic evaluation was performed. Surgery time, blood loss, range of motion of the elbow, forearm rotation, and complications were recorded. Elbow joint function was evaluated by Mayo Elbow Performance Score (MEPS). RESULTS: The mean follow-up period was 19.6 months (range, 12-36 months). The average clinical healing time for fractures was 11.2 ± 3.2 weeks (range, 8-20 weeks). Fracture united in all patients. Two patients showed slight delayed union, but union was achieved eventually. The mean time from injury to surgery was 6.3 ± 3.1 days (range, 2-15 days). The average surgical time was 68.1 ± 11.5 min (range, 50-90 min), and the mean blood loss was 75.2 ± 26.5 mL (range, 40-120 mL). The mean range of flexion was 122.5° ± 10.5°(range, 95°-140°). The mean range of extension was 8.5° ± 5.8°(range, 0°-20°). The mean range of pronation was 79.7° ± 8.0°(range, 65°-90°). The mean range of supination was 80.5° ± 7.1°(range, 60°-90°). The mean MEPS at final follow-up was 89.8 ± 9.0 (range, 60-100). Based on the MEPS, 18 (75%) patients had excellent, five (20.8%) patients had good, and one (4.2%) patient had fair. None of the 24 patients suffered vascular or nerve injury. One patient showed superficial infection, which was treated with surgical dressing. CONCLUSIONS: The vertical or parallel technique of the micro-locking plate is an excellent method for treating Dubberley B-type capitellar fractures.

Serum MicroRNA Differences Between Fracture in Postmenopausal Women with and without Diabetes.

OBJECTIVE: To screen serum microRNAs (miRNAs) which could discriminate fracture status in postmenopausal women with or without diabetes. METHODS: The miRNA expression profile dataset GSE70318 was downloaded from Gene Expression Omnibus (GEO) database. This dataset composed of 74 samples, among these, 55 postmenopausal women was selected for bioinformatics analysis, including 19 osteoporotic fracture patients with type-2 diabetes, 19 osteoporotic fracture patients without type-2 diabetes, and 17 healthy control subjects. These samples were divided into two groups: fracture patients with diabetes vs healthy subjects (FH group) and fracture patients without diabetes vs healthy subjects (DFH group). Then, the differentially expressed miRNA (DEMs) in FH group and DFH group were respectively identified. The target genes of DEMs were predicted, followed by functional enrichment analysis. Furthermore, DEMs related to long non-coding RNAs (lncRNAs) were screened, and DEMs-lncRNA-target genes network was constructed. Subsequently, principal component analysis (PCA) of DEMs was performed to further explore the expression characteristics of the selected miRNAs in different types of fracture samples. Finally, the expression level of significant DEMs was calculated by quantitative real-time polymerase chain reaction (qPCR) to verify the accuracy of the results of bioinformatics analysis. RESULTS: A total of 18 and 23 DEMs were identified in FH and DFH groups, respectively. Gene ontology (GO) analysis showed that genes in FH group were significantly enriched in regulation of transcription (GO: 0045449) and genes in DFH group were mainly enriched in cellular response to hormone stimulus (GO: 0032870). Meanwhile, pathway analysis indicated that genes in FH group were primarily enriched in T cell receptor signaling pathway (hsa04660) and genes in DFH group were mainly implicated in neurotrophin-signaling pathway (hsa04722). Moreover, the miRNA-lncRNA analysis revealed that miR-155-5p regulated by lncRNA MIR155HG was up-regulated in FH group; in addition, the miR-181c was significantly up-regulated and miR-375 was observably down-regulated in DFH group. Furthermore, PCA analysis suggested that the screened miRNAs were able to differentiate these two types of fractures in postmenopausal women. The miR-181c and miR-375 might be regarded as potential predictors for fracture, while miR-155-5p might be a candidate diagnostic biomarker for diabetic fracture. Finally, the results of qPCR were consistent with that of microarray data. CONCLUSIONS: Overall, these three miRNAs might be regarded as potential diagnostic biomarkers to discriminate fracture status in postmenopausal women with and or without diabetes, and they served a putative role in the pathogenesis of these two diseases. However, these findings were only observed in serum samples and further clinical trials are urgently demanded to validate our results.

Treatment of atrophic nonunion via autogenous ilium grafting assisted by vertical fixation of double plates: A case series of patients.

OBJECTIVE: To investigate the efficacy of the treatment of atrophic nonunion using structural autogenous ilium bone grafting in combination with vertical fixation of double plates. METHODS: This retrospective study analysed the clinical data from consecutive patients with atrophic nonunion who underwent autogenous ilium grafting in combination with double-plate vertical fixation. The injury type and the bone affected by nonunion, the duration of nonunion and the outcomes following surgery were recorded for all patients. RESULTS: The study enrolled 43 patients with atrophic nonunion of the upper and lower limbs: 17 patients with tibial nonunion, 21 with femoral nonunion, four with humeral nonunion and one with radial shaft nonunion. The mean duration of postoperative follow-up was 14.5 months (range, 8-28 months). A total of 43 of 43 patients (100%) achieved a healed nonunion fracture without the occurrence of complications such as infection, fracture of internal fixation or pain in the harvesting site. Comprehensive postoperative assessments of bone healing and function were observed to be good and/or excellent in all 43 patients. CONCLUSION: Structural autogenous ilium grafting used in combination with double-plate vertical fixation can provide a stable structural environment for near optimal bone healing in patients with atrophic nonunion.

Pathogenesis and Treatment Strategies for Pilon Fractures With Ankle Dislocation.

The present study investigated the pathogenesis and treatment strategies for pilon fractures with ankle dislocation. A total of 58 patients (47 males and 11 females) who had sustained pilon fractures with ankle dislocation were treated. The mean patient age was 48.1 years. Using the AO classification, 8 cases were type B2, 17 were type B3, and 33 were type C3. The dislocation was medial in 13 cases, lateral in 9, anterior in 11, posterior in 14, and longitudinal in 9. Radiologic examinations were conducted to evaluate the postoperative reduction, dislocation correction, fracture healing, and internal fixation. Ankle function was evaluated according to the Kofoed and Danborg scoring system. The patients were followed up for 4 to 27 months. Anatomic reduction was achieved in 39 cases (67.24%), good reduction in 13 (22.41%), and poor reduction in 6 (10.34%). No internal implant failure occurred, and the fractures had healed after 2 to 4.3 (mean 2.8) months. The rate of good or excellent ankle recovery was 84.00% for those with type B fractures, 75.76% for those with type C, 76.92% for those with medial dislocation, 77.78% for lateral dislocation, 81.82% for anterior dislocation, 78.57% for posterior dislocation, and 81.82% for longitudinal dislocation. Pilon fractures often occur with ankle dislocation in different directions. In such cases, the original anatomy should be restored and the longitudinal alignment recovered to minimize complications as much as possible.

[Surgical treatment strategy of the floating shoulder injury].

OBJECTIVE: To discuss the clinical characteristics and the surgical treatment strategy of the floating shoulder injury. METHODS: 26 cases with the floating shoulder injury between January 2006 and January 2012 were retrospectively evaluated. There were 15 males and 11 females with an average age of 35.2 (22-60) years. According to Wong's classification of floating shoulder injury: type IA, 3 cases; type IB, 9 cases; type II, 4 cases; type IIIA, 6 cases; type IIIB, 4 cases. All the 26 cases had accepted the surgical treatment. We observed the postoperative fracture reduction, damage repair, fracture healing and internal fixation through the X-ray films. We also evaluated the shoulder function regularly according to the Constant scores and Herscovici evaluation criteria. RESULTS: The 26 cases were followed up for an average of 16.8 (12-24) months.All the fractures healed for a mean time of 2.4 months, the mean Constant score was 89.4 (60-100). The effect of Herscovici evaluation criteria: excellent, 15 cases; good, 8 cases;fair, 3 cases;the excellent rate 88.5%. CONCLUSION: Open reduction and internal fixation is an effective method for the treatment of floating shoulder injury, but we should select the reset sequence and fixation methods according to the type of fracture and degree of displacement.