Natural killer/T-cell lymphoma (NKTCL) is a malignant proliferation of CD56(+) and cytoCD3(+) lymphocytes with aggressive clinical course, which is prevalent in Asian and South American populations. ...The molecular pathogenesis of NKTCL has largely remained elusive. We identified somatic gene mutations in 25 people with NKTCL by whole-exome sequencing and confirmed them in an extended validation group of 80 people by targeted sequencing. Recurrent mutations were most frequently located in the RNA helicase gene DDX3X (21/105 subjects, 20.0%), tumor suppressors (TP53 and MGA), JAK-STAT-pathway molecules (STAT3 and STAT5B) and epigenetic modifiers (MLL2, ARID1A, EP300 and ASXL3). As compared to wild-type protein, DDX3X mutants exhibited decreased RNA-unwinding activity, loss of suppressive effects on cell-cycle progression in NK cells and transcriptional activation of NF-κB and MAPK pathways. Clinically, patients with DDX3X mutations presented a poor prognosis. Our work thus contributes to the understanding of the disease mechanism of NKTCL.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract The analgesic efficacy and safety of periarticular multimodal drug injection (PMDI) compared with femoral nerve block (FNB) for postoperative pain management in total knee arthroplasty (TKA) ...still remains controversial. We therefore conducted a meta-analysis to quantitatively compare PMDI to FNB in TKA. 10 randomized controlled trials (RCTs) with 744 TKAs in 728 patients were included in this study. The meta-analysis showed that single shot FNB may have better pain relief in the early postoperative period compared with single shot PMDI, and continuous PMDI provided postoperative analgesia comparable to that of continuous FNB. No significant difference was seen in regard to the complications between the two groups. However, due to the variation of the included studies, no firm conclusions can be drawn.
Background
Previous articles about MAKO robotic‐assisted total hip replacement (THR) were mainly in patients with comparatively normal anatomy.
Methods
From July 2020 to June 2021, we performed MAKO ...robotic‐assisted THR in three hip‐fused patients. We assessed the accuracy of prostheses implantation, collected clinical data, and discussed the value of this technique in this kind of patients.
Result
All three patients achieved good leg length and prostheses position. A patient got femoral artery injury during the surgery. Moreover, she developed a thrombus. All three patients got acceptable Visual Analogue Scale scores and function recovery 6 months later.
Conclusion
MAKO robotic‐assisted THR achieved excellent prosthesis position in hip fused patients. More cases are needed to confirm this advantage. The function recovery was acceptable. Caution should be paid to protect the surrounding abnormal arteries, especially in a limited surgical field.
The debridement, antibiotics, and implant retention (DAIR) procedure is an established therapeutic option for periprosthetic knee infections (PKI). However, the efficacy and the indication for this ...procedure are still controversial.
All the relevant literatures were systematically reviewed and analyzed. The present study aimed to assess the success rate of DAIR in the management of PKI, identify the factors associated with prognosis of DAIR, and establish a simple algorithm for predicting a high success rate of DAIR.
Totally, 33 studies with 1266 cases were included. The overall success rate following DAIR in the management of PKI was 57.11%. In the subgroup analyses, the factors of "the time from symptoms to debridement was < 3 weeks" and "the bacterial species other than methicillin-resistant Staphylococcus aureus" significantly improved the success rate of DAIR and thus were defined as the major criteria. The statistically insignificant factors of "the open debridement and liner exchange" and "the comorbidity of rheumatoid arthritis" were set as the minor criteria. The success rate of DAIR for PKI meeting all the major criteria and no less than one minor criterion was 80.98%, which was significantly higher than the overall success rate of DAIR (p < 0.05).
PKI cases meeting two major criteria and no less than one minor criterion may confer a high success rate of DAIR. This simple algorithm may contribute to identifying the appropriate PKI patient for DAIR treatment and predicting the prognosis of DAIR.
Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy is widely used in peripheral T cell lymphoma (PTCL). Here we conducted a phase 2, multicenter, randomized, ...controlled trial, comparing the efficacy and safety of CEOP/IVE/GDP alternating regimen with CEOP in newly diagnosed PTCL.
PTCL patients, except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, were 1:1 randomly assigned to receive CEOP/IVE/GDP (CEOP, cyclophosphamide 750 mg/m
, epirubicin 70 mg/m
, vincristine 1.4 mg/m
maximum 2 mg on day 1, and prednisone 60 mg/m
maximum 100 mg on days 1-5 every 21 days, at the first and fourth cycle; IVE, ifosfamide 2000 mg/m
on days 1-3, epirubicin 70 mg/m
on day 1, and etoposide 100 mg/m
on days 1-3 every 21 days, at the second and fifth cycle; and GDP, gemcitabine 1000 mg/m
on days 1 and 8, cisplatin 25 mg/m
on days 1-3, and dexamethasone 40 mg on days 1-4 every 21 days, at the third and sixth cycle) and CEOP (every 21 days for 6 cycles). Analysis of efficacy and safety was of the intent-to-treatment population. The primary endpoint was a complete response rate at the end of treatment. Meanwhile, whole exome sequencing and targeted sequencing were performed in 62 patients with available tumor samples to explore prognostic biomarkers in this cohort as an exploratory post hoc analysis.
Among 106 patients, 53 each were enrolled to CEOP/IVE/GDP and CEOP. With 51 evaluable patients each in two groups, a complete response rate of the CEOP/IVE/GDP group was similar to that of the CEOP group (37.3% vs. 31.4%, p = 0.532). There was no difference in median progression-free survival (PFS; 15.4 months vs. 9.2 months, p = 0.122) or overall survival (OS; 24.3 months vs. 21.9 months, p = 0.178). Grade 3-4 hematological and non-hematological adverse events were comparable. Histone modification genes were most frequently mutated (25/62, 40.3%), namely KMT2D, KMT2A, SETD2, EP300, and CREBBP. Multivariate analysis indicated that CREBBP and IDH2 mutations were independent factors predicting poor PFS and OS (all p < 0.001), while KMT2D predicting poor PFS (p = 0.002).
CEOP/IVE/GDP alternating regimen showed no remission or survival advantage to standard chemotherapy. Future clinical trials should aim to develop alternative regimen targeting disease biology as demonstrated by recurrent mutations in epigenetic factors.
The study was registered on ClinicalTrial.gov (NCT02533700) on August 27, 2015.
BACKGROUNDAs the main component of oral contraceptives (OCs), ethinylestradiol (EE) has been widely applied as a model drug to induce murine intrahepatic cholestasis. The clinical counterpart of ...EE-induced cholestasis includes women who are taking OCs, sex hormone replacement therapy, and susceptible pregnant women. Taking intrahepatic cholestasis of pregnancy (ICP) as an example, ICP consumes the medical system due to its high-risk fetal burden and the impotency of ursodeoxycholic acid in reducing adverse perinatal outcomes. AIMTo explore the mechanisms and therapeutic strategies of EE-induced cholestasis based on the liver immune microenvironment. METHODSMale C57BL/6J mice or invariant natural killer T (iNKT) cell deficiency (Jα18-/- mice) were administered with EE (10 mg/kg, subcutaneous) for 14 d. RESULTSBoth Th1 and Th2 cytokines produced by NKT cells increased in the liver skewing toward a Th1 bias. The expression of the chemokine/chemokine receptor Cxcr6/Cxcl16, toll-like receptors, Ras/Rad, and PI3K/Bad signaling was upregulated after EE administration. EE also influenced bile acid synthase Cyp7a1, Cyp8b1, and tight junctions ZO-1 and Occludin, which might be associated with EE-induced cholestasis. iNKT cell deficiency (Jα18-/- mice) robustly alleviated cholestatic liver damage and lowered the expression of the abovementioned signaling pathways. CONCLUSIONHepatic NKT cells play a pathogenic role in EE-induced intrahepatic cholestasis. Our research improves the understanding of intrahepatic cholestasis by revealing the hepatic immune microenvironment and also provides a potential clinical treatment by regulating iNKT cells.
Abstract Introduction With development in the techniques of reduction and fixation, there has been a controversy in comparison between intramedullary nailing (IMN) and plating for the treatment of ...distal tibial metaphyseal fracture (DTF). The study aimed to investigate: (1) which fixation, IMN or plating, was better in the clinical outcomes and in the complications for the treatment of DTF and (2) which modifying variables affected the comparative results between the two modalities. Methods PubMed, EMBASE, OVID, Scopus, ISI Web of Science, the Cochrane Library, Google Scholar and specific orthopaedic journals were searched from inception to July 2013, using the search strategy of ‘(‘Fracture Fixation, Intramedullary’ MeSH) AND (‘Tibial Fractures’ MeSH) AND (plate OR plating)’. All prospective and retrospective controlled trials comparing function, pain, bone union and complications between IMN and plating for DTF were identified. Our analysis had no limitation of the language or the publication year. The primary outcome measurements were complication rate, union time, operation time and hospital stays, while the secondary outcome measurements were functional score and pain score. Result Fourteen of 6620 studies with 842 patients were included. IMN was probably preferential to plating for DTF given its higher functional score ( p = 0.01), lower risk of infection ( p = 0.02) and comparable pain score ( p = 0.33), total complication rate ( p = 0.53) and time to union ( p = 0.86). However, plating had a lower malunion rate than IMN ( p < 0.0001). All the results were based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence of moderate quality. Conclusions With a satisfying alignment obtained, IMN may be preferential to plating for fixation of DTF with better function and lower risk of infection. However, IMN showed higher malunion rate for fixation of DTF. With the biases in our meta-analysis, it will ultimately require a rigorous and adequately powered randomised controlled trial (RCT) to prove. Level of evidence Level III, therapeutic study (systematic review).
It remains unclear whether conservative treatment should be used to treat the common undisplaced femoral neck fractures that develop in the elderly. Herein, we systematically review the rates of ...union and avascular necrosis after conservative and surgical treatment of undisplaced femoral neck fractures.
We searched the EMBASE, PubMed, OVID, Cochrane Library, Web of Science, and Scopus databases for randomized controlled trials or observational studies that assessed the outcomes of conservative or surgical treatments of undisplaced femoral neck fractures. No language or publication year limitation was imposed. Statistical analyses were performed with the aid of the chi-squared test. We evaluated the quality of each publication and the risk of bias.
Twenty-nine studies involving 5071 patients were ultimately included; 1120 patients were treated conservatively and 3951 surgically. The union rates were 68.8% (642/933) and 92.6% (635/686) in the former and latter groups, respectively (p < 0.001). The avascular necrosis rate in the conservatively treated group was 10.3% (39/380), while it was 7.7% (159/2074) in the surgically treated group (p = 0.09).
Surgery to treat undisplaced femoral neck fractures was associated with a higher union rate and a tendency toward less avascular necrosis than conservative treatment.
Postoperative squeaking in patients who applied the fourth-generation ceramic bearing in primary hip replacement has not been reported systematically; we aim to study the squeaking incidence in the ...fourth-generation ceramic bearing and related risk factors for squeaking, and we also attempt to explore the relationship between squeaking and prosthetic brands.
The PubMed, Embase, and Cochrane library were searched, and 14 articles were finally included. Patients' demographic data, surgical-related information, and prosthesis data were extracted. The occurrence rate of squeaking was calculated by meta-analysis, and subgroup analysis was performed based on prosthetic brands and follow-up time. Regression analysis was further applied to investigate the relationship between various risk factors and squeaking.
The squeaking incidence in patients with the fourth-generation ceramic bearing was 3%. Age, gender, body mass index, and abduction and anteversion angles of acetabular cup might have no influence on squeaking. The squeaking incidence was significantly high with the presence of Delta Motion cup (DePuy, Warsaw, Indiana) and Secure-Fit stem (Stryker, Kalamazoo, MI), and the overall incidence of DePuy femoral stem was relatively small except for the Summit femoral stem. And there was no significant difference of squeaking incidence between less than 5-year and more than or equal to 5-year follow-up subgroups.
In our study, squeaking in the fourth-generation ceramic bearing occurred at a rate of 3%; occurrence rate was high when the Delta Motion cup was applied. We hope for more relevant researches to focus on this issue.
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