TLR9 Deficiency in B Cells Promotes Immune Tolerance via Interleukin-10 in a Type 1 Diabetes Mouse Model

Toll-like receptor 9 (TLR9) is highly expressed in B cells, and B cells are important in the pathogenesis of type 1 diabetes (T1D) development. However, the intrinsic effect of TLR9 in B cells on β-cell autoimmunity is not known. To fill this knowledge gap, we generated NOD mice with a B-cell–specific deficiency of TLR9 (TLR9^fl/fl/CD19-Cre+ NOD). The B-cell–specific deletion of TLR9 resulted in near-complete protection from T1D development. Diabetes protection was accompanied by an increased proportion of interleukin-10 (IL-10)–producing B cells. We also found that TLR9-deficient B cells were hyporesponsive to both innate and adaptive immune stimuli. This suggested that TLR9 in B cells modulates T1D susceptibility in NOD mice by changing the frequency and function of IL-10–producing B cells. Molecular analysis revealed a network of TLR9 with matrix metalloproteinases, tissue inhibitor of metalloproteinase-1, and CD40, all of which are interconnected with IL-10. Our study has highlighted an important connection of an innate immune molecule in B cells to the immunopathogenesis of T1D. Thus, targeting the TLR9 pathway, specifically in B cells, may provide a novel therapeutic strategy for T1D treatment.     

Opportunistic Infections After Induction With Alemtuzumab or Basiliximab: A 3-Year Kidney Transplantation Experience

BackgroundAntibody induction immunosuppression is commonly used in kidney transplantation to decrease the risk of early acute rejection. However, infectious complications may arise in patients treated with higher intensity induction immunosuppression. In this study, we compared the rate of opportunistic infections during the 3 years after kidney transplantation in recipients who received either alemtuzumab or basiliximab for induction therapy.MethodsAll renal transplant recipients from our center who received induction with alemtuzumab between 2011 and 2016 were included and matched 1:2 (by age and date of transplant) to renal transplant recipients who received basiliximab. The primary outcome was the rate of opportunistic infections.ResultsTwenty-seven patients received alemtuzumab (mean age = 50.8 years; SD ±12), and 54 received basiliximab (mean age = 50.8 years; SD ±11.8). Infections within 3 years posttransplant were not different between groups: BK viremia (P = .99), BK nephritis (P = .48), cytomegalovirus infection (P = .13), varicella zoster virus (P = .22), and all infections (P = .87). Time to infection (P = .67), patient survival (P = .21), and time to rejection (P = .098) were similar in both groups. There were also no group differences in delayed graft function (P = .76), graft loss (P = .97), or rejection (P = .2).ConclusionThe rate of infection was not significantly increased in recipients receiving lymphocyte-depleting alemtuzumab compared to recipients receiving basiliximab induction therapy, despite receiving similar maintenance immunosuppression. Although the immunologic risks differed between the 2 groups, there was no observable difference in clinical outcomes.     

Systematic review of outcomes and meta-analysis of risk factors for prognosis after liver resection for hepatocellular carcinoma without cirrhosis

Long-term overall survival (OS) after liver resection for non-cirrhotic hepatocellular carcinoma (NCHCC) has been reported recently. The aim of this study was to review outcomes systematically and analyze risk factors for survival after surgical resection for HCC without cirrhosis. A literature search was performed of the PubMed and Embase databases for papers published between January 1995 and October 2012, which focused on hepatic resection for HCC without underlying cirrhosis. Cochrane systematic review methodology was used for this review. Outcomes were OS, operative mortality and disease-free survival (DFS). Pooled hazard ratios (HR) were calculated using the random effects model for parameters considered as potential prognostic factors. Totally, 26 retrospective case series were eligible for inclusion. The 1-, 3- and 5-year OS rate after surgical resection of NCHCC ranged from 62% to 100%, 46.3%–78.0%, and 30%–64%, respectively. The corresponding DFS rates ranged from 48.7% to 84%, 31.0%–66.0%, and 24.0%–58.0%, respectively. Five variables were related to poor survival: multiple tumors (HR 1.68, 95%CI 1.25–2.11); larger tumor size (HR 2.66, 95%CI 1.69–3.63); non-clear resection margin (R0 resection) (HR 3.52, 95%CI 1.63–5.42); poor tumor stage (HR 2.61, 95%CI 1.64–3.58); and invasion of the lymphatic vessels (HR 4.85, 95%CI 2.67–7.02). In sum, hepatic resection provides excellent OS rates for patients with NCHCC, and results have tended to improve recently. Risk factors for poor prognosis comprise multiple tumors, lager tumor size, non-R0 resection and invasion of the lymphatic vessels.     

Effects of platelet‐rich plasma on the healing of sternal wounds: A meta‐analysis

Sternal wound infection (SWI) is a devastating complication after cardiac surgery. Platelet‐rich plasma (PRP) may have a positive impact on sternal wound healing. A systematic review with meta‐analyses was performed to evaluate the clinical effectiveness of topical application of autologous PRP for preventing SWI and promoting sternal wound healing compared to placebo or standard treatment without PRP. Relevant studies published in English or Chinese were retrieved from the Cochrane Central Register of Controlled Trials (The Cochrane Library), PubMed, Ovid EMBASE, Web of Science, Springer Link, and the WHO International Clinical Trials Registry Platform (ICTRP) using the search terms “platelet‐rich plasma” and “sternal wound” or “thoracic incision.” References identified through the electronic search were screened, the data were extracted, and the methodological quality of the included studies was assessed. The meta‐analysis was performed for the following outcomes: incidence of SWI, incidence of deep sternal wound infection (DSWI), postoperative blood loss (PBL), and other risk factors. In the systematic review, totally 10 comparable studies were identified, involving 7879 patients. The meta‐analysis for the subgroup of retrospective cohort studies (RSCs) showed that the incidence of SWI and DSWI in patients treated with PRP was significantly lower than that in patients without PRP treatment. However, for the subgroup of randomized controlled trials (RCTs), there was no significant difference in the incidence of SWI or DSWI after intervention between the PRP and control groups. There was no significant difference in PBL in both RCTs and RSCs subgroups. Neither adverse reactions nor in‐situ recurrences were reported. According to the results, PRP could be considered as a candidate treatment to prevent SWI and DSWI. However, the quality of the evidence is too weak, and high‐quality RCTs are needed to assess its efficacy on preventing SWI and DSWI.     

The anterior versus posterior approach for the treatment of ossification of the posterior longitudinal ligament in the cervical spine: A systematic review and meta-analysis

Study Design: Systematic review and meta-analysis.Objective: To compare the effectiveness and safety between anterior and posterior approach, and determine the best surgical methods for the treatment of ossification of the posterior longitudinal ligament (OPLL) in the cervical spine.Methods: We searched the Cochrane Library, PubMed, CNKI and Wanfang Med Data databases from January 2007 to March 2018. Japanese Orthopaedic Association (JOA) scores, cervical lordosis, functional recovery rates, excellent and good outcomes of the surgical approaches, and complication and reoperation rates were analyzed. RevMan 5.3 was utilized for data analysis.Results: Eleven studies were included in the meta-analysis. By comparing the anterior and posterior approaches for the treatment of OPLL in the cervical spine, statistically significant differences were found in the preoperative initial JOA, the postoperative final JOA scores, functional recovery rates, complication rates, excellent and good outcomes of the surgical approaches and reoperation rates. However, no statistically significant difference in the occurrence of the preoperative and postoperative cervical lordosis was noted.Conclusion: The anterior approach is superior to the posterior approach in terms of the postoperative final JOA score, functional recovery rate, and clinical outcomes. Although the complication and reoperation rates of the anterior approach are higher than those of the posterior approach. We recommend the anterior approach for the treatment of OPLL when patients with occupying ratio ≥ 60%. In addition, high-quality studies with long-term follow-up and large sample size are also needed.