Immunosuppressive properties of mesenchymal stem cells

Mesenchymal stem cells (MSC) can be isolated from different adult tissues including bone marrow, adipose tissue, cord blood and placenta. MSCs modulate the immune function of the major immune cell populations involved in alloantigen recognition and elimination, including antigen presenting cells, T cells, B cells and natural killer cells. Many clinical trials are currently underway that employ MSCs to treat human immunological diseases. However, the molecular mechanism that mediates the immunosuppressive effect of MSCs is still unclear and the safety of using MSC in patient needs further confirmation. Here, we review the cytokines that activate MSCs and the soluble factors produced by MSCs, which allow them to exert their immunosuppressive effects. We review the mechanism responsible, at least in part, for the immune suppressive effects of MSCs and highlight areas of research required for a better understanding of MSC immune modulation.     

Erratum to: Unresectable Hepatocellular Carcinoma: Radioembolization Versus Chemoembolization: A Systematic Review and Meta-analysis

CardioVascular and Interventional Radiology -     

Asymptomatic Gluteal Tendinopathies Negatively Impact Outcomes of Total Hip Arthroplasty: A Propensity Score-Matched Study

BackgroundThe purpose of this study is to compare outcomes after total hip arthroplasty (THA) in patients with preoperative asymptomatic gluteus medius and minimus (GMM) pathology to a control group with no GMM pathology.MethodsPatients undergoing THA for osteoarthritis between August 2012 and March 2018 were retrospectively reviewed. Asymptomatic GMM pathology was considered as the presence of gluteal tendinopathy diagnosed by magnetic resonance imaging (MRI) without the following clinical symptoms: Trendelenburg gait or test, abductor weakness, and lateral thigh tenderness. Patients with asymptomatic GMM pathology were matched (1:1) to patients without GMM pathology on MRI. Two-year data were collected on patient-reported outcomes including Harris Hip Score, Forgotten Joint Score, pain, and satisfaction. Postoperative clinical examination, radiographic measures, complications, and revisions for both groups were reviewed.ResultsFifty cases of asymptomatic GMM pathology were successfully matched to 50 hips without GMM pathology on MRI. Patients with asymptomatic GMM pathology demonstrated significantly worse outcomes regarding 2-year Harris Hip Score (86.24 vs 92.39, P = .04), VAS for pain (1.82 vs 0.98, P = .05), and patient satisfaction (7.69 vs 9.16, P = .002). The study group exhibited significantly higher rates of lateral hip pain postoperatively. Two cases (4%) in the control group underwent a revision THA and 4 cases (8%) in the study group underwent revision THA.ConclusionIn patients undergoing THA for osteoarthritis, those with asymptomatic GMM pathology experience inferior 2-year postoperative patient-reported outcomes compared to a matched group. This finding should raise awareness surrounding this important pathology’s negative impact on surgical outcomes, thus warranting increased vigilance, and possibly justifying concomitant treatment, even in cases of asymptomatic GMM tears.Level of EvidenceLevel III - Retrospective comparative prognostic study.     

Minimum Five-Year Outcomes of Hip Resurfacing: Propensity-Score Matched Against Total Hip Arthroplasty Control Groups

BackgroundThe aim of this study is to evaluate clinical outcomes of patients undergoing Birmingham hip resurfacing (BHR) with a minimum 5-year follow-up and compare these outcomes to 2 matched control groups of patients undergoing either direct anterior approach (DAA) or posterior approach (PA) total hip arthroplasty (THA).MethodsData between September 2008 and April 2015 were retrospectively reviewed. Male patients were included if they underwent a THA or BHR with minimum 5-year patient-reported outcomes. BHR patients were propensity-score matched in a 1:1 ratio to 2 control groups of patients: one group who underwent DAA THA and one group who underwent PA THA.ResultsFifty BHR patients were propensity-score matched to 2 control groups: 50 cases of PA THA and 50 cases of DAA THA. Both control groups were well matched with respect to demographics. The BHR 5-year patient-reported outcomes were comparable to both control groups. The BHR cohort compared favorably to the PA THA group with no significant differences in their average Forgotten Joint Score (77.9, 79.4, P = .84 respectively) and the number of patients reporting a score greater than or equal to 50 were also comparable, 41 (82%), 42 (84%), P = .79 respectively.ConclusionBHR yielded good functional status and outcomes, which compared favorably with control groups of DAA THA and PA THA. Decision-making should be based upon other factors such as potential risk factors, the surgeon’s and patient’s preferences, and the patient’s physical demand.     

Gender based differences in management and outcomes of cholecystitis

Background

During the reproductive years, women have a 4-fold higher prevalence of gallstones than men, making gallbladder disease a critically important topic in women's health. Among age-matched women and men hospitalized for cholecystitis, gender based differences in demographics, management, and economic and clinical outcomes were identified.

Methods

A cross-sectional study was conducted using the Nationwide Inpatient Sample. Outcomes were mortality, complications, length of stay, and cost.

Results

Women accounted for 65% of admissions for cholecystitis, with women more likely to have shorter time to surgery (1.6 vs 1.9 days) and laparoscopy (86 vs 76%) (P < .05). After cholecystectomy, women had lower mortality (.6% vs 1.1%), fewer complications (16.9 vs 24.1), shorter lengths of stay (4.2 vs 5.4 days), and lower costs ($10,556 vs $13,201) (P < .05). On multivariate analysis of age-matched patients, women had lower odds of mortality (odds ratio [OR], .75), complications (OR, .86), length of stay (OR, .95), and cost (OR, .93). Longer time to surgery and open cholecystectomy were independent predictors of worse outcomes.

Conclusions

In cholecystitis and cholecystectomy, women have better clinical and economic outcomes then age-matched men.     

TLR4 phosphorylation at tyrosine 672 activates the ERK/c-FOS signaling module for LPS-induced cytokine responses in macrophages

TLRs engage numerous adaptor proteins and signaling molecules, enabling a complex series of post-translational modifications (PTMs) to mount inflammatory responses. TLRs themselves are post-translationally modified following ligand-induced activation, with this being required to relay the full spectrum of proinflammatory signaling responses. Here, we reveal indispensable roles for TLR4 Y672 and Y749 phosphorylation in mounting optimal LPS-inducible inflammatory responses in primary mouse macrophages. LPS promotes phosphorylation at both tyrosine residues, with Y749 phosphorylation being required for maintenance of total TLR4 protein levels and Y672 phosphorylation exerting its pro-inflammatory effects more selectively by initiating ERK1/2 and c-FOS phosphorylation. Our data also support a role for the TLR4-interacting membrane proteins SCIMP and the SYK kinase axis in mediating TLR4 Y672 phosphorylation to permit downstream inflammatory responses in murine macrophages. The corresponding residue in human TLR4 (Y674) is also required for optimal LPS signaling responses. Our study, thus, reveals how a single PTM on one of the most widely studied innate immune receptors orchestrates downstream inflammatory responses.