Retrospective Evaluation of the Effect of Mycophenolate Mofetil Dosage on Survival of Kidney Grafts Based on Biopsy Results

IntroductionPlasma concentration monitoring is commonly used to adjust immunosuppressant dosage in transplant recipients, but adjustment is often based on clinical experience rather than rigorous quantitative indicators.MethodsWe examined the effect of mycophenolate mofetil (MMF) dosage on graft survival by pathologic and immunologic analysis of 88 kidney recipients who were given a postoperative immunosuppressive regimen of tacrolimus (FK506), MMF, and corticosteroids. Patients were given a conventional dosage (≥1.5 g/d; n = 40) or a reduced dosage (n = 48) of MMF owing to postoperative adverse side effects.ResultsThe reduced-dose group included patients given low doses (≤1.0 g/d; n = 27), ultra-low doses (≤0.5 g/d; n = 15), and those who discontinued MMF (n = 6). The dose reduction group had increased acute rejection, chronic rejection, and graft dysfunction, poorer pathologic scores, and increased cell infiltration of graft tissue (CD4, CD8, CD68, and CD138 positivity) and expression of interleukin-2R and HLA-DR. Finally, hazard analysis indicated that patients given low doses and ultra-low doses of MMF had poorer long-term kidney grafts survival (hazard ratios of 1.52 and 1.78, respectively).ConclusionsThese results indicate the importance of using an appropriate dosage of MMF in kidney transplant recipients.     

Immunosuppressive Activity of Adipose Tissue-Derived Mesenchymal Stem Cells in a Rat Model of Hind Limb Allotransplantation

Many reports have shown that bone marrow–derived mesenchymal stem cells exhibit immunosuppressive effects in allogeneic transplantation. However, few reports have evaluated the immunosuppressive properties of adipose tissue–derived mesenchymal stem cells (ASCs) in vitro and in vivo. In this study, we investigated the immunosuppressive characteristics of ASCs, and investigated whether ASCs originating from donor rats prolong allotransplant survival in a rat hind limb allotransplantation model. T-cell proliferation stimulated by allogeneic stimuli or mitogen with or without ASCs originating from the donor was assessed in vitro. The effects of cellular contact or soluble factors on the inhibition of T-cell proliferation were also evaluated. In the in vivo study, cultured ASCs (1 × 10⁵) that originated from the donor were injected into recipient animals intravenously immediately after operation, followed by 1 dose per day for 3 consecutive days post-transplantation. When immune rejection occurred, the survival time of allotransplants was determined and rejected tissue was histologically and immunochemically assessed for determining regulatory T-cell infiltration. ASCs inhibited the T-cell proliferation stimulated by alloantigen or mitogen in a dose-dependent manner, and recipient T cells proliferated less in animals treated with ASCs than in controls. Although ASCs were separated from T cells, ASCs persisted to elicit a suppressive effect. ASC culture supernatants did not inhibit T-cell proliferation; however, supernatants obtained from the mixed lymphocyte reaction in the presence of ASCs suppressed T-cell proliferation. ASCs prolonged allotransplant survival time, reduced inflammatory cell infiltration, and induced regulatory T cells. In conclusion, ASCs can exhibit in vitro immunosuppressive properties and prolong allotransplant survival time in a rat hind limb composite tissue allotransplantation model, possibly through the induction of regulatory T cells.     

Chronic rhinosinusitis and progression of cognitive impairment in dementia

AimThe relationship between chronic inflammatory disease and cognitive decline is still unclear, but there is increasing evidence to support the role of systemic inflammation. The aim of this study was to investigate if chronic rhinosinusitis (CRS) in dementia or mild cognitive impairment (MCI) is associated with the progression of cognitive decline.Material and methodsWe retrospectively reviewed the data of patients who complained of memory impairment, and underwent brain magnetic resonance imaging (MRI) from January 2006 to April 2019. According to the Mini-Mental State Examination (MMSE) score, subjects (n = 661) were divided into three groups: dementia (≤ 17), MCI (18–23), and normal (≥ 24). CRS was defined as a total score of greater than or equal to 4 according to the Lund–Mackay scoring system using brain MRI. Multiple logistic regression analyses estimated adjusted odds ratio (aOR) for the association between CRS and dementia or MCI. Among the subjects with follow-up MMSE (n = 286), a repeated-measures ANOVA was used to assess the difference of changes in MMSE scores between the groups with and without CRS.ResultsAccording to the initial MMSE score, there were 221 subjects with dementia, 195 with MCI, and 245 with normal results. CRS was not significantly associated with dementia (aOR = 1.519, CI = 0.909–2.538, P = 0.111), while being suggestively associated with MCI (aOR = 1.740, CI = 1.041–2.906, P = 0.034). The MMSE scores at follow-up decreased further in subjects with CRS than in those without CRS (P = 0.009). Especially, in the initial dementia group, there was a significant between-group difference in the MMSE score from baseline to follow-up (13.6 ± 4.3 to 11.1 ± 6.3 in CRS group vs. 13.5 ± 3.3 to 14.4 ± 5.4 in no CRS group, P = 0.002).ConclusionThe result of the present study implies a potential association between CRS and progression of cognitive decline. Physicians should be aware of this possibility in patients with clinically diagnosed CRS.     

Biomechanical and histological evaluation of four different titanium implant surface modifications: an experimental study in the rabbit tibia

Objectives

This study presents a biomechanical comparison of bone response to commercially pure titanium screws with four different types of surface topographies placed in the tibial metaphysis of 30 rabbits.

Materials and methods

One hundred twenty implants were tested double-blinded: (a) blasted, acid-etched, and discrete crystal deposition (DCD), (b) blasted, (c) acid-etched, and (d) blasted and acid-etch. Resonance frequency analysis (RFA/ISQ), reverse torque values (RTV), and bone-to-implant contact (BIC) were measured at the time of implant insertion (day 0), 15, 28, and 56 days of healing.

Results

All groups tested demonstrated increased RFA/ISQ and RTV results over the time course. At 15 days, the blasted, acid-etched, and DCD group demonstrated a non-significant trend toward higher values when compared to the blasted and etched group (33.0?±?16 vs. 26.3?±?12 Ncm, p?=?.16). At 56 days, the groups utilizing blasting to create additional surface roughness (Sa?>?1 micron) showed a statistical significant difference in RTQ versus the non-blasted group (38.5?±?14 vs. 29.5?±?9 Ncm, p?=?.03).

Conclusions

Within the limitations of this study, only the increase in surface roughness (Ra?>?1) at 56 days demonstrated statistically significant effects on RTQ. Other additional surface features, such as sub-micron scale DCD, demonstrated improved healing trends but without significance for clinical applications.