Acute Antibody-Mediated Rejection in Living ABO-Incompatible Kidney Transplantation: Long-Term Impact and Risk Factors

The impact of acute antibody-mediated rejection (AAMR) on the long-term outcome on ABO-incompatible (ABOI) kidney transplantation is not well understood. We retrospectively analyzed the long-term impact of AAMR and risk factors for AAMR in 57 consecutive recipients performed between 1999 and 2004. Nineteen patients (33%) who developed AAMR within 3 months posttransplantation constituted of the AMR group. The graft survival rate was significantly lower in the AMR group (AMR vs. non-AMR, respectively; 5 years: 84% vs. 95%; 8 years: 45% vs. 95%; p = 0.009). The prevalence of transplant glomerulopathy at 1 year posttransplantation was significantly higher in the AMR group (AMR 64% vs. non-AMR 3%, p < 0.001). Multivariate analysis demonstrated that anti-blood group IgG antibody titers of 1:32 at the time of transplantation (OR, 9.52; p = 0.041) and donor-specific anti-HLA antibodies (DSHA) detected by Luminex single bead method (OR, 5.68; p = 0.015) were independent risk factors for AAMR regardless of baseline anti-blood group IgG antibody titers. Our results indicate that AAMR has a heavy impact on the long-term outcome and preoperative DSHA appears to have a more significant association with poor graft outcomes than anti-blood group antibodies, even in ABOI kidney transplantation.     

Optimal therapeutic concentration of tacrolimus in adult patients undergoing reduced-intensity cord blood transplantation

To investigate the effectiveness and safety of GVHD prophylaxis using FK506 alone as a continuous infusion, 104 patients who underwent reduced-intensity cord blood transplantation were retrospectively reviewed. The respective incidence of acute GVHD was 25 grade 1(24. 1%), 19 grade2(18. 3%), 15 grade3(14. 4%), and 4 grade4(3. 8%), which are comparable to that in the literature. The incidences of grade 2 and greater acute GVHD were 32 out of 69(46. 4%)for those whose wholeblood concentration of FK506 werele ss than 13 ng/mL, whereas 6 out of 35(17. 1%)for those FK5 06 were greater than 13 ng/mL. The differenceies between above and below 13 ng/mL were statistically significant(p=0. 008). There were 19 cases(18. 3%)of renal dysfunction, although none required hemodialysis. There were only 4 patients who discontinued FK506, which further confirmed the safety of FK506 alone. Together with our previous report on the upper limit of FK506(17 ng/mL)and these results, we recommend the optimal serum concentration of FK506 to range from 13 to 17 ng/ mL.     

Immunological status in three patients, thirty years after living related renal transplantation: antibody production in long-term survivors

There have been few studies of the immune status of long-term follow-up patients after living-donor kidney transplantation. We investigated the immune status from the immunologic and pathologic standpoint of three long surviving recipients who had received renal grafts more than 30 years earlier. Anti-HLA antibodies that had not been present before transplantation were detected in one recipient with three HLA mismatches. One recipient with identical HLA showed positive for the crossmatch test, but not for the panel reactive antibody test (PRA), thus showing that this patient had HLA antibodies against HLA minor histocompatibility antigens, etc. Only one patient with established microchimerism was stable without any antibody production. Pathologically, chronic allograft nephropathy with C4d staining suggestive of antibody-mediated rejection was observed in both patients with HLA antibodies. Physicians should clinically manage patients by always bearing in mind the presence of anti-donor antibodies during long-term regular follow-up of transplanted kidneys.     

Attenuation of natural killer cell activity during 2-h exercise in individuals with spinal cord injuries

DESIGN: Non-randomized study. OBJECTIVE: To determine natural killer cell cytotoxic activity (NKCA) to 2-h arm ergometer exercise in persons with spinal cord injuries (SCI) and the underlying mechanism of such response. SETTING: University of Occupational and Environmental Health, Japan. METHODS: We examined NKCA response to 2-h arm crank ergometer exercise at 60% of maximum oxygen consumption (VO(2max)) in SCI and able-bodied persons. NKCA and plasma concentrations of prostaglandin E(2) (PGE(2)), adrenaline and cortisol were measured before, during and immediately after the exercise. The study included seven subjects with SCI between Th11 and L4 and six able-bodied persons. RESULTS: NKCA in able-bodied subjects increased (P<0.05) at 60 min of exercise and immediately after the exercise, and remained elevated up to 2 h after exercise. However, NKCA in SCI decreased (P<0.05) immediately after exercise but recovered at 2 h after exercise. Plasma adrenaline in both groups increased significantly (P<0.05) immediately after exercise and returned to baseline level 2 h after the exercise. Plasma cortisol in both groups remained constant throughout the study. In SCI, PGE(2) significantly increased immediately after 2 h exercise and returned to the baseline level 2 h after exercise; however, it remained unchanged during the test in able-bodied subjects. CONCLUSION: Our results suggested that increase of PGE(2) in SCI partially contributes to NKCA.     

Selection bias due to delayed comprehensive genomic profiling in Japan

Patients with advanced cancer undergo comprehensive genomic profiling in Japan only after treatment options have been exhausted. Patients with a very poor prognosis were not able to undergo profiling tests, resulting in a selection bias called length bias, which makes accurate survival analysis impossible. The actual impact of length bias on the overall survival of patients who have undergone profiling tests is unclear, yet appropriate methods for adjusting for length bias have not been developed. To assess the length bias in overall survival, we established a simulation-based model for length bias adjustment. This study utilized clinicogenomic data of 8813 patients with advanced cancer who underwent profiling tests at hospitals throughout Japan between June 2019 and April 2022. Length bias was estimated by the conditional Kendall τ statistics and was significantly positive for 13 of the 15 cancer subtypes, suggesting a worse prognosis for patients who underwent profiling tests in early timing. The median overall survival time in colorectal, breast, and pancreatic cancer from the initial survival-prolonging chemotherapy with adjustment for length bias was 937 (886–991), 1225 (1152–1368), and 585 (553–617) days, respectively (median; 95% credible interval). Adjusting for length bias made it possible to analyze the prognostic relevance of oncogenic mutations and treatments. In total, 12 tumor-specific oncogenic mutations correlating with poor survival were detected after adjustment. There was no difference in survival between FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) or gemcitabine with nab-paclitaxel-treated groups as first-line chemotherapy for pancreatic cancer. Adjusting for length bias is an essential part of utilizing real-world clinicogenomic data.     

Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness

BACKGROUND: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a noninvasive technique that has been shown to coagulate benign and malignant tumors. The purpose of this study was to evaluate MRgFUS safety and effectiveness for the ablation of breast carcinomas. STUDY DESIGN: Thirty women with biopsy-proved breast cancer underwent MRgFUS treatment. Gadolinium-enhanced MR images were used for treatment planning and posttreatment radiologic assessment of treated tissue, and temperature-sensitive MR images provided real-time treatment monitoring. After MRgFUS, all 30 women underwent wide excision or mastectomy. The extent of thermal ablation was assessed with tumor histology. RESULTS: Treatment was well tolerated, with a minimum of adverse effects, especially when performed under local anesthesia. On pathologic examination, mean (+/-SD) necrosis of the targeted breast tumors was 96.9 +/- 4% (median 100%, range 78% to 100%) of tumor volume. Fifteen (53.5%) of 28 evaluable patients had 100% necrosis of the ablated tumor; only 3 patients (10.7%) had less than 95% necrosis. In 28 (93.3%) patients, 100% of the malignancy was within the treatment field, and 98% and 95% of tumor lay within the treatment field in 2 remaining patients. Retrospective analysis in two patients with residual tumor showed treatment was not delivered to the full recommended area, reaffirming the need for precise localization and the value of contrast-enhanced images for treatment planning. CONCLUSIONS: MRgFUS has great potential to become a viable noninvasive replacement for lumpectomy. Additional studies focusing on posttreatment image-based evaluation are needed.     

The contribution of quasi-joint stiffness of the ankle joint to gait in patients with hemiparesis

Background

The role of ankle joint stiffness during gait in patients with hemiparesis has not been clarified. The purpose of this study was to determine the contribution of quasi-joint stiffness of the ankle joint to spatiotemporal and kinetic parameters regarding gait in patients with hemiparesis due to brain tumor or stroke and healthy individuals.

Methods

Spatiotemporal and kinetic parameters regarding gait in twelve patients with hemiparesis due to brain tumor or stroke and nine healthy individuals were measured with a 3-dimensional motion analysis system. Quasi-joint stiffness was calculated from the slope of the linear regression of the moment–angle curve of the ankle joint during the second rocker.

Findings

There was no significant difference in quasi-joint stiffness among both sides of patients and the right side of controls. Quasi-joint stiffness on the paretic side of patients with hemiparesis positively correlated with maximal ankle power (r = 0.73, P < 0.01) and gait speed (r = 0.66, P < 0.05). In contrast, quasi-joint stiffness in controls negatively correlated with maximal ankle power (r = − 0.73, P < 0.05) and gait speed (r = − 0.76, P < 0.05).

Interpretation

Our findings suggested that ankle power during gait might be generated by increasing quasi-joint stiffness in patients with hemiparesis. In contrast, healthy individuals might decrease quasi-joint stiffness to avoid deceleration of forward tilt of the tibia. Our findings might be useful for selecting treatment for increased ankle stiffness due to contracture and spasticity in patients with hemiparesis.