Ischemia-reperfusion injury in renal transplantation is independent of the immunologic background

BACKGROUND: Adhesion molecule expression is important to early transplant failure. However, whether or not adhesion molecule-facilitated inflammation is antigen-dependent is unknown. We tested this hypothesis. METHODS: Rat renal grafts were four-hours cold-preserved in University of Wisconsin (UW) solution, transplanted to syngeneic or allogeneic recipients, and harvested after 2, 6, 12, 24, and 48 hours and after 1 week. The first allogeneic group receive no immunosuppression; two additional groups received either low (1.5 mg/kg) or standard (5 mg/kg) cyclosporine A (CsA). Renal function and morphology were determined; frozen sections were immunostained for P-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), leukocyte function associated molecule-1 (LFA-1), very late antigen-4 (VLA-4), as well as for neutrophils and monocytes. RESULTS: Selectins increased rapidly at 2 hours and quickly decreased by 12 hours. While P-selectin was expressed on vasculature, L-selectin was found on inflammatory cells. Neutrophil influx and that of LFA-1-positive cells occurred early, peaked between 12 and 24 hours, and paralleled the maximal impairment in renal function. ICAM-1 and PECAM-1 showed similar kinetics and a diffuse distribution. VCAM-1 increased more slowly after 12 hours, peaked at 24 hours, and was localized predominantly on the endothelium of elastic vessels. Between 24 hours and 1 week, all grafts progressively developed dense VLA-4-positive monocytic infiltrates adjacent to vessels expressing VCAM-1. Functional, morphological, and immunohistochemical parameters did not differ between isografts and allografts at one week. However, by day 10, allografts showed severe vascular and cellular rejection, while injury in isografts resolved. Immunosuppression with CsA did not reverse the inflammation induced by ischemia-reperfusion injury. CONCLUSIONS: The early inflammation after ischemia-reperfusion injury is largely independent of the immunologic background. We suggest that initial injury prevention should receive the highest priority.     

Turkish pepper (extra hot)

A 38 year old female office worker was admitted with a newly discovered blood pressure of 250/110 mm Hg. Evaluation for secondary forms of hypertension was negative and treatment was begun. Sodium excretion was markedly reduced, plasma aldosterone was normal, and plasma renin activity was low. Therefore, presence of an aldosterone-like activity was suspected. Eventually, the patient confessed to abusing "Turkish Pepper", a brand of Scandinavian liquorice candies and "Fisherman's Friend", another brand of liquorice candies, concurrently. After eliminating liquorice from her diet, the hypertension disappeared thus allowing her antihypertensive treatment to be stopped.     

Molecular monitoring of tumour load kinetics predicts disease progression after non-myeloablative allogeneic stem cell transplantation in multiple myeloma.

BACKGROUND: Non-myeloablative allogeneic stem cell transplantation followed by immunomodulatory therapies is considered a potentially curative approach in the treatment of multiple myeloma and most effective in a minimal residual disease setting. PATIENTS AND METHODS: The aim of this study was to find the most sensitive real-time PCR assay (TaqMan), based on the IGH rearrangement, to quantify the tumour load of 11 patients with multiple myeloma after non-myeloablative allogeneic transplantation. Patient-allele specific primers (ASO) and the TaqMan probe were derived from CDR2 and CDR3 hypervariable regions of IGH, while consensus primers were located within the FR3 and FR4/JH regions. Four different approaches of primer combinations were tested. RESULTS: ASO-forward and -reverse primers together with the clone-specific TaqMan probe were the most sensitive approach compared with the JH (P=0.071) or the FR3 consensus primer (P <0.001). The detection limit amounted to 1/10(4)-1/10(5) cells. Consecutively, 120 samples from 11 patients prior and post allogeneic transplantation were analysed. Three patients reached complete clinical remission accompanied by molecular remission. Disease progression or relapse was seen in six patients. In five, molecular progressive disease was detected prior to the clinical diagnosis of progression or relapse. CONCLUSION: Patient-specific real-time IGH-PCR provides the opportunity for earlier treatment intervention.     

Long‐term Radiological and Clinical Outcome after Lumbar Spinal Fusion Surgery in Patients with Degenerative Spondylolisthesis: A Prospective 6‐Year Follow‐up Study

ObjectiveTo assess which radiological alignment parameters are associated with a satisfactory long‐term clinical outcome after performing lumbar spinal fusion for treating degenerative spondylolisthesis.MethodsThis single‐center prospective study assessed the relation between radiological alignment parameters measured on standing lateral lumbar spine radiographs and the patient‐reported outcome using four different questionnaires (COMI, EQ‐5D, ODI and VAS) as primary outcome measures (level of evidence: II). The following spinopelvic alignment parameters were used: gliding angle, sacral inclination, anterior displacement, sagittal rotation, lumbar lordosis, sacral slope, pelvic tilt and pelvic incidence. Furthermore, the length of stay and perioperative complications were documented. Only cases from 2013 to 2015 of low‐grade degenerative lumbar spondylolisthesis (Meyerding grades I and II) were considered. The patients underwent open posterior lumbar fusion surgery by pedicle screw instrumentation and cage insertion. The operative technique was either a posterior lumbar interbody fusion (PLIF) or a transforaminal lumbar interbody fusion (TLIF) performed by three different senior orthopedic surgeons. Exclusion criteria were spine fractures, minimally invasive techniques, underlying malignant diseases or acute infections, previous or multisegmental spine surgery as well as preoperative neurologic impairment. Of 89 initially contacted patients, 17 patients were included for data analysis (11 males, six females).ResultsThe data of 17 patients after mono‐ or bisegmental lumbar fusion surgery to treat low‐grade lumbar spondylolisthesis and with a follow‐up time of least 72 months were analyzed. The mean age was 66.7 ± 11.3 years. In terms of complications two dural tears and one intraoperative bleeding occurred. The average body mass index (BMI) was 27.6 ± 4.4 kg/m² and the average inpatient length of stay was 12.9 ± 3.8 days (range: 8–21). The long‐term clinical outcome correlated significantly with the change of the pelvic tilt (r _s = −0.515, P < 0.05) and the sagittal rotation (r _s = −0.545, P < 0.05). The sacral slope was significantly associated with the sacral inclination (r _s = 0.637, P < 0.01) and the pelvic incidence (r _s = 0.500, P < 0.05). In addition, the pelvic incidence showed a significant correlation with the pelvic tilt (r _s = 0.709, P < 0.01). The change of the different clinical scores over time also correlated significantly between the different questionnaires.ConclusionsThe surgical modification of the pelvic tilt and the sagittal rotation are the two radiological alignment parameters that can most accurately predict the long‐term clinical outcome after lumbar interbody fusion surgery.     

Meta-Analysis of Short vs. Prolonged Dual Antiplatelet Therapy after Drug-Eluting Stent Implantation and Role of Continuation with either Aspirin or a P2Y12 Inhibitor Thereafter

Aim: The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation is an ongoing debate and novel data has emerged. The aim of this meta-analysis was to assess outcomes of short vs. control DAPT duration. In addition, the role of single antiplatelet therapy (SAPT) after DAPT with either aspirin or P2Y₁₂ inhibitor monotherapy was analyzed. Methods: The authors searched MEDLINE and Cochrane databases and proceedings of international meetings for randomized controlled trials (RCT) comparing ≤ 3 months with ≥ 6 months DAPT after DES implantation. The primary and co-primary outcomes of interest were definite or probable stent thrombosis (ST) and bleeding. In addition, we performed an analysis on studies who continued with either aspirin or P2Y₁₂ monotherapy after DAPT. Results: 9 RCTs comprising 41,864 patients were included and we analyzed a short DAPT duration of median 1.5 months vs. 12.1 months in the control group. The risk for ST was similar with short vs. control DAPT duration (0.5 vs. 0.5%; hazard ratio 1.17[95% CI 0.89-1.54];p=0.26). Bleeding was significantly reduced with short vs. control DAPT duration (1.9 vs. 3.0%; 0.65[0.54-0.77];p＜0.0001). ST was not different between short vs. control DAPT duration in the analysis of the 4 RCTs who continued with aspirin after DAPT and the 5 P2Y₁₂ RCTs, respectively, and no heterogeneity was detected (p=0.861). Bleeding was also reduced with short vs. control DAPT in both the aspirin (1.2 vs. 1.7%; 0.71[0.51-0.99];p=0.04) and P2Y₁₂ inhibitor studies (2.1 vs. 3.4%; 0.62[0.47-0.80];p=0.0003) and no heterogeneity was detected (p=0.515). Conclusions: Our meta-analysis shows that short DAPT ≤ 3 months followed by SAPT reduces bleeding and is not associated with an increase in ST. The results were consistent within the aspirin and P2Y₁₂ SAPT studies.