Clinical validation of a novel enzyme‐linked immunosorbent spot assay‐based in vitro diagnostic assay to monitor cytomegalovirus‐specific cell‐mediated immunity in kidney transplant recipients: a multicenter,longitudinal, prospective,observational study

Impaired cytomegalovirus (CMV)‐specific cell‐mediated immunity (CMV‐CMI) is a major cause of CMV reactivation and associated complications in solid‐organ transplantation. Reliably assessing CMV‐CMI is desirable to individually adjust antiviral and immunosuppressive therapy. This study aimed to evaluate the suitability of T‐Track^® CMV, a novel IFN‐γ ELISpot assay based on the stimulation of peripheral blood mononuclear cells with pp65 and IE‐I CMV proteins, to monitor CMV‐CMI following kidney transplantation. A prospective longitudinal multicenter study was conducted in 86 intermediate‐risk renal transplant recipients. CMV‐CMI, CMV viral load, and clinical complications were monitored over 6 months post‐transplantation. Ninety‐five percent and 88–92% ELISpot assays were positive pre‐ and post‐transplantation, respectively. CMV‐specific response was reduced following immunosuppressive treatment and increased in patients with graft rejection, indicating the ability of the ELISpot assay to monitor patients' immunosuppressive state. Interestingly, median pp65‐specific response was ninefold higher in patients with self‐clearing viral load compared to antivirally treated patients prior to first viral load detection (P < 0.001), suggesting that reactivity to pp65 represents a potential immunocompetence marker. Altogether, T‐Track^® CMV is a highly sensitive IFN‐γ ELISpot assay, suitable for the immunomonitoring of CMV‐seropositive renal transplant recipients, and with a potential use for the risk assessment of CMV‐related clinical complications (ClinicalTrials.gov Identifier: NCT02083042).     

Managing Traps and Pitfalls During Initial Steps of an ECMO Retrieval Program Using a Miniaturized Portable System: What Have We Learned From the First Two Years?

The aim of this study was to provide early and mid‐term results of the newly established extracorporeal membrane oxygenation (ECMO) retrieval service in a tertiary cardiothoracic center using the miniaturized portable Cardiohelp System (Maquet, Rastatt, Germany). A particular attention was paid to organizational and logistic specifics as well as challenges and pitfalls associated with initial phase of the program. From January 2015 until January 2017 a heterogenic group of 28 consecutive patients underwent ECMO implantation in distant hospitals for acute cardiac, pulmonary or combined failure as a bridge‐to‐decision and were subsequently transported to our institution. Each cannulation was performed bedside on intensive care units (ICU) using the Seldinger's technique. Early outcomes and mid‐term overall survival with up to two‐year follow‐up along with the impact of ongoing cardiopulmonary resuscitation (CPR) on outcome were presented. Also, changes in hemodynamics and tissue perfusion factors 24 h after ECMO implantation were evaluated. ECMO implantations were performed in 15 distant departments with the median distance of 23(10;40) (maximum 60) km. A total of 15 patients (54%) were cannulated under CPR with the median duration of 30(20;110) (maximum 180) min. After 24 h of support there were significant improvements in SvO₂ (P = 0.021), mean arterial pressure (P = 0.027), FiO₂ (P = 0.001), lactate (P = 0.001), and pH (P < 0.001). The mean ECMO support duration was 96 ± 100 (maximum 384) hours, whereas 11 patients (40%) were weaned off support and discharged from hospital. Overall cumulative survival in patients without the need for CPR was 61.5% at one week and 38.5% at 1 month, 6 month, and 1 year, whereas patients requiring CPR survived in 40% at one week, and 33.3% at 1 month, 6 month, and 1 year (Log‐Rank (Mantel‐Cox) P = 0.374, Breslow (Generalized Wilcoxon) P = 0.162). Our initial experience shows that launching new ECMO retrieval programs in centers with sufficient ICU capacities and local ECMO experience can be feasible and associated with acceptable “real world” results despite the initial learning curve. Rapid logistical organization and team flexibility are the key points to ensure comparable survival of patients requiring prolonged CPR.     

Increased Neutrophil-to-Lymphocyte Ratio is Associated with Unfavorable Functional Outcome in Acute Ischemic Stroke

Neurocritical Care - Inflammatory response is the hallmark of secondary brain injury in stroke patients. Neutrophil-to-lymphocyte ratio (NLR) emerged as a marker for functional outcome in several...     

The TIM-1:TIM-4 pathway enhances renal ischemia-reperfusion injury

CD4+ T cells contribute to the pathogenesis of ischemia-reperfusion injury, which is the primary cause of delayed graft failure after kidney transplantation. The TIM-1:TIM-4 pathway participates in the activation/differentiation of CD4+ T cells, suggesting that it may modulate ischemia-reperfusion injury. Here, we studied the role of TIM-1 in a murine uninephrectomized renal ischemia-reperfusion injury model. Blocking the TIM-1:TIM-4 pathway with an antagonistic monoclonal antibody protected renal function and diminished reperfusion injury resulting from 30 minutes of ischemia. Histologic examination showed significantly less evidence of renal damage as evidenced by diminished tubular necrosis, preservation of the brush border, fewer cast formations, and less tubular dilation. Blocking TIM-1 also reduced the number of apoptotic cells and diminished local inflammation within ischemic kidneys, the latter shown by decreased recruitment of macrophages, neutrophils, and CD4+ T cells and by reduced local production of proinflammatory cytokines. Furthermore, TIM-1 blockade significantly improved survival after ischemia-reperfusion injury. Taken together, these data suggest that the TIM-1:TIM-4 pathway enhances injury after renal ischemia-reperfusion injury and may be a therapeutic target.     

Calcineurin inhibitor dose‐finding before kidney transplantation in HIV patients

Kidney transplantation in HIV‐infected patients is associated with a higher rate of graft rejection as well as an increased toxicity of the immunosuppressive therapy. Specifically, the use of the calcineurin inhibitor tacrolimus is problematic because of a narrow therapeutic range, a high interindividual variability of trough levels, and multiple interactions with combination antiretroviral therapy (cART). Our objective was to establish the optimal individual immunosuppressive dose for the time after kidney transplantation. We administered a temporary course of immunosuppressive therapy in three HIV‐infected patients with end‐stage renal disease (ESRD) after wait‐listing and prior to transplantation for deceased donor kidney transplantation. Starting with a tacrolimus dose of 1 mg twice daily, the dose was titrated to reach a tacrolimus trough level of 8–12 ng/ml. HIV had been diagnosed 7–14 years prior. All patients had no detectable HIV‐1 RNA while on cART. All three patients had been on chronic dialysis for 4, 7, and 10 years. In two patients, the intended tacrolimus trough levels of 8–12 ng/ml were achieved within a month. The required tacrolimus dose ranged from 0.5 mg thrice weekly to 10 mg daily. In one case, ventricular tachycardia occurred, so the immunosuppressive therapy was switched to cyclosporine A. So far, two patients have been transplanted successfully. In summary, dose‐finding of immunosuppressive therapy with tacrolimus in patients on cART before renal transplantation is feasible and appears useful to minimize immunosuppressive therapy‐related complications in the post‐transplantation period.     

Modified Lapidus arthrodesis with plantar plate and compression screw for treatment of hallux valgus with hypermobility of the first ray: A preliminary report

BackgroundTMT-1 arthrodesis is an established method in hallux valgus surgery, but it is technically demanding and typically calls for a period of postoperative immobilization.MethodsIn this cohort study, initial experience with a plantar plate is described. 58 patients (59 arthrodesis) were included.ResultsThe mean duration of protected full weight bearing was 7 weeks. 94.12% patients were satisfied with the results, bony union was achieved in 98.31%. The Foot Function Index improved by 33 to a mean of 8 (p < .001). The postoperative Mayo Clinic Forefoot Score was excellent in 47.04 and good in 47.04%. The mean hallux valgus angle improved by 24.4–13.2° (p < .001). The mean first intermetatarsal angle improved by 11.2–5.2° (p < .001).ConclusionInitial experience with this form of fixation appears to provide suitable stability, allow early-protected weight bearing, with an acceptable level of complications.