Novel Therapeutic Concepts for Complex Femoropopliteal Lesions Using the Jetstream Atherectomy System.

INTRODUCTION: The presence of severe arterial calcification is associated with less favorable outcomes in terms of procedural and clinical success as well as higher rates of major adverse limb events. Recent studies incorporating rotational atherectomy for effective preparation of severely calcified lesions demonstrate beneficial procedural outcomes by obtaining maximal luminal gain and improved long-term outcomes. METHODS: This prospective single-center, observational study includes patients with severely calcified femoropopliteal lesions with chronic limb ischemia Rutherford 1-5 between January 2017 and July 2019, who underwent atherectomy using the Jetstream Atherectomy system, followed by drug-coated balloon angioplasty. Lesion calcification was categorized by the Peripheral Arterial Calcium Scoring System (PACSS), whereas lesion complexity was classified by the Transatlantic Inter-Society Consensus (TASC). Safety and efficacy aspects in terms of vessel injury, thromboembolism, and clinical success were systematically analyzed up to 12 months of follow-up (FU). RESULTS: In 162 consecutive patients, 210 non-stented and 22 stented lesions were treated. Twelve (7.4%) patients received bail-out stenting. Mean lesion length was 24.2±4.8 cm; 51% were chronic total occlusions (mean occlusion length 18.2±5.1 cm). TASC C lesions were present in 38 patients (23.5%) and TASC D lesions in 124 patients (76.5%). The mean PACCS score was 3.3±0.9. Device success was achieved in 88%; procedural success was noted in 99% of the lesions. Embolic protection device was used in 11.7%. Perforation or dissection occurred in none of the cases. Asymptomatic peripheral embolization was noted in 10 patients (6.2%). Clinical FU at 12 months was available in 157 of 162 patients (96.9%). At 12 month FU, (1) mean Rutherford classification at baseline of 3.7±0.6 significantly dropped to 1.0±0.9 (p<0.05), (2) baseline mean anke-brachial index (ABI) of 0.4±0.1 significantly increased to 0.8±0.2 (p<0.05), (3) 92.6% were free from target lesion revascularization (TLR), (4) 95.1% were free from target vessel revascularization (TVR), and (5) binary restenosis measured by duplex occurred in 22 patients (13.6%). Multivariate analyses showed lesion length as predictive of stent placement (p=0.02), whereas both lesion length (p=0.006) and PACCS score (p=0.02) are predictive of clinical success. CONCLUSION: Rotational atherectomy in combination with drug-coated balloon (DCB) can be safely performed in long, calcified (non-) occlusive lesions with a relatively low rate of bail-out stenting and favorable clinical mid-term results. CLINICAL IMPACT: In this prospective, single arm study we demonstrated that combination treatment using rotational atherectomy and DCB is safe and effective in complex and calcified TASC C/D femoropopliteal lesions in patients with claudication or CLTI in a real-world clinical setting. Despite mean lesion length of >20cm and a relatively high rate of chronic total occlusions, the rate of bail-out stenting was surprisingly low (7.4%), whereas the rates of freedom from TLR and TVR were surprisingly high. Thus, our study may encourage vascular specialists to choose an endovascular -first approach even in such complex and calcified femoropopliteal lesions and occlusions in daily clinical practice.

Periprocedural transfusion in patients undergoing transfemoral transcatheter aortic valve implantation.

OBJECTIVES: The aim of this investigation was to identify patient's characteristics and periprocedural variables related to periprocedural transfusion in transfemoral Transcatheter Aortic Valve Implantation (tf-TAVI). BACKGROUND: Transfusion of allogenic red-blood cells (RBC) in tf-TAVI and the number of transfused units has been linked to an increased 30-day mortality. In line with the trend of minimization and cost-effectiveness, transfusion should be avoided, wherever possible. METHODS: Between 2007 and 2015, 1,734 procedures were analyzed from our prospective registry for RBC-transfusion. Multiple logistic regression analysis was used to identify the dependent variables. RESULTS: Transfusion was considered necessary in 14% (n = 243) of the patients. Female gender (OR [95% CI]) (1.680 [1.014-2.783]) and preprocedural moderate (7.594 [4.404-13.095]) and severe anemia (8.202 [0.900-74.752]) according to WHO were the most important preprocedural variables. Periprocedural, pericardial effusion (12.109 [3.753-39.063]), emergency extracorporeal circulation (54.5288 [6.178-481.259]) and major vascular injury (2.647 [1.412-4.962]) were related to transfusion. The same applies to moderate (4.255 [1.859-9.740]) and severe anemia (31.567 [8.560-116.416]) as well as periprocedural experience (0.072 [0.035-0.149] - 0.141[0.079-0.251], P < 0.001) CONCLUSION: Procedural experience, serious adverse events, low pre- and periprocedural Hb levels and female gender were the main variables relating to transfusion. Even in experienced high-volume centers, transfusion is still necessary in a considerable number of patients.

Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery.

AIMS: Very little data exist regarding the effect of cardiopulmonary bypass (CPB) on cefuroxime (CXM) pharmacokinetics in children less than one year of age. METHODS: 50 mg kg-1 CXM i.v. after induction were followed by 75 mg kg-1 into the CPB circuit. In 42 patients undergoing cardiac surgery, 15-20 samples were obtained between 5 and 360 min after the first dose. Total CXM concentrations were measured by high-performance liquid chromatography and a pharmacokinetic/pharmacodynamic (PK/PD) modelling was performed. RESULTS: Using a fixed protein binding of 15.6% for CXM, peak plasma concentrations of unbound CXM were 229 ± 52 µg ml-1 after the first bolus and 341 ± 86 µg ml-1 on CPB. Nadir concentrations before CPB were 69 ± 20 µg ml-1 and six hours later decreased to 41 ± 19 µg ml-1 with and 24 ± 14 µg ml-1 without CPB. A two-compartment model was fitted with the main covariates body weight, CPB and postmenstrual age (PMA). PK parameters were as follows: systemic clearance, 5.15 [95% CI 4.5-5.8] l h-1 ; central volume of distribution, 11.25 [9.41-13.09] l; intercompartmental clearance, 18.19 [14.79-21.58] l h-1 ; and peripheral volume, 17.07 [15.7-18.5] L. ƒT > MIC of 32 µg ml-1 for an 8-h time period was between 70 and 100% (2.5-10 kg BW). According to our simulation, 25 mg ml-1 CXM as a primary bolus and into the prime plus a 5 mg kg-1  h-1 infusion maintain CXM concentrations continuously above 32 µg ml-1 . CONCLUSIONS: The routine dosing regimen provided was sufficient for prophylaxis, but continuous dosing can provide a higher percentage of ƒT > MIC.

Pharmacokinetics of tranexamic acid in neonates and infants undergoing cardiac surgery.

AIM: Tranexamic acid (TXA) continues to be one of the antifibrinolytics of choice during paediatric cardiac surgery. However, in infants less than 1 year of age, the optimal dosing based on pharmacokinetic (PK) considerations is still under discussion. METHODS: Forty-three children less than 1 year of age were enrolled, of whom 37 required the use of cardiopulmonary bypass (CPB) and six were operated on without CPB. Administration of 50 mg kg-1 TXA intravenously at the induction of anaesthesia was followed by 50 mg kg-1 into the CPB prime in the CPB group. Plasma concentrations of TXA were analysed by gas chromatography-mass spectrometry. PK data were investigated using nonlinear mixed-effect models. RESULTS: A two-compartment model was fitted, with the main covariates being allometrically scaled bodyweight, CPB, postmenstrual age (PMA). Intercompartmental clearance (Q), peripheral volume (V2), systemic clearance, (CL) and the central volume (V1) were calculated. Typical values of the PK parameter estimates were as follows: CL = 3.78 [95 % confidence interval (CI) 2.52, 5.05] l h-1 ; central volume of distribution = 13.6 (CI 11.7, 15.5) l; Q = 16.3 (CI 13.5, 19.2) l h-1 ; V2 = 18.0 (CI 16.1, 19.9) l. Independently of age, 10 mg kg-1 TXA as a bolus, a subsequent infusion of 10 mg kg-1 h-1 , then a 4 mg kg-1 bolus into the prime and a reduced infusion of 4 mg kg-1 h-1 after the start of CPB are required to maintain TXA concentrations continuously above 20 µg ml-1 , the threshold value for an effective inhibition of fibrinolysis and far lower than the usual peak concentrations (the '10-10-4-4 rule'). CONCLUSIONS: The introduction of a modified dosing regimen using a starting bolus followed by an infusion and a CPB prime bolus would prohibit the potential risk of seizures caused by high peak concentrations and also maintain therapeutic plasma concentration above 20 µg ml-1 .

Accuracy of subthalamic nucleus targeting by T2, FLAIR and SWI-3-Tesla MRI confirmed by microelectrode recordings.

BACKGROUND: Successful deep brain stimulation is mostly dependent on accurate positioning of the leads at the optimal target points. We investigated whether the identification of the subthalamic nucleus in T2-weighted 3-T MRI, fluid-attenuated inversion recovery 3-T MRI and susceptibility-weighted 3-T MRI is confirmed by intraoperative neurological microelectrode recording. METHODS: We evaluated 182 microelectrode recording leads in 21 patients with bilateral deep brain stimulation, retrospectively. Consequently, 728 electrode contact positions in T2-weighted 3-T MRI, 552 electrode contact positions in fluid-attenuated inversion recovery 3-T MRI and 490 electrode contact positions in susceptibility-weighted 3-T MRI were evaluated for a positive nucleus subthalamicus signal. RESULTS: The highest sensitivity was measured for fluid-attenuated inversion recovery 3-T MRI with 82.5 %, while the highest specificity was observed for susceptibility-weighted 3-T MRI with 90.6 %. The negative predictive value was nearly equal for susceptibility-weighted MRI and fluid-attenuated inversion recovery MRI with 87.5 % vs. 87.1 %, but the positive predictive value was higher in susceptibility-weighted 3-T MRI (86.0 %) than in the other MRI sequences. CONCLUSIONS: The susceptibility-weighted 3-T MRI-based subthalamic nucleus localization shows the best accuracy compared with T2-weighted and fluid-attenuated inversion recovery 3-T MRI. Therefore, the susceptibility-weighted 3-T MRI should be preferred for surgical planning when the operation procedure is performed under general anesthesia without microelectrode recordings.

The perioperative course of factor XIII and associated chest tube drainage in newborn and infants undergoing cardiac surgery.

BACKGROUND: Perioperative acquired factor XIII deficiency has been looked upon as a potential cause of postoperative bleeding in adult cardiac surgery. METHODS: Forty-four infants were prospectively studied for the time course of factor XIII in plasma and the effect on chest tube drainage (CTD) and transfusion requirements in the first 24 h after surgery. A reconstituted blood prime (RBP) with fresh-frozen plasma (FFP) and packed red blood cells (PRBC) was used. Samples were taken at baseline, after cardiopulmonary bypass and upon arrival in the ICU. Differences in blood loss and transfusion requirements based on a cutoff value of 70% factor XIII activity at the time of ICU admission were also calculated. RESULTS: Baseline factor XIII activity was 79%, decreased to 71% after CPB (P = 0.102) and increased back up to 77% at ICU arrival (P = 0.708). There was no significant correlation between factor XIII, CTD, age, cyanosis, platelet count, and transfusion requirements at any time point. Only preoperative fibrinogen levels correlated significantly with factor XIII activity. Perioperative blood transfusions (PRBC P = 0.712, FFP P = 0.909, platelets P = 0.807) and chest tube losses (P = 0.424 at 6 h and P = 0.215 at 24 h) were not significantly different above or below a 70% factor XIII activity at ICU arrival. CONCLUSION: Factor XIII activity in infants with congenital heart defects is within the lower range of normal adults, independent of patient's age and the presence of cyanosis. Reconstituted blood prime maintains factor XIII activity at sufficient levels during pediatric cardiac surgery. We could not detect a correlation between FXIII and CTD.

Synchronous Urinary Bladder Urothelial Carcinoma and Transitional Cell Carcinoma of the Ovary: A Case Report.

Transitional cell carcinoma (TCC) of the ovary is a rare subtype of epithelial ovarian tumours defined as a tumour composed of epithelial elements, histologically resembling urothelium and its neoplasms. Ovarian metastases from primary urinary tract carcinomas are rare. The differential diagnosis of primary TCC of the ovary versus metastatic bladder TCC is challenging because of histological similarity. We present the case of a 49-year-old premenopausal woman who was initially diagnosed with non-invasive papillary urothelial carcinoma of bladder (NIPUC) and after 2 years with a synchronous TCC of the ovary while being investigated for suspected relapse. She underwent a radical cystectomy, total hysterectomy, bilateral salpingo-oopharectomy, and pelvic lymph node dissection. The final diagnosis of synchronous NIPUC of the bladder and TCC of the ovary was made by histopathology and immunohistochemical studies.

Intraplacental Choriocarcinoma in Twin Pregnancy Causing Fetomaternal Haemorrhage and Single Twin Demise: Case Report.

Gestational choriocarcinoma is a rare aggressive form of gestational trophoblastic neoplasia. In cases of intraplacental choriocarcinoma, the tumour is confined to the placenta. Intraplacental choriocarcinoma in twin pregnancies is a very rare occurrence with less than 5 previously reported cases in the literature. In this case, a 34-year-old primiparous woman, pregnant with dichorionic diamniotic twins, underwent an emergency caesarean section for fetal distress at 35 weeks gestation after presenting in preterm labour. Twin A was delivered with no signs of life. The demise was attributed to fetomaternal haemorrhage (FMH) secondary to intraplacental choriocarcinoma. The mother's HCG normalised quickly postpartum with no radiological signs of metastatic disease. She has been managed conservatively with monthly HCG surveillance with no signs of recurrence. Twin B remains well with negative HCG surveillance. Although gestational choriocarcinoma can be aggressive and associated with poor obstetric outcomes, it has a good prognosis when diagnosed and treated early. The importance of detailed histopathological placental examination and clinical suspicion for choriocarcinoma following FMH is highlighted by this case.

Neither moxifloxacin nor cefuroxime produces significant attenuation of inflammatory mediator release in patients exposed to cardiopulmonary bypass: a randomized controlled trial.

OBJECTIVES: In vitro and experimental studies in animals have established the anti-inflammatory effects of moxifloxacin. Cardiopulmonary bypass (CPB) leads to an inflammatory response. The aim of this study was to assess whether the inflammatory cytokine response to CPB is reduced with a perioperative antibiotic prophylaxis, either moxifloxacin or cefuroxime (the standard prophylaxis). PATIENTS AND METHODS: Twenty-eight patients scheduled for elective coronary artery bypass grafting with CPB were randomly assigned to receive either moxifloxacin or cefuroxime as the perioperative antibiotic prophylaxis. Interleukin (IL)-6, -8, -10 and tumour necrosis factor-α (TNF-α) serum concentrations were determined at eight time points before and after CPB. RESULTS: In both groups, all cytokine concentrations significantly increased after the start of CPB. There were no statistically significant differences between the moxifloxacin and cefuroxime groups at any point; IL-6 concentrations [median (interquartile range)] 240 min after CPB, the primary endpoint, were 364 (192-598) and 465 (325-906) pg/mL (P = 0.323), respectively. CONCLUSIONS: Neither moxifloxacin nor cefuroxime produced significant attenuation of the inflammatory cytokine response to CPB. The reasons why moxifloxacin did not have significant anti-inflammatory effects in this unique clinical situation may be: (i) the inflammatory response to CPB may be different from that of infectious disease states that were used to establish the immunomodulatory effects of moxifloxacin; and (ii) a single intravenous dose, which was used in this investigation, may not lead to high enough plasma and intracellular concentrations.

Diffuse Peritoneal Malignant Mesothelioma Presenting with Abnormal Uterine Bleeding: Case Report.

This report describes a highly unusual case of malignant peritoneal mesothelioma (MPM), who presented with abnormal menstrual bleeding due to diffuse infiltration of the uterus. MPM is a rare entity, which on initial clinical presentation can be indistinguishable from a primary gynecological malignancy such as ovarian cancer. As differential diagnosis is challenging among primary care physicians, gynecologists, gynecological oncologists, and pathologists, misdiagnosis and subsequent mismanagement are not uncommon. Immunohistochemical stains were required in our case to help to make the final diagnosis. We included multiple mesothelial markers such as calretinin, CK5/6, WT-1, and D240 in our analysis, in addition to epithelial markers such as Claudin-4, BerEP4, B72.3, and PAX-8, to exclude metastatic adenocarcinoma.

Are the point-of-care diagnostics MULTIPLATE and ROTEM valid in the setting of high concentrations of heparin and its reversal with protamine?

OBJECTIVES: To evaluate the in vitro effects of high concentrations of heparin and its reversal with protamine on routine laboratory parameters as well as on modified thromboelastogram (ROTEM; TEM International, Munich, Germany) and impedance aggregometry (MULTIPLATE; Dynabyte, Munich, Germany). DESIGN: An observational, nonrandomized in vitro study. SETTING: A single-center, university hospital. PARTICIPANTS: Ten healthy volunteers. INTERVENTIONS: Heparinization of whole blood to levels of 2, 4, 6, and 8 IU/mL of heparin and reversal with protamine. For MULTIPLATE measurements, heparin levels up to 20 IU/mL were tested. MEASUREMENTS AND MAIN RESULTS: The present results show that the prothrombin time (PT) and fibrinogen measurements are altered significantly by heparin concentrations above 2 IU/mL. Protamine reversal also affected coagulation tests except for the fibrinogen. The INTEM test using the ROTEM system was influenced significantly by heparin concentrations of 2 IU/mL or higher, whereas EXTEM measurements remained stable up to 4 IU/mL. The findings for the FIBTEM test were stable up to 6 IU/mL but then declined to values less than 50% of baseline at 8 IU/mL. HEPTEM results remained valid under all concentrations of heparin tested. The effect of protamine on ROTEM was seen mainly in the INTEM and HEPTEM measurements. Heparin concentrations up to a level of 20 U/mL had no effect on MULTIPLATE measurements. Effects of protamine on MULTIPLATE became significant at heparin-to-protamine ratios below 1:1 and were more pronounced for adenosine diphosphate than for thrombin receptor-activated protein testing. CONCLUSIONS: Neither fibrinogen (Clauss) nor derived fibrinogen or FIBTEM testing is valid in the setting of high concentrations of heparin unless antagonized by heparinase. Reversal of heparin with protamine worsens platelet function at all ratios as detected by aggregometry (MULTIPLATE) and thromboelastography (ROTEM), starting at a 1:1 ratio. Therefore, appropriate coagulation testing under cardiopulmonary bypass conditions should be selected carefully according to heparin levels. In particular, fibrinogen values are falsely low at heparin levels of 2 IU/mL and above. Therefore, newer algorithms promoting the correction of fibrinogen levels on cardiopulmonary bypass should be based on appropriate testing.

Seizures after open heart surgery: comparison of ε-aminocaproic acid and tranexamic acid.

OBJECTIVE: Although the lysine analogs tranexamic acid (TXA) and aminocaproic acid (EACA) are used widely for antifibrinolytic therapy in cardiac surgery, relatively little research has been performed on their safety profiles, especially in the setting of cardiac surgery. Two antifibrinolytic protocols using either TXA or aminocaproic acid were compared according to postoperative outcome. DESIGN: A retrospective analysis. SETTING: A university-affiliated hospital. PARTICIPANTS: Six hundred four patients undergoing cardiac surgery. INTERVENTIONS: One cohort of 275 consecutive patients received TXA; a second cohort of 329 consecutive patients was treated with EACA. Except for antifibrinolytic therapy, the anesthetic and surgical teams and their protocols remained unchanged. MEASUREMENTS AND MAIN RESULTS: Besides major outcome criteria, namely postoperative bleeding, the need for allogeneic transfusions, operative revision because of bleeding, postoperative renal dysfunction, neurologic events, heart failure, and in-hospital mortality, the authors specifically sought differences between the groups concerning seizures. The 2 cohorts were comparable over a range of perioperative factors. Postoperative seizures occurred significantly more frequently in TXA patients (7.6% v 3.3%, p = 0.019), whereas EACA patients had a higher incidence of postoperative renal dysfunction (20.0% v 30.1%, p = 0.005). There were no differences in all other measured major outcome factors. CONCLUSION: Both lysine analogs are associated with significant side effects, which must be taken into account when performing risk-benefit analyses of their use. Their use should be restricted to patients at high risk for bleeding; routine use on low-risk patients undergoing standard surgeries should face renewed critical reappraisal.

The Superficial Anastomosing Veins of the Human Brain Cortex: A Microneurosurgical Anatomical Study.

Introduction: In this microneurosurgical and anatomical study, we characterized the superficial anastomosing veins of the human brain cortex in human specimens. Material and Methods: We used 21 brain preparations fixed in formalin (5%) that showed no pathological changes and came from the autopsy sections. The superficial veins were dissected out of the arachnoid with the aid of a surgical microscope. Results: We dissected nine female and 12 male brain specimens, with an average age of 71 ± 11 years (range 51-88 years). We classified the superficial veins in five types: (I) the vein of Trolard as the dominat vein; (II) the vein of Labbé as the dominant vein; (III) a dominant sylvian vein group, and the veins of Trolard and Labbé nonexistent or only rudimentary present without contact to the Sylvian vein group; (IV) very weak sylvian veins with the veins of Trolard and Labbé codominant; and V) direct connection of Trolard and Labbé bypassing the Sylvian vein group. The vein of Trolard was dominant (Type I) in 21.4% and the vein of Labbé (Type II) in 16.7%. A dominant sylvian vein group (Type III) was found in 42.9%. Type IV and Type V were found in 14.3 and 4.7% respectively. Conclusion: No systematic description or numerical distribution of the superior anastomotic vein (V. Trolard) and inferior anastomotic vein (V. Labbé) has been found in the existing literature. This study aimed to fill this gap in current literature and provide data to neurosurgeons for the practical planning of surgical approaches.

Is major burn injury associated with coagulopathy? The value of thrombelastometry in the detection of coagulopathy in major burn injury: A prospective observational study.

BACKGRUND: The coagulation status of burn patients is generally impaired and is a major factor of the deteriorating burn patients' overall situation. In trauma and other patient groups, the differential diagnosis of coagulation impairment has been largely improved by the use of rotational thromboelastometry (ROTEM®). The aim of this prospective observational study was the differentiated observation of coagulopathy in severely burned patients using standard parameters and ROTEM® thrombelastometry during the relevant stages of burn disease. PATIENTS AND METHODS: Twelve patients that sustained at least 20% third degree burns of total body surface area (TBSA) were included in the study. Standard and ROTEM® coagulation analyses were performed on admission and then twice daily during the first 14 days following burn trauma. RESULTS: Although the initial assessment of DIC was similar for both standard labs and ROTEM® measurements, more patients were detected to be in a state of worsening coagulation status for a longer time in ROTEM® than in standard measurements. In addition, one patient was rated in to be in decompensated DIC for 3 days according to ROTEM® measurements, while no patient was rated to be in a decompensated DIC based on standard parameters. CONCLUSION: This study points towards a more complex picture and higher occurrence of DIC in burn patients when thrombelastometric measurements like ROTEM® are taken into account in addition to standard coagulation parameters.

Targeted in-vitro-stimulation reveals highly proliferative multi-virus-specific human central memory T cells as candidates for prophylactic T cell therapy.

Adoptive T cell therapy (ACT) has become a treatment option for viral reactivations in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). Animal models have shown that pathogen-specific central memory T cells (TCM) are protective even at low numbers and show long-term survival, extensive proliferation and high plasticity after adoptive transfer. Concomitantly, our own recent clinical data demonstrate that minimal doses of purified (not in-vitro- expanded) human CMV epitope-specific T cells can be sufficient to clear viremia. However, it remains to be determined if human virus-specific TCM show the same promising features for ACT as their murine counterparts. Using a peptide specific proliferation assay (PSPA) we studied the human Adenovirus- (AdV), Cytomegalovirus- (CMV) and Epstein-Barr virus- (EBV) specific TCM repertoires and determined their functional and proliferative capacities in vitro. TCM products were generated from buffy coats, as well as from non-mobilized and mobilized apheresis products either by flow cytometry-based cell sorting or magnetic cell enrichment using reversible Fab-Streptamers. Adjusted to virus serology and human leukocyte antigen (HLA)-typing, donor samples were analyzed with MHC multimer- and intracellular cytokine staining (ICS) before and after PSPA. TCM cultures showed strong proliferation of a plethora of functional virus-specific T cells. Using PSPA, we could unveil tiniest virus epitope-specific TCM populations, which had remained undetectable in conventional ex-vivo-staining. Furthermore, we could confirm these characteristics for mobilized apheresis- and GMP-grade Fab-Streptamer-purified TCM products. Consequently, we conclude that TCM bare high potential for prophylactic low-dose ACT. In addition, use of Fab-Streptamer-purified TCM allows circumventing regulatory restrictions typically found in conventional ACT product generation. These GMP-compatible TCM can now be used as a broad-spectrum antiviral T cell prophylaxis in alloHSCT patients and PSPA is going to be an indispensable tool for advanced TCM characterization during concomitant immune monitoring.

The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients.

BACKGROUND: Our aim was to investigate postoperative complications and mortality after administration of aprotinin compared to tranexamic acid in an unselected, consecutive cohort. METHODS: Perioperative data from consecutive cardiac surgery patients were prospectively collected between September 2005 and June 2006 in a university-affiliated clinic (n = 1188). During the first 5 mo, 596 patients received aprotinin (Group A); in the next 5 mo, 592 patients were treated with tranexamic acid (Group T). Except for antifibrinolytic therapy, the anesthetic and surgical protocols remained unchanged. RESULTS: The pre- and intraoperative variables were comparable between the treatment groups. Postoperatively, a significantly higher incidence of seizures was found in Group T (4.6% vs 1.2%, P < 0.001). This difference was also significant in the primary valve surgery and the high risk surgery subgroups (7.9% vs 1.2%, P = 0.003; 7.3% vs 2.4%, P = 0.035, respectively). Persistent atrial fibrillation (7.9% vs 2.3%, P = 0.020) and renal failure (9.7% vs 1.7%, P = 0.002) were also more common in Group T, in the primary valve surgery subgroup. On the contrary, among primary coronary artery bypass surgery patients, there were more acute myocardial infarctions and renal dysfunction in Group A (5.8% vs 2.0%, P = 0.027; 22.5% vs 15.2%, P = 0.036, respectively). The 1-yr mortality was significantly higher after aprotinin treatment in the high risk surgery group (17.7% vs 9.8%, P = 0.034). CONCLUSION: Both antifibrinolytic drugs bear the risk of adverse outcome depending on the type of cardiac surgery. Administration of aprotinin should be avoided in coronary artery bypass graft and high risk patients, whereas administration of tranexamic acid is not recommended in valve surgery.

Restoration of ankle movements with the ActiGait implantable drop foot stimulator: a safe and reliable treatment option for permanent central leg palsy.

OBJECT The ActiGait drop foot stimulator is a promising technique for restoration of lost ankle function by an implantable hybrid stimulation system. It allows ankle dorsiflexion by active peroneal nerve stimulation during the swing phase of gait. In this paper the authors report the outcome of the first prospective study on a large number of patients with stroke-related drop foot. METHODS Twenty-seven patients who experienced a stroke and with persisting spastic leg paresis received an implantable ActiGait drop foot stimulator for restoration of ankle movement after successful surface test stimulation. After 3 to 5 weeks, the stimulator was activated, and gait speed, gait endurance, and activation time of the system were evaluated and compared with preoperative gait tests. In addition, patient satisfaction was assessed using a questionnaire. RESULTS Postoperative gait speed significantly improved from 33.9 seconds per 20 meters to 17.9 seconds per 20 meters (p < 0.0001), gait endurance from 196 meters in 6 minutes to 401 meters in 6 minutes (p < 0.0001), and activation time from 20.5 seconds to 10.6 seconds on average (p < 0.0001). In 2 patients with nerve injury, surgical repositioning of the electrode cuff became necessary. One patient showed a delayed wound healing, and in another patient the system had to be removed because of a wound infection. Marked improvement in mobility, social participation, and quality of life was confirmed by 89% to 96% of patients. CONCLUSIONS The ActiGait implantable drop foot stimulator improves gait speed, endurance, and quality of life in patients with stroke-related drop foot. Regarding gait speed, the ActiGait system appears to be advantageous compared with foot orthosis or surface stimulation devices. Randomized trials with more patients and longer observation periods are needed to prove the long-term benefit of this device.

Sedation or general anesthesia for transcatheter aortic valve implantation (TAVI).

Transfemoral transcatheter aortic valve implantation (TAVI) is nowadays a routine therapy for elderly patients with severe aortic stenosis (AS) and high perioperative risk. With growing experience, further development of the devices, and the expansion to "intermediate-risk" patients, there is increasing interest in performing this procedure under conscious sedation (TAVI-S) rather than the previously favoured approach of general anesthesia (TAVI-GA). The proposed benefits of TAVI-S include; reduced procedure time, shorter intensive care unit (ICU) length of stay, reduced need for intraprocedural vasopressor support, and the potential to perform the procedure without the direct presence of an anesthetist for cost-saving reasons. To date, no randomized trial data exists. We reviewed 13 non-randomized studies/registries reporting data from 6,718 patients undergoing TAVI (3,227 performed under sedation). Patient selection, study methods, and endpoints have differed considerably between published studies. Reported rates of in-hospital and longer-term mortality are similar for both groups. Up to 17% of patients undergoing TAVI-S require conversion to general anesthesia during the procedure, primarily due to vascular complications, and urgent intubation is frequently associated with hemodynamic instability. Procedure related factors, including hypotension, may compound preexisting age-specific renal impairment and enhance the risk of acute kidney injury. Hypotonia of the hypopharyngeal muscles in elderly patients, intraprocedural hypercarbia, and certain anesthetic drugs, may increase the aspiration risk in sedated patients. General anesthesia and conscious sedation have both been used successfully to treat patients with severe AS undergoing TAVI with similar reported short and long-term mortality outcomes. The authors believe that the significant incidence of complications and unplanned conversion to general anesthesia during TAVI-S mandates the start-to-finish presence of an experienced cardiac anesthetist in order to optimize patient outcomes. Good quality randomized data is needed to determine the optimal anesthetic regimen for patients undergoing TAVI.

The effect of cyanosis on perioperative platelet function as measured by multiple electrode aggregometry and postoperative blood loss in neonates and infants undergoing cardiac surgery.

OBJECTIVES: Platelet dysfunction is one of the major haematological disturbances of cardiopulmonary bypass (CPB). In addition, cyanosis is known to cause further coagulation disturbances. METHODS: We prospectively studied 110 children under 1 year of age for the effects of cyanosis on baseline platelet aggregation, the time course of function on cardiopulmonary bypass, the effect on chest tube drainage (CTD) and the transfusion requirements. Using multiple electrode aggregometry (MULTIPLATE™) with the activators adenosine diphosphate (ADP) and thrombin-related activation peptide (TRAP), platelet aggregation was assessed and examined for predictive value. RESULTS: Neonates under 30 days of age (n = 51) and infants (n = 59) were separated for analysis. Cyanosis had no significant effect on platelet function during the first 24 h after surgery. Similarly, there was no association to perioperative platelet function, CTD or exposures to blood products. ADP after protamine correlated significantly with the total number of exposures for neonates and infants and CTD at 6 h in the newborn group. Upon intensive care unit admission, ADP values correlated to the total number of exposures to blood products. No other platelet function value was able to clinically predict CTD or subsequent blood transfusion requirements. CONCLUSIONS: In our study population, we observed no clinically significant effect of cyanosis on baseline and the perioperative course of platelet function, CTD and the number of exposures to blood products. Therefore, children under 1 year of age do not require a different approach with regard to platelet transfusions, independent of cyanosis. Clinically, platelet function was not a reliable predictor of CTD or blood transfusion requirements.