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.

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.

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.

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.

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.

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.

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 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 .

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.

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 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.

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.

Serum concentrations and pharmacokinetics of moxifloxacin in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass.

Although cephalosporins are recommended as primary agents, moxifloxacin may be a suitable second-line antibiotic in cardiac surgery, especially if additional Gram-negative coverage is warranted. Cardiopulmonary bypass (CPB) may alter the pharmacokinetics of drugs in numerous ways. Since no such data exist, the aim of this study was to assess the serum concentrations and pharmacokinetics of moxifloxacin in patients undergoing cardiac surgery with CPB. Fourteen coronary artery bypass graft surgery patients received an intravenous infusion of 400 mg moxifloxacin as peri-operative antibiotic prophylaxis. At 15 time points throughout a 24-h period, serum samples were obtained to measure moxifloxacin concentrations using high-performance liquid chromatography. In addition, a non-compartmental pharmacokinetic analysis, i.e. area under the concentration-time curve (AUC), volume of distribution at steady state (V(SS)), drug clearance (CL), elimination half-life (t(1/2)) and mean residence time (MRT), was performed in five patients. Apart from a slight transient decrease in moxifloxacin concentration at the onset, CPB did not affect the concentration-time curve. Mean ± standard deviation maximum drug concentration (C(max)) (5.12 ± 1.58 µg/mL), AUC (36.5 ± 5.40 µgh/mL), VSS (2.03 ± 0.30 L/kg), CL (11.2 ± 1.91 L/h), t(1/2) (9.47 ± 0.92 h) and MRT (12.9 ± 1.52 h) were comparable with historical data for healthy volunteers. We conclude that CPB does not alter the pharmacokinetics of moxifloxacin. No dose adjustments, especially with regard to the CPB circuit and its priming volume, are necessary in cardiac surgical patients.

Use of automated external defibrillators in the occupational setting in Germany: a pilot study.

OBJECTIVE: Automated external defibrillators (AEDs) are widely used to increase survival of patients with sudden cardiac arrest (SCA). Despite these experiences only few data exist dealing with SCA at the workplace or AED usage in the occupational setting. METHODS: In a pilot study, occupational physicians throughout Germany were contacted and queried about the utilization of AED and the primary success rate (return of spontaneous circulation; ROSC). RESULTS: Of 232 occupational physicians, 155 (67%) stated that the enterprise provided at least one AED. Overall, 63 AED utilizations were analyzed. An ROSC was reported in 42 patients (67%). In 48% (n = 20) ROSC was established before the arrival of the EMS. CONCLUSION: Our study showed a high proportion of patients with ROSC after SCA. Increased attention should be turned to workplace SCA and AED programs.

Two consecutive open heart operations in a small child with heparin-induced thrombocytopenia type II using anticoagulation with heparin and tirofiban.

We report the use of the platelet glycoprotein IIb/IIIa antagonist tirofiban for cardiac surgery in a small child with active heparin-induced thrombocytopenia type II, including description of the postoperative course.

Novel serial positive enrichment technology enables clinical multiparameter cell sorting.

A general obstacle for clinical cell preparations is limited purity, which causes variability in the quality and potency of cell products and might be responsible for negative side effects due to unwanted contaminants. Highly pure populations can be obtained best using positive selection techniques. However, in many cases target cell populations need to be segregated from other cells by combinations of multiple markers, which is still difficult to achieve--especially for clinical cell products. Therefore, we have generated low-affinity antibody-derived Fab-fragments, which stain like parental antibodies when multimerized via Strep-tag and Strep-Tactin, but can subsequently be removed entirely from the target cell population. Such reagents can be generated for virtually any antigen and can be used for sequential positive enrichment steps via paramagnetic beads. First protocols for multiparameter enrichment of two clinically relevant cell populations, CD4(high)/CD25(high)/CD45RA(high) 'regulatory T cells' and CD8(high)/CD62L(high)/CD45RA(neg) 'central memory T cells', have been established to determine quality and efficacy parameters of this novel technology, which should have broad applicability for clinical cell sorting as well as basic research.