Inflammation induces hemorrhage in thrombocytopenia

The role of platelets in hemostasis is to produce a plug to arrest bleeding. During thrombocytopenia, spontaneous bleeding is seen in some patients but not in others; the reason for this is unknown. Here, we subjected thrombocytopenic mice to models of dermatitis, stroke, and lung inflammation. The mice showed massive hemorrhage that was limited to the area of inflammation and was not observed in uninflamed thrombocytopenic mice. Endotoxin-induced lung inflammation during thrombocytopenia triggered substantial intra-alveolar hemorrhage leading to profound anemia and respiratory distress. By imaging the cutaneous Arthus reaction through a skin window, we observed in real time the loss of vascular integrity and the kinetics of skin hemorrhage in thrombocytopenic mice. Bleeding-observed mostly from venules-occurred as early as 20 minutes after challenge, pointing to a continuous need for platelets to maintain vascular integrity in inflamed microcirculation. Inflammatory hemorrhage was not seen in genetically engineered mice lacking major platelet adhesion receptors or their activators (alphaIIbbeta3, glycoprotein Ibalpha [GPIbalpha], GPVI, and calcium and diacylglycerol-regulated guanine nucleotide exchange factor I [CalDAG-GEFI]), thus indicating that firm platelet adhesion was not necessary for their supporting role. While platelets were previously shown to promote endothelial activation and recruitment of inflammatory cells, they also appear indispensable to maintain vascular integrity in inflamed tissue. Based on our observations, we propose that inflammation may cause life-threatening hemorrhage during thrombocytopenia.

Microcirculatory parameters after isotonic and hypertonic colloidal fluid resuscitation in acute hemorrhagic shock

BACKGROUND: Volume resuscitation is one of the primary therapeutic goals in hemorrhagic shock, but data on microcirculatory effects of different colloidal fluid resuscitation regimen are sparse. We investigated sublingual mucosal microcirculatory parameters during hemorrhage and after fluid resuscitation with gelatin, hydroxyethyl starch, or hypertonic saline and hydroxyethyl starch in pigs. METHODS: To induce hemorrhagic shock, 60% of calculated blood volume was withdrawn. Microvascular blood flow was assessed by laser Doppler velocimetry. Microcirculatory hemoglobin oxygen saturation was measured with a tissue reflectance spectrophotometry, and side darkfield imaging was used to visualize the microcirculation and to quantify the flow quality. Systemic hemodynamic variables, systemic acid base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after hemorrhage, and after fluid resuscitation with a fixed volume regimen. RESULTS: Systemic hemodynamic parameters returned or even exceeded to baseline values in all three groups after fluid resuscitation, but showed significantly higher filling pressures and cardiac output values in animals treated with isotonic colloids. Microcirculatory parameters determined in gelatin and hydroxyethyl starch resuscitated animals, and almost all parameters except microvascular hemoglobin oxygen saturation in animals treated with hypertonic saline and hydroxyethyl starch, were restored after treatment. DISCUSSION: Hemorrhaged pigs can be hemodynamically stabilized with either isotonic or hypertonic colloidal fluids. The main finding is an adequate restoration of sublingual microcirculatory blood flow and flow quality in all three study groups, but only gelatin and hydroxyethyl starch improved microvascular hemoglobin oxygen saturation, indicating some inadequate oxygen supply/demand ratio maybe due to a better restoration of systemic hemodynamics in isotonic colloidal resuscitated animals.

Aseptic intussuscepted incidental appendectomy: three successful cases

BACKGROUND: Incidental appendectomy remains a controversial issue. We aimed to collect experience using a modified surgical technique that could be applied securely in infants. METHODS: We performed aseptic intussuscepted incidental appendectomy (AIIA) in three patients using a technique that is thought to assure appendix necrosis along with intact cecal wall. RESULTS: There was no perioperative morbidity due to AIIA in the three patients. In two infants the necrotic appendix was found in the diaper. One infant died secondary to diaphragmatic hernia. Autopsy with histological examination revealed that the cecum was intact along with appendix necrosis. CONCLUSIONS: Modified AIIA could securely be performed in the 3 reported cases. We advocate prospective evaluation of the method.

Effect of phrenic nerve palsy on early postoperative lung function after pneumonectomy: a prospective study

BACKGROUND The issue of phrenic nerve preservation during pneumonectomy is still an unanswered question. So far, its direct effect on immediate postoperative pulmonary lung function has never been evaluated in a prospective trial. METHODS We conducted a prospective crossover study including 10 patients undergoing pneumonectomy for lung cancer between July 2011 and July 2012. After written informed consent, all consecutive patients who agreed to take part in the study and in whom preservation of the phrenic nerve during operation was possible, were included in the study. Upon completion of lung resection, a catheter was placed in the proximal paraphrenic tissue on the pericardial surface. After an initial phase of recovery of 5 days all patients underwent ultrasonographic assessment of diaphragmatic motion followed by lung function testing with and without induced phrenic nerve palsy. The controlled, temporary paralysis of the ipsilateral hemidiaphragm was achieved by local administration of lidocaine 1% at a rate of 3 mL/h (30 mg/h) via the above-mentioned catheter. RESULTS Temporary phrenic nerve palsy was accomplished in all but 1 patient with suspected catheter dislocation. Spirometry showed a significant decrease in dynamic lung volumes (forced expiratory volume in 1 second and forced vital capacity; p < 0.05) with the paralyzed hemidiaphragm. Blood oxygen saturation levels did not change significantly. CONCLUSIONS Our results show that phrenic nerve palsy causes a significant impairment of dynamic lung volumes during the early postoperative period after pneumonectomy. Therefore, in these already compromised patients, intraoperative phrenic nerve injury should be avoided whenever possible.

Living Renal Allograft Transplantation: Diffusion-weighted MR Imaging in Longitudinal Follow-up of the Donated and the Remaining Kidney.

Purpose To determine whether diffusion-weighted (DW) magnetic resonance (MR) imaging in living renal allograft donation allows monitoring of potential changes in the nontransplanted remaining kidney of the donor because of unilateral nephrectomy and changes in the transplanted kidney before and after transplantation in donor and recipient, respectively, and whether DW MR parameters are correlated in the same kidney before and after transplantation. Materials and Methods The study protocol was approved by the local ethics committee; written informed consent was obtained. Thirteen healthy kidney donors and their corresponding recipients prospectively underwent DW MR imaging (multiple b values) in donors before donation and in donors and recipients at day 8 and months 3 and 12 after donation. Total apparent diffusion coefficient (ADCT) values were determined; contribution of microcirculation was quantified in perfusion fraction (FP). Longitudinal changes of diffusion parameters were compared (repeated-measures one-way analysis of variance with post hoc pairwise comparisons). Correlations were tested (linear regression). Results ADCT values in nontransplanted kidney of donors increased from a preexplantation value of (188 ± 9 [standard deviation]) to (202 ± 11) × 10(-5) mm(2)/sec in medulla and from (199 ± 11) to (210 ± 13) × 10(-5) mm(2)/sec in cortex 1 week after donation (P < .004). Medullary, but not cortical, ADCT values stayed increased up to 1 year. ADCT values in allografts in recipients were stable. Compared with values obtained before transplantation in donors, the corticomedullary difference was reduced in allografts (P < .03). Cortical ADCT values correlated with estimated glomerular filtration rate in recipients (R = 0.56, P < .001) but not donors. Cortical ADCT values in the same kidney before transplantation in donors correlated with those in recipients on day 8 after transplantation (R = 0.77, P = .006). FP did not show significant changes. Conclusion DW MR imaging depicts early adaptations in the remaining nontransplanted kidney of donors after nephrectomy. All diffusion parameters remained constant in allograft recipients after transplantation. This method has potential monitoring utility, although assessment of clinical relevance is needed. © RSNA, 2013 Online supplemental material is available for this article.

Acute effects of stochastic resonance whole body vibration

AIM: To investigate the acute effects of stochastic resonance whole body vibration (SR-WBV) training to identify possible explanations for preventive effects against musculoskeletal disorders. METHODS: Twenty-three healthy, female students participated in this quasi-experimental pilot study. Acute physiological and psychological effects of SR-WBV training were examined using electromyography of descending trapezius (TD) muscle, heart rate variability (HRV), different skin parameters (temperature, redness and blood flow) and self-report questionnaires. All subjects conducted a sham SR-WBV training at a low intensity (2 Hz with noise level 0) and a verum SR-WBV training at a higher intensity (6 Hz with noise level 4). They were tested before, during and after the training. Conclusions were drawn on the basis of analysis of variance. RESULTS: Twenty-three healthy, female students participated in this study (age = 22.4 ± 2.1 years; body mass index = 21.6 ± 2.2 kg/m2). Muscular activity of the TD and energy expenditure rose during verum SR-WBV compared to baseline and sham SR-WBV (all P < 0.05). Muscular relaxation after verum SR-WBV was higher than at baseline and after sham SR-WBV (all P < 0.05). During verum SR-WBV the levels of HRV were similar to those observed during sham SR-WBV. The same applies for most of the skin characteristics, while microcirculation of the skin of the middle back was higher during verum compared to sham SR-WBV (P < 0.001). Skin redness showed significant changes over the three measurement points only in the middle back area (P = 0.022). There was a significant rise from baseline to verum SR-WBV (0.86 ± 0.25 perfusion units; P = 0.008). The self-reported chronic pain grade indicators of pain, stiffness, well-being, and muscle relaxation showed a mixed pattern across conditions. Muscle and joint stiffness (P = 0.018) and muscular relaxation did significantly change from baseline to different conditions of SR-WBV (P < 0.001). Moreover, muscle relaxation after verum SR-WBV was higher than after sham SR-WBV (P < 0.05). CONCLUSION: Verum SR-WBV stimulated musculoskeletal activity in young healthy individuals while cardiovascular activation was low. Training of musculoskeletal capacity and immediate increase in musculoskeletal relaxation are potential mediators of pain reduction in preventive trials.

Re-thinking resuscitation: leaving blood pressure cosmetics behind and moving forward to permissive hypotension and a tissue perfusion-based approach

Definitions of shock and resuscitation endpoints traditionally focus on blood pressures and cardiac output. This carries a high risk of overemphasizing systemic hemodynamics at the cost of tissue perfusion. In line with novel shock definitions and evidence of the lack of a correlation between macro- and microcirculation in shock, we recommend that macrocirculatory resuscitation endpoints, particularly arterial and central venous pressure as well as cardiac output, be reconsidered. In this viewpoint article, we propose a three-step approach of resuscitation endpoints in shock of all origins. This approach targets only a minimum individual and context-sensitive mean arterial blood pressure (for example, 45 to 50 mm Hg) to preserve heart and brain perfusion. Further resuscitation is exclusively guided by endpoints of tissue perfusion irrespectively of the presence of arterial hypotension ('permissive hypotension'). Finally, optimization of individual tissue (for example, renal) perfusion is targeted. Prospective clinical studies are necessary to confirm the postulated benefits of targeting these resuscitation endpoints.

Relative indexes of cutaneous blood perfusion measured by real-time laser Doppler imaging (LDI) in healthy volunteers.

We used real-time LDI to study regional variations in microcirculatory perfusion in healthy candidates to establish a new methodology for global perfusion body mapping that is based on intra-individual perfusion index ratios. Our study included 74 (37 female) healthy volunteers aged between 22 and 30 years (mean 24.49). Imaging was performed using a recent microcirculation-imaging camera (EasyLDI) for different body regions of each volunteer. The perfusion values were reported in Arbitrary Perfusion Units (APU). The relative perfusion indexes for each candidate's body region were then obtained by normalization with the perfusion value of the forehead. Basic parameters such as weight, height, and blood pressure were also measured and analyzed. The highest mean perfusion value was reported in the forehead area (259.21APU). Mean perfusion in the measured parts of the body correlated positively with mean forehead value, while there was no significant correlation between forehead blood perfusion values and room temperature, BMI, systolic blood pressure and diastolic blood pressure (p=0.420, 0.623, 0.488, 0.099, respectively). Analysis of the data showed that perfusion indexes were not significantly different between male and female volunteers except for the ventral upper arm area (p=.001). LDI is a non-invasive, fast technique that opens several avenues for clinical applications. The mean perfusion indexes are useful in clinical practice for monitoring patients before and after surgical interventions. Perfusion values can be predicted for different body parts for patients only by taking the forehead perfusion value and using the perfusion index ratios to obtain expected normative perfusion values.

Transdiaphragmatic Resuscitative Open Cardiac Massage: Description of the Technique and a First Case-Series of an Alternative Approach to the Heart

Abstract BACKGROUND: The purpose of this paper is to describe the transdiaphragmatic approach to the heart for open CPR in patients that arrest at laparotomy and to present a first case series of patients that have undergone this procedure. METHODS: All patients who had undergone intraperitoneal transdiaphragmatic open CPR between January 1, 2002 and December 31, 2012 were retrieved from the operation registry at Bern University Hospital, Switzerland. Transdiaphragmatic access to the heart is initiated with a 10-cm-long anterocaudal incision in the central tendon of the diaphragm--approximately at 2 o'clock. Internal cardiac compression through the diaphragmatic incision can be performed from both sides of the patient. From the right side of the patient, cardiac massage is performed with the right hand and vice versa. RESULTS: A total of six patients were identified that suffered cardiac arrest during laparotomy with open CPR performed through the transdiaphragmatic approach. Four patients suffered cardiac arrest during orthotopic liver transplantation and two trauma patients suffered cardiac arrest during damage control laparotomy. In three patients, cardiac activity was never reestablished. However, three patients regained a perfusion heart rhythm and two of these survived to the ICU. One patient ultimately survived to discharge. CONCLUSIONS: In patients suffering cardiac arrest during laparotomy, the transdiaphragmatic approach allows for a rapid, technically easy, and almost atraumatic access to the heart, with excellent CPR performance. After this potentially life-saving procedure, pulmonary or surgical site complications are expected to occur much less compared with the conventionally performed emergency department left-sided thoracotomy.

Evaluation of treatment response after chemoembolisation (TACE) in hepatocellular carcinoma using real time image fusion of contrast-enhanced ultrasound (CEUS) and computed tomography (CT)--preliminary results.

OBJECTIVE To evaluate treatment response of hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with a new real-time imaging fusion technique of contrast-enhanced ultrasound (CEUS) with multi-slice detection computed tomography (CT) in comparison to conventional post-interventional follow-up. MATERIAL AND METHODS 40 patients with HCC (26 male, ages 46-81 years) were evaluated 24 hours after TACE using CEUS with ultrasound volume navigation and image fusion with CT compared to non-enhanced CT and follow-up contrast-enhanced CT after 6-8 weeks. Reduction of tumor vascularization to less than 25% was regarded as "successful" treatment, whereas reduction to levels >25% was considered as "partial" treatment response. Homogenous lipiodol retention was regarded as successful treatment in non-enhanced CT. RESULTS Post-interventional image fusion of CEUS with CT was feasible in all 40 patients. In 24 patients (24/40), post-interventional image fusion with CEUS revealed residual tumor vascularity, that was confirmed by contrast-enhanced CT 6-8 weeks later in 24/24 patients. In 16 patients (16/40), post-interventional image fusion with CEUS demonstrated successful treatment, but follow-up CT detected residual viable tumor (6/16). Non-enhanced CT did not identify any case of treatment failure. Image fusion with CEUS assessed treatment efficacy with a specificity of 100%, sensitivity of 80% and a positive predictive value of 1 (negative predictive value 0.63). CONCLUSIONS Image fusion of CEUS with CT allows a reliable, highly specific post-interventional evaluation of embolization response with good sensitivity without any further radiation exposure. It can detect residual viable tumor at early state, resulting in a close patient monitoring or re-therapy.

Renal microvascular assembly and repair: power and promise of molecular definition.

Developmental assembly of the renal microcirculation is a precise and coordinated process now accessible to experimental scrutiny. Although definition of the cellular and molecular determinants is incomplete, recent findings have reframed concepts and questions about the origins of vascular cells in the glomerulus and the molecules that direct cell recruitment, specialization and morphogenesis. New findings illustrate principles that may be applied to defining critical steps in microvascular repair following glomerular injury. Developmental assembly of endothelial, mesangial and epithelial cells into glomerular capillaries requires that a coordinated, temporally defined series of steps occur in an anatomically ordered sequence. Recent evidence shows that both vasculogenic and angiogenic processes participate. Local signals direct cell migration, proliferation, differentiation, cell-cell recognition, formation of intercellular connections, and morphogenesis. Growth factor receptor tyrosine kinases on vascular cells are important mediators of many of these events. Cultured cell systems have suggested that basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) promote endothelial cell proliferation, migration or morphogenesis, while genetic deletion experiments have defined an important role for PDGF beta receptors and platelet-derived growth factor (PDGF) B in glomerular development. Receptor tyrosine kinases that convey non-proliferative signals also contribute in kidney and other sites. The EphB1 receptor, one of a diverse class of Eph receptors implicated in neural cell targeting, directs renal endothelial migration, cell-cell recognition and assembly, and is expressed with its ligand in developing glomeruli. Endothelial TIE2 receptors bind angiopoietins (1 and 2), the products of adjacent supportive cells, to signals direct capillary maturation in a sequence that defines cooperative roles for cells of different lineages. Ultimately, definition of the cellular steps and molecular sequence that direct microvascular cell assembly promises to identify therapeutic targets for repair and adaptive remodeling of injured glomeruli.

Arterial blood pressure targets in septic shock: is it time to move to an individualized approach?

Xu and colleagues evaluated the impact of increasing mean arterial blood pressure levels through norepinephrine administration on systemic hemodynamics, tissue perfusion, and sublingual microcirculation of septic shock patients with chronic hypertension. The authors concluded that, although increasing arterial blood pressure improved sublingual microcirculation parameters, no concomitant improvement in systemic tissue perfusion indicators was found. Here, we discuss why resuscitation targets may need to be individualized, taking into account the patient's baseline condition, and present directions for future research in this field.

Post-operative monitoring of free muscle transfers by Laser Doppler Imaging: A prospective study.

PURPOSE Despite different existing methods, monitoring of free muscle transfer is still challenging. In the current study we evaluated our clinical setting regarding monitoring of such tissues, using a recent microcirculation-imaging camera (EasyLDI) as an additional tool for detection of perfusion incompetency. PATIENTS AND METHODS This study was performed on seven patients with soft tissue defect, who underwent reconstruction with free gracilis muscle. Beside standard monitoring protocol (clinical assessment, temperature strips, and surface Doppler), hourly EasyLDI monitoring was performed for 48 hours. Thereby a baseline value (raised flap but connected to its vascular bundle) and an ischaemia perfusion value (completely resected flap) were measured at the same point. RESULTS The mean age of the patients, mean baseline value, ischaemia value perfusion were 48.00 ± 13.42 years, 49.31 ± 17.33 arbitrary perfusion units (APU), 9.87 ± 4.22 APU, respectively. The LDI measured values in six free muscle transfers were compatible with hourly standard monitoring protocol, and normalized LDI values significantly increased during time (P < 0.001, r = 0.412). One of the flaps required a return to theatre 17 hours after the operation, where an unsalvageable flap loss was detected. All normalized LDI values of this flap were under the ischaemia perfusion level and the trend was significantly descending during time (P < 0.001, r = -0.870). CONCLUSION Due to the capability of early detection of perfusion incompetency, LDI may be recommended as an additional post-operative monitoring device for free muscle flaps, for early detection of suspected failing flaps and for validation of other methods.

Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model.

BACKGROUND Lymphedema is an underdiagnosed pathology which in industrialized countries mainly affects cancer patients that underwent lymph node dissection and/or radiation. Currently no effective therapy is available so that patients' life quality is compromised by swellings of the concerned body region. This unfortunate condition is associated with body imbalance and subsequent osteochondral deformations and impaired function as well as with an increased risk of potentially life threatening soft tissue infections. METHODS The effects of PRP and ASC on angiogenesis (anti-CD31 staining), microcirculation (Laser Doppler Imaging), lymphangiogenesis (anti-LYVE1 staining), microvascular architecture (corrosion casting) and wound healing (digital planimetry) are studied in a murine tail lymphedema model. RESULTS Wounds treated by PRP and ASC healed faster and showed a significantly increased epithelialization mainly from the proximal wound margin. The application of PRP induced a significantly increased lymphangiogenesis while the application of ASC did not induce any significant change in this regard. CONCLUSIONS PRP and ASC affect lymphangiogenesis and lymphedema development and might represent a promising approach to improve regeneration of lymphatic vessels, restore disrupted lymphatic circulation and treat or prevent lymphedema alone or in combination with currently available lymphedema therapies.

Ultra-low-dose dual-source CT coronary angiography with high pitch: diagnostic yield of a volumetric planning scan and effects on dose reduction and imaging strategy

OBJECTIVE To evaluate the role of an ultra-low-dose dual-source CT coronary angiography (CTCA) scan with high pitch for delimiting the range of the subsequent standard CTCA scan. METHODS 30 patients with an indication for CTCA were prospectively examined using a two-scan dual-source CTCA protocol (2.0 × 64.0 × 0.6 mm; pitch, 3.4; rotation time of 280 ms; 100 kV): Scan 1 was acquired with one-fifth of the tube current suggested by the automatic exposure control software [CareDose 4D™ (Siemens Healthcare, Erlangen, Germany) using 100 kV and 370 mAs as a reference] with the scan length from the tracheal bifurcation to the diaphragmatic border. Scan 2 was acquired with standard tube current extending with reduced scan length based on Scan 1. Nine central coronary artery segments were analysed qualitatively on both scans. RESULTS Scan 2 (105.1 ± 10.1 mm) was significantly shorter than Scan 1 (127.0 ± 8.7 mm). Image quality scores were significantly better for Scan 2. However, in 5 of 6 (83%) patients with stenotic coronary artery disease, a stenosis was already detected in Scan 1 and in 13 of 24 (54%) patients with non-stenotic coronary arteries, a stenosis was already excluded by Scan 1. Using Scan 2 as reference, the positive- and negative-predictive value of Scan 1 was 83% (5 of 6 patients) and 100% (13 of 13 patients), respectively. CONCLUSION An ultra-low-dose CTCA planning scan enables a reliable scan length reduction of the following standard CTCA scan and allows for correct diagnosis in a substantial proportion of patients. ADVANCES IN KNOWLEDGE Further dose reductions are possible owing to a change in the individual patient's imaging strategy as a prior ultra-low-dose CTCA scan may already rule out the presence of a stenosis or may lead to a direct transferal to an invasive catheter procedure.