Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation

A decrease in light transmittance before clot formation, manifesting as a biphasic waveform (BPW) pattern in coagulation assays, was previously correlated with the onset of disseminated intravascular coagulation (DIC). In this study of 1187 consecutive admissions to the intensive care unit, the degree of this change on admission predicts DIC better than D-dimer measurements. Additionally, the BPW preceded the time of DIC diagnosis by 18 hours, on average, in 56% (203 of 362) of DIC patients. The BPW is due to the rapid formation of a precipitate and coincident turbidity change on recalcification of plasma. The isolated precipitate contains very-low-density lipoprotein (VLDL) and C-reactive protein (CRP). The addition of CRP and Ca(++) to normal plasma also causes the precipitation of VLDL and IDL, but not LDL or HDL. The K(d) of the CRP/VLDL interaction is 340 nM, and the IC(50) for Ca(++) is 5.0 mM. In 15 plasmas with the BPW, CRP was highly elevated (77-398 microg/mL), and the concentration of isolated VLDL ranged from 0.082 to 1.32 mM (cholesterol). The turbidity change on recalcification correlates well with the calculated level of the CRP-VLDL complex. Clinically, the BPW better predicts for DIC than either CRP or triglyceride alone. The complex may have pathophysiological implications because CRP can be detected in the VLDL fraction from sera of patients with the BPW, and the VLDL fraction has enhanced prothrombinase surface activity. The complex has been designated lipoprotein complexed C-reactive protein.     

Troxacitabine and imatinib mesylate combination therapy of chronic myeloid leukaemia: preclinical evaluation

The in vitro and in vivo activity of a deoxycytidine analogue, troxacitabine, alone or in combination with imatinib mesylate (IM), was evaluated against human chronic myeloid leukaemia (CML) cell lines both sensitive (KBM5 and KBM7) and resistant (KBM5-R and KBM7-R) to IM. These cell lines differ in their sensitivity to IM but all showed similar sensitivity to treatment with troxacitabine (IC50 = 0.5-1 micromol/l). Combined treatment with troxacitabine and IM revealed additive or synergistic effects. Greater apoptotic response was seen with combined treatment than with either agent alone in KBM7-R cells. In clonogenic assays, troxacitabine showed activity against mononuclear cells from CML patients (IC50 = 0.01 micromol/l) with either IM-sensitive or resistant disease. In vivo efficacy studies were carried out in severe combined immunodeficient mice bearing KBM5 or KBM5-R cells. Troxacitabine was administered i.p. daily for 5 d starting on day 20, at doses of 5, 10, 20, or 25 mg/kg. IM was administered i.p. twice a day for 10 d at a dose of 50 mg/kg starting on day 25. In this setting of late stage disease, troxacitabine led to a significant increase in life span, while IM did not. When IM was combined with troxacitabine at 10 and 25 mg/kg in the KBM5 xenograft model, a further increase in life span was observed and some mice achieved long-term survival. These data indicate that the combination of troxacitabine and IM has significant preclinical activity in advanced CML and that clinical evaluation of this combination is warranted.     

Dual antiplatelet therapy plus postoperative heparin and dextran is safe and effective for reducing risk of embolic stroke during aneurysm coiling

Background

Thromboembolic events represent a clinically significant cause of neurological morbidity during the endovascular management of cerebral aneurysms. We have implemented an anti-thromboembolic regimen consisting of pre- and postoperative dual antiplatelet therapy, as well as postoperative anticoagulation using heparin and dextran. The aims of our study were to examine the effect of this regimen on thromboembolic rates during elective aneurysm coiling, and to elucidate risk factors associated with the development of thromboembolic events in this setting.

Methods

We conducted a retrospective review of patients who underwent elective intracranial aneurysm coiling between January 2005 and February 2012. The primary outcome of interest was the occurrence of a clinically significant peri-procedural thromboembolic event. Secondary outcomes included the occurrence of a central nervous system (CNS) or systemic hemorrhage.

Results

During the study period, 312 patients underwent elective aneurysm coiling and six (2 %) thromboembolic events occurred; three (1 %) occurred in the group that received the anti-thromboembolic regimen (261 patients) and three (6 %) occurred in the group that did not receive the regimen (51 patients), resulting in a statistically significant difference (P?=?0.024). Both the presence of a hypercoagulable state (P?=?0.014) and the lack of the anti-thromboembolic regimen (P?=?0.043) were significantly associated with the occurrence of a thromboembolic event.

Conclusions

This study provides evidence that the regimen described here is safe and reduces thromboembolic complications during elective aneurysm coiling. Ours is likely the most aggressive regimen in the published literature and significantly reduced the rate of thromboembolism without any significant increase hemorrhagic complications.     

Deep neural network for automatic characterization of lesions on 68Ga-PSMA-11 PET/CT

European Journal of Nuclear Medicine and Molecular Imaging - This study proposes an automated prostate cancer (PC) lesion characterization method based on the deep neural network to determine tumor...     

Minimally invasive surgery training using multiple port sites to improve performance

Background

Structural learning theory suggests that experiencing motor task variation enables the central nervous system to extract general rules regarding tasks with a similar structure—rules that can subsequently be applied to novel situations. Complex minimally invasive surgery (MIS) requires different port sites, but switching ports alters the limb movements required to produce the same endpoint control of the surgical instrument. The purpose of the present study was to determine if structural learning theory can be applied to MIS to inform training methods.

Methods

A tablet laptop running bespoke software was placed within a laparoscopic box trainer and connected to a monitor situated at eye level. Participants (right-handed, non-surgeons, mean age = 23.2 years) used a standard laparoscopic grasper to move between locations on the screen. There were two training groups: the M group (n = 10) who trained using multiple port sites, and the S group (n = 10) who trained using a single port site. A novel port site was used as a test of generalization. Performance metrics were a composite of speed and accuracy (SACF) and normalized jerk (NJ; a measure of movement ‘smoothness’).

Results

The M group showed a statistically significant performance advantage over the S group at test, as indexed by improved SACF (p < 0.05) and NJ (p < 0.05).

Conclusions

This study has demonstrated the potential benefits of incorporating a structural learning approach within MIS training. This may have practical applications when training junior surgeons and developing surgical simulation devices.     

Activated clotting time differential is a superior method of monitoring anticoagulation following coronary angioplasty

The standard high-range activated clotting time (sHR ACT) is used to monitor anticoagulation postangioplasty (PTCA), but may be unreliable. We assessed the accuracy of a new method we termed the ACT differential (ACT Diff), obtained by measuring the difference between an sHR ACT and a heparinase ACT from the same sample. Heparinase removes heparin from its sample and provides a current heparin-free baseline. For phase 1 of the study, the sHR ACT, ACT Diff, and laboratory APTT were measured in 250 samples from 75 PTCA patients. In 125 samples with an APTT prolonged but within measurement range, linear regression against the APTT was performed. The correlation coefficient was 0.74 for the ACT Diff and 0.24 for the sHR ACT. An ACT Diff of 15–25 sec was found to equal an APTT of 2.5–3.5 × control. In 50 samples with a normal activated partial thromboplastin time (APT), there was good differentiation by the ACT Diff of results from those adequately heparinized, with a value of 0.9 ± 4.4 sec. The sHR ACT was 114 ± 15.5 sec, and could not reliably distinguish between anticoagulated and nonanticoagulated samples. In 75 samples obtained with a high APTT (above measurement range), the ACT Diff was >30 sec in 95% of samples, and again this allowed differentiation from therapeutic samples. The equivalent sHR ACT was 148 sec, and could not reliably distinguish between anticoagulated and overanticoagulated samples as the ACT Diff could. In phase 2, to examine the clinical usefulness of the ACT Diff, 286 patients were managed post-PTCA by starting heparin when ACT Diff fell to <50 sec, maintaining ACT Diff at 15–25 sec during heparin infusions, and following cessation of heparin, by removing sheaths when the ACT Diff was <7 sec. These patients were compared to a control group of 250 patients. Major bleeding (5% vs. 0.5%, P < 0.005) and minor bleeding (30% vs. 13%, P < 0.001) were significantly reduced in the group managed using the ACT Diff. The reduction in bleeding was thought to be due to the rapid availability of reliable results. Abrupt closure was low in both groups (0% with ACT Diff vs. 0.8%). No other thrombotic events occurred. Following phases 1 and 2, the ACT Diff replaced the APTT in all PTCA patients at this institution. In the 18 mo from July 1993, 1,104 patients were managed this way. Incidence of major bleeding (0.2%), transfusion requirement (0.1%), false anneurysm (0.6%), and abrupt closure during heparin infusion (0.1%) remained low. In conclusion, the ACT Diff is more accurate than an sHR ACT, and its clinical use in PTCA patients is associated with a very low incidence of complications from anticoagulation. Its routine use should be considered by units unable to obtain rapid APTT results. © 1996 Wiley-Liss, Inc.