A Novel Intraoperative Transient Variant of Immune Thrombocytopenia.

Immune thrombocytopenia, also known as immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a very low number of platelets and associated excessive bleeding. Primary ITP is a diagnosis of exclusion and secondary causes of ITP including lymphoproliferative disorders, medications, and certain infections must be ruled out during workup. This is the first report to highlight intraoperative ITP or an ITP-like novel variant in the perioperative setting leading to increased bleeding. The patient's extensive workup failed to reveal any secondary causative factors. The clinical presentation of ITP was transient. She received tranexamic acid (TXA), intravenous steroids, and intravenous immunoglobulins (IVIG) and recovered without complication. This case report explores a potentially underreported cause for intraoperative and postoperative hemorrhage in surgical patients.

Stakeholder Engagement Significantly Decreased Colorectal Surgical Site Infections.

Background: Patients and care providers raised concerns about the increased incidence of colorectal surgical site infection (SSI) at a community hospital in Baltimore compared with peer institutions. Patients and Methods: A preliminary analysis was performed that identified several modifiable targets for interventions to reduce SSIs in this patient population. The intervention focused on wide engagement of all stakeholder groups across the spectrum of care including physicians, pharmacists, nurses, administrators, and patients. The engagement process involved hospital-wide educational sessions, adoption and implementation of the best clinical guidelines, and utilization of the electronic medical record system to reinforce compliance and ensure quality control. Data for SSIs in colorectal surgical procedures were collected prior to the intervention (January 1, 2017 to March 31, 2018) and after implementation (April 1, 2018 to October 31, 2018). Results: A total of 355 cases (229 pre-intervention group, 126 post-intervention group) met the inclusion criteria; the two groups were comparable with respect to all the key parameters except the procedure type and use of endoscopy. Multivariable logistic regression modeling was utilized to evaluate the effects of the stakeholder engagement intervention while adjusting for potential confounders. The incidence of colorectal SSIs was substantially lower after the intervention (2.78% vs. 8.73%, p = 0.02). This reduction was robust to adjustment for covariates in regression modeling (p = 0.04). Conclusions: Informed stakeholder engagement helped bring cohesion to the inherently fragmented elements of the care delivery model and was associated with decreased incidence of colorectal SSIs.

Endothelial alterations in a canine model of immune thrombocytopenia.

Bleeding heterogeneity amongst patients with immune thrombocytopenia (ITP) is poorly understood. Platelets play a role in maintaining endothelial integrity, and variable thrombocytopenia-induced endothelial changes may influence bleeding severity. Platelet-derived endothelial stabilizers and markers of endothelial integrity in ITP are largely underexplored. We hypothesized that, in a canine ITP model, thrombocytopenia would lead to alterations in the endothelial ultrastructure and that the Von Willebrand factor (vWF) would serve as a marker of endothelial injury associated with thrombocytopenia. Thrombocytopenia was induced in healthy dogs with an antiplatelet antibody infusion; control dogs received an isotype control antibody. Cutaneous biopsies were obtained prior to thrombocytopenia induction, at platelet nadir, 24 hours after nadir, and on platelet recovery. Cutaneous capillaries were assessed by electron microscopy for vessel thickness, the number of pinocytotic vesicles, the number of large vacuoles, and the number of gaps between cells. Pinocytotic vesicles are thought to represent an endothelial membrane reserve that can be used for repair of damaged endothelial cells. Plasma samples were assessed for vWF. ITP dogs had significantly decreased pinocytotic vesicle numbers compared to control dogs (P = 0.0357) and the increase in plasma vWF from baseline to 24 hours correlated directly with the endothelial large vacuole score (R = 0.99103; P < 0.0001). This direct correlation between plasma vWF and the number of large vacuoles, representing the vesiculo-vacuolar organelle (VVO), a permeability structure, suggests that circulating vWF could serve as a biomarker for endothelial alterations and potentially a predictor of thrombocytopenic bleeding. Overall, our results indicate that endothelial damage occurs in the canine ITP model and variability in the degree of endothelial damage may account for differences in the bleeding phenotype among patients with ITP.

A significant proportion of venous thromboembolism events in general surgical patients occurs after discharge: analysis of the ACS-NSQIP Essentials database.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in general surgical patients. METHODS: The ACS-NSQIP database was queried and VTE data were collected and analyzed to assess the incidence of VTE at a 500-bed, non-profit, teaching, inner city, community hospital and similar peer institutions from January 1, 2006 to December 31, 2011. RESULTS: Post-discharge VTE events accounted for 40% of all VTE events within 30 days of discharge. Data show a significant proportion of post-discharge VTE events that may be preventable with extending VTE prophylaxis in the post-discharge period. CONCLUSION: This is the first paper to report on this high post-discharge incidence of VTE in general surgical patients and to recommend continuation of VTE prophylaxis in the post-discharge period.

Plasma levels of sphingosine 1-phosphate are strongly correlated with haematocrit, but variably restored by red blood cell transfusions.

Anaemia and RBC (red blood cell) transfusion may be associated with worse clinical outcomes, especially with longer blood storage duration prior to transfusion. The mechanisms underlying these harmful effects are unknown. RBCs have been proposed to buffer plasma S1P (sphingosine 1-phosphate), a lysophospholipid essential for the maintenance of endothelial integrity and important in the regulation of haematopoietic cell trafficking. The present study examined the effect of anaemia, RBC transfusion and RBC storage duration on plasma S1P levels. Plasma S1P from 30 individuals demonstrated a linear correlation with Hct (haematocrit; R2 = 0.51, P < 0.001) with no evidence for a plateau at Hct values as low as 19%. RBC transfusion in 23 anaemic patients with baseline mean Hct of 22.2 ± 0.34% (value is the mean ± S.D.) increased Hct to 28.3 ± 0.6% at 72 h. Despite an Hct increase, RBC transfusion failed to elevate plasma S1P consistently. A trend towards an inverse correlation was observed between RBC storage duration and the post-transfusion increase in plasma S1P. After 30 days of storage, RBC S1P decreased to 19% of that observed in fresh (3-7-day-old) RBC segments. RBC membranes contain low levels of both S1P phosphatase and S1P lyase activities that may account for the decline in S1P levels with storage. Our results support a role for RBCs in buffering plasma S1P and identify a disturbance in the capacity after transfusion. Changes in S1P content may contribute to an RBC storage lesion. Further studies should investigate the clinical significance of alterations in circulating S1P levels and the potential value of enriching stored RBCs with S1P.

Lipid phosphate phosphatase 3 enables efficient thymic egress.

The signaling lipid sphingosine-1-phosphate (S1P) stabilizes the vasculature, directs lymphocyte egress from lymphoid organs, and shapes inflammatory responses. However, little is known about how S1P distribution is controlled in vivo, and it is not clear how a ubiquitously made lipid functions as a signal that requires precise spatial and temporal control. We have found that lipid phosphate phosphatase 3 (LPP3) enables efficient export of mature T cells from the thymus into circulation, and several lines of evidence suggest that LPP3 promotes exit by destroying thymic S1P. Although five additional S1P-degrading enzymes are expressed in the thymus, they cannot compensate for the loss of LPP3. Moreover, conditional deletion of LPP3 in either epithelial cells or endothelial cells is sufficient to inhibit egress. These results suggest that S1P generation and destruction are tightly regulated and that LPP3 is essential to establish the balance.

Functional interactions of alcohol-sensitive sites in the N-methyl-D-aspartate receptor M3 and M4 domains.

The N-methyl-D-aspartate receptor is an important mediator of the behavioral effects of ethanol in the central nervous system. Previous studies have demonstrated sites in the third and fourth membrane-associated (M) domains of the N-methyl-D-aspartate receptor NR2A subunit that influence alcohol sensitivity and ion channel gating. We investigated whether two of these sites, Phe-637 in M3 and Met-823 in M4, interactively regulate the ethanol sensitivity of the receptor by testing dual substitution mutants at these positions. A majority of the mutations decreased steady-state glutamate EC(50) values and maximal steady-state to peak current ratios (I(ss)/I(p)), whereas only two mutations altered peak glutamate EC(50) values. Steady-state glutamate EC(50) values were correlated with maximal glutamate I(ss)/I(p) values, suggesting that changes in glutamate potency were attributable to changes in desensitization. In addition, there was a significant interaction between the substituents at positions 637 and 823 with respect to glutamate potency and desensitization. IC(50) values for ethanol among the mutants varied over the approximate range 100-325 mm. The sites in M3 and M4 significantly interacted in regulating ethanol sensitivity, although this was apparently dependent upon the presence of methionine in position 823. Molecular dynamics simulations of the NR2A subunit revealed possible binding sites for ethanol near both positions in the M domains. Consistent with this finding, the sum of the molecular volumes of the substituents at the two positions was not correlated with ethanol IC(50) values. Thus, there is a functional interaction between Phe-637 and Met-823 with respect to glutamate potency, desensitization, and ethanol sensitivity, but the two positions do not appear to form a unitary site of alcohol action.