Complement component 3 and complement factor H protein levels are altered in brain tissues from people with human immunodeficiency virus: A pilot study.

People with HIV (PWH) continue to suffer from dysfunction of the central nervous system, as evidenced by HIV-associated neurocognitive disorder (HAND), despite antiretroviral therapy and suppressed viral loads. As PWH live longer they may also be at risk of age-related neurodegenerative diseases such Alzheimer's disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). The complement system is associated with deposition of AD-related proteins such as beta amyloid (Aß), neuroinflammation, and neurological dysfunction in PWH. Complement component 3 (C3) is a key protagonist in the complement cascade and complement factor H (CFH) is an antagonist of C3 activity. We investigated the relationship between C3 and CFH levels in the brain and Aß plaques and neurological dysfunction in 22 PWH. We analyzed by immunoblot C3 and CFH protein levels in frontal cortex (FC) and cerebellum (CB) brain specimens from PWH previously characterized for Aß plaque deposition. C3 and CFH protein levels were then correlated with specific cognitive domains. C3 protein levels in the FC were significantly increased in brains with Aß plaques and in brains with HAND compared to controls. In the CB, C3 levels trended higher in brains with Aß plaques. Overall C3 protein levels were significantly higher in the FC compared to the CB, but the opposite was true for CFH, having significantly higher levels of CFH protein in the CB compared to the FC. However, only CFH in the FC showed significant correlations with specific domains, executive function and motor performance. These findings corroborate previous results showing that complement system proteins are associated with HAND and AD neuropathogenesis.

Comparison of complication rates and incidences associated with different peripherally inserted central catheters (PICC) in patients with hematological malignancies: a retrospective cohort study.

Patients with hematological malignancies (HM) or undergoing hematopoietic cell transplantation (HCT) require reliable vascular access. Peripherally inserted central catheters (PICC) meet this need, however, studies suggest these patients have higher rates of PICC-associated complications. This retrospective cohort study evaluates the influence of PICC type on the rates and incidences of complications. Four hundred and eighty-five dual lumen PICCs were inserted into 469 complex patients with HM or undergoing HCT: 161 Groshong®, 60 PowerPICC® Solo, 165 BioFlo®, and 99 Arrow®. The rates and incidences of complications differed significantly across the PICC types. The overall rate of complication ranged from 7.40 to 26.4/1000 catheter days (CDs). The rate of deep vein thrombosis (0.31-1.48/1000 CDs) and occlusion differed across the PICC types, while the rate of central line-associated bloodstream infection (0.53-0.74/1000 CDs) did not. Following multivariate adjustment, PICC type was associated with complication rate. This highlights that PICC type should be considered in clinical decisions.

Low-Dose Antithymocyte Globulin for Graft-versus-Host-Disease Prophylaxis in Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation.

Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (alloHCT). Prophylactic in vivo T cell depletion with antithymocyte globulin (ATG) has been associated with decreased GVHD rates in many alloHCT settings. Despite decades of clinical study, optimal ATG dosing has not been established. Understanding that higher rates of GVHD are observed with matched unrelated donor (MUD) versus matched related donor (MRD) alloHCT, at our institution MUD alloHCT recipients have historically had low-dose Thymoglobulin (total dose, 2.5 mg/kg; Genzyme-Sanofi, Cambridge, MA) added to our standard MRD GVHD prophylaxis regimen. In this retrospective cohort study we assessed post-HCT the effectiveness of our uniquely low-dose ATG strategy by comparing ATG exposed (MUD) and unexposed (MRD) alloHCT recipients for GVHD and other clinical HCT outcomes. This retrospective single-center study included all HCT patients transplanted for any malignant indication at The Ottawa Hospital from 2009 to 2014. MUD patients received rabbit ATG (Thymoglobulin) at a total dose of 2.5 mg/kg given over 2 days (.5 mg/kg on day -2; 2.0 mg/kg on day -1 before stem cell infusion) in addition to standard GVHD prophylaxis. Primary outcomes assessed were incidence of acute and chronic GVHD, defined as new-onset GVHD requiring systemic immunosuppressive therapy at less or more than 100 days, respectively. Secondary outcomes included disease relapse and survival. There were 110 and 77 patients in the ATG exposed (MUD) and unexposed (MRD) cohorts, respectively. At baseline there were no significant differences in median age at transplant, sex, disease indication or risk index, graft source, conditioning regimen, or intensity between cohorts. A higher proportion of 7/8 mismatched donor transplants (13% versus 3%, P = .02) and a higher median CD34+ dose (7.9 versus 4.9 × 108 cells; P < .01) was observed in the ATG exposed cohort. No differences were noted in platelet engraftment. ATG exposed patients had significantly shorter time to neutrophil engraftment than the unexposed cohort (16 versus 19 days, respectively; P < .01). ATG exposed patients had significantly lower rates of GVHD than ATG unexposed patients (57% versus 79%; P = .01), with differences predominantly in rates of chronic GVHD (18% versus 44%, P < .01). At median follow-up of 28 (range, 3 to 69) and 25 (range, 2 to 73) months for survivors in ATG exposed and unexposed cohorts, respectively, no significant differences in overall survival (median overall survival not met for either cohort), relapse incidence (26% versus 29%, P = .73), or relapse-free survival (RFS) (not met in ATG exposed and 26 months in ATG unexposed, P = .22) were observed between groups. The ATG exposed cohort had significantly higher GVHD-free RFS (GRFS) with a 2-year GRFS of 23% versus 3% (P = .003). There were no significant differences between cohorts in proportion of patientswith post-HCT infectious episodes or intensive care unit admissions. Here we report significantly lower rates of chronic GVHD and significant improvement in GRFS in an ATG exposed MUD alloHCT cohort compared with an ATG unexposed MRD cohort. These findings were observed without differences in relapse, survival, infectious complications, or intensive care unit admissions. Our findings highlight the association of unconventionally low-dose ATG with improved GVHD outcomes and suggest a need for prospective study of ATG use in lower doses.

Outcomes in a nurse-led peripherally inserted central catheter program: a retrospective cohort study.

BACKGROUND: Peripherally inserted central catheters (PICCs) provide enormous benefit to patients. However, recent publications have highlighted relatively high PICC-associated complication rates. We report on patient and device outcomes from a nurse-led program. METHODS: We performed a retrospective analysis of a prospective cohort of consecutive patients undergoing PICC insertion at The Ottawa Hospital between Jan. 1, 2013 and Dec. 31, 2014. Of the 8314 BioFlo PASV PICCs inserted, we randomly selected a sample of 700 and obtained a complete data set for 656. We measured the cumulative incidence of major complications (catheter-related bloodstream infections and deep vein thrombosis) and use of a thrombolytic to alleviate occlusions. RESULTS: The total number of catheter days was 58 486, and the median dwell time 45 days. We observed 4 cases of catheter-related bloodstream infection (0.6% [95% CI 0.17%-1.55%]) (0.07/1000 catheter days). Ten patients (1.5% [95% CI 0.83%-2.78%]) (0.17/1000 catheter days) had catheter-related deep venous thrombosis. At least 1 dose of thrombolytic was required in 75 catheters (11.4% [95% CI 8.61%-13.39]), 31 (7.1%) of the 436 single-lumen catheters and 113 (25.7%) of the 440 lumina of dual-lumen catheters (p < 0.001). INTERPRETATION: We attribute our low rates of major complications to a nurse-led expert insertion team, standardized care and maintenance protocols, high insertion volumes, novel catheter material and continuous quality-improvement initiatives that are implemented and evaluated regularly. We conclude that the considerable benefits PICCs provide to patients are attained with a low risk of major complications.

Delayed clamping of the umbilical cord after delivery and implications for public cord blood banking.

BACKGROUND: Public banking of umbilical cord blood units (CBUs) containing higher numbers of cells ensures timely engraftment after transplantation for increasing numbers of patients. Delayed clamping of the umbilical cord after birth may benefit some infants by preventing iron deficiency. Implications of delayed cord clamping for public cord blood banking remains unclear. STUDY DESIGN AND METHODS: CBUs collected by Canadian Blood Services at one collection site between November 1, 2014, and March 17, 2015, were analyzed. The delay in cord clamping after birth was timed and classified as "no delay," 20 to 60 seconds, more than 60 seconds, or more than 120 seconds. RESULTS: Of 367 collections, 100 reported no delay in clamping while clamping was delayed by 20 to 60 seconds (n = 69), more than 60 seconds (n = 98), or more than 120 seconds (n = 100) in the remaining cases. The mean volume and total nucleated cells (TNCs) in units with no delay in clamping were significantly greater than mean volumes for all categories of delayed clamping (Tukey's test, p < 0.05 for each comparison). The proportion of units with more than 1.5 × 10(9) TNCs was significantly reduced when clamping was delayed (p = 5.5 × 10(-8) ). The difference was most marked for cords that were clamped more than 120 seconds after delivery (6.2% compared with 39%). CONCLUSIONS: Delayed cord clamping greatly diminishes the volume and TNC count of units collected for a public cord blood bank. Creating an inventory of CBUs with high TNC content may take more time than expected.