Comparison of Haemonetics Cell Saver 5+ and manual density separation for optimum depletion of red blood cells and preservation of CD34+ cells in major ABO-incompatible bone marrow grafts.

BACKGROUND AIMS: The current approach for preventing hemolysis of red blood cells (RBCs) in major ABO-incompatible bone marrow (BM) grafts after infusion is to deplete RBCs from BM products before transplantation. Traditionally, manual density separation (MDS) using Ficoll-Hypaque (Cytiva Sweden AB, Uppsala, Sweden has been used to accomplish RBC depletion. This process yields good CD34+ cell recovery, but it requires open manipulation and is labor-intensive and time-consuming. We hypothesized that an alternative automated method using Haemonetics Cell Saver 5+ (Haemonetics Corporation, Boston, MA, USA) would offer equivalent RBC depletion and CD34+ cell recovery. Small marrow volumes from pediatric donors can be processed using Cell Saver (CS) without adding the third-party RBCs necessary for other automated methods. METHODS: This retrospective analysis comprised data from 58 allogeneic BM grafts. RBC depletion and CD34+ cell recovery from BM using MDS (35 grafts) were compared with CS (14 grafts). Nine products underwent RBC depletion using CS with Ficoll (CS-F) when RBC volume was less than 125 mL. RESULTS: Linear regression analysis of log transformation of CD34+ cell recovery adjusted for log transformation of both baseline CD34+ cell content and baseline total volume showed no significant difference between MDS and CS (estimated coefficient, -0.121, P = 0.096). All products contained an RBC volume of less than 0.25 mL/kg post-processing. CD34+ cell recovery with CS-F was comparable to MDS and CS and suitable for pediatric recipients of allogeneic hematopoietic cell transplantation. CONCLUSIONS: We provide evidence that an automated method using Haemonetics Cell Saver 5+ achieves RBC depletion and CD34+ cell recovery comparable to MDS when adjusting for baseline factors.

Serologic Responses following a Single Dose of SARS-Cov-2 Vaccination in Allogeneic Stem Cell Transplantation Recipients.

Immunocompromised individuals were not included in formal trials of SARS-CoV-2 mRNA vaccines. Subsequent studies in patients with hematologic malignancies and solid organ transplantation recipients suggest inferior responses to vaccination. We determined antibody responses to a single dose of vaccines in one of the most vulnerable patient groups, allogeneic hematopoietic cell transplantation (allo-HCT) recipients. Pfizer-BioNTech (PB) or AstraZeneca (AZ) SARS-CoV-2 vaccines were administered at least 3 months post-transplantation to 55 adult allo-HCT recipients. We found that older age and concurrent use of immunosuppressive medications were significantly associated with lack of antibody response to vaccination. Only 21% of patients on systemic immunosuppression mounted a response, compared with 58% of patients not on immunosuppression (P = .006). We also show that responses to the AZ vaccine may be superior to responses to the PB vaccine in this cohort. These findings highlight the need for novel immunogenic vaccine formulations and schedules in these highest-risk patients, as well as continued public healthy safety measures to protect the most vulnerable members of our society.

Continuous erector spinae plane block versus intercostal nerve block in patients undergoing video-assisted thoracoscopic surgery: a pilot randomized controlled trial.

BACKGROUND: The optimal analgesia method in video-assisted thoracoscopic surgery (VATS) remains controversial. Intercostal nerve blockade (ICNB) is limited by its duration of action. The erector spinae plane (ESP) block has the potential to provide satisfactory analgesia for VATS; however, the effectiveness of continuous ESP versus surgeon-performed ICNB has not been investigated. The objectives of this study were to establish feasibility of patient recruitment and follow-up before undertaking a fully powered randomized controlled trial (RCT); and, secondarily, to compare opioid usage, pain control, and sensory blockade. METHODS: This feasibility RCT was undertaken at St Joseph's Hospital, Hamilton, Ontario, Canada, and included 24 patients (>18 years) having elective VATS with at least one overnight stay. Exclusion criteria were patient refusal, body mass index >40 kg/m2, contraindications to neuraxial analgesia techniques as per the American Society of Regional Anesthesia and Pain guidelines, known allergy to local anesthetics, language or comprehension barriers, procedures with a higher chance of open surgery, and regular opioid use for ≥3 months preoperatively. Patients underwent either continuous ESP (n=12) or surgeon-performed ICNB (n=12). All patients received routine intraoperative anesthesia care and multimodal analgesia. Feasibility criteria were recruitment rate of two patients/week and full follow-up in all patients in-hospital. We compared opioid consumption, postoperative pain scores (0-10 numerical rating scale), adverse events, patient satisfaction, and distribution of sensory blockade as clinical outcomes (secondary). RESULTS: Feasibility of primary outcomes was successfully demonstrated. Five patients had an epidural in anticipation of open surgery. Mean opioid consumption as equivalent morphine units was less in the ESP group over the first 24 h (mean difference, 1.63 [95% CI -1.20 to 4.45]) and 48 h (mean difference, 2.34 [95% CI -1.93 to 6.61]). There were no differences in adverse effects. CONCLUSIONS: A fully powered RCT is feasible with modifications. Our results also suggest that continuous ESP is safe and can decrease opioid needs. However, it is important to consider procedures to improve compliance to protocol and adherence to assigned interventions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03176667 . Registered June 5, 2017.

Scabies and impetigo in Timor-Leste: A school screening study in two districts.

INTRODUCTION: Scabies and impetigo are common and important skin conditions which are often neglected in developing countries. Limited data have been published on the prevalence of scabies and impetigo in Timor-Leste. Sequelae including cellulitis, bacteraemia, nephritis, acute rheumatic fever and rheumatic heart disease contribute significantly to the burden of disease. METHODS: School students were recruited from schools in Dili (urban) and Ermera (rural) in Timor-Leste for an epidemiological study in October 2016. A standard questionnaire was used to record demographics, anthropometry and skin examination results. Impetigo and scabies were diagnosed based on clinical examination of exposed surfaces, and clinical photographs were reviewed for correlation by an infectious diseases paediatrician. Prevalence of scabies and impetigo were calculated and binary risk factor associations were described using relative risks and 95% confidence intervals. Adjusted odds ratios were calculated using logistic regression multivariate analysis. Continuous variables were analysed for associations using the Mann-Whitney Rank Sum test. RESULTS: The study enrolled 1396 students; median age 11 years (interquartile range (IQR) 9-15). The prevalence of scabies was 22.4% (95% CI 20.2-24.7%) and active impetigo 9.7% (95% CI 8.3-11.4%); 68.2% of students had evidence of either active or healed impetigo. Students in Ermera were more likely than those in Dili to have scabies (prevalence 32.0% vs 5.2%, aOR 8.1 (95% CI 5.2-12.4), p<0.01). There was no difference in the prevalence of active impetigo between urban and rural sites. More than a third of participants were moderately or severely underweight. Stunting was markedly more common in the rural district of Ermera. CONCLUSION: Scabies and impetigo are common in Timor-Leste, with very high prevalence of scabies in the rural district of Ermera. Improvements in prevention and treatment are needed, with prioritised activities in the rural areas where prevalence is highest.

Physicians' perspectives on the informational needs of low-risk prostate cancer patients.

Despite the evidence indicating that decision aids (DA) improve informed treatment decision making for prostate cancer (PCa), physicians do not routinely recommend DAs to their patients. We conducted semi-structured interviews with urologists (n = 11), radiation oncologists (n = 12) and primary care physicians (n = 10) about their methods of educating low-risk PCa patients regarding the treatment decision, their concerns about recommending DAs, and the essential content and format considerations that need to be addressed. Physicians stressed the need for providing comprehensive patient education before the treatment decision is made and expressed concern about the current unevaluated information available on the Internet. They made recommendations for a DA that is brief, applicable to diverse populations, and that fully discloses all treatment options (including active surveillance) and their potential side effects. Echoing previous studies showing that low-risk PCa patients are making rapid and potentially uninformed treatment decisions, these results highlight the importance of providing patient education early in the decision-making process. This need may be fulfilled by a treatment DA, should physicians systematically recommend DAs to their patients. Physicians' recommendations for the inclusion of particular content and presentation methods will be important for designing a high quality DA that will be used in clinical practice.

Retrospective cohort analysis comparing the incidence of deep vein thromboses between peripherally-inserted and long-term skin tunneled venous catheters in hemato-oncology patients.

BACKGROUND: The introduction of central venous catheters has advanced medical care, particularly in hemato-oncology. However these can be associated with an increased thrombotic risk. Previous studies have compared the rate of thrombotic events between peripherally- inserted (PICCs) and long term skin tunneled catheters (LTSTCs) noting fewer complications associated with the latter, though this has rarely translated into clinical practice. The objectives of our study was to compare the cumulative incidence of thrombotic events between peripherally-inserted and long term skin tunneled venous catheters. PATIENTS/METHODS: We performed a retrospective, single center cohort analysis of patients with hematological malignancies who had either a PICC or LTSTC line inserted between January 2010 through January 2013. Cumulative incidences of thrombotic events were compared between the two groups, and post-thrombotic complications were also examined. RESULTS: 346 patients had a PICC inserted with cumulative incidence of symptomatic thrombosis of 5.8%, while 237 patients had a LTSTC inserted with a cumulative incidence of 1.7% (p = 0.003). Post-thrombotic complication rates, particularly infection, were higher in the PICC group compared to the LTSTC group (p = 0.597). CONCLUSIONS: Our study showed that the incidence of thrombotic events in hemato-oncology patients was significantly lower in those who had a LTSTC compared to PICC line. As the use of central venous lines increases in hemato-oncology patient care, a randomized trial comparing PICCs and LTSTCs is necessary to address which venous access is most appropriate in this cohort of patients, with minimal risk of morbidity and mortality.

Ca2+-pumps and Na2+-Ca2+-exchangers in coronary artery endothelium versus smooth muscle.

Vascular endothelial cells (EC) and smooth muscle cells (SMC) require a decrease in cytoplasmic Ca2+ concentration after activation. This can be achieved by Ca2+ sequestration by the sarco-/endoplasmic reticulum Ca2+ pumps (SERCA) and Ca2+ extrusion by plasma membrane Ca2+ pumps (PMCA) and Na+-Ca2+-exchangers (NCX). Since the two cell types differ in their structure and function, we compared the activities of PMCA, NCX and SERCA in pig coronary artery EC and SMC, the types of isoforms expressed using RT-PCR, and their protein abundance using Western blots. The activity of NCX is higher in EC than in SMC but those of PMCA and SERCA is lower. Consistently, the protein abundance for NCX protein is higher in EC than in SMC and those of PMCA and SERCA is lower. Based on RT-PCR experiments, the types of RNA present are as follows: EC for PMCA1 while SMC for PMCA4 and PMCA1; EC for SERCA2 and SERCA3 and SMC for SERCA2. Both EC and SMC express NCX1 (mainly NCX1.3). PMCA, SERCA and NCX differ in their affinities for Ca2+ and regulation. Based on these observations and the literature, we conclude that the tightly regulated Ca2+ removal systems in SMC are consistent with the cyclical control of contractility of the filaments and those in EC are consistent with Ca2+ regulation of the endothelial nitric oxide synthase near the cell surface. The differences between EC and SMC should be considered in therapeutic interventions of cardiovascular diseases.

Enhancing patient safety through electronic medical record documentation of vital signs.

As technology becomes more sophisticated in healthcare, there is increasing need to measure its impact on key quality indicators, such as error reduction, patient safety, and cost-benefit ratios. When a product is designed to decrease medical errors, the baseline error rate must be determined before implementation to accurately measure the impact. Given the opportunity to adopt a technology that would eliminate the need to manually document vital signs, a large Florida hospital decided to measure the current process and error rate of vital signs documentation. University Community Hospital in Tampa, Fla., designed a two-phase study to evaluate this process. Phase I of the study evaluated errors in the electronic medical record and traditional manual documentation. The results demonstrate that use of an EMR can reduce vital sign documentation errors by more than half compared with traditional manual documentation in paper charts. Researchers found the error rate for electronic vital signs documentation to be less than 5 percent, compared with the paper chart error rate of 10 percent.

Hypotonic shock stimulates ascorbate release from coronary artery endothelial cells by a Ca2+ -independent pathway.

In endothelial cells, anion channels open upon osmotic swelling during shear stress and hypotonic shock. Therefore, we examined the effects of hypotonic shock on release of the antioxidant anion ascorbate from pig coronary artery endothelial cells. Hypotonic shock potentiated ascorbate release from freshly isolated or cultured pig coronary artery endothelial cells; subsequently cultured endothelial cells were used. The hypotonic shock-induced increase in Asc release was rapid, depended on the degree of hypotonic shock, and not due to membrane leakiness. Stimulating P2Y2 like receptors in endothelial cells with ATP causes ascorbate release via a Ca2+ -mediated pathway. Hypotonic shock-induced release differed from the Ca2+-mediated Asc release because: (a) the increase in release with hypotonic shock was additive to that with ATP or A23187 (Ca2+ -ionophore), (b) apyrase, suramin or removing extracellular Ca2+ did not affect the hypotonic shock-stimulated release, (c) anion channel blockers inhibited the release by the two pathways differently, and (d) hypotonic shock increased the ascorbate release from endothelial cells and cultured smooth muscle cells whereas the Ca2+ -mediated ascorbate release occurred only in endothelial cells. Accumulation of ascorbate by endothelial cells was examined at extracellular ascorbate concentrations of 10 (Na+ -ascorbate symporter not saturated) and 5000 microM (Na+ -ascorbate symporter saturated). Hypotonic shock and A23187 decreased ascorbate accumulation at 10 microM ascorbate but increased it at 5000 microM. The effects of the two treatments were additive and also differed from each other with substitution of gluconate for extracellular chloride. Thus, ascorbate release from endothelial cells can be potentiated by two distinct pathways - hypotonic shock mediated and ATP/Ca2+ stimulated.

Ca2+-mediated ascorbate release from coronary artery endothelial cells.

1.--The addition of Ca(2+) ionophore A23187 or ATP to freshly isolated or cultured pig coronary artery endothelial cells (PCEC) potentiated the release of ascorbate (Asc). Cultured PCEC were used to characterize the Ca(2+)-mediated release. An increase in Ca(2+)-mediated Asc release was observed from PCEC preincubated with Asc, Asc-2-phosphate or dehydroascorbic acid (DHAA). 2.--The effects of various ATP analogs and inhibition by suramin were consistent with the ATP-induced release being mediated by P2Y2-like receptors. 3.--ATP-stimulated Asc release was Ca(2+)-mediated because (a) ATP analogs that increased Asc release also elevated cytosolic [Ca(2+)], (b) Ca(2+) ionophore A23187 and cyclopiazonic acid stimulated the Asc release, (c) removing extracellular Ca(2+) and chelating intracellular Ca(2+)inhibited the ATP-induced release, and (d) inositol-selective phospholipase C inhibitor U73122 also inhibited this release. 4.--Accumulation of Asc by PCEC was examined at Asc concentrations of 10 microM (Na(+)-Asc symporter not saturated) and 5 mM (Na(+)-Asc symporter saturated). At 10 microM Asc, A23187 and ATP caused an inhibition of Asc accumulation but at 5 mM Asc, both the agents caused a stimulation. Substituting gluconate for chloride did not affect the basal Asc uptake but it abolished the effects of A23187. 5.--PCEC but not pig coronary artery smooth muscle cells show a Ca(2+)- mediated Asc release pathway that may be activated by agents such as ATP.

Phase II trial of paclitaxel, ifosfamide, and carboplatin in extensive-stage small cell lung cancer.

Extensive-stage small cell lung cancer (ES-SCLC) remains a therapeutic challenge to the medical oncologists. We evaluated the triplet combination of paclitaxel (175 mg/m(2) over 1 h), ifosfamide (2.5 gm/m(2) over 1 h) and carboplatin (AUC=6 over 0.5 h) (PIC) all given on day 1 of a 21 day schedule. Thirty-five patients were entered with a median age of 59 years (range 40-79). The ECOG PS was 0-1 in 86%. A median of 6 cycles were delivered (range 1-6). The principal toxicity was neutropenia with 66% of patients experiencing grade 4 neutropenia. Only 9% of patients experienced febrile neutropenia. One treatment-related death (3%) due to neutropenic sepsis occurred. Non-hematologic toxicity was minimal. The overall response rate was 71% (15% complete response, 56% partial responses). Quality of life appeared to be stable across time. The median survival time was 9.5 months (95% confidence interval (CI), 6.7-13.2 months) with a 1- and 2-year survival rates of 43% (95% CI, 26-59%) and 16% (95% CI, 2-30%). PIC has activity in ES-SCLC and is associated with a response rate and survival profile similar to other combinations in this disease setting. This regimen has a tolerable toxicity profile and a favorable and convenient administration schedule.