Bleeding assessment following central venous catheter placement, a direct comparison of prospective and retrospective analyses.

BACKGROUND: Reported bleeding incidences following central venous catheter (CVC) placement highly depend on methods of bleeding assessment. To determine the direction and magnitude of the bias associated with retrospective data collection, we used data from the PACER randomized controlled trial and a previous retrospective cohort study. STUDY DESIGN AND METHODS: A patient-level comparison of CVC-related bleeding severity was made among (1) the prospectively collected clinical bleeding assessment of the PACER trial, (2) centralized assessment of CVC insertion site photographs, and (3) retrospective chart review. Interrater reliability for photographic bleeding assessment and retrospective chart review was assessed using Cohen's κ. The magnitude of underreporting of both methods compared to prospective clinical bleeding assessment at different cutoff points of clinically relevant bleeding was assessed using McNemar's test. RESULTS: Interrater reliability was acceptable for both methods (κ = 0.583 and κ = 0.481 for photographic assessment and retrospective chart review, respectively). Photographic bleeding assessment led to significant underreporting of bleeding complications at all cutoff points. Retrospective chart review led to significant underreporting of minor bleeding complications, with an odds ratio (95% CI) of 0.17 (0.044-0.51) for the cutoff point grade 1 (i.e., self-limiting or requiring at most 20 min of manual compression) or higher. There was no significant underreporting of major bleeding complications with retrospective chart review. DISCUSSION: Centralized photographic bleeding assessment and retrospective chart review lead to biased bleeding assessment compared to prospective clinical bleeding assessment.

Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia.

BACKGROUND: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. METHODS: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. RESULTS: We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. CONCLUSIONS: The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.).

Biotinylated Platelets: A Promising Labeling Technique?

Labeling of platelets (PLTs) is essential for research purposes, in order to measure the recovery and survival of transfused PLTs in vivo. Biotinylation is a promising new alternative to the gold standard of radioactive labeling. This review highlights 4 key publications that provide significant insights into biotin-labeled PLTs (bioPLTs). Stohlawetz et al. established that transfusion of bioPLTs in human recipients is possible. De Bruin et al. developed a standardized, reproducible protocol for biotinylation of PLTs as a promising method to trace and isolate transfused PLTs in vivo, with reduced levels of PLT activation markers. Muret et al. developed a nonwashing biotin labeling method to implement in a blood bank environment. Finally, in a preclinical study, Ravanat et al. showed that different densities of biotin can be used to concurrently monitor multiple populations of human PLTs in the circulation of the same subject. These studies have made major contributions to the development of bioPLTs as a viable option for use in human research, and indicate that bioPLTs can be safely administered, preferably at a low density of biotin.

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19-Induced Acute Respiratory Distress Syndrome: An Inverse Probability Weighted Analysis.

Although venovenous extracorporeal membrane oxygenation (VV ECMO) has been used in case of COVID-19 induced acute respiratory distress syndrome (ARDS), outcomes and criteria for its application should be evaluated. OBJECTIVES: To describe patient characteristics and outcomes in patients receiving VV ECMO due to COVID-19-induced ARDS and to assess the possible impact of COVID-19 on mortality. DESIGN SETTING AND PARTICIPANTS: Multicenter retrospective study in 15 ICUs worldwide. All adult patients (> 18 yr) were included if they received VV ECMO with ARDS as main indication. Two groups were created: a COVID-19 cohort from March 2020 to December 2020 and a "control" non-COVID ARDS cohort from January 2018 to July 2019. MAIN OUTCOMES AND MEASURES: Collected data consisted of patient demographics, baseline variables, ECMO characteristics, and patient outcomes. The primary outcome was 60-day mortality. Secondary outcomes included patient characteristics, COVID-19-related therapies before and during ECMO and complication rate. To assess the influence of COVID-19 on mortality, inverse probability weighted (IPW) analyses were used to correct for predefined confounding variables. RESULTS: A total of 193 patients with COVID-19 received VV ECMO. The main indication for VV ECMO consisted of refractory hypoxemia, either isolated or combined with refractory hypercapnia. Complications with the highest occurrence rate included hemorrhage, an additional infectious event or acute kidney injury. Mortality was 35% and 45% at 28 and 60 days, respectively. Those mortality rates did not differ between the first and second waves of COVID-19 in 2020. Furthermore, 60-day mortality was equal between patients with COVID-19 and non-COVID-19-associated ARDS receiving VV ECMO (hazard ratio 60-d mortality, 1.27; 95% CI, 0.82-1.98; p = 0.30). CONCLUSIONS AND RELEVANCE: Mortality for patients with COVID-19 who received VV ECMO was similar to that reported in other COVID-19 cohorts, although no differences were found between the first and second waves regarding mortality. In addition, after IPW, mortality was independent of the etiology of ARDS.

Aged versus fresh autologous platelet transfusion in a two-hit healthy volunteer model of transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a severe complication of blood transfusion that is thought of as a two-hit event: first the underlying patient condition (e.g., sepsis), and then the transfusion. Transfusion factors include human leukocyte antigen antibodies or biologic response modifiers (BRMs) accumulating during storage. Preclinical studies show an increased TRALI risk with longer stored platelets, clinical studies are conflicting. We aim to discover whether longer platelet concentrate (PC) storage time increases TRALI risk in a controlled human experiment. STUDY DESIGN AND METHODS: In a randomized controlled trial, 18 healthy male volunteers received a first hit of experimental endotoxemia (2 ng/kg lipopolysaccharide), and a second hit of fresh (2-day old) or aged (7-day old) autologous PC, or physiological saline. After 6 h, changes in TRALI pathways were determined using spirometry, chest X-ray, and bronchoalveolar lavage (BAL). RESULTS: All subjects reacted adequately to lipopolysaccharide infusion and satisfied SIRS criteria (increased pulse [>90/min] and temperature [>38°C]). There were no differences between the saline, fresh, and aged PC groups in BAL-fluid protein (95 ± 33 µg/ml; 83 ± 21 µg/ml and 104 ± 29 µg/ml, respectively) and relative neutrophil count (1.5 ± 0.5%; 1.9 ± 0.8% and 1.3 ± 0.8%, respectively), nor in inflammatory BAL-fluid BRMs (Interleukin-6, CXCL8, TNFα , and myeloperoxidase), clinical respiratory parameters, and spirometry results. All chest X-rays were normal. CONCLUSIONS: In a human endotoxemia model of autologous platelet transfusion, with an adequate first hit and platelet storage lesion, transfusion of 7-day-old PC does not increase pulmonary inflammation compared with 2-day-old PC.

Variation in haplotypes in single cysts of assemblages C and D, but not of assemblage E of Giardia duodenalis.

BACKGROUND: Giardia duodenalis, a single-celled intestinal parasite, is divided into eight assemblages (A-H), with differences in host specificity. Giardia duodenalis reproduces asexually and cycles between the binucleated trophozoite (4 N) and the infectious cyst with four nuclei (16 N). Interaction between the nuclei is limited. Therefore, genetic drift causes differences in genetic make-up between the non-daughter nuclei; the allelic sequence heterozygosity (ASH). The ASH is low (0.01%-0.0023%) for the related assemblages A and E, higher (0.43-0.53) for assemblage B and much higher (0.74% -0.89%) for the assemblage C and D at the root of the phylogenetic tree. The heterozygosity in assemblage F, in the same clade as assemblage A and E, was unknown. The heterozygosity in the sequences of the gdh and dis3 genes was used as proxy for the ASH and whole genome amplification of single cysts followed by cloning and Sanger sequencing of dis3 fragment could reveal the genetic variation within the cyst. The aim of the study was to determine the level of heterozygosity within pooled and single cysts of different assemblages. RESULTS: The heterozygosity in gdh and dis3 was determined in pooled cysts of the assemblages A to F. Heterozygosity in the isolates of the assemblages C (n = 2) and D (n = 1) ranged from 0.41% to 0.82% for gdh and dis3 and no heterozygosity was found in the isolates of the assemblages A (n = 4), E (n = 3) and F (n = 3). The heterozygosity in assemblage B (n = 7) was intermediate (0% to 0.62%). Next, the number of haplotypes of dis3 was determined for single cysts of assemblages C, D and E. In the assemblages C and D, two to four haplotypes were found per cyst, while in assemblage E only one haplotype was identified. CONCLUSIONS: Having high heterozygosity is characteristic for the assemblages C and D, while having a low heterozygosity is characteristic for the clade with the assemblages A, E and F. Presence of more than 1 haplotype per cyst in assemblage C and D suggests differences between the non-daughter nuclei, in contrast to the one haplotype in assemblage E.

A Healthcare Physician Can Be Trained to Perform Intestinal Ultrasound in Children With Inflammatory Bowel Disease.

OBJECTIVES: Training healthcare physicians to perform intestinal ultrasound (IUS) during outpatient visits with equal accuracy as radiologists could improve clinical management of IBD patients. We aimed to assess whether a healthcare-physician can be trained to perform IUS, with equal accuracy compared with experienced radiologists in children with iBD, and to assess inter-observer agreement. METHODS: Consecutive children, 6 to 18 years with IBD or suspicion of IBD, who underwent ileo-colonoscopy were enrolled. iUS was performed independently by a trained healthcare-physician and a radiologist in 1 visit. Training existed of an international training curriculum for IUS. Operators were blinded for each other's IUS, and for the ileocolonoscopy. Difference in accuracy of IUS by the healthcare-physician and radiologist was assessed using areas under the ROC curve (AUROC). Inter-observer variability was assessed in terminal ileum (TI), transverse colon (TC) and descending-colon (DC), for disease activity (ie, bowel wall thickness [BWT] >2 mm with hyperaemia or fat-proliferation, or BWT >3 mm). RESULTS: We included 73 patients (median age 15, interquartile range [IQR]:13-17, 37 [51%] female, 43 [58%] with Crohn disease). AUROC ranged between 0.71 and 0.81 for the healthcare-physician and between 0.67 and 0.79 for radiologist (P  > 0.05). Inter-observer agreement for disease activity per segment was moderate (K: 0.58 [SE: 0.09], 0.49 [SE: 0.12], 0.52 [SE: 0.11] respectively for TI, TC, and DC). CONCLUSIONS: A healthcare- physician can be trained to perform IUS in children with IBD with comparable diagnostic accuracy as experienced radiologists. The interobserver agreement is moderate. Our findings support the usage of IUS in clinical management of children with IBD.

Contribution of Coagulopathy on the Risk of Bleeding After Central Venous Catheter Placement in Critically Ill Thrombocytopenic Patients.

Critically ill patients often undergo central venous catheter placement during thrombocytopenia and/or coagulopathy. It is unclear whether severe coagulopathy increases the risk of postprocedural bleeding in critically ill patients with severe thrombocytopenia. DESIGN: Single-center retrospective cohort study. SETTING: Academic mixed ICU in Amsterdam, the Netherlands. PATIENTS: Consecutive severely thrombocytopenic (platelet count ≤ 50 × 109/L) patients who underwent central venous catheter placement between February 2016 and February 2020. INTERVENTIONS: Central venous catheter placement in patients with both severe thrombocytopenia and severe coagulopathy (international normalized ratio > 1.5 and/or activated partial thromboplastin time > 45 s) versus patients with severe thrombocytopenia and normal or mildly prolonged international normalized ratio and activated partial thromboplastin time. MEASUREMENTS AND MAIN RESULTS: We included 289 central venous catheter placements in 175 patients, 112 in patients with and 172 in patients without severe coagulopathy. Median (interquartile range) platelet count was 27 (16-38) and equal for both groups. There were 44 bleeding episodes at the central venous catheter insertion site (15.5%), of which four (1.4%) were grade 2 and two (0.7%) were grade 3. There were 19 bleeding episodes (17.0%) versus 25 bleeding episodes (14.5%) in the coagulopathy and noncoagulopathy groups, of which one and five were of grade 2 or higher, respectively. After correction for confounders, coagulopathy had no effect on bleeding: odds ratio (95% CI) 0.96 (0.24-3.88). Before central venous catheter placement, 116 (40.8%) patients received platelet transfusion. Bleeding at the central venous catheter insertion site occurred in 19 of 116 patients (16.4%) and 25 of 168 patients (14.9%) who did and did not receive platelet transfusion. After correction for confounders, platelet transfusion had no effect on bleeding: odds ratio (95% CI) 0.73 (0.18-2.83). CONCLUSIONS: Coagulopathy was not associated with an increased bleeding risk in severely thrombocytopenic ICU patients undergoing ultrasound guided central venous catheter placement. Prophylactic platelet transfusion in patients with severe thrombocytopenia was not associated with a reduced risk of bleeding.

Five versus seven days of nitrofurantoin for urinary tract infections in women with diabetes: a retrospective cohort study.

OBJECTIVE: To compare the effectiveness of 5 versus 7 days of nitrofurantoin treatment for urinary tract infection (UTI) in women with diabetes. METHODS: Data were collected retrospectively from Dutch general practitioners between 2013 and 2020. Nitrofurantoin prescriptions with a duration of 5 days (5DN) or 7 days (7DN) in women with diabetes were included. Inverse propensity weighting was performed to calculate adjusted risk differences (RD) for treatment failure within 28 days. Secondary outcomes were 14-day treatment failure, severe treatment failure and 28-day treatment failure in defined risk groups. RESULTS: Nitrofurantoin was prescribed in 6866 episodes, 3247 (47.3%) episodes with 5DN and 3619 (52.7%) episodes with 7DN. Patients in the 7DN group had more co-morbidities, more diabetes-related complications and were more insulin-dependent. There were 517/3247 (15.9%) failures in the 5DN group versus 520/3619 (14.4%) in the 7DN group. The adjusted RD for failure within 28 days was 1.4% (95% CI -0.6 to 3.4). CONCLUSION: We found no clinically significant difference in treatment failure in women with diabetes with UTI treated with either 5DN or 7DN within 28 days. A 5-day treatment should be considered to reduce cumulative nitrofurantoin exposure in DM patients.

Influence of donor cytomegalovirus (CMV) status on severity of viral reactivation after allogeneic stem cell transplantation in CMV-seropositive recipients.

We investigated the role of donor cytomegalovirus (CMV) serostatus on reactivation of CMV infection in CMV-infected transplant recipients. Reactivation of CMV infection occurred more frequently in patients receiving a CMV-positive graft but was less severe than in patients receiving a CMV-negative graft. These data suggest roles for both virus as well as CMV-specific immunity present in the graft.

Long-term outcomes of eye-conserving treatment with Ruthenium(106) brachytherapy for choroidal melanoma.

PURPOSE: To evaluate long-term outcomes of eye-conserving treatment using Ruthenium-106 plaque brachytherapy with or without transpupillary thermotherapy (TTT) for small to intermediate size choroidal melanomas. METHODS: Outcomes of 425 consecutive patients were analysed. The median basal tumour diameter was 10.9 mm (range 4.8-15.9 mm), and the median apical height 4.2 mm (range 1.2-9.3 mm). Brachytherapy doses ranged from 400 to 600Gy with TTT (86%), or from 600 to 800Gy without TTT (14%), specified at the scleral surface. Kaplan-Meier survival curves, log-rank tests and Cox regression analysis were used for analysis. RESULTS: Median follow-up was 50 months. Five-year actuarial local control was 96%. Five-year overall and metastases-free survival rates were 79.6% and 76.5%. Prognostic factors for metastasis-free survival were peripheral location (p=0.02) and smaller basal diameter (p<0.001). No dose effect relationships were found. Radiation side effects were frequent, with 2- and 5-year rates free of radiation complications of 60% and 35%. Five-year enucleation rate was 4.4% (10 for local recurrence, 7 for complications). Cosmetic and functional (visual acuity >0.10) eye preservation rates were 96% and 52% at 5 years. CONCLUSIONS: Ruthenium-106 brachytherapy for choroidal melanoma provides excellent rates of local control and eye preservation.

Myocardial metabolism, catecholamine balance, and left ventricular function during coronary artery surgery: effects of nitroprusside and nifedipine.

The effects of nitroprusside and nifedipine on myocardial oxygen consumption (MVO2), catecholamine release, and left ventricular (LV) function (using 2D transesophageal echocardiography) were compared. Thirty-seven patients undergoing coronary artery surgery, anesthetized with fentanyl, 100 micrograms/kg, were studied. All had good LV function and had been receiving long-term oral beta-blocking therapy. Patients were randomly allocated to one of three groups. Group C (n = 12) received no vasodilator and served as control. Group S (n = 13) received nitroprusside at an initial rate of 1 microgram/kg/min. Group N (n = 12) received nifedipine at an initial rate of 0.7 microgram/kg/min. Baseline measurements were obtained ten minutes after intubation. Vasodilator therapy was then started in groups S and N. Infusion rates were adjusted to maintain systolic blood pressure (SBP) between 80% and 120% of baseline values. Additional measurements were made ten minutes after the start of the infusion, ie, before surgery (in group C immediately before surgery), and after sternotomy when the pericardium was opened. The mean (+/- SD) total dose requirements were 1.9 +/- 0.5 micrograms/kg/min for nitroprusside and 1.1 +/- 0.2 micrograms/kg/min for nifedipine. The mean (+/- SD) total infusion time was 31 +/- 5 minutes for nitroprusside and 32 +/- 11 minutes for nifedipine. After sternotomy, heart rate increased in all groups. At this time arterial blood pressure and systemic vascular resistance (SVR) increased in group C. SVR was decreased after the first ten minutes of nitroprusside infusion and after sternotomy in group S. Coronary sinus blood flow, MVO2, and myocardial norepinephrine release increased in group N, but not in groups C or S. After sternotomy, LV percentage area reduction increased in groups S and N, but not in group C. In group N there was a significant correlation (r = 0.65; P less than .05) between the increases in MVO2 and LV percentage area reduction, an estimate of myocardial function. Lactate production occurred in two patients in group C after sternotomy. This was not associated with ECG changes, but in one patient regional wall motion abnormalities developed. No evidence of myocardial ischemia was observed in groups S and N. However, in contrast to nitroprusside, the use of nifedipine was associated with increases in MVO2, myocardial norepinephrine release, and inotropy.

Investigating the phenomenon of helplessness in mentally retarded adults.

Helplessness, or the inability to take effective action in a problem situation, appears to involve both behavioral-motivational and competence factors. As a personality characteristic, it may cause difficulties in community adjustment for mentally retarded persons. Helplessness in a group of mentally retarded adults was investigated through a set of behavioral and questionnaire measures specifically adapted for this population. Similar measures were applied to a CA control group. Both institutionalized and noninstitutionalized retarded subjects exhibited significantly more signs of helplessness than did the nonretarded control subjects. The results support the hypothesis that helplessness is a meaningful personality dimension among retarded persons and can be objectively measured.