Endobronchial Valves in Treatment of Persistent Air Leak: European case-series study and Best Practice Recommendations - from an Expert Panel.

Introduction Persistent air leak (PAL) is associated with prolonged hospitalization, high morbidity and increased treatment costs. Conservative treatment consists of observation, chest tube drainage and pleurodesis. Guidelines recommend surgical evaluation if air leak does not respond after 3-5 days. One-way endobronchial valves (EBV) have been proposed as a treatment option for patients with PAL in which surgical treatment is not feasible, high risk or has failed. We aimed to provide a comprehensive overview of reported EBV use for PAL and issue best practice recommendations based on multicenter experience. Methods We conducted a retrospective observational case-series study at four different European academic hospitals and provided best practice recommendations based on our experience. A systematic literature review was performed to summarize the current knowledge on EBV in PAL. Results We enrolled 66 patients, male (66.7%), median age 59.5 years. The most common underlying lung disease was chronic obstructive pulmonary disease (39.4%), and lung cancer (33.3%). The median time between pneumothorax and valve placement was 24.5 days (IQR: 14.0-54.3). Air leak resolved in 40/66 patients (60.6%) within thirty days after endobronchial valve treatment. Concerning safety outcome, no procedure related mortality was reported and complication rate was low (6.1%). 5 patients (7.6%) died in the first 30 days after intervention. Conclusion EBV placement is a treatment option in patients with persistent air leak (PAL). In this multicenter case-series of high risk patients not eligible for lung surgery, we show that EBV placement resulted in air leak resolution in 6 out of 10 patients with a low complication rate. Considering the minimally invasive nature of EBV to treat PAL as opposed to surgery, further research should investigate if EBV treatment should be expanded in low to intermediate risk PAL patients.

An Infant with Bilateral Keratitis: From Infectious to Genetic Diagnosis.

BACKGROUND Tyrosinemia Type II (TYRII) is a rare autosomal recessive inborn error of metabolism caused by deficiency of tyrosine aminotransferase (TAT), leading to hypertyrosinemia. TYRII patients often present in the first year of life with ocular and cutaneous findings, including corneal ulcers, pseudodendritic keratitis, and palmoplantar hyperkeratosis. The corneal involvement is often mistaken for herpes simplex virus (HSV) keratitis, which is a much commoner condition. CASE REPORT A previously healthy 10-month-old male infant was referred to Ophthalmology for acute onset photophobia. Bilateral dendritiform corneal lesions raised the suspicion for herpetic keratitis. Additionally, a papular, crusted lesion was found on his thumb after a few days of hospitalization, also raising concerns about HSV. The patient's clinical condition seemed to improve under intravenous acyclovir and supportive treatment. A conjunctival swab and crusted lesion on the thumb were tested for HSV using a polymerase chain reaction (PCR) technique, and both were negative. Nevertheless, given the clinical presentation and the favorable course of signs and symptoms, hospital discharge was planned with oral acyclovir. It was halted by an alternative diagnosis of autosomal recessive inborn error of metabolism, tyrosinemia type II, confirmed by elevated plasma tyrosine level and later by molecular analysis requested as a confirmatory investigation by the genetics medical team. CONCLUSIONS The corneal involvement in TYRII is often mistaken for HSV keratitis, and clinical course alone should not halt further investigations to rule out TYRII. Clinicians should suspect TYRII clinically when its characteristic ocular dendritiform lesions are present, namely in infancy or early childhood, and even in the absence of its typical cutaneous palmoplantar hyperkeratosis plaques.

Residents as Research Subjects: Balancing Resident Education and Contribution to Advancing Educational Innovations.

Background: Research in education advances knowledge and improves learning, but the literature does not define how to protect residents' rights as subjects in studies or how to limit the impact of their participation on their clinical training. Objective: We aimed to develop a consensual framework on how to include residents as participants in education research, with the dual goal of protecting their rights and promoting their contributions to research. Methods: A nominal group technique approach was used to structure 3 iterative meetings held with the pre-existing residency training program committee and 7 invited experts between September 2018 and April 2019. Thematic text analysis was conducted to prepare a final report, including recommendations. Results: Five themes, each with recommendations, were identified: (1) Freedom of participation: participation, non-participation, or withdrawal from a study should not interfere with teacher-learner relationship (recommendation: improve recruitment and consent forms); (2) Avoidance of over-solicitation (recommendation: limit the number of ongoing studies); (3) Management of time dedicated to participation in research (recommendations: schedule and proportion of time for study participation); (4) Emotional safety (recommendation: requirement for debriefing and confidential counseling); and (5) Educational safety: data collected during a study should not influence clinical assessment of the resident (recommendation: principal investigator should not be involved in the evaluation process of learners in clinical rotation). Conclusions: Our nominal group technique approach resulted in raising 5 specific issues about freedom of participation of residents in research in medical education, over-solicitation, time dedicated to research, emotional safety, and educational safety.

Comparison of the Effect of Holder Pasteurization and High-Pressure Processing on Human Milk Bacterial Load and Bioactive Factors Preservation.

OBJECTIVES: This project aims at comparing the impact of Holder pasteurization (HoP) and high-pressure processing (HPP) on bacterial load and retention of immunological components in human milk. METHODS: Human milk samples discarded by the Public Mothers' milk bank (Montreal, Canada) for bacterial purpose were pooled (n = 6) and pasteurized either by heating in a water bath (62.5°C, 30 minutes) or by HPP treatment (425 MPa, four cycles of 6 minutes, initial milk temperature of 4°C or 37°C). Bacterial load, lysozyme activity, and levels of immunoglobulins, lactoferrin, lipase, and 26 cytokines were analyzed. Untreated milk samples from same pools served as control. RESULTS: HPP treatment of milk allows a similar elimination of bacteria than HoP; bacterial counts were under the detection limit [<3 colony-forming units (CFU)/mL] in 50% of milk pools after HPP treatment, compared to 17% for HoP. With initial heating of samples to 37°C before HPP treatment, inactivation to an extent under the detection limit was reached in 67% of pools. There is no significant difference in IgA, lysozyme, and cytokines concentrations between untreated milk and all treatment methods. While no significant difference was observed in the amount of lipase (P > 0.07) and IgG (P > 0.11) between untreated milk and HPP-treated milk samples, HoP seems to be damaging for these factors (P < 0.04). IgM is well preserved in HPP-4°C samples compared to untreated milk (P = 0.07) whereas a decrease is observed for this immunoglobulin levels in HPP-37°C and HoP samples (P < 0.01). Lactoferrin activity, is well maintained in HPP-37°C milk samples in comparison to untreated milk samples (P = 0.52). A decrease in activity of this molecule is noted for samples treated with HPP at 4°C (P = 0.02) and this decrease is even more pronounced for HoP samples (P = 0.004). CONCLUSIONS: HPP is a promising alternative to HoP for treatment of human milk intended to preterm babies. Our results demonstrate that HPP treatment of human milk provides safe milk with less detrimental effects on the biochemically and immunologically active milk components than HoP.

Parents' perspectives, information needs and healthcare preferences when consulting for their children with bronchiolitis: A qualitative study.

AIM: Bronchiolitis is the leading cause of hospitalisation in infants, but parental experiences have not been well described. This study explored parents' experiences and asked them how they wanted to receive information. METHODS: A qualitative study was conducted in a tertiary paediatric hospital in Québec, Canada. It consisted of semi-structured interviews with 15 parents of 13 children with bronchiolitis. The interview guide was constructed by a multidisciplinary team that included a parent. The interviews, which were transcribed verbatim, were conducted until no new themes emerged. RESULTS: We interviewed eight mothers, three fathers and two couples for 22-70 minutes: six were carried out in person during the bronchiolitis episode, and seven were phone interviews after a median interval time of 107 days. Parents were very worried about their child's health and their lack of knowledge about bronchiolitis contributed to their anxiety. They found education resources informative, but expressed a strong need for support and reassurance from healthcare teams. The two groups provided similar feedback, regardless of when they were interviewed or whether their child was admitted. CONCLUSION: Although bronchiolitis is common in infancy, parental knowledge was low. Standardised educational tools were useful, but insufficient to meet all their needs.

Rhesus D Antigenic Determinants on Residual Red Blood Cells in Apheresis and Buffy Coat Platelet Concentrates.

BACKGROUND: The level of residual red blood cells (RBCs) in platelet concentrates (PCs) is of interest because of clinical concerns related to alloimmunization to RBC antigens in transfused patients. This work aims at characterizing and quantifying the levels of intact and fragmented RBCs in apheresis (AP-PCs) and buffy coat PCs (BC-PCs) to assess their potential risk for RhD antigen alloimmunization. METHODS: After staining with anti-CD41 (platelets) and anti-CD235a (RBCs) antibodies, the size and density of RhD antigen on intact and fragmented RBCs were analyzed by flow cytometry. RESULTS: Residual RBC counts were 29 ± 22 × 106/unit in AP-PCs and 121 ± 54 × 106/unit in BC-PCs, which correspond to about 3 and 11 µL of RBCs by product, respectively. RhD expression was about 4 times higher on RBC particles in AP-PCs, and these particles contribute to 66 and 75% of the total antigenic load in BC-PCs and AP-PCs, respectively. CONCLUSIONS: Processing methods influence the quantity and nature of contaminating residual RBCs and RBC-derived particles in PCs. The estimation of residual RBCs in these blood products is generally based on measurements of intact RBCs, which might underestimate the risk for alloim-munization in transfused patients. The question of whether these RBC-derived particles can produce an immune response and, thus, should then be taken into consideration for Rh immune prophylactic treatments, remains to be clarified.

Pulmonary hypertension-targeted therapies in heart failure: A systematic review and meta-analysis.

BACKGROUND: Pulmonary hypertension (PH) due to left heart failure (HF) is the most common form of PH. However, treatment is unclear because there are conflicting results about safety and efficacy of PH-targeted therapies. OBJECTIVES: To assess the effects of PH-targeted therapy on exercise capacity in HF patients. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched from January 1990 to July 2017 for randomized controlled trials comparing PH-targeted therapies to conventional therapy in HF. The primary outcome was to assess the effects on exercise capacity. Secondary outcomes included mortality, hospitalisation, NT-proBNP levels, echocardiographic and hemodynamics parameters and discontinuation rate. RESULTS: 22 studies were included (n = 5448), including 3, 8 and 11 studies with low, high and unknown risk of bias, respectively. PH-targeted therapies were associated with an improvement of exercise capacity (standardized mean difference 0.29;95%CI:0.08-0.50, p = 0.006). Pre-specified subgroup analyses found that this improvement was predominantly observed in studies evaluating phosphodiesterase-5 inhibitors and prostanoids and in patients with reduced ejection fraction. Moreover, systolic pulmonary artery pressure measured by echocardiography was improved (mean difference: -7.5mmHg; [95%CI]: -14.9,-0.1, p = 0.05), which was also entirely driven by studies evaluating phosphodiesterase-5 inhibitors. However, PH-targeted therapies were associated with an increased treatment discontinuation rates and a potential increase in mortality compared to standard treatment. CONCLUSIONS: In conclusion, PH-targeted therapies and especially phosphodiesterase-5 inhibitors may improve exercise capacity in patients with HF. However, an increase in adverse outcomes was likely. Moreover, most studies were at high or unknown risk of bias, precluding confident conclusions about the effects of PH-targeted therapies.

Bordetella holmesii Contamination of Platelet Concentrates: Revisiting the Definition of a Positive Culture.

Bacterial contamination remains the most important infectious risk of platelet transfusion. After an initially positive result, a second test is performed on the blood products and the initial culture bottle to confirm the contamination. Based on the blood center's decision algorithm used, results can be either confirmed negative, positive, or indeterminate, or be unconfirmed or discordant. Here, we report the first cases of platelet concentrates contaminated with Bordetella holmesii The in vitro growth characteristics of this unusual contaminant in platelet concentrate were investigated. Two B. holmesii strains isolated from platelet concentrates, as well as a control strain (Serratia marcescens), were spiked into platelet concentrates (PCs) at 1 and 10 CFU/ml. PCs were stored at 20 to 24°C under agitation. Samples were collected on days 2, 3, 4, and 7 for colony count and for bacterial screening using the BacT/Alert 3D system. Two PCs were detected as being positive for B. holmesii However, recultures were negative. In vitro, B. holmesii did not grow but remained detectable in PCs. Its viability diminished rapidly in contact with human plasma. Upon screening using the BacT/Alert 3D system, the majority of products spiked with B. holmesii were negative. This is the first description of PCs contaminated with B. holmesii This bacterium survives in blood products and remains dormant at low concentrations in blood products stored at room temperature, thus making difficult its detection with the BacT/Alert 3D system. The present definition of a true-positive culture of PCs may be overly restrictive for certain bacterial strains.

Pulmonary micro-tumor emboli resulting in paradoxical emboli: a case report.

Pulmonary tumor embolism (PTE) is a rare manifestation of cancer. It is characterized by the presence of tumor cell emboli in the pulmonary arterioles and capillaries leading to an elevation of pulmonary vascular resistance. The ante-mortem diagnosis is difficult. We report a case of PTE associated with recurrent breast cancer that presented with neurological symptoms due to paradoxical cerebral embolism.

Timing of gamma irradiation and blood donor sex influences in vitro characteristics of red blood cells.

BACKGROUND: There are few studies investigating the effect of irradiation on red blood cells (RBCs) during storage. This study analyzed changes in in vitro quality of RBCs irradiated at several points during storage with the aim of providing evidence to support current maximum pre- and postirradiation storage limits. STUDY DESIGN AND METHODS: Each of seven participating centers produced four pools of 7 standard RBC units (SAGM, AS-3, or PAGGSM), which were then split back into 7 units. All units in a pool were from sex-matched blood donors. Every week during 6 weeks of refrigerated storage, 1 unit was irradiated, while 1 unit was not irradiated (control). Units were tested weekly for biochemical variables, morphology, and mechanical fragility. RESULTS: The earlier during storage that units were irradiated, the higher the hemolysis and K+ at end of storage. Irrespective of the timing of irradiation, there was a rapid increase in extracellular K+ , followed by a more gradual increase in hemolysis. ATP levels decreased faster in irradiated units and were reduced below accepted values if irradiated early. Irradiated female RBCs had an absolute lower hemolysis and K+ level compared to male RBCs at all time points. CONCLUSIONS: The method of blood component manufacturing determined the absolute levels of hemolysis and potassium in irradiated and nonirradiated units, but did not influence the effect that timing of irradiation had on the in vitro quality characteristics. This study provides support for the current Council of Europe guidelines on the time limitations for the irradiation of RBCs.

Optimization of cord blood unit sterility testing: impact of dilution, analysis delay, and inhibitory substances.

BACKGROUND: Different methods are used by cord blood banks to prepare samples for sterility testing. Suboptimal methods can result in the release of contaminated products. In our organization, samples are prepared by diluting the final product in RPMI-1640 medium. In this work, we have compared our method with different approaches to verify whether optimization should be sought. STUDY DESIGN AND METHODS: Cord blood units (n = 6 units per bacterial strain) characterized to contain inhibitory substances or not were inoculated (10 colony-forming units/mL) with Streptococcus agalactiae, Staphylococcus epidermidis, Klebsiella pneumoniae, Escherichia coli, or Bacteroides fragilis. After plasma and red blood cell removal, stem cell concentrates were diluted in RPMI-1640, thioglycollate, or the unit's plasma. These products, as well as final product, plasma, and red blood cell fractions, were held from 0 to 72 hours at 20 to 24°C before inoculation in culture bottles and detection using the BacT/ALERT 3D system. RESULTS: Dilution of cell concentrates in RPMI-1640 allowed bacterial detection in 93.3% of noninhibitory cord blood samples after a 24-hour storage period. Thioglycollate medium better promoted bacterial growth in inhibitory cord blood samples that were held for 72 hours before testing (66.7%) compared with RPMI-1640 (45.0%). Less than 33% of all spiked plasma samples were detected by the BacT/ALERT 3D system. CONCLUSION: Diluting cord blood samples in culture medium containing bacterial growth promoting substances is a suitable option for sterility testing, whereas the use of plasma should be proscribed, because it might lead to false-negative results. Because inhibitory substances affect bacterial growth, inoculation of culture bottles should be done rapidly after sample preparation.

Microparticle and mitochondrial release during extended storage of different types of platelet concentrates.

On activation, platelets release vesicles called microparticles (MPs). MPs are heterogeneous with regard to the presence or absence of mitochondria. We quantified MPs in platelet concentrates (PCs) taking their mitochondrial content into account. Platelet-rich plasma (PRP), buffy coat (BC) and apheresis (AP) PCs were tested through 7 days of storage. A combination of flow cytometry and spanning-tree progression analysis of density-normalized events (SPADE) was used to determine MP and mitochondrial release during storage. All the PC biochemical parameters complied with transfusion standards at all times. Platelet activation markers increased during storage and were higher for PRP than other types of PCs. Concentrations of MPs and extracellular mitochondria interpreted by SPADE algorithm were significantly higher in PRP than other in PCs and were stable throughout storage. The mode of preparation, rather than storage duration, impacts the release of MPs and mitochondria in PCs.

Changing the 30-min Rule in Canada: The Effect of Room Temperature on Bacterial Growth in Red Blood Cells.

BACKGROUND: To maintain product quality and safety, the '30-min rule' requires the discard of red blood cells (RBCs) that are exposed to uncontrolled temperatures for more than 30 min. Recent studies suggest this rule may safely be extended to a 60-min rule. METHODS: A pool-and-split design study (N = 4) was run in parallel at Canadian Blood Services (SAGM RBCs) and Héma-Québec (AS-3 RBCs). RBCs were spiked with ∼1 colony-forming unit/ml of mesophilic and psychrophilic bacteria. Control units remained in storage at 1-6 °C for 42 days. Test 30 (T30) and T60 units were exposed to room temperature (RT) six times during storage, each time for 30 and 60 min, respectively. Bacterial proliferation was monitored. RESULTS: Mesophilic bacteria do not proliferate in RBCs. The growth of psychrophilic bacteria is not significantly different in RBCs exposed for 30 or 60 min to RT (p < 0.05). CONCLUSION: The study findings were the final evidence to support extension from a 30-min rule to a 60-min rule in Canada.

Pressure Infusion Cuff and Blood Warmer during Massive Transfusion: An Experimental Study About Hemolysis and Hypothermia.

BACKGROUND: Blood warmers were developed to reduce the risk of hypothermia associated with the infusion of cold blood products. During massive transfusion, these devices are used with compression sleeve, which induce a major stress to red blood cells. In this setting, the combination of blood warmer and compression sleeve could generate hemolysis and harm the patient. We conducted this study to compare the impact of different pressure rates on the hemolysis of packed red blood cells and on the outlet temperature when a blood warmer set at 41.5°C is used. METHODS: Pressure rates tested were 150 and 300 mmHg. Ten packed red blood cells units were provided by Héma-Québec and each unit was sequentially tested. RESULTS: We found no increase in hemolysis either at 150 or 300 mmHg. By cons, we found that the blood warmer was not effective at warming the red blood cells at the specified temperature. At 150 mmHg, the outlet temperature reached 37.1°C and at 300 mmHg, the temperature was 33.7°C. CONCLUSION: To use a blood warmer set at 41.5°C in conjunction with a compression sleeve at 150 or 300 mmHg does not generate hemolysis. At 300 mmHg a blood warmer set at 41.5°C does not totally avoid a risk of hypothermia.

Retrospective Attention Gates Discrete Conscious Access to Past Sensory Stimuli.

Cueing attention after the disappearance of visual stimuli biases which items will be remembered best. This observation has historically been attributed to the influence of attention on memory as opposed to subjective visual experience. We recently challenged this view by showing that cueing attention after the stimulus can improve the perception of a single Gabor patch at threshold levels of contrast. Here, we test whether this retro-perception actually increases the frequency of consciously perceiving the stimulus, or simply allows for a more precise recall of its features. We used retro-cues in an orientation-matching task and performed mixture-model analysis to independently estimate the proportion of guesses and the precision of non-guess responses. We find that the improvements in performance conferred by retrospective attention are overwhelmingly determined by a reduction in the proportion of guesses, providing strong evidence that attracting attention to the target's location after its disappearance increases the likelihood of perceiving it consciously.

How does the extraction of local and global auditory regularities vary with context?

How does the human brain extract regularities from its environment? There is evidence that short range or 'local' regularities (within seconds) are automatically detected by the brain while long range or 'global' regularities (over tens of seconds or more) require conscious awareness. In the present experiment, we asked whether participants' attention was needed to acquire such auditory regularities, to detect their violation or both. We designed a paradigm in which participants listened to predictable sounds. Subjects could be distracted by a visual task at two moments: when they were first exposed to a regularity or when they detected violations of this regularity. MEG recordings revealed that early brain responses (100-130 ms) to violations of short range regularities were unaffected by visual distraction and driven essentially by local transitional probabilities. Based on global workspace theory and prior results, we expected that visual distraction would eliminate the long range global effect, but unexpectedly, we found the contrary, i.e. late brain responses (300-600 ms) to violations of long range regularities on audio-visual trials but not on auditory only trials. Further analyses showed that, in fact, visual distraction was incomplete and that auditory and visual stimuli interfered in both directions. Our results show that conscious, attentive subjects can learn the long range dependencies present in auditory stimuli even while performing a visual task on synchronous visual stimuli. Furthermore, they acquire a complex regularity and end up making different predictions for the very same stimulus depending on the context (i.e. absence or presence of visual stimuli). These results suggest that while short-range regularity detection is driven by local transitional probabilities between stimuli, the human brain detects and stores long-range regularities in a highly flexible, context dependent manner.