Quality validation of platelets obtained from the Haemonetics and Trima Accel automated blood-collection systems

BackgroundPlatelet transfusion is required to treat haemo-oncology or trauma patients. Platelet apheresis (PA) performed with apheresis equipment has increased rapidly in recent years. Leucocyte-reduced platelet apheresis (LRPA) can reduce the risk of platelet refractoriness and febrile nonhemolytic transfusion reactions (FNHTRs) for transfusion. Accordingly, this study aimed to investigate and compare the platelet metabolic and functional responses between PA performed with Haemonetics and LRPA performed with Trima Accel cell separator.MethodsThe qualities of platelets collected through PA and LRPA were evaluated in terms of visual appearance, morphology, platelet-aggregation changes, metabolic activities, and bacterium-screening test during 5-day storage. Statistical analyses included two-sample t-test and generalised estimating equation(GEE) method.ResultsDuring 5-day storage in LRPA, residual leucocytes were all <1.0×10⁶, and the parameters of platelet function were as follows: platelet aggregated to agonists such as adenosine 5′-diphosphate (ADP) and collagen, and the extent of shape change and pO₂ showed no statistically significant difference between PA and LRPA. The hypotonic shock reaction (HSR) on days 0, 1, and 3 were significantly higher in LRPA than in PA (71.78±6.92 vs. 64.10±7.42; P=0.002; 71.53±8.98 vs. 62.96±9.84; P=0.007; 68.05±7.28 vs. 57.76±6.80; P<0.0001, respectively). Values of mean platelet volume (MPV) were statistically larger in PA than in LRPA on days 0, 1, and 3. On day 5, the swirling score was higher in LRPA than in PA. The mean lactate levels had no statistically significant difference between PA and LRPA. Moreover, no growth was observed through bacterium-screening test conducted on 40 samples.ConclusionComparison of LRPA and PA products collected from the Trima Accel and Haemonetics automated blood-collection systems, respectively, revealed that both products possessed good platelet qualities even though additional processes are needed to reduce leucocytes. Furthermore, investigating the outcomes of other apheresis instruments with focus on the safety of donors, products, and recipients is necessary.     

Minor salivary glands: Clinical,histological and immunohistochemical features of common and less common pathologies

Hundreds of minor salivary glands (MiSGs) are scattered in the oral cavity located at the submucosa layer. Beside their role in the oral cavity lubrication and immunity defence system, MiSGs are beneficial tissue source for diagnosing oral and non-oral related diseases. The advantage of MiSGs as a diagnostic tool reside on their fairly simple excisional procedure on one hand and negligible impact of the normal secretion capability of the salivary gland system on the other hand. The review focuses on pathologies related to developmental, reactive, metabolic, inflammatory and immunologic conditions, Iatrogenic causes and other undefined causes.     

Prevalence and risk factors for endogenous fungal endophthalmitis in adult patients with candidemia at a tertiary care hospital in the Republic of Korea over 13 years

BackgroundEndogenous fungal endophthalmitis (EFE) is a critical complication of candidemia. We conducted a study to investigate the prevalence and risk factors for EFE.MethodsAdult candidemia patients ≥ 19 years who underwent an ophthalmological examination at a tertiary care hospital in the Republic of Korea from 2006 to 2018 were enrolled.ResultsThere was a total of 152 adult candidemia patients analyzed. EFE was found in 29 patients (19.1%). Patients were categorized into two groups (Non-endophthalmitis [NE] and endophthalmitis [E]). Between the two groups, there was no significant difference in terms of age, sex, and underlying comorbidities. However, there were more Candida albicans candidemia, abnormal alanine aminotransferase (ALT) at the time of candidemia diagnosis, receipt of antifungal treatment ≥ 48 hours after onset of candidemia symptoms and blood culture sample (AOCS), and candidemia clearance ≥ 5 days after initiation of antifungal treatment (AIAT) in the E group. A predictive model for the E was created, which had an area of 0.811 under the receiver operating characteristics curve. In a multivariate logistic regression analysis, C. albicans candidemia, ALT at the time of candidemia diagnosis, receipt of antifungal treatment ≥ 48 hours AOCS, and candidemia clearance ≥ 5 days AIAT were significantly associated with EFE.ConclusionEFE occurred in 19% of adult patients with candidemia. Adult candidemia patients with C. albicans candidemia, abnormal ALT, receipt of antifungal treatment ≥ 48 hours AOCS, and candidemia clearance ≥ 5 days AIAT need to be closely monitored for the possibility of EFE.     

First successful pregnancy outcome after twelve abortions in a Tunisian-woman with the rare p phenotype

IntroductionAnti-PP1P k alloantibody, is produced in the serum of individuals with the rare p phenotype. It is associated with severe haemolytic transfusion reactions, recurrent spontaneous early abortions as well as haemolytic disease of the foetus and newborn. Anti-PP1P k alloimmunization in pregnancy differ from others in their physiopathology. It seems that the placenta would be the main target of anti-PP1P k antibody.Case reportThis report concerns a 35 year old female, with a history of a high incidence (12) of early and recurrent miscarriages. She was found to have the extremely rare p phenotype and anti-PP1P k antibody in her serum. Her 13th pregnancy was successfully managed by plasmapheresis. No substitution fluid was added. Oral hydration was recommended before and after the apheresis sessions. 12 plasmapheresis cycles were performed before a healthy term female infant weighing 3 kg600 g, was delivered by caesarean section at 38 weeks of gestation.ConclusionPlasmapheresis seems to be the treatment of choice in the management of anti-PP1P k fetomaternal incompatibilities. However in this case, we opted for an original and less expensive protocol. We did resort, neither to substitution fluid nor to intravenous immunoglobulin.     

Cryptococcal meningitis presented as sudden hearing loss: A case study

BackgroundThis case report emphasizes that cryptococcal meningitis could be uncommonly presented to otolaryngologists as sudden onset of hearing loss, especially in patients with underlying diseases that could cause immunocompromise, and highlights the importance of differentiated diagnosis on sudden hearing loss before steroid therapy. It also demonstrates that prompt and sufficient fungicidal therapy with appropriate supportive treatment is crucial for a good prognosis on cryptococcal meningitis.Case presentationA diabetic adult with untreated chronic hepatitis B was admitted complaining of sudden onset of left-sided hearing loss, following unexpected aggravating headache with meningeal signs after hospitalization with days of intratympanic steroid therapy. Cryptococcal meningitis was confirmed through lumbar puncture showing positive India ink staining and microbial culture of the cerebrospinal fluid (CSF). Fortunately, the patient recovered after prompt and adequate fungicidal therapy plus appropriate supportive treatment at last, though persistent hearing loss remained.ConclusionsCryptococcal meningitis could be presented in a very concealed way as sudden hearing loss, especially in patients with underlying diseases that could cause immunosuppression. Differentiated diagnosis on sudden hearing loss before steroid therapy is important.     

Heart transplantation in Danon disease: Long term single centre experience and review of the literature

Danon disease is characterized by hypertrophic cardiomyopathy, skeletal myopathy, and intellectual disability due to deficiency of the lysosome-associated membrane protein-2 (LAMP-2). Although heart transplantation is considered an option for end stage Danon cardiomyopathy, scarce information is available about long term follow up. We report on long term follow up (14.7 years, IQ range 9–21 years) of 4 patients, transplanted for Danon disease cardiomyopathy, showing two LAMP-2 gene variants, the novel c.815T > C and the previously reported c.294G > A. We have also analysed previous published paper on this topic comparing available data from different follow up. Being a skeletal and cardiac muscle disease, with systemic effects, long term results about HTx are indispensable to justify any treatments in this subset of patients.     

Reflections on extraordinary knowing: Insight into the nature of the mind

Scientists have spent considerable time and effort studying and mapping the geography of the brain, with the expectation that this understanding will lead to insights related to the nature of the mind. This article discusses evidence that, while the mind utilizes sensory information processed by the brain, awareness is not limited to these structures. Research studies give evidence supporting the mind's ability to expand awareness to include perception of objects and events not available to the five senses. This awareness also extends to moments in the future, including the mind's ability to access information seconds or even days in advance of the occurrence. A major brain filter that limits this capacity for expanded awareness is the Default Mode Network (DMN). We summarize research showing that when the DMN activity is reduced, e.g., through meditation, ingestion of neuromodulatory drugs, or NDEs, filtering within the brain is reduced, there is a concomitant development of new connectivity, and these neural changes are correlated with access to expanded awareness.     

Homing of granulocytes transfused in perineal cellulitis in a RAC2 deficiency child monitored by chimerism quantification methods

Granulocyte transfusions can be used to treat infections when appropriate antibiotic and anti-fungal drugs have proved ineffective. We report a case of clinical efficacy of 18 granulocyte transfusions for perineal cellulitis in a 3-week-old RAC2-deficient newborn girl. This RAC2 deficiency is characterized by severe phagocyte defects including defective superoxide formation, adhesion and chemotaxis deficiency. In order to check that the granulocytes infused had reached the lesion site, the infiltration of donor cells was quantified by next generation sequencing (NGS) and digital droplet PCR after identification of DNA specific markers for donor and patient. After the 6th transfusion, 20% circulating cells and 55% cells isolated by swabbing from the lesion site were donor cells, confirming the infiltration of polynuclear cells in the perineal lesion site. These results strengthen the indication of granulocyte transfusions, and its continuation until the healing process of the skin is complete. This clinical case report highlights the potential efficacy of granulocyte transfusions to treat skin lesions in RAC2-deficient patients, a process which could be monitored by molecular biology tools for chimerism quantification.     

Allergen-induced DNA release by the airway epithelium amplifies type 2 immunity

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Nitric oxide donors offer protection to RBC from storage lesion

BackgroundRed blood cell (RBC), which is the most commonly transfused blood component, due to its ability to save a life in absence of any other blood components, can be stored up to maximum 6 weeks by following standard preservation procedure. During storage, RBC undergoes various biophysical and biochemical changes (commonly known as storage lesion) for which blood transfusion with “old RBC” shows a lot of clinical problems especially relevant to critically ill patients. Recent research on S-nitrosylation of haemoglobin to improve oxygen delivery of banked blood revealed the important role of nitric oxide (NO) in protecting storage lesion.Materials and methodsIn the present study, we used various “NO donating” chemicals with different NO release dynamics and chemistries in RBC storage cocktails to test the effects of NO on storage lesion. Changes in different storage markers were evaluated after 7 days storage of pre-treated RBC.ResultsAll the NO donors have shown protection against hemolysis. However, S-nitroso glutathione (GSNO) ranks first in shielding RBCs from storage lesion and additionally, it helps in elevating the value of 2, 3-di phosphoglycerate (2, 3-DPG), improving the RBC membrane fluidity and decreasing the adhesion towards endothelial monolayer.DiscussionPresent study reveals that NO released from NO donors confers protection against storage lesions of the RBC. Further, the study confirms that pre-treatment with GSNO, a NO donor and a nitrosylating agent, ensures the best protection to RBC during low temperature storage, when compared to other NO donor treatments.     

Usefulness of gait parameters obtained from inertial sensors attached to the lower trunk and foot for assessment of gait performance in the early postoperative period after total knee arthroplasty

BackgroundThis study was performed to (i) compare gait parameters obtained from inertial sensors attached to the lower trunk and foot between patients in the early postoperative period after total knee arthroplasty (TKA) and healthy age- and sex-matched controls and (ii) elucidate the association between the gait parameters and patient-reported outcome measures (PROMs).MethodThe gait performance of 19 patients who had undergone TKA was assessed using inertial sensors and PROMs obtained from the Knee Injury and Osteoarthritis Outcome Score (KOOS) 1 week before hospital discharge. The patients walked along a 15-m walkway and we calculated the following gait parameters: walking speed, coefficient of variation (CV) of stride time, unbiased autocorrelation coefficient (AC), harmonic ratio (HR), and symmetry index (SI). The same gait parameter data from 19 age- and sex-matched healthy adults (controls) were obtained from our past study.ResultsThe TKA group demonstrated slower walking speed, larger CV of stride time, lower HR in all three directions, lower AC in the vertical direction, and higher SI in the vertical direction than the healthy control group (all p < 0.05). Correlation analysis revealed that the SI in the anteroposterior direction was significantly correlated with the KOOS symptoms subscore and ADL subscore (p < 0.05).ConclusionsPatients in the early postoperative period after TKA exhibited worse gait performance as assessed by inertial sensors compared with healthy controls. Gait symmetry was correlated with PROMs. These results indicate the usefulness of assessing gait parameters after TKA.     

Diagnosis at different stages of paracoccidioidomycosis with oral manifestation: Report of two cases

Paracocciodiomycosis (PCDM) is a chronic systemic fungal infection, mainly affecting residents and rural workers, being characterized by a long incubation period, which it can take months or years without clinical manifestations, making diagnosis late and difficult. Depending on the stage of the disease, it can cause sequelae and low quality of life, so its correct diagnosis is of great importance for the accurate treatment. Therefore, the aim of this report is to present two cases of diagnosis of patients with PCDM at different stages, who developed chronic manifestations, pain, clinical involvement of the oral cavity and in one case also presented lung injury with fibrosis, as well as to weight loss, dysphagia and cachexia. Both of patients were treated with antifungal therapy and it was observed total remission of the lesions and no recurrences were detected.     

Targeted protein degraders march towards the clinic for neurodegenerative diseases

Protein degraders are emerging as potent therapeutic tools to address neurological disorders and many complex diseases. It offered several key advantages, including the doses, drug resistance, and side effects over traditional occupancy-based inhibitors. Translation of chemical degraders into a clinical therapy for neurodegenerative disorders has a well-documented knowledge and resource gap. Researchers strive to develop clinical candidates employing chemical degraders' technologies, including hydrophobic tagging, molecular glues, proteolysis targeting chimeras (PROTACs), specific and nongenetic Inhibitor of Apoptosis Protein (IAP)-dependent protein erasers (SNIPERs), autophagy targeted chimeras, and autophagosome-tethered compounds for targeted degradation of pathological markers in neurodegenerative disease. Herein, we examined the present state of chemical-mediated targeted protein degradation in the quest for medications to treat neurodegenerative diseases. We further identified targeted degraders under clinical development for neurodegenerative diseases summarizing pertinent discoveries guiding the future of degradation therapeutics. We also addressed the necessary pharmacological interventions needed to achieve unprecedented therapeutic efficacy and its associated challenges.     

Contribution of survivin to the immune system,allergies and autoimmune diseases

In addition to malignancies, survivin (a member of the apoptosis inhibitor family) has been implicated in the pathogenesis of inflammatory disorders, including autoimmune and allergic diseases. Survivin is constantly expressed in the proliferating hematopoietic progenitor cells, and it is re-expressed in the mature cells of the innate and adaptive immunity, upon activation. Survivin enhances the expression of co-stimulatory molecules and MHC class II molecules in dendritic cells, and promotes the lifespan of macrophages, neutrophils, and eosinophils, while suppressing natural killer (NK) cell activity. Survivin has been implicated in T cell maturation, T cell expansion, effector CD4⁺ T cell differentiation, maintenance of memory CD4⁺ T and CD8⁺ T cells, as well as antibody production. Upregulated expression of survivin was indicated in the T cells as well as various samples collected from allergic patients. Survivin can contribute to the pathogenesis of allergic diseases via the promotion of the Th2 polarization, promoting IL-4 expression, compromising activation-induced cell death (AICD) in Th2 cells, and preventing apoptosis of eosinophils, as well as, amplification of eosinophilia. Moreover, survivin can interfere with clonal deletion of autoreactive T and B cells, as well as suppress Treg cell development and activity supporting the development of autoimmune diseases. This review discusses the role of survivin in immunity, allergy and autoimmunity as well as provides evidence that survivin may be considered as a novel therapeutic target for the treatment of allergic and autoimmune diseases.