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1.
Am J Transplant ; 24(7): 1172-1179, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38215981

RESUMO

Renal ex vivo normothermic machine perfusion (NMP) is under development as an assessment tool for high-risk kidney grafts and as a means of achieving more physiologically accurate organ preservation. On-going hemolysis has been reported during NMP, as this technique relies on red blood cells for oxygen delivery. In this study, we confirm the occurrence of progressive hemolysis during 6-hour kidney NMP. NMP-associated erythrostasis in the glomeruli and in peri-glomerular vascular networks points to an interaction between the red blood cells and the graft. Continuous hemolysis resulted in prooxidative changes in the perfusate, which could be quenched by addition of fresh frozen plasma. In a cell-based system, this hemolysis induced redox stress and exhibited toxic effects at high concentrations. These findings highlight the need for a more refined oxygen carrier in the context of renal NMP.


Assuntos
Eritrócitos , Transplante de Rim , Preservação de Órgãos , Oxigênio , Perfusão , Eritrócitos/metabolismo , Preservação de Órgãos/métodos , Oxigênio/metabolismo , Humanos , Hemólise , Animais , Masculino , Rim/metabolismo
2.
Vox Sang ; 119(8): 801-808, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38754975

RESUMO

BACKGROUND AND OBJECTIVES: Near-infrared (NIR) light has been successfully applied to improve the quality of mouse platelets during storage. Because it is suspected that the mitochondria contain the primary photon acceptor, we hypothesized that human platelets for transfusion may be affected similarly and could benefit from NIR light treatment. MATERIALS AND METHODS: The optimal light dose was determined using portions of platelet concentrates (PCs) in PAS-E. A pool-and-split design was used to prepare PCs in PAS-E or plasma (n = 6). On day 1, one unit of both pairs was illuminated with 830 nm light (light-emitting diodes, 15 J/cm2). PCs were stored at 22°C and sampled regularly for analysis. Data were compared with their corresponding controls with a paired two-sided t-test. RESULTS: Illuminated platelets in PAS-E were less activated with significantly lower CD62P expression (day 8: 10.8 ± 1.8 vs. 12.2 ± 2.6, p < 0.05) and lower Annexin A5 binding (day 8: 11.8 ± 1.9 vs. 13.1 ± 2.4, ns). They produced significantly less lactate resulting in a higher pH (days 6-10). ATP content and mitochondrial membrane potential were not affected. Although these trends were also observed for PCs in plasma, the differences did not reach statistical significance as compared with the control group. CONCLUSION: Our study demonstrates that the glycolysis rate of human platelets can be modulated through the use of NIR, possibly through mitochondrial aerobic metabolism, but this requires confirmation. If NIR illumination can be further optimized, it may potentially become a useful tool in situations in which glycolysis and platelet activation are exacerbated.


Assuntos
Plaquetas , Preservação de Sangue , Plaquetas/metabolismo , Plaquetas/citologia , Humanos , Preservação de Sangue/métodos , Raios Infravermelhos , Feminino , Masculino , Selectina-P/metabolismo
3.
Transfusion ; 63(12): 2273-2280, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37909172

RESUMO

INTRODUCTION: In 2018, platelet (PLT) additive solution-E (PAS-E) was introduced. The implementation of PAS-E was expected to diminish the number of allergic reactions in recipients following a PLT transfusion. Here, we evaluated the efficacy and safety of transfusions with PLTs stored in PAS-E. STUDY DESIGN AND METHODS: After implementation of PAS-E, data were collected from 2 cohorts of patients with hematological disorders as well as oncology patients, receiving PLTs in PAS-E. A similar patient group in a recent RCT, receiving PLTs in plasma, was used as a historical control group for both cohorts. Endpoints were corrected count increments (CCIs), bleeding scores (only reported in cohort 1), and the incidence of adverse reactions. RESULTS: In cohort 1, the mean 1-h CCI was 14.3 ± 6.9, and the 24-h CCI was 8.7 ± 5.6. In cohort 2, the 1-h CCI was 11.6 ± 7.8 and the 24-h CCI was 7.0 ± 6.1. In the control group, the 1-h CCI was 15.4 ± 5.5 and 24-h CCI 8.7 ± 4.8. Bleeding complications of WHO grade ≥2 occurred in 40% of patients in cohort 1 compared to 44% in plasma PCs. The incidence of adverse reactions was 1.2% in the two PAS-E cohorts, compared to 3.0% in plasma PCs. National hemovigilance data showed a significant reduction in allergic reactions with PAS-E PC transfusions as compared to plasma PCs with an odds ratio of 0.46 (CI 95% 0.37-0.58). CONCLUSION: The CCIs of PLTs in PAS-E were decreased compared to plasma PCs, but clinically acceptable. Allergic transfusion reactions were decreased in PAS-E PCs compared to plasma PCs.


Assuntos
Hipersensibilidade , Reação Transfusional , Humanos , Plaquetas , Transfusão de Plaquetas/efeitos adversos , Segurança do Sangue , Reação Transfusional/etiologia , Preservação de Sangue , Hipersensibilidade/etiologia
4.
Vox Sang ; 118(2): 165-177, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36510371

RESUMO

BACKGROUND AND OBJECTIVES: DEHP, di(2-ethylhexyl) phthalate, is the most common member of the class of ortho-phthalates, which are used as plasticizers. The Medical Device Regulation has restricted the use of phthalates in medical devices. Also DEHP has been added to the Annex XIV of REACH, "Registration, Evaluation, Authorisation and Restriction of Chemicals" due to its endocrine disrupting properties to the environment. As such, the sunset date for commercialisation of DEHP-containing blood bags is May 27th 2025. There are major concerns in meeting this deadline as these systems have not yet been fully validated and/or CE-marked. Also, since DEHP is known to affect red cell quality during storage, it is imperative to transit to non-DEHP without affecting blood product quality. Here, EBA members aim to establish common grounds on the evaluation and assessment of blood components collected, prepared and stored in non-DEHP devices. MATERIALS AND METHODS: Based on data as well as the input of relevant stakeholders a rationale for the validation of each component was composed. RESULTS: The red cell components will require the most extensive validation as their quality is directly affected by the absence of DEHP, as opposed to platelet and plasma components. CONCLUSION: Studies in the scope of evaluating the quality of blood products obtained with non-DEHP devices, under the condition that they are carried out according to these recommendations, could be used by all members of the EBA to serve as scientific support in the authorization process specific to their jurisdiction or for their internal validation use.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Humanos , Preservação de Sangue , Plastificantes
5.
Transfusion ; 62(12): 2609-2620, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36278429

RESUMO

BACKGROUND: Platelets (PLTs) differ in glycolytic activity, resulting in rapid acidification of 'poor' storing PLT concentrates (PCs) in plasma, or depletion of glucose when stored in PLT additive solution (PAS). We aimed to understand why PLT glycolysis rates vary between donors and how this affects storage performance. STUDY DESIGN AND METHODS: Buffy coats from donors <45, 45-70 and >70 years were selected and single-donor PCs in plasma or PAS-E were prepared. PCs were stored for 8 days at 22 ± 2°C and sampled regularly for analysis. Mitochondrial activity was analyzed with an Oroboros oxygraph. Age groups, or subgroups divided into quartiles based on glucose consumption, were analyzed with ANOVA. RESULTS: In each comparison, PCs of the different groups were not different in volume and cellular composition. PLTs with the highest glucose consumption had a higher initial mean platelet volume (MPV) and developed higher CD62P expression and Annexin A5 binding during storage. Higher glycolytic activity in these PLTs was not a compensation for lower mitochondrial ATP production, because mitochondrial ATP-linked respiration of fresh PLTs correlated positively with MPV (R2  = 0.71). Donors of high glucose-consuming PLTs had more health-related issues. Storage properties of PCs from donors over 70 were not significantly different compared to PCs from donors younger than 45 years. CONCLUSIONS: High glucose-consuming PCs developing higher activation levels, not only displayed enhanced mitochondrial activity but were also found to contain larger PLTs, as determined by MPV. Storage performance of PLTs was found to be associated with donor health, but not with donor age.


Assuntos
Trifosfato de Adenosina , Volume Plaquetário Médio , Humanos
6.
Vox Sang ; 117(7): 913-919, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35405038

RESUMO

The buffy coat method as a source for platelet concentrates was developed in the 1970s and is still used in many blood centres around the world. Development of the method sparked various technological advances in blood collection, processing and storage. At the time, the need for platelet concentrates sharply increased because of better treatment regimens for (onco)haematological diseases, which forced blood centres to standardize and automate their production processes as much as the technology would allow. In this review, a historical overview of the Dutch experiences is provided in the context of the international developments.


Assuntos
Plaquetas , Preservação de Sangue , Buffy Coat , Humanos
7.
Vox Sang ; 117(10): 1163-1170, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36102116

RESUMO

BACKGROUND AND OBJECTIVES: Di-ethyl-hexyl-phthalate (DEHP) is currently the main plasticizer used for whole blood collection systems. However, in Europe, after May 2025, DEHP may no longer be used above 0.1% (w/w) in medical devices. DEHP stabilizes red cell membranes, thereby suppressing haemolysis during storage. Here we compared in vitro quality parameters of red cell concentrates (RCCs) collected and stored in DEHP-, DINCH- or DINCH/BTHC-PVC hybrid blood bags with saline-adenine-glucose-mannitol (SAGM) or phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM) storage solution. Last, we performed haemovigilance surveillance for RCC collected in DINCH-PVC and stored in PAGGSM/BTHC-PVC. MATERIALS AND METHODS: In vitro quality parameters of RCC were determined during 42 days of storage. Haemovigilance surveillance was conducted to compare the frequency and type of transfusion reaction. RESULTS: Haemolysis levels were increased in SAGM/BTHC-PVC as compared to SAGM/DEHP-PVC (0.66% ± 0.18% vs. 0.36% ± 0.17%). PAGGSM storage solution was able to adequately suppress haemolysis to levels observed during storage in SAGM/DEHP-PVC, both in BTHC-PVC (0.38% ± 0.12%), and to a slightly lesser extent in DINCH-PVC (0.48% ± 0.17%). A total of 1650 PAGGSM/BTHC-PVC and 5662 SAGM/DEHP-PVC RCC were transfused yielding a transfusion reaction frequency of 0.24% (95% CI 0.0000-0.0048) and 0.44% (95% CI 0.0027-0.0061) respectively. CONCLUSION: The in vitro quality of RCC stored in PAGGSM/BTHC-PVC and SAGM/DEHP-PVC is comparable. There is no indication that transfusion of erythrocytes stored in PAGGSM/BTHC-PVC results in increased transfusion reaction frequency. These initial results provide a basis for further clinical evaluation to narrow down the confidence interval of transfusion reaction frequency.


Assuntos
Carcinoma de Células Renais , Dietilexilftalato , Neoplasias Renais , Reação Transfusional , Adenina/farmacologia , Preservação de Sangue/métodos , Butiratos , Carcinoma de Células Renais/metabolismo , Eritrócitos/metabolismo , Glucose/metabolismo , Guanosina , Hemólise , Humanos , Neoplasias Renais/metabolismo , Manitol/farmacologia , Fosfatos/metabolismo , Plastificantes , Cloreto de Polivinila , Cloreto de Sódio
8.
BJU Int ; 125(6): 817-826, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32124514

RESUMO

OBJECTIVES: To evaluate the activity of intravesical mitomycin-C (MMC) to ablate recurrent low-risk non-muscle-invasive bladder cancer (NMIBC) and assess whether it may enable patients to avoid surgical intervention for treatment of recurrence. PATIENTS AND METHODS: CALIBER is a phase II feasibility study. Participants were randomized (2:1) to treatment with four once-weekly MMC 40-mg intravesical instillations (chemoablation arm) or to surgical management. The surgical group was included to assess the feasibility of randomization. The primary endpoint was complete response to intravesical MMC in the chemoablation arm at 3 months, reported with exact 95% confidence intervals (CIs). Secondary endpoints included time to subsequent recurrence, summarized by Kaplan-Meier methods. RESULTS: Between February 2015 and August 2017, 82 patients with visual diagnosis of recurrent low-risk NMIBC were enrolled from 24 UK hospitals (chemoablation, n = 54; surgical management, n =28). The median follow-up was 24 months. Complete response at 3 months was 37.0% (20/54; 95% CI 24.3-51.3) with chemoablation and 80.8% (21/26; 95% CI 60.6-93.4) with surgical management. Amongst patients with complete response at 3 months, a similar proportion was recurrence-free by 12 months in both groups (84%). Amongst those with residual disease at 3 months, the 12-month recurrence-free proportion was lower in the surgical management group (40.0%) than in the chemoablation group (84%). Recruitment stopped early as chemoablation did not meet the prespecified threshold of 45% complete responses at 3 months. CONCLUSION: Intravesical chemoablation in low-risk NMIBC is feasible and safe, but did not demonstrate sufficient response in the present trial. After chemoablation there may be a reduction in recurrence rate, even in non-responders, that is greater than with surgery alone. Further research is required to investigate the role and optimal schedule of neoadjuvant intravesical chemotherapy prior to surgery for NMIBC.


Assuntos
Antibióticos Antineoplásicos , Mitomicina , Neoplasias da Bexiga Urinária , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/uso terapêutico , Qualidade de Vida , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
9.
Clin Anat ; 33(5): 689-695, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31581316

RESUMO

INTRODUCTION: The fibrocartilagenous plantar plates of the forefoot are biomechanically important, forming the primary distal attachment for the plantar aponeurosis. They are integral to the function of the windlass mechanism in supporting the arches of the foot in gait. Dissection of the cadaveric hallux revealed an organised sagittal thickening of the dorsal side of the flexor hallucis longus (FHL) sheath, which attached the interphalangeal plantar plate to the metatarsophalangeal (MTP) plantar plate. A description of a similar structure was made in 1984 when it was termed the flexor hallucis capsularis interphalangeus (FHCI) - however, it has not been researched since, and we aim to study it further and identify its characteristics. METHOD: Eight specimens were dissected from four cadavers. Two were stained and examined under magnification in both polarized and non polarized light. The remaining 6 were subjected to micrometer testing of their tensile properties. RESULTS: Both the histological features and mechanical properties were consistent with tendon; with cross sectional area, ultimate tensile strength and stiffness varying between specimens. CONCLUSIONS: Based on its location and properties, the FHCI tendon may be involved in limiting dorsiflexion of the first MTP joint and could have clinical relevance in pathological processes around both the first and second MTP joints. Clin. Anat., 33:689-695, 2020. © 2019 Wiley Periodicals, Inc.


Assuntos
Hallux/anatomia & histologia , Músculo Esquelético/anatomia & histologia , Tendões/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Dissecação , Hallux/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Tendões/fisiologia
10.
Hemoglobin ; 43(2): 77-82, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31190578

RESUMO

A 4-year-old boy, a ß-thalassemia (ß-thal) carrier, with an unexplained severe chronic microcytic anemia was referred to us. Sequencing of the α-globin genes revealed a Hb Charlieu [α106(G13)Leu→Pro, HBA1: c.320T>C, p.Leu107Pro] mutation present on both HBA1 genes. Quantitative polymerase chain reaction (qPCR) confirmed αCharlieu mRNA in the proband and his parents, showing that the mutation does not affect mRNA stability. However, we were unable to detect the Hb Charlieu protein by capillary electrophoresis (CE), reverse phase electrophoresis, cation exchange electrophoresis or isoelectric focusing. Mass spectrometry (MS) allowed us to confirm the presence of the Hb Charlieu peptide in erythrocyte progenitors. These findings suggest that the mutation affects the stability of αCharlieu. As hemoglobin (Hb) heat stability tests showed no abnormalities in erythrocytes, we speculated that αCharlieu is already degraded during red blood cell (RBC) development. The clinical severity in the proband and the presence of new methylene blue-stained aggregates in his reticulocytes indicates that incorporation of αCharlieu destabilizes Hb. This, combined with an excess of unstable free α-globins as the result of ß-thal minor, results in severely impaired erythropoiesis and, as a consequence, severe and chronic microcytic anemia in the proband.


Assuntos
Homozigoto , Mutação/genética , Pré-Escolar , Humanos , Masculino
12.
Eur J Haematol ; 98(6): 584-589, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28295642

RESUMO

OBJECTIVE: Here, we present a 7-year-old patient suffering from severe haemolytic anaemia. The most common cause of chronic hereditary non-spherocytic haemolytic anaemia is red blood cell pyruvate kinase (PK-R) deficiency. Because red blood cells rely solely on glycolysis to generate ATP, PK-R deficiency can severely impact energy supply and cause reduction in red blood cell lifespan. We determined the underlying cause of the anaemia and investigated how erythroid precursors in the patient survive. METHODS: PK activity assays, Western blot and Sanger sequencing were employed to determine the underlying cause of the anaemia. Patient erythroblasts were cultured and reticulocytes were isolated to determine PK-R and PKM2 contribution to glycolytic activity during erythrocyte development. RESULTS: We found a novel homozygous mutation (c.583G>A) in the PK-R coding gene (PKLR). Although this mutation did not influence PKLR mRNA production, no PK-R protein could be detected in the red blood cells nor in its precursors. In spite of the absence of PK-R, the reticulocytes of the patient exhibited 20% PK activity compared with control. Western blotting revealed that patient erythroid precursors, like controls, express residual PKM2. CONCLUSIONS: We conclude that PKM2 rescues glycolysis in PK-R-deficient erythroid precursors.


Assuntos
Anemia Hemolítica Congênita não Esferocítica/genética , Proteínas de Transporte/genética , Eritroblastos/enzimologia , Proteínas de Membrana/genética , Piruvato Quinase/deficiência , Piruvato Quinase/genética , Erros Inatos do Metabolismo dos Piruvatos/genética , Reticulócitos/enzimologia , Hormônios Tireóideos/genética , Anemia Hemolítica Congênita não Esferocítica/enzimologia , Anemia Hemolítica Congênita não Esferocítica/patologia , Sequência de Bases , Diferenciação Celular , Criança , Consanguinidade , Eritroblastos/patologia , Expressão Gênica , Glicólise/genética , Homozigoto , Humanos , Masculino , Proteínas de Membrana/deficiência , Mutação , Células Mieloides/citologia , Células Mieloides/enzimologia , Cultura Primária de Células , Erros Inatos do Metabolismo dos Piruvatos/enzimologia , Erros Inatos do Metabolismo dos Piruvatos/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reticulócitos/patologia , Hormônios Tireóideos/deficiência , Proteínas de Ligação a Hormônio da Tireoide
13.
J R Nav Med Serv ; 102(1): 22-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29984975

RESUMO

Musculoskeletal injuries of the shoulder are a common presentation in primary care. Injuries to this highly mobile region can have a profound impact on the range of movement, resulting in severe functional limitation. The shoulder can also be one of the more complicated regions to examine due to its high mobility, poor localisation of pain and numerous supporting structures. This article aims to review the anatomy of the shoulder, examination technique and the pathology underlying common acute injuries in order to provide guidance to medical personnel deployed with the Royal Navy and Royal Marines.


Assuntos
Instabilidade Articular/terapia , Militares , Lesões do Ombro/diagnóstico , Lesões do Ombro/terapia , Humanos , Instabilidade Articular/diagnóstico , Instabilidade Articular/etiologia , Amplitude de Movimento Articular , Lesões do Ombro/etiologia
14.
Support Care Cancer ; 23(10): 3015-23, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25739752

RESUMO

PURPOSE: Work is an important quality of life indicator for many cancer survivors. There is, however, a lack of appropriate support to help survivors with work integration. As a result, many survivors are forced to independently navigate their return to work, experiencing unnecessary pitfalls in the process. As a preliminary step toward addressing this current gap in survivorship support, we explored the work integration experiences of 20 cancer survivors, 10 women and 10 men. METHODS: Photovoice methods were combined with two individual interviews per participant. Participant-produced photographs and interview transcripts were analyzed to identify key themes. RESULTS: Both commonalities and gender-differentiated motivations underlying work integration emerged. Female and male participants both demonstrated and discussed differentiated manners of coping. Men expressed a propensity for productivity and active engagements over talking used predominantly by women. CONCLUSION: Appreciation of men's proclivity for productivity and activity suggests that a gender-tailored approach to rehabilitation may enhance male survivors' participation and the utility of rehabilitation efforts.


Assuntos
Neoplasias/reabilitação , Retorno ao Trabalho/psicologia , Adaptação Psicológica , Adulto , Feminino , Identidade de Gênero , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Fotografação , Qualidade de Vida , Sobreviventes/psicologia
15.
Dis Esophagus ; 28(5): 483-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24898890

RESUMO

Esophageal cancer recurrence rates after esophagectomy are high, and locally recurrent or distant metastatic disease has poor prognosis. Management is limited to palliative chemotherapy and symptomatic interventions. We report our experience of four patients who have undergone successful liver resection for metastases from esophageal cancer. All underwent esophagectomy and were referred to our unit with metastatic recurrent liver disease, two with solitary metastases and two with multi-focal disease. The patients underwent multidisciplinary assessment and proceeded to a course of neoadjuvant chemotherapy followed by open or laparoscopic liver resection. Three patients were male, and the mean age was 57.5 (range 44-71) years. Response to chemotherapy ranged from partial to complete response. Following liver resection, two patients developed recurrent disease at 5 and 15 months, and both had disease-specific mortality at 10 and 21 months, respectively. The other two patients remain disease free at 22 and 92 months. Recurrent metastatic esophageal cancer continues to have a poor prognosis, and the majority of patients with liver involvement will not be candidates for hepatic resection. However, this series suggests that in selected patients, liver resection of metastases from esophageal cancer combined with neoadjuvant and adjuvant chemotherapy is feasible, but further research is required to determine whether this can offer a survival advantage.


Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/terapia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Intervalo Livre de Doença , Esofagectomia , Feminino , Hepatectomia/métodos , Humanos , Laparoscopia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia , Estudos Prospectivos
16.
Blood Transfus ; 22(4): 292-302, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-38557319

RESUMO

Thrombocytopenia (defined as a platelet count <150×109/L) is a common condition in preterm neonates and may occur in 18-35% of all infants admitted to the Neonatal Intensive Care Unit (NICU). Neonatal platelet functionality in terms of reactivity is often described as reduced compared to adults, even in healthy, term neonates. However, this platelet "hyporeactivity" does not correspond to a global functional impairment of the normal delicately balanced neonatal hemostatic system. The extent to which neonatal thrombocytopenia and platelet hyporeactivity contribute to the bleeding risk in preterm neonates remains unknown. Prophylactic platelet transfusions are often administered to them to reduce the risk of bleeding. However, recent literature indicates that adopting a higher platelet transfusion threshold than a lower one results in significantly higher death rates or major bleeding and can be harmful. Although the mechanism by which this occurs is not entirely clear, a mismatch between adult transfused platelets and the neonatal hemostatic system, as well as volume overload, are speculated to be potentially involved. Therefore, future research should consider novel transfusion products that may be more suitable for premature neonates. Blood products derived from umbilical cord blood (UCB) are promising, as they might perfectly match neonatal blood features. Here, we discuss the current knowledge about UCB-derived products, focusing on UCB-derived platelet concentrates and their potential for future clinical application. We will discuss how they may overcome the potential risks of transfusing adult-derived platelets to premature infants while maintaining efficacy.


Assuntos
Plaquetas , Sangue Fetal , Transfusão de Plaquetas , Humanos , Recém-Nascido , Transfusão de Plaquetas/métodos , Sangue Fetal/citologia , Plaquetas/citologia , Plaquetas/metabolismo , Recém-Nascido Prematuro , Trombocitopenia Neonatal Aloimune/terapia , Feminino , Hemorragia/terapia , Hemorragia/etiologia
17.
Ophthalmol Ther ; 12(6): 3347-3359, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37843772

RESUMO

INTRODUCTION: Allogeneic serum from blood donors is starting to be used to treat patients with dry eye disease (DED). However, the optimal dose is not known. We therefore aimed to evaluate the clinical efficaciousness and user-friendliness of micro-sized versus conventional-sized allogeneic serum eye drops (SEDs). METHODS: In a randomized trial, patients with DED first receive micro-sized SEDs (7 µl/unit) for 1 month, followed by a 1-month washout, before receiving conventional-sized SEDs (50 µl/unit) for 1 month; or vice versa. The primary endpoint was the Ocular Surface Disease Index (OSDI) score. Secondary endpoints were tear break-up time (TBT), tear production (TP), and presence of corneal punctate lesions (CP). The user-friendliness of both application systems was also compared. A linear mixed model for cross-over design was applied to compare both treatments. RESULTS: Forty-nine patients completed the trial. The mean OSDI score significantly improved from 52 ± 3 to 41 ± 3 for micro-sized SEDs, and from 54 ± 3 to 45 ± 3 for conventional-sized SEDs. Non-inferiority (margin = 6) of micro-sized SEDs was established. We demonstrate a significant improvement for TBT in case of conventional-sized SEDs and for CP in both treatment groups. TP trended towards an improvement in both treatment groups. The user-friendliness of the conventional drop system was significantly higher. CONCLUSIONS: For the first time, non-inferiority of micro-sized allogeneic SEDs was established. The beneficial effect of both SED volumes was similar as measured by the OSDI score. Although user-friendliness of the micro drop system was significantly lower, it is an attractive alternative as it saves valuable donor serum. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03539159).

18.
Diabet Med ; 29(7): 869-77, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22414336

RESUMO

AIMS: The ever-increasing prevalence of diabetes places pressure on the provision of diabetic retinopathy screening services. As the first study of its kind, we aimed to determine preferences for diabetic retinopathy screening in people with diabetes and to examine the trade-offs between frequency of screening and other service attributes. METHODS: A questionnaire including a discrete choice experiment was administered to people (n = 198) attending diabetic retinopathy screening at eight clinics across Wales, United Kingdom. The discrete choice experiment contained eight pairwise choices in which screening provision was described by five attributes: frequency of screening; travel time; results time; ability of screening to detect other changes; and explanation of results. Data were analysed using logistic regression techniques. RESULTS: We gained a response rate of 86.4% from the 198 questionnaires administered at clinics; 160 complete responses were analysed. Respondents valued four out of the five attributes [ability of screening to detect other changes (P = 0.000), explanation of results (P = 0.024), frequency of screening (P = 0.000) and travel time (P = 0.007)]. Results time was insignificant (P = 0.122). Respondents were willing to wait an additional 12, 2 and 1 month between screening tests to have a test that was able to detect additional changes, to have their results explained in person rather than by letter and to have a 15-min reduction in travel time, respectively. CONCLUSIONS: Respondents were willing to accept a longer screening interval, as long as preferences for other attributes of service provision (ability of screening to detect other changes, explanation of results and travel time) were made available.


Assuntos
Comportamento de Escolha , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico , Programas de Rastreamento/métodos , Preferência do Paciente/estatística & dados numéricos , Encaminhamento e Consulta , Adulto , Idoso , Idoso de 80 Anos ou mais , Comunicação , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Inquéritos e Questionários , Fatores de Tempo , Viagem , País de Gales/epidemiologia , Adulto Jovem
19.
Diabet Med ; 29(7): 878-85, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22414383

RESUMO

AIMS: To obtain the views of people with diabetes about the provision of diabetic retinopathy screening services; and the interval of screening. METHODS: Between October 2009 and January 2010, people with diabetes attending diabetic retinopathy screening clinics across Wales were asked to complete a questionnaire comprising of two parts: the first asking about their health, diabetes history, demographic characteristics and views about the diabetic retinopathy screening service, and the second asking about the costs of attending the screening. RESULTS: The response rate was 40% (n = 621) from 1550 questionnaires distributed at diabetic retinopathy clinics, with 600 complete responses analysed. Respondents had a mean known duration of diabetes of 8.5 years (sd 7.8) and had attended for screening on average 3.2 times (sd 1.6) in the last 5 years. Sixty-eight per cent (n = 408) of respondents reported having their eyes screened approximately once a year. Eighty-five per cent (n = 507) felt that they should have their eyes screened every year. However, 65% (n = 390) of respondents would accept screening at 2- or 3-year intervals if medical evidence showed that it was safe. The reported personal costs incurred by respondents attending diabetic retinopathy screening were low. CONCLUSION: Our study suggests that people with diabetes undergoing diabetic retinopathy screening would accept a greater screening interval, provided that adequate clinical evidence and medical reassurance were given.


Assuntos
Retinopatia Diabética/diagnóstico , Retinopatia Diabética/economia , Hemoglobinas Glicadas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/sangue , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Masculino , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Preferência do Paciente , Qualidade de Vida , Inquéritos e Questionários , País de Gales/epidemiologia , Adulto Jovem
20.
Blood Adv ; 6(21): 5798-5810, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-35349634

RESUMO

Severe malarial anemia (SMA) is the main cause of malaria-associated infant mortality in malaria endemic countries. One major factor that contributes to SMA is the accumulation of uninfected red blood cells (uRBCs) in the spleen. We report the activation of adhesion molecules Lutheran/basal cell adhesion molecule (Lu/BCAM) and CD44 on uRBCs from Plasmodium falciparum in vitro cultures and patients with malaria that mediates adherence to the splenic extracellular matrix (ECM) components laminin-α5 and hyaluronic acid (HA), respectively. This tight ECM-adhesion molecule interaction was associated with elevated intracellular Ca2+ levels, increased shedding of microvesicles, and Lu/BCAM clustering on altered uRBCs. Moreover, we observed that a soluble parasite-derived factor promoted the adhesive phenotype of uRBCs, as the incubation of RBCs with filtered malaria-conditioned medium reproduced the same adhesive effect in malaria culture-derived uRBCs. Eventually, Lu/BCAM and CD44 activation facilitate the adherence to ECM components of the red pulp, resulting in the enhanced splenic retention of uRBCs. Our results suggest a novel adhesion molecule-dependent mechanism that augments malaria-induced anemia.


Assuntos
Anemia Falciforme , Malária , Humanos , Sistema do Grupo Sanguíneo Lutheran/metabolismo , Moléculas de Adesão Celular/genética , Eritrócitos/metabolismo
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