Topical blood products modulate the effects of ophthalmic antibiotics against common bacterial pathogens in dogs with infectious keratitis.

Bacterial keratitis is a common and serious condition that often leads to vision impairment and potential loss of the eye if not treated promptly and adequately. Topical blood products are often used concurrently with topical antibiotics, helping to mitigate corneal 'melt' from proteases released on the ocular surface. However, blood products are rich in albumin and could affect the efficacy of antibiotics due to drug-protein binding. In this study, serum and plasma samples were harvested from 10 healthy dogs and 10 healthy horses, obtaining fresh and frozen (1 month at -20°C) aliquots for in vitro experiments. Albumin levels were quantified using species-specific ELISA kits. Thirty bacteria (10 Staphylococcus pseudintermedius, 10 Streptococcus canis, 10 Pseudomonas aeruginosa), isolated from canine patients with infectious keratitis, were each tested with blank plates as well as commercial susceptibility plates (Sensititre™ JOEYE2) to assess the minimal inhibitory concentration (MIC) of 17 different antibiotics in the absence (control) or presence of eight test groups: serum or plasma (fresh or frozen) from canines or equines. Albumin concentrations ranged from 13.8-14.6 mg/mL and 25.9-26.5 mg/mL in canine and equine blood products, respectively. A direct antimicrobial effect was observed mostly with equine vs. canine blood products (specifically serum and to a lesser degree plasma), and mostly for Staphylococcus pseudintermedius isolates. MICs generally increased in the presence of blood products (up to 10.8-fold), although MICs also decreased (down to 0.25-fold) for selected antibiotics and ocular pathogens. Median (range) fold changes in MICs were significantly greater (p = 0.004) with the canine blood products [2 (0.67-8.1)] than the equine blood products [2 (0.5-5)]. In practice, clinicians should consider equine over canine blood products (lesser impact on antimicrobial susceptibility), serum over plasma (greater antimicrobial effects), and administering the blood product ≥15 min following the last antibiotic eyedrop to minimize the amount of albumin-antibiotic binding in tear film.

Clinical efficacy of blood derivatives on wound healing: A systematic review and network meta-analysis.

This study aims to evaluate the clinical effects of different blood derivatives on wound healing using network meta-analysis. PubMed, Embase, OVID, Web of Science, SCOPUS and Cochrane Central were searched to obtain studies about blood derivatives on wound healing until October 2023. R 4.2.0 and Stata 15.0 softwares were used for data analysis. Forty-four studies comprising 5164 patients were included. The results of network meta-analysis showed that the healing area from high to low was GF + ORCCB, ORCCB, GF, PRF, Unnas paste dressing, APG, PRP injection, PRP, PRP + thrombin gel, PPP, HPL, CT. The healing time from low to high was PRP + thrombin gel, GF, PRP, PC + K, PC, APG, PRF, CT, Silver sulfadiazine ointment. The number of patients cured from high to low was APG, PRP injection, PRP, Aurix, PRF, Leucopatch, HPL, Antimicrobial Ointment Dressing, CT, 60 µg/cm2 repifermin, 120 µg/cm2 repifermin, AFG, PPP. The order of analgesic effect from high to low was AFG, Aminogam gel, PRF, PRP, Oxidised oil, APG, GF, CT. The order of the number of wound infection cases from low to high is APG, 20 µg/cm2 repifermin, 60 µg/cm2 repifermin, PRP, LeucoPatch, CT, PPP, Antiseptic ointment dressing. Healing area: GF + ORCCB had the best effect; Healing time: PRP + thrombin gel took the shortest time. The number of cured patients and the reduction of wound infection: APG has the best effect. Analgesic effect: AFG has the best effect. More studies with large sample sizes are needed to confirm the above findings.

Efficacy and safety of blood derivatives therapy in Alzheimer's disease: a systematic review and meta-analysis.

BACKGROUND: Blood derivatives therapy is a conventional clinical treatment, while the treatment for Alzheimer's disease (AD) is relatively novel. To provide clinical references for treating AD, this meta-analysis was performed to evaluate the efficacy and safety of blood derivatives therapy on the patients with AD. METHODS: A systematic articles search was performed for eligible studies published up to December 6, 2021 through the PubMed, Embase, Cochrane library, ClinicalTrials.gov , Chinese National Knowledge Infrastructure database, and Wanfang databases. The included articles were screened by using rigorous inclusion and exclusion criteria. Study selection and data-extraction were performed by two authors independently. Random effects model or fixed effects model was used. Quality of studies and risk of bias were evaluated according to the Cochrane risk of bias tool. All analyses were conducted using Review Manager 5.4. The study was designed and conducted according to the Preferring Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. RESULTS: A total of three plasma administrations (two plasma exchange and one young plasma infusion) and five intravenous immunoglobulin (IVIG) randomized controlled trials with a sample size of 1148 subjects diagnosed with AD were included. There was no significant difference in cognitive improvement and all-cause discontinuation between intervention and placebo groups (RR 1.10, 95% CI 0.79-1.54). And Intervention groups showed not a statistically significant improvement in cognition of included subjects measured by the ADAS-Cog (MD 0.36, 95% CI 0.87-1.59), ADCS-ADL (MD -1.34, 95% CI - 5.01-2.32) and NPI (MD 2.20, 95% CI 0.07-4.32) score compared to the control groups. IVIG is well tolerated for AD patients even under the maximum dose (0.4 g/kg), but it is inferior to placebo in Neuropsychiatric Inventory scale in AD patients (MD 2.19, 95% CI 0.02-4.37). CONCLUSIONS: The benefits of blood derivatives therapy for AD are limited. It is necessary to perform well-designed randomized controlled trials with large sample sizes focusing on the appropriate blood derivatives for the specific AD sub-populations in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021233886.

Efficacy and Safety of Blood Derivative Therapy for Patients with COVID-19: A Systematic Review and Meta-Analysis.

Background: The outbreak of COVID-19 has resulted in more than 200 million infections and 4 million deaths. The blood derivative therapy represented by intravenous immunoglobulin (IVIG) and convalescent plasma (CP) therapy may be the promising therapeutics for COVID-19. Methods: A systematic article search was performed for eligible studies published up to August 3, 2021, through the PubMed, Embase, Cochrane Library. The included articles were screened by using rigorous inclusion and exclusion criteria. All analyses were conducted using Review Manager 5.4. Quality of studies and risk of bias were evaluated. Results: A total of 5 IVIG therapy and 13 CP therapy randomized controlled trials were included with a sample size of 13,696 subjects diagnosed with COVID-19. IVIG could reduce the mortality compared with the control group (RR 0.65, 95% CI: 0.46-0.93, p = 0.02). The use of CP did not effectively reduce the mortality (RR 0.97, 95% CI: 0.91-1.03, p = 0.38), the length of hospital stay (MD -0.47, 95% CI: -4.13 to 3.20, p = 0.80), and the mechanical ventilation use (RR = 0.98, 95% CI: 0.89-1.07, p = 0.62) of the patients with COVID-19. Treatment with IVIG or CP was not significantly associated with an increase in reported adverse events (RR 1.07, 95% CI: 0.94-1.22, p = 0.28). Conclusions: Treatment with IVIG could be effective and safe to improve survival for patients with COVID-19. But the benefit of CP in the treatment of COVID-19 is limited. The certainty of the evidence was moderate for all outcomes.

Características clinicoepidemiológicas de pacientes tratados con hemoderivados en un hospital de Santiago de Cuba / Clinical and epidemiological characteristics of patients treated with blood-derivatives in a hospital from Santiago de Cuba

Introducción: El uso de hemoderivados es una práctica habitual en los hospitales y muy efectiva en determinadas situaciones clínicas. Objetivo: Caracterizar clínica y epidemiológicamente a pacientes tratados con hemoderivados en el Hospital Provincial Docente Dr. Joaquín Castillo Duany de Santiago de Cuba. Métodos: Se realizó un estudio descriptivo y transversal de 394 pacientes que estuvieron ingresados en el Hospital Provincial Docente Dr. Joaquín Castillo Duany de Santiago de Cuba, desde enero hasta junio de 2018, que recibieron transfusión de hemoderivados. Los datos se obtuvieron de las historias clínicas y para el procesamiento se empleó el paquete estadístico SPSS, versión 23. Resultados: En la serie predominaron el sexo masculino (50,7 %), la transfusión de eritrocitos y los pacientes transfundidos con cifras de hemoglobina entre 70 y 89 g/L (47,7 %). En el Servicio de Cirugía General fue donde más se transfundió (43,2 %) y, en general, se detectaron múltiples deficiencias en las órdenes de transfusiones. Conclusiones: No existieron diferencias significativas en cuanto al sexo y los pacientes intervenidos quirúrgicamente fueron los que más recibieron este tratamiento. Hubo incumplimiento del protocolo hospitalario previsto y la omisión de datos en las órdenes de transfusiones afectó la calidad de la hemovigilancia.

Introduction: The use of blood-derivatives is an usual practice in hospitals and very effective in certain clinical situations. Objective: To characterize clinical and epidemiologically patients treated with blood-derivatives at Dr. Joaquín Castillo Duany Teaching Provincial Hospital in Santiago de Cuba. Methods: A descriptive and cross-sectional study of 394 patients that were admitted to Dr. Joaquín Castillo Duany Teaching Provincial Hospital and received blood-derivatives transfusion was carried out in Santiago de Cuba, from January to June, 2018. The data were obtained from the medical records and for its processing the SPSS statistical package, version 23 was used. Results: In the series there was a prevalence of the male sex (50.7 %), transfusion of erythrocytes and transfused patients with hemoglobin figures between 70 and 89 g/L (47.7 %). There were more transfusions in the General Surgery Service (43.2 %) and, in general, multiple deficiencies were detected in the orders of transfusions. Conclusions: As for sex there were no significant differences and patients surgically intervened were those that received this treatment more times. There was no fulfilment of the foreseen hospital protocol and the omission of data in the orders of transfusions affected the blood safety quality.

Therapeutic considerations for patients with chronic plantar fasciitis (Review).

Heel pain is a common complaint in the population, leading to a limitation in daily activities and a poor quality of life. Chronic plantar fasciitis is the most common cause of heal pain. Despite its name, which suggests inflammation, the underlying process is rather a degenerative one. The clinical course is often chronic or relapsing, as a challenge to physicians to find the most effective therapeutically approach. First-line treatment consists of rest, shoe modification, orthosis and physiotherapy. Physical exercise is an important tool which can be combined with other therapeutic options. Medication is usually administered in acute cases, in the form of simple analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) or opioids, in different regimens. For chronic evolution, the use of NSAIDs is controversial. Second-line treatment includes extracorporeal shock wave therapy and corticosteroid local injection. New therapies have emerged, as autologous blood derivatives and prolotherapy, with growing evidence, to be included in clinical practice. The present review article discusses the therapeutic options for patients with chronic plantar fasciitis, to with an aim to shed light on the treatment strategies for this condition.

Natural-Based Hydrogels for Tissue Engineering Applications.

In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due to their ability to mimic the native tissues' extracellular matrix and biocompatibility. However, the majority of these natural materials failed to provide satisfactory cues to guide cell differentiation toward the formation of new tissues. In addition, the integration of technological advances, such as 3D printing, microfluidics and nanotechnology, in tissue engineering has obsoleted the first generation of natural-origin hydrogels. During the last decade, a new generation of hydrogels has emerged to meet the specific tissue necessities, to be used with state-of-the-art techniques and to capitalize the intrinsic characteristics of natural-based materials. In this review, we briefly examine important hydrogel crosslinking mechanisms. Then, the latest developments in engineering natural-based hydrogels are investigated and major applications in the field of tissue engineering and regenerative medicine are highlighted. Finally, the current limitations, future challenges and opportunities in this field are discussed to encourage realistic developments for the clinical translation of tissue engineering strategies.

Plasma Rich in Growth Factors for the Treatment of Cicatrizing Conjunctivitis.

PURPOSE: The objective was to evaluate the clinical results obtained from the use of immunosafe plasma rich in growth factors (isPRGF) in the treatment of patients with cicatrizing conjunctivitis (CC) who had not responded to the usual therapy. PATIENTS AND METHODS: This is a retrospective study that included patients diagnosed with CC, in whom isPRGF was used in different phases (I: eye drops; II: eye drops and injectable; III: eye drops, injectable and surgical treatment) to achieve control of the inflammation. As a clinical follow-up of the patients, the better corrected visual acuity (BCVA), degree of inflammation (measured from 1 to 4), the severity of the CC, Schirmer I test, IOP and TBUT were analyzed. The adverse events were also evaluated. RESULTS: Ten eyes (6 patients) were evaluated, 50% corresponded to Stevens-Johnson Syndrome and 50% to ocular mucous membrane pemphigoid. The mean age was 59.7 ± 16.5 (39-80) years, and 50% were women. Fifty per cent of the cases were initially considered severe CC, and 10% of the cases (one eye of one patient) were considered severe CC at the end of the treatment (p = 0.046). The initial degree of inflammation was 2 in 4 eyes, 3 in two eyes, and 4 in 4 eyes, and final inflammation degree was 1 in all cases (p = 0.004). Twenty per cent of the cases achieved stability in Phase I of the treatment with immunosafe PRGF, 70% with both Phases I and II, and only one case underwent Phase III to achieve stability. The IOP improved significantly (p = 0.027) though the BCVA, TBUT and Schirmer I test showed no significant changes. The follow-up time was 23.1 ± 6.7 (13.6-30.3) months. No adverse effects were reported. CONCLUSION: Treatment with PRGF technology in its injectable and topical immunosafe formulations may be a novel alternative for the treatment of patients with CC, given its complement activity modulating effect, as well as its anti-inflammatory, antifibrotic and regenerative properties.

Evaluation of ultraviolet-C and spray-drying processes as two independent inactivation steps on enterotoxigenic Escherichia coli K88 and K99 strains inoculated in fresh unconcentrated porcine plasma.

The objectives of this study were to assess the effectiveness of an ultraviolet (UV-C, 254 nm) irradiation system and the spray-drying method as two independent safety steps on inactivation of Escherichia coli K88 and K99 spiked in porcine plasma at 6·46 ± 0·04 log10  ml-1 and 6·78 ± 0·67 log10  ml-1 respectively for UV-C method, and at 7·31 ± 0·39 log10  ml-1 and 7·66 ± 0·11 log10  ml-1 , respectively for the spray-drying method. The UV-C method was performed at different UV light doses (from 750 to 9000 J l-1 ) using a pilot plant UV-C device working under turbulent flow. Spray-drying treatment was done at inlet temperature 220 ± 1°C and two different outlet temperatures, 80 ± 1°C or 70 ± 1°C. Results indicated that UV-C treatment induced a 4 log10 viability reduction for both E. coli at 3000 J l-1 . Full inactivation of both E. coli strains was achieved in all spray-dried samples dehydrated at both outlet temperatures. The special UV-C system design for turbid liquid porcine plasma is a novel treatment that can provide an additional redundant biosafety feature that can be incorporated into the manufacturing process for spray-dried animal plasma. SIGNIFICANCE AND IMPACT OF THE STUDY: The safety of raw materials from animal origin such as spray-dried porcine plasma (SDPP) may be a concern for the swine industry. Ultraviolet treatment at 254 nm (UV-C) of liquid plasma has been proposed as an additional biosafety feature in the manufacturing process of SDPP. We found that UV-C exposure in the liquid plasma at 3000 J l-1 reduces about 4 log10 ml-1 for E. coli K88 and K99. Full inactivation of both E. coli strains was achieved in all spray-dried samples. The incorporation of UV-C treatment to liquid plasma improves the robustness of the SDPP manufacturing process.

Blood derivatives awaken in regenerative medicine strategies to modulate wound healing.

Blood components play key roles in the modulation of the wound healing process and, together with the provisional fibrin matrix ability to selectively bind bioactive molecules and control its spatial-temporal presentation, define the complex microenvironment that characterize this biological process. As a biomimetic approach, the use of blood derivatives in regenerative strategies has awakened as a source of multiple therapeutic biomolecules. Nevertheless, and despite their clinical relevance, blood derivatives have been showing inconsistent therapeutic results due to several factors, including proper control over their delivery mechanisms. Herein, we highlight recent trends on the use biomaterials to protect, sequester and deliver these pools of biomolecules in tissue engineering and regenerative medicine approaches. Particular emphasis is given to strategies that enable to control their spatiotemporal delivery and improve the selectivity of presentation profiles of the biomolecules derived from blood derivatives rich in platelets. Finally, we discussed possible directions for biomaterials design to potentiate the aimed regenerative effects of blood derivatives and achieve efficient therapies.

Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A Systematic Scoping Review

Abstract Although the biological properties of mesenchymal stem cells (MSC) are well-characterized in vitro, MSC clinical application is still far away to be achieved, mainly due to the need of xenogeneic substances for cell expansion, such as fetal bovine serum (FBS). FBS presents risks regarding pathogens transmissions and internalization of animal's proteins, which can unleash antigenic responses in patients after MSC implantation. A wide range of venous blood derivatives (VBD) has been reported as FBS substitutes showing promising results. Thus, the aim of this study was to conduct a systematic scoping review to analyze whether VBD are effective FBS substitutes for MSC ex vivo expansion. The search was performed in SciVerse ScopusTM, PubMed, Web of ScienceTM, BIREME, Cochrane library up to January 2016. The keywords were selected using MeSH and entry terms. Two independent reviewers scrutinized the records obtained considering specific inclusion criteria. The included studies were evaluated in accordance with a modified Arksey and O' Malley's framework. From 184 found studies, 90 were included. Bone marrow mesenchymal stem cells (BMMSC) were presented in most of these studies. Overall, VBD allowed for either, maintenance of MCS's fibroblast-like morphology, high proliferation, high colony-formation ability and maintenance of multipotency. Besides. MSC expanded in VBD supplements presented higher mitogen activity than FBS. VBD seems to be excellent xeno-free serum for ex vivo expansion of mesenchymal stem cells. However, an accentuated heterogeneity was observed between the carried out protocols for VBD isolation did not allowing for direct comparisons between the included studies.

Resumo Embora as propriedades biológicas das células-tronco mesenquimais (MSC) sejam bem caracterizadas in vitro, a aplicação clínica das MSC ainda está longe de ser alcançada, principalmente devido à necessidade de substâncias xenogênicas para expansão celular, como o soro fetal bovino (FBS). O FBS apresenta riscos quanto às transmissões de patógenos e à internalização de proteínas animais, o que pode desencadear respostas antigênicas em pacientes após a implantação das MSC. Uma vasta gama de derivados do sangue venoso (VBD) têm sido relatada como substitutos do FBS mostrando resultados promissores. Assim, o objetivo deste estudo foi conduzir uma revisão de escopo sistemática para analisar se VBD poderiam ser substitutos do FBS eficazes para expansão das MSC em condições ex vivo. A pesquisa foi realizada no SciVerse Scopus, PubMed, Web of Science, BIREME e biblioteca Cochrane até janeiro de 2016. As palavras-chave foram selecionadas usando MeSH e entre termos. Dois revisores independentes examinaram os registros obtidos considerando critérios de inclusão específicos. Os estudos incluídos foram avaliados de acordo com uma estrutura modificada de Arksey e O 'Malley. Dos 184 estudos encontrados, 90 foram incluídos. As células-tronco da medula óssea (BMMSC) foram utilizadas na maior parte destes estudos. Em geral, o VBD permitiu tanto a manutenção da morfologia semelhante a fibroblastos das MCS, alta proliferação, alta capacidade de formação de colônias e manutenção de multipotêncialidade. Além disso, as MSC expandidas em suplementos derivados do sangue venoso apresentaram uma maior atividade mitogênica do que as expandidas em FBS. Os VBD parecem ser excelentes soro livres de agentes xenogênicos para expansão ex vivo de MSC. Entretanto, observou-se uma heterogeneidade acentuada entre os protocolos realizados para o isolamento VBD, não permitindo assim comparações diretas entre os estudos incluídos.

Raman and Energy Dispersive Spectroscopy (EDS) Analyses of a Microsubstance Adhering to a Fiber of the Turin Shroud.

The Raman spectrum of a microsubstance, smeared on a fiber coming from the Shroud of Turin, was compared with numerous spectra published for old or modern pigment dyes, whole bloods, dried bloods, red blood cells, albumin, very ancient blood stains, and various "degradation" products of heme. Within the wavenumber measure accuracy, it is shown that all Raman lines detected above background could correspond to vibration frequencies found in biliverdin-derived compounds except a weak line that we tentatively attributed to amide I. Biliverdin is known as an oxidative ring cleavage product of the heme of blood. Energy dispersive spectroscopy (EDS) analysis of the sample confirms an elemental composition fully compatible with this hypothesis. Therefore, it is very likely that this microsubstance contains products of heme including heme/biliverdin-derived compounds and protein traces (amide I). Nevertheless, other measures will be necessary to confirm it. This method of identification, adding EDS to Raman spectrometry can be applied to nondestructive testing (NDT) of many other microsamples.

Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration.

Platelet rich blood derivatives have been widely used in different fields of medicine and stem cell based tissue engineering. They represent natural cocktails of autologous growth factor, which could provide an alternative for recombinant protein based approaches. Platelet rich blood derivatives, such as platelet rich plasma, have consistently shown to potentiate stem cell proliferation, migration, and differentiation. Here, we review the spectrum of platelet rich blood derivatives, discuss their current applications in tissue engineering and regenerative medicine, reflect on their effect on stem cells, and highlight current translational challenges.

An updated approach to viral hepatitis E.

Viral hepatitis E (VHE) is considered to be the most common acute viral hepatitis worldwide. Since the 1980s, VHE has been reported in developing countries. Although VHE is not a reportable disease in many developed countries, it is evidently on the rise even in these countries [1].In Europe, VHE is no longer an imported disease and efforts have been made to map VHE cases in both humans and animals to be able to update the recommendations for VHE prevention, risk assessment for blood product and organ transplants recipients, prevention strategies for severe and chronic VHE, and laboratory test algorithms.

La hemotransfusión en los Testigos de Jehová como un problema de las Ciencias Médicas / Blood transfusion in Jehovah's Witnesses as a problem in Medical Sciences

Introducción: los Testigos de Jehová basan sus creencias sobre una interpretación literal de la Biblia y no aceptan la transfusión de sangre o sus derivados. Pero no siempre se consigue por medio de las opciones médicas a la transfusión, evitar la muerte del individuo en determinadas circunstancias: ello plantea un conflicto bioético. Objetivo: analizar algunos aspectos bioéticos y legales, que puedan ayudar al anestesiólogo cubano a una mejor comprensión de este conflicto y a su solución ante la perspectiva de hemotransfundir a un paciente Testigos de Jehová. Desarrollo: los peligros de la transfusión sanguínea hacen considerar siempre medidas alternativas. Los pacientes Testigos de Jehová plantean un desafío a las Ciencias Médicas que ha estimulado el avance del conocimiento y la tecnología sobre dichas alternativas en beneficio de todos los pacientes; pero renegar tácitamente de la transfusión puede eventualmente introducir la posibilidad de que un paciente muera aunque existan opciones para salvarle. La práctica compele establecer antes de cualquier procedimiento quirúrgico protocolos específicos y líneas de comunicación entre paciente, anestesiólogo, cirujano, administración del hospital y el consejo legal. Conclusiones: el progreso de las investigaciones en las Ciencias Médicas está llamado a sustituir la reposición de sangre o sus derivados por las implicaciones biológicas que estos tratamientos médicos conllevan y no por cortapisas de un fanatismo religioso, que intenta arrebatar argumentos científicos para justificar sus creencias. En nuestro medio este conflicto bioético tiene solución dentro de un marco ético y legal en el que prevalece el bien supremo: la vida humana.

Background: Jehovah's Witnesses base their beliefs on a literal interpretation of the Bible and do not accept blood transfusions or its derivatives. But, by means of medical options to transfusion, the prevention of the death of the individual in certain circumstances is not always achieved: this causes a bioethical conflict. Objective: to analyze some bioethical and legal aspects that can help the Cuban anesthesiologist to a better understanding of this conflict and its solution in the perspective of giving a blood transfusion to a Jehovah's Witness patient. Development: the dangers of blood transfusion make us consider alternative measures. Jehovah's Witness patients pose a challenge to the Medical Sciences that has stimulated the advance of knowledge and technology on such alternatives for the benefit of all patients, but tacitly deny blood transfusion may eventually introduce the possibility that a patient dies even when there are options to save him. Practice obliges to establish specific protocols and lines of communication between patient, anesthesiologist, surgeon, hospital management, and legal advice before any surgical procedure. Conclusions: the progress of research in the Medical Sciences is oriented to substitute blood replacement or its derivatives because of the biological implications that these treatments bear rather than the obstacles of a religious fanaticism that tries to snatch scientific arguments to justify their beliefs. In our means, this bioethical conflict is solved within an ethical and legal framework in which a supreme good prevails: human life.

La hemotransfusión en los Testigos de Jehová como un problema de las Ciencias Médicas / Blood transfusion in Jehovah's Witnesses as a problem in Medical Sciences

Introducción: los Testigos de Jehová basan sus creencias sobre una interpretación literal de la Biblia y no aceptan la transfusión de sangre o sus derivados. Pero no siempre se consigue por medio de las opciones médicas a la transfusión, evitar la muerte del individuo en determinadas circunstancias: ello plantea un conflicto bioético. Objetivo: analizar algunos aspectos bioéticos y legales, que puedan ayudar al anestesiólogo cubano a una mejor comprensión de este conflicto y a su solución ante la perspectiva de hemotransfundir a un paciente Testigos de Jehová. Desarrollo: los peligros de la transfusión sanguínea hacen considerar siempre medidas alternativas. Los pacientes Testigos de Jehová plantean un desafío a las Ciencias Médicas que ha estimulado el avance del conocimiento y la tecnología sobre dichas alternativas en beneficio de todos los pacientes; pero renegar tácitamente de la transfusión puede eventualmente introducir la posibilidad de que un paciente muera aunque existan opciones para salvarle. La práctica compele establecer antes de cualquier procedimiento quirúrgico protocolos específicos y líneas de comunicación entre paciente, anestesiólogo, cirujano, administración del hospital y el consejo legal. Conclusiones: el progreso de las investigaciones en las Ciencias Médicas está llamado a sustituir la reposición de sangre o sus derivados por las implicaciones biológicas que estos tratamientos médicos conllevan y no por cortapisas de un fanatismo religioso, que intenta arrebatar argumentos científicos para justificar sus creencias. En nuestro medio este conflicto bioético tiene solución dentro de un marco ético y legal en el que prevalece el bien supremo: la vida humana(AU)

Background: Jehovah's Witnesses base their beliefs on a literal interpretation of the Bible and do not accept blood transfusions or its derivatives. But, by means of medical options to transfusion, the prevention of the death of the individual in certain circumstances is not always achieved: this causes a bioethical conflict. Objective: to analyze some bioethical and legal aspects that can help the Cuban anesthesiologist to a better understanding of this conflict and its solution in the perspective of giving a blood transfusion to a Jehovah's Witness patient. Development: the dangers of blood transfusion make us consider alternative measures. Jehovah's Witness patients pose a challenge to the Medical Sciences that has stimulated the advance of knowledge and technology on such alternatives for the benefit of all patients, but tacitly deny blood transfusion may eventually introduce the possibility that a patient dies even when there are options to save him. Practice obliges to establish specific protocols and lines of communication between patient, anesthesiologist, surgeon, hospital management, and legal advice before any surgical procedure. Conclusions: the progress of research in the Medical Sciences is oriented to substitute blood replacement or its derivatives because of the biological implications that these treatments bear rather than the obstacles of a religious fanaticism that tries to snatch scientific arguments to justify their beliefs. In our means, this bioethical conflict is solved within an ethical and legal framework in which a supreme good prevails: human life(AU)

Mejora de la calidad en el consentimiento informado / Enhancement of informed consent quality / Melhora da qualidade no consentimento informado

Objetivo: Aplicar un círculo de mejora al consentimiento informado para la transfusión de hemoderivados. Pacientes y Método: Durante 10 meses se incluyeron 577 pacientes intervenidos en el Hospital General Reina Sofía de Murcia. Seleccionamos 6 criterios relacionados con el cumplimiento de la normativa sobre transfusiones. Tras el análisis de calidad, se aplicaron medidas correctoras y se reevaluaron los criterios. Los datos se compararon con los estándares en ambos periodos y entre periodos. En la primera evaluación se obtuvo un pobre cumplimiento de los criterios. Basándonos en el análisis de factores asociados al incumplimiento y la priorización resultante del diagrama de Pareto, el plan de intervención se dividió en actividad docente y modificaciones organizativas. Resultados: Todos los criterios estaban por debajo del estándar (p<0,001). En la segunda evaluación el cumplimiento de todos los criterios mejoró significativamente respecto de la primera; aun así los resultados continúan, también significativamente, por debajo de los estándares establecidos. Conclusiones: El cumplimiento de los 6 criterios era mínimo al inicio del estudio; las medidas correctoras fueron adecuadas, puesto que mejoraron todos ellos en la segunda evaluación, pero es necesario insistir en estas medidas ya que continuamos por debajo del estándar establecido.

Aim: To apply an enhancement circle for informed consent for transfusion of blood derivatives. Patients and Method: During 10 months 577 intervened patients were included in General Hospital Reina Sofia of Murcia, Spain. Six criteria were selected related to compliance with transfusion norms. After quality analysis, corrected measures were taken and the criteria were re evaluated. Data were compared with standards in both periods and between periods. In the first evaluation a poor compliance to criteria was observed. Based on the analysis of factors associated to lack of compliance and the resulting priorization from Pareto’s diagram, the intervention plan was divided in teaching activity and management modifications. Results: all criteria were under the standard (p<0.001). In the second evaluation, compliance for all criteria was significantly enhance with respect to the first; but nevertheless, results continue, also significantly, under established standards. Conclusions: Compliance to the six criteria was minimum at the beginning of the study; corrected measures were adequate, since they enhance all of them in the second evaluation, but it is necessary to insist in these measures since we continue under the established standard.

Objetivo: Aplicar um círculo de melhora ao consentimento informado para a transfusão de hemoderivados. Pacientes e Método: Durante 10 meses foram incluídos 577 pacientes internados no Hospital General Reina Sofía de Murcia. Selecionamos 6 critérios relacionados com o cumprimento da norma sobre transfusões. Após a análise de qualidade, foram aplicadas medidas corretoras e se reavaliaram os critérios. Os dados foram comparados com os padrões em ambos periodos e entre periodos. Na primeira avaliação se obteve um pobre cumprimento dos critérios. Baseando-nos na análise de fatores associados ao incumprimento e a priorização resultante do diagrama de Pareto, o plano de intervenção se dividiu em atividade docente e modificações organizativas. Resultados: Todos os critérios estavam abaixo do padrão (p<0,001). Na segunda avaliação o cumprimento de todos os critérios melhorou significativamente com respeito à primeira; ainda assim os resultados continuam, também significativamente, abaixo dos padrões estabelecidos. Conclusões: O cumprimento dos 6 critérios era mínimo ao início do estudo; as medidas corretoras foram adequadas, posto que melhoraram todos eles na segunda avaliação, porém é necessário insistir nestas medidas já que continuamos abaixo do padrão estabelecido.

A new methodology for polyvalent intravenous immunoglobulin solution production with a two-stage process of viral inactivation

Highly purified intravenous immunoglobulin G concentrate (IV IgG) was produced with the use of polyethylene glycol associated to a single-stage precipitation by ethanol, instead of the classic Cohn-Oncley process, which employs cold alcohol as the precipitating agent, in a three-stage process. Precipitation of crude fraction containing more than 95% of immunoglobulin G was performed by liquid chromatography with a cation exchanger, CM-Sepharose, as a stationary phase. During the process, the product was subjected to two-stage viral inactivation. The first stage was performed by the action of sodium caprylate, 30 mM at pH 5.1+/- 0.1, and the second stage was performed by the action of a solvent-detergent mixture. The finished product was formulated at 5% with 10% sucralose as the stabilizing agent. The process yields 3.3g of IgG/liter of plasma. The finished product analysis showed an anti-complementary activity lower than 1CH50. Polymer and aggregate percent levels were lower than 3% in the five batches studied. The analysis of neutralizing capacity showed the presence of antibacterial and antiviral antibodies in at least three times higher concentrations than the levels found in source plasma. The finished product fulfilled all purity requirements stated in the 4th edition of the European pharmacopeia.

Obteve-se concentrado de imunoglobulina G intravenosa IgGIV, altamente purificado, utilizando-se polietilenoglicol associado a uma única etapa de precipitação por etanol, em substituição ao tradicional método descrito por Cohn-Oncley, que emprega, em três etapas, o mesmo álcool resfriado, como agente precipitante. A purificação da fração bruta contendo mais de 95% de imunoglobulina G foi realizada utilizando-se cromatografia líquida com um trocador de cátion, a CM-Sepharose, como fase estacionária. Durante o processamento o produto foi submetido a dupla inativação viral sendo a primeira pela ação do caprilato de sódio, 30 mM a pH 5,1+/- 0,1 e a segunda por ação de mistura de solvente/detergente. O produto acabado foi formulado a 5% utilizando-se sucralose 10% como estabilizante. O rendimento da metodologia foi de 3,3g de IgG/litro de plasma. A análise do produto acabado demonstrou atividade anti-complementar inferior a 1CH50. O valor percentual de polímeros e agregados em cinco lotes realizados foi inferior a 3%. O estudo da capacidade de neutralização demonstrou a presença de anticorpos anti-bacterianos e anti-virais em concentração pelo menos três vezes maior que o plasma de origem. O produto acabado apresentou conformidade com todos os requisitos de pureza dispostos na farmacopéia européia IV edição.

Plasma derivatives and strategies for reaching self-sufficiency in Liguria: the role of the Transfusion Medicine Service of the Gaslini Institute.

BACKGROUND: Since 2002, Liguria has been part of the Interregional Agreement on Plasma Derivatives (AIP) stipulated among some Regions of north Italy with the aim of contributing to self-sufficiency of the interregional system through exchanges between the facilities lacking products and those with an excess. In Liguria , the management of plasma derivates is entrusted to the Regional Centre for Co-ordination and Compensation (CRCC) which, with strategies of compensation, tries to guarantee that the needs for plasma derivates are covered in the hospitals in its territory. The Services of Immunohaematology and Transfusion Medicine (SIMT) have a goal of increasing the production of plasma in order to participate actively in achieving regional self-sufficiency. METHODS: The SIMT of the G. Gaslini Institute introduced some strategies aimed at reaching this goal. The increase in the number of donations made with a cell separator, the introduction of multicomponent donations of plasma and platelets and the collection of high concentration platelet concentrates led to a considerable increase category A plasma sent for fractioning. Finally, the implementation of shared guidelines on the use of blood components enabled the clinical use of the plasma collected to be kept under control. RESULTS AND CONCLUSIONS: The analysis of the trends of consumption of the most widely used plasma derivatives showed an increase in the overall demands, which can be attributed to the paediatric focus of our hospital and to its highly specialised wards. ON THE BASIS OF THE INDUSTRIAL TECHNICAL YIELD, IT WAS POSSIBLE TO CALCULATE THE THEORETICAL COVERAGE OF THE REQUIREMENTS FOR PLASMA: this highlighted a better theoretical coverage for albumin but a shortfall of intravenous immunoglobulins. The amount of plasma necessary to meet the theoretical needs was calculated for each plasma derivative, revealing that the derivative requiring the greatest volume of plasma is intravenous immunoglobulins. This finding confirms the change in the "driving product": it is now the consumption of intravenous immunoglobulins that determines the amount of plasma that is sent for industrial processing.