End-of-life practices in patients with devastating brain injury in Spain: implications for organ donation. / Prácticas clínicas al final de la vida en pacientes con daño cerebral catastrófico en España: implicaciones para la donación de órganos.

OBJECTIVE: To describe end-of-life care practices relevant to organ donation in patients with devastating brain injury in Spain. DESIGN: A multicenter prospective study of a retrospective cohort. PERIOD: 1 November 2014 to 30 April 2015. SETTING: Sixty-eight hospitals authorized for organ procurement. PATIENTS: Patients dying from devastating brain injury (possible donors). Age: 1 month-85 years. PRIMARY ENDPOINTS: Type of care, donation after brain death, donation after circulatory death, intubation/ventilation, referral to the donor coordinator. RESULTS: A total of 1,970 possible donors were identified, of which half received active treatment in an Intensive Care Unit (ICU) until brain death (27%), cardiac arrest (5%) or the withdrawal of life-sustaining therapy (19%). Of the rest, 10% were admitted to the ICU to facilitate organ donation, while 39% were not admitted to the ICU. Of those patients who evolved to a brain death condition (n=695), most transitioned to actual donation (n=446; 64%). Of those who died following the withdrawal of life-sustaining therapy (n=537), 45 (8%) were converted into actual donation after circulatory death donors. The lack of a dedicated donation after circulatory death program was the main reason for non-donation. Thirty-seven percent of the possible donors were not intubated/ventilated at death, mainly because the professional in charge did not consider donation alter discarding therapeutic intubation. Thirty-six percent of the possible donors were never referred to the donor coordinator. CONCLUSIONS: Although deceased donation is optimized in Spain, there are still opportunities for improvement in the identification of possible donors outside the ICU and in the consideration of donation after circulatory death in patients who die following the withdrawal of life-sustaining therapy.

Intensive care practices in brain death diagnosis and organ donation.

We conducted a multicentre study of 1844 patients from 42 Spanish intensive care units, and analysed the clinical characteristics of brain death, the use of ancillary testing, and the clinical decisions taken after the diagnosis of brain death. The main cause of brain death was intracerebral haemorrhage (769/1844, 42%), followed by traumatic brain injury (343/1844, 19%) and subarachnoid haemorrhage (257/1844, 14%). The diagnosis of brain death was made rapidly (50% in the first 24 h). Of those patients who went on to die, the Glasgow Coma Scale on admission was ≤ 8/15 in 1146/1261 (91%) of patients with intracerebral haemorrhage, traumatic brain injury or anoxic encephalopathy; the Hunt and Hess Scale was 4-5 in 207/251 (83%) of patients following subarachnoid haemorrhage; and the National Institutes of Health Stroke Scale was ≥ 15 in 114/129 (89%) of patients with strokes. Brain death was diagnosed exclusively by clinical examination in 92/1844 (5%) of cases. Electroencephalography was the most frequently used ancillary test (1303/1752, 70.7%), followed by transcranial Doppler (652/1752, 37%). Organ donation took place in 70% of patients (1291/1844), with medical unsuitability (267/553, 48%) and family refusal (244/553, 13%) the main reasons for loss of potential donors. All life-sustaining measures were withdrawn in 413/553 of non-donors (75%).

Brain death organ donation potential and life support therapy limitation in neurocritical patients.

OBJECTIVE: To analyze the profile, incidence of life support therapy limitation (LSTL) and donation potential in neurocritical patients. STUDY DESIGN: A multicenter prospective study was carried out. SETTING: Nine hospitals authorized for organ harvesting for transplantation. PATIENTS: All patients consecutively admitted to the hospital with GCS < 8 during a 6-month period were followed-up until discharge or day 30 of hospital stay. STUDY VARIABLES: Demographic data, cause of coma, clinical status upon admission and outcome were analyzed. LSTL, brain death (BD) and organ donation incidence were recorded. RESULTS: A total of 549 patients were included, with a mean age of 59.0 ± 14.5 years. The cause of coma was cerebral hemorrhage in 27.0% of the cases.LSTL was applied in 176 patients (32.1%). In 78 cases LSTL consisted of avoiding ICU admission. Age, the presence of contraindications, and specific causes of coma were associated to LSTL. A total of 58.1% of the patients died (n=319). One-hundred and thirty-three developed BD (24.2%), and 56.4% of these became organ donors (n=75). The presence of edema and mid-line shift on the CT scan, and transplant coordinator evaluation were associated to BD. LSTL was associated to a no-BD outcome. Early LSTL (first 4 days) was applied in 9 patients under 80 years of age, with no medical contraindications for donation and a GCS ≤ 4 who finally died in asystole. CONCLUSIONS: LSTL is a frequent practice in neurocritical patients. In almost one-half of the cases, LSTL consisted of avoiding admission to the ICU, and on several occasions the donation potential was not evaluated by the transplant coordinator.

Cytotoxicity and mycotoxin production of shellfish-derived Penicillium spp., a risk for shellfish consumers.

In order to assess the putative toxigenic risk associated with the presence of fungal strains in shellfish-farming areas, Penicillium strains were isolated from bivalve molluscs and from the surrounding environment, and the influence of the sample origin on the cytotoxicity of the extracts was evaluated. Extracts obtained from shellfish-derived Penicillia exhibited higher cytotoxicity than the others. Ten of these strains were grown on various media including a medium based on mussel extract (Mytilus edulis), mussel flesh-based medium (MES), to study the influence of the mussel flesh on the production of cytotoxic compounds. The MES host-derived medium was created substituting the yeast extract of YES medium by an aqueous extract of mussel tissues, with other constituent identical to YES medium. When shellfish-derived strains of fungi were grown on MES medium, extracts were found to be more cytotoxic than on the YES medium for some of the strains. HPLC-UV/DAD-MS/MS dereplication of extracts from Penicillium marinum and P. restrictum strains grown on MES medium showed the enhancement of the production of some cytotoxic compounds. The mycotoxin patulin was detected in some P. antarcticum extracts, and its presence seemed to be related to their cytotoxicity. Thus, the enhancement of the toxicity of extracts obtained from shellfish-derived Penicillium strains grown on a host-derived medium, and the production of metabolites such as patulin suggests that a survey of mycotoxins in edible shellfish should be considered.

Continuously evaluating performance in deceased donation: the Spanish quality assurance program.

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

Logistics and strategy of multiorgan procurement involving total face allograft.

The face is the latest body structure to be added to the field of transplantation and the learning curve is ongoing. In the scenario of multiorgan recovery, the face is a nonvital 'organ' structure compared with other life-saving organs. To date, the face has been the first 'organ' to be procured in a multiorgan procurement. A technique for simultaneous recovery of the whole face, heart, lungs, liver, pancreas and kidneys is described. Thirty professionals participated in the procedure, of whom 13 were surgeons. No tracheotomy was performed. A mask of the donor's face was made from a mold impression. Duration of the procedure from skin incision to the end of surgery was 7.3 h. The face was perfused with Wisconsin solution through a cannula inserted into the aortic arch between the origin of the brachiocephalic arterial trunk and the left subclavian artery. Blood requirements consisted of 4 units of packed red blood cells. After the procedure, the mask was placed on the donor's face. All recovered grafts functioned immediately. In summary, simultaneous multiorgan procurement including the whole face is feasible, effective and saves time without jeopardizing life-saving organs and without the need for tracheotomy.

[Intensive care to facilitate organ donation. ONT-SEMICYUC recommendations]. / Cuidados intensivos orientados a la donación de órganos. Recomendaciones ONT-SEMICYUC.

Intensive care to facilitate organ donation (ICOD) is defined as the initiation or continuation of life-sustaining measures, such as mechanical ventilation, in patients with a devastating brain injury with high probability of evolving to brain death and in whom curative treatment has been completely dismissed and considered futile. ICOD incorporates the option to organ donation allowing a holistic approach to end-of-life care, consistent with the patients wills and values. Should the patient not evolve to brain death, life-supportive treatment must be withdrawal and controlled asystolia donation could be evaluated. ICOD is a legitimate practice, within the ethical and legal regulations that contributes increasing the accessibility of patients to transplantation, promoting health by increasing deceased donation by 24%, and with a mean of 2.3 organs transplanted per donor, and collaborating with the sustainability of health-care system. This ONT-SEMICYUC recommendations provide a guide to facilitate an ICOD harmonized practice in spanish ICUs.

Donor referral from outside the intensive care unit: A multidisciplinary cooperation model using communication apps and redefining refereal criteria.

OBJECTIVE: We evaluate the impact of a web-based collaborative system on the referral of possible organ donors from outside of the intensive care unit (ICU). STUDY DESIGN: Cohort prospective study. SETTINGS: University hospital. PATIENTS AND INTERVENTION: In 2015 a virtual collaborative system using a cross-platform instant messaging application replaced the previous 2014 protocol for the referral of patients outside of the ICU with a severe brain injury in whom all treatment options were deemed futile by the attending team to the donor coordination (DC). Once the DC evaluated the medical suitability and likelihood of progression to brain death (BD), the option of intensive care to facilitate organ donation (ICOD) was offered to the patient's relatives. This included admission to the ICU and elective non-therapeutic ventilation (ENTV), where appropriate. RESULTS: A two-fold increase of referrals was noted in 2015 [n=46/74; (62%)] compared to 2014 [n=13/40; (32%)]; p<0.05. Patients were mostly referred from the stroke unit (58.6%) in 2015 and from the emergency department (69.2%) in 2014 (p<0.01). Twenty (2015: 42.5%) and 4 (2014: 30.7%) patients were discarded as donors mostly due to medical unsuitability. Family accepted donation in 16 (2015: 62%) and 6 (2014: 66%) cases, all admitted to the ICU and 10 (2015: 62.5%) and 3 (50%) being subject to ENTV. Ten (2015: 66.6%) and 5 (2014: 83.3%) patients progressed to BD, 60.5±20.2 and 44.4±12.2h after referral respectively. Nine (2015) and 4 (2014) of these patients became utilized donors, representing 29.0% (2015) and 13.0% (2014) of the BD donors in the hospital during the study period (p<0.05). CONCLUSION: The implementation of a virtual community doubled the number of patients whose families were presented with the option of donation prior to their death.

Feline Leukaemia Virus Associated with Leukaemia in Cats in Santa Catarina, Brazil.

Leukaemia is a haemopoietic neoplasm originating from myeloid or lymphoid precursors in the bone marrow and may be either acute or chronic. These tumours are rare, but occur more frequently in cats because of an association with the feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV). To the best of our knowledge, no studies conducted in Brazil to date have analysed the association between leukaemia and FeLV and FIV infection in cats. The aim of this study was to perform a histopathological analysis of feline leukaemia and evaluate the association between leukaemia and FeLV and FIV infection in cats. The study evaluated 37 cats with leukaemia diagnosed between 2009 and 2017. The animals underwent necropsy examination, histopathology and immunohistochemistry with anti-FeLV gp70 and anti-FIV p24 gag antibodies. Of the evaluated animals, 54% (20/37) were males and 43.2% (16/37) were females. With respect to the life stage of the animals, 24.3% (9/37) were junior, 32.4% (12/37) were prime, 18.9% (7/37) were mature and 10.8% (4/37) were senior, and five animals were of unknown age. Myeloid leukaemia occurred in 56.8% (21/37) of the cases and lymphocytic leukaemia occurred in 43.2% (16/37) of the cases. Acute leukaemia (73%, 27/37) was more common than chronic leukaemia (27%, 10/37). The positivity for FeLV (78.4%, 29/37) and FIV (16.2%, 6/37) indicated a high association between FeLV infection and tumour development in the study region.

"Non-Touch" Vena Cava Technique as an Improvement in Combined Lung and Liver Procurement in Controlled Donation After Circulatory Death.

The number of organs retrieved from donation after circulatory death (DCD) donors has continued to rise in recent years. The functional superiority of DCD organs is achieved when the lungs are perfused with cold perfusion and livers with normothermic regional perfusion (NRP). Thus, a precise surgical technique is required to combine thoracic and abdominal organ procurement. The technique used at our center consists of a rapid laparotomy and middle sternotomy, then the abdominal aorta (Ao) and abdominal inferior vena cava (VC) are cannulated and the descending thoracic Ao is cross-clamped. NRP is started at that point. As a variation of previously described techniques, the thoracic vena cava is not initially clamped in order to improve the return of blood volume to the NRP circuit. The pulmonary artery is cannulated to flush the lungs and the left atrial appendage is opened for drainage. After 120 minutes, NRP perfusion is stopped and the organs are flushed with cold preservation solution. In 2016, 3 livers and 6 lungs were harvested at our center using the technique described. After a minimum follow-up of 1 year, no evidence of biliary complications was observed. The combined procurement of lungs after room temperature perfusion and liver after NRP without initial clamping of the thoracic VC is feasible, with excellent function post-transplantation.

Factors related to limitation of life support within 48h of intensive care unit admission: A multicenter study.

OBJECTIVE: To determine factors related to limitations on life support within 48h of intensive care unit (ICU) admission. STUDY DESIGN: Prospective multicenter study. SETTING: Eleven ICUs. PATIENTS: All patients who died and/or had limitations on life support after ICU admission during a four-month period. VARIABLES: Patient characteristics, hospital characteristics, characteristics of limitations on life support. Time-to-first-limitation was classified as early (<48h of admission) or late (≥48h). We performed univariate, multivariate analyses and CHAID (chi-square automatic interaction detection) analysis of variables associated with limitation of life support within 48h of ICU admission. RESULTS: 3335 patients were admitted; 326 (9.8%) had limitations on life support. A total of 344 patients died; 247 (71.8%) had limitations on life support (range among centers, 58.6%-84.2%). The median (p25-p75) time from admission to initial limitation was 2 (0-7) days. CHAID analysis found that the modified Rankin score was the variable most closely related with early limitations. Among patients with Rankin >2, early limitations were implemented in 71.7% (OR=2.5; 95% CI: 1.5-4.4) and lung disease was the variable most strongly associated with early limitations (OR=12.29; 95% CI: 1.63-255.91). Among patients with Rankin ≤2, 48.8% had early limitations; patients admitted after emergency surgery had the highest rate of early limitations (66.7%; OR=2.4; 95% CI: 1.1-5.5). CONCLUSION: Limitations on life support are common, but the practice varies. Quality of life has the greatest impact on decisions to limit life support within 48h of admission.

Medical Students for Tissue Procurement, a 10-Year Experience in a Large University Hospital: An Exportable Model?

OBJECTIVE: The objective of this study was to describe tissue procurement activity performed during 10 years (2004-2014) by trained medical students in a large university hospital. METHODS: In this study, third to sixth year medical students were trained as in-hospital Tissue Coordinators (Tc) to perform tissue procurement activity on a 24/7 schedule supervised by an on-call senior Transplant Coordinator (sTC) in a large university hospital. Tc duty consisted of detection, initial evaluation of all hospital deaths, donor's family approach for tissue donation, and retrieval logistics organization, including corneal tissue retrieval after training and certification. They also assist sTC in organ procurement activity. RESULTS: A total of 18,931 deaths were prospectively evaluated, 79% of whom (n = 14,879) presented medical contraindications for tissue donation. Of the remaining 4052 (21%) potential tissue donors (PTD), 2522 (62%) were not converted into real donors, mostly due to family refusal (66%; n = 1650) followed by detection system failure and other logistical issues (34%; n = 872). A total of 2814 corneal units, 225 skin donations, 327 muscleskeletal tissue donations, 91 blood vessels donations, and 177 heart valve donations were obtained from the remaining 1530 (38%) real donors. Tissue potentiality increased from 19% to 43% throughout the study period as a consequence of the fluctuating acceptance criteria used by tissue banks depending on tissue demand. CONCLUSIONS: The tissue donation program performed by trained students was successful in achieving a high and sustainable tissue donation rate in a large university hospital.

Theoretic rates of potential tissue donation in a university hospital.

BACKGROUND: Catalonia and Spain have the highest rates of organ donation in the world. The National Transplant Organization studied the rates of potential and actual donors through the Quality Guarantee Program, but this research did not estimate potential tissue donation (PTD). The aim of this study was to define the theoretical rates of PTD at our university hospital in order to assess the main factors that exerted the greatest influence on tissue donation (TD). METHODS: We prospectively studied all deaths from May 1, of 2001 to May 31, of 2002 using a specific protocol. The selection of cornea, vessels, skin, and bone had been established by the recommendations of the Spanish Association of Tissue Banks (AEBT). We considered each deceased person as a PTD when there was no medical contraindication (MC), and obtained blood samples for serologic determinations. RESULTS: Among the 1960 deaths, 1444 (73.6%) displayed MC for TD. Only 516 (26.3%) patients were evaluated as PTD cases. Two hundred twenty-two cases (65%) were rejected due to lack of blood samples for serologic determination. The remaining 294 PTD cases were considered: family refusal of TD in 120 (40%) and consent in 174 (60%). All were corneal donors; 46 (26%) had been multitissue donors (20 vessels, 35 skin, and 30 bones) including 26 (56.5%) who were also organ donors. CONCLUSIONS: PTD cases at a university hospital represented about 25% of deaths but only 30% of PTDs actually became donors.

Full face transplantation organization, development, and results--the Barcelona experience: a case report.

The initial experience in facial composite tissue allotransplantation has demonstrated that it is surgically feasible, safe, and reproducible. A robust team approach is necessary to warrant successful outcomes. We designed a specific face organ donation that limits facial donation requests followed by synchronous in situ dissection with the internal organs that has proved to be efficient and safe for face and solid organ procurement and transplantation. The first human full face transplantation in our institution was performed on March 27, 2010. The holistic team approach of donation and procurement proved to be effective and reproducible; the recipient showed excellent outcomes at 12 months.

Potencialidad de donación de órganos en muerte encefálica y limitación del tratamiento de soporte vital en los pacientes neurocríticos / Potential of organ donation in brain death and limitation of life support treatment in neurocritical patients

Objetivo. Analizar el perfil, la incidencia de limitaciónde tratamiento de soporte vital (LTSV) y la potencialidad de donación de órganos enpacientes neurocríticos. Diseño Multicéntrico prospectivo. Ámbito Nueve centros autorizados para extracción de órganos para trasplante...

Impact of health related quality of life in Catalonia liver transplant patients.

OBJECTIVE: Our aim was to study the changes in the Health Related Quality of Life (HRQoL) during the first year following liver transplantation. MATERIALS AND METHODS: Among 159 patients awaiting orthotopic liver transplantation (OLT) who were prospectively studied at 4 hospitals in Catalonia, 108 actually obtained an organ. HRQoL over time, namely, before, as well as at 3 and 12 months after transplantation, was recorded using the Short Form-36 (SF-36) and the Liver Disease Quality of Life (LDQOL 1.0). After we searched medical, clinical, and sociodemographic records to examine the studied variables on the HRQoL at each moment, the significance was explored using t tests and one-way analysis of variance (ANOVA). RESULTS: Comparison of the SF-36 dimensions before and at 3 months after transplantation revealed almost all domains to show significant improvements (P < .01), except bodily pain, role-physical, social functioning, and PCS. Comparisons between 3 and 12 months after transplantation showed only significant improvements in role-physical, physical functioning, and PCS (P < .05). The other dimensions showed similar or slightly better scores, but the differences were not significant. For LDQOL 1.0 before and 3 months after transplantation, the dimensions with significant differences (P < .01) were: effects of liver disease on activities of daily living; concentration; health distress; sleep problems; stigmata of liver disease; and sexual function. Comparing 3 and 12 months posttransplantation, no dimension showed a significant improvement. A negative correlation existed between hypertensive patients and PCS on the SF-36 (P < .001). The clinical diagnosis of alcoholic liver disease showed better scores in some dimensions of the LDQOL than the other diagnoses. Female subjects showed significantly worse HRQoL than men (P < .001). Child-Pugh and Model for End-Stage Liver Disease (MELD) classifications were not associated with the HRQoL either before or after transplantation. CONCLUSIONS: The most important finding in this study was that all domains showed significant improvements in HRQoL at 3 months after transplantation with only slight improvements at 12 months.

Pattern of tracheal colonization during mechanical ventilation.

The relationship between gastric (GC) and tracheal (TC) colonization and the development of ventilator-associated pneumonia (VAP) remains controversial. TC, GC, and pharyngeal (PC) colonization were studied serially in 80 patients with mechanical ventilation (MV) to ascertain the routes and onset of TC. Simultaneous sample from pharynx, stomach, and trachea were obtained throughout the MV period. Quantitative cultures were performed. Seventy-two patients (90%) had TC at some time during MV. Only 19 patients presented TC after PC or GC by the same microorganisms. Indigenous gram-negative and gram-positive microorganisms colonized mainly the trachea from the start of or during MV without previous PC or GC (p < 0.05). Pseudomonas were the microorganisms causing TC principally during MV without previous PC or GC (p < 0.005). Enterobacteria produced TC without a preferential route. Of the 12 patients who developed VAP, the microorganisms responsible had already colonized the trachea in 10 patients. Only 10 of the 21 microorganisms isolated in VAP had previously colonized the pharynx or stomach. In summary, although some microorganisms have preferential routes for producing TC, the microorganisms isolated frequently change during MV. TC precedes VAP in most patients, but only a minority develop a VAP; therefore, together with TC other factors must be involved in VAP development.

Toxigenic saprophytic fungi in marine shellfish farming areas.

Toxigenic saprophytic fungi were isolated from samples of shellfish, sediment and seawater obtained from marine shellfish farming areas. The 456 strains identified included 12 different genera, with a clear predominance (68%) of Penicillium, Aspergillus, Trichoderma and Cladosporium. To assess the risk of poisoning due to the presence of these fungi in shellfish farming areas, the strains were cultured in liquid medium, filtered, and tested on larvae of Artemia salina, a small crustacean highly sensitive to mycotoxins. Thirty-five point five percent of the strains proved active with this test. This study confirms the existence of fungi in shellfish farming areas, as suggested by our earlier work showing that filter-feeding shellfish accumulate toxic metabolites of fungal origin. The presence of fungi in the marine environment represents a real risk of poisoning through the consumption of contaminated shellfish.