Optimización de los resultados del programa de bipartición hepática para trasplante split / Liver bipartition program for «SPLIT» transplantation: Optimization results

Introducción: El trasplante hepático (TH) split es un procedimiento extendido por toda Europa. En 2018 en Cataluña, se redefinió la distribución de donantes, siendo candidatos potenciales para split todos aquellos menores de 35 años y se flexibilizó la selección del adulto para el injerto derecho. El objetivo del estudio es evaluar el efecto de estas modificaciones en la utilización de donantes para split, en las listas de espera (LE) y en los resultados de los adultos que recibieron un injerto split. Métodos: Estudio observacional y retrospectivo; dos periodos de recogida de datos «pre» (2013-2017) y «post» (2018-2021). Los resultados de los receptores adultos se analizaron mediante un propensity score matching. Resultados: En el primer periodo fueron registrados tres donantes y se trasplantaron tres pacientes pediátricos y dos adultos; en el periodo post se obtuvieron 24 donantes, realizándose el trasplante en 19 adultos y 24 receptores infantiles. Al comparar las LE se evidenció una disminución significativa tanto en la de adultos (p = 0,0001) como en la infantil (p = 0,0004) y hasta en tres ocasiones no hubo receptores en la LE infantil. No se observaron diferencias significativas en cuanto a morbilidad o mortalidad, ni en la supervivencia global en el grupo de receptores adultos de injertos split. Conclusiones: La flexibilidad en la selección del receptor adulto y la nueva distribución de donantes ayuda a aumentar la tasa de bipartición, permitiendo reducir la LE pediátrica sin afectar los resultados en los trasplantados adultos ni su estancia en LE.(AU)

Introduction: SPLIT liver transplantation is a procedure performed throughout Europe. In 2018 in Catalonia, the distribution of donors was redefined, being potential candidates for SPLIT all those under 35 years and it was made flexible the adult selection for the right graft. The study aim is to evaluate the effect of this modification on the use of SPLIT donors on the adult/pediatric waiting lists, as well as to evaluate the post-transplant results of adults who received a SPLIT donor. Methods: Observational and retrospective study; 2 data collection periods «PRE» (2013–2017) and «POST» (2018–2021). The adults recipients results were analyzed by a propensity score matching. Results: In the first period, three donors were registered and three pediatric patients and two adults received a transplant. In the POST period, 24 donations with liver bipartition were made, performing the transplant in 19 adults and 24 children. When comparing the adults waiting lists, a significant decrease was evidenced, both for adults (p = 0.0001) and on the children's waiting list (p = 0.0004), and up to three times there were no recipients on the pediatric waiting list. No significant differences between hospital morbidity or mortality or overall survival were observed in the group of adult recipients of SPLIT grafts. Conclusions: The flexibility in the selection of the adult recipient and the new distribution of donors makes possible to increase the bipartition rate, reducing the pediatric waiting list without worsening the adults results transplant recipients or their permanence on the waiting list.(AU)

Optimized results of the liver partition program for split-liver transplantation.

INTRODUCTION: Split liver transplantation is a procedure performed throughout Europe. In 2018 in Catalonia, the distribution of donors was redefined, being potential candidates for SPLIT all those under 35-years and it was made flexible the adult selection for the right graft. The study aim is to evaluate the effect of this modifications on the use of Split donors on the adult/pediatric waiting lists, as well as to evaluate the post-transplant results of adults who received a Split donor. METHODS: Observational and retrospective study; 2 data collection periods "PRE" (2013-2017) and "POST" (2018-2021). The adults recipients results were analyzed by a propensity score matching. RESULTS: In the first period 3 donors were registered and 3 pediatric patients and 2 adults recieved a transplant. In the POST period, 24 donations with liver bipartition were made, performing the transplant in 19 adults and 24 childrens. When comparing the adults waiting lists, a significant decrease was evidenced, both for adults (p = 0,0001) and on the children's waiting list (p = 0,0004), and up to 3 times there were no recipients on the pediatric waiting list. No significant differences between hospital morbidity or mortality or overall survival were observed in the group of adult recipients of Split grafts. CONCLUSIONS: The flexibility in the selection of the adult recipient and the new distribution of donors makes possible to increase the bipartition rate, reducing the pediatric waiting list without worsening the adults results transplant recipients or their permanence on the waiting list.

A notable proportion of liver transplant candidates with alcohol-related cirrhosis can be delisted because of clinical improvement.

BACKGROUND & AIMS: To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). METHODS: We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. RESULTS: One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. CONCLUSIONS: A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. LAY SUMMARY: Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable.

Is electromyography a predictive test of patient response to biofeedback in the treatment of fecal incontinence?

AIM: Biofeedback is effective in more than 70% of patients with fecal incontinence. However, reliable predictors of successful treatment have not been identified. The aim was to identify clinical variables and diagnostic tests, particularly electromyography, that could predict a successful outcome. METHODS: We included 135 consecutive women with fecal incontinence treated with biofeedback. Clinical evaluation, manometry, ultrasonography, electromyography, and pudendal nerve terminal motor latency were performed before therapy. Treatment outcome was assessed using a symptoms diary, Wexner incontinence score and the patient's subjective perception. RESULTS: According to the symptoms diaries, 106 (78.5%) women had a good clinical result and 29 (21.5%) had a poor result. There were no differences in age, severity and type of fecal incontinence. Maximum resting pressure (39.3 ± 19.1 mmHg vs. 33.7 ± 20.2 mmHg; P = 0.156) and maximum squeeze pressure (91.8 ± 33.2 mmHg vs. 79.8 ± 31.2 mmHg; P = 0.127) were higher in patients having good clinical outcome although the difference was not significant. There were no differences in the presence of sphincter defects or abnormalities in electromyographic recordings. Logistic regression analysis found no independent predictive factor for good clinical outcome. CONCLUSIONS: Biofeedback is effective in more than 75% of patients with fecal incontinence. Clinical characteristics of patients and results of baseline tests have no predictive value of response to therapy. Specifically, we found no association between severity of electromyographic deficit and clinical response.

Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study.

BACKGROUND: Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a severe but treatable autoimmune disorder which diagnosis depends on sensitive and specific antibody testing. We aimed to assess the sensitivity and specificity of serum and CSF antibody testing in patients with anti-NMDA receptor encephalitis, and the relation between titres, relapses, outcome, and epitope repertoire. METHODS: In this observational study, we used rat brain immunohistochemistry and cell-based assays (CBA) with fixed or live NMDA receptor-expressing cells to determine the sensitivity and specificity of antibody testing in paired serum and CSF samples. Samples were obtained at diagnosis from patients with anti-NMDA receptor encephalitis and from control participants worldwide. We deemed a patient to be antibody positive if their serum, their CSF, or both tested positive with both immunohistochemistry and CBA techniques; we determined titres with serial sample dilution using brain immunohistochemistry. We examined samples from 45 patients (25 with good outcome [modified Rankin Scale, mRS 0-2], ten with poor outcome [mRS 3-6], and ten with relapses) at three or more timepoints. We determined the epitope repertoire in the samples of 23 patients with CBA expressing GluN1-NMDA receptor mutants. FINDINGS: We analysed samples from 250 patients with anti-NMDA receptor encephalitis and 100 control participants. All 250 patients had NMDA receptor antibodies in CSF but only 214 had antibodies in serum (sensitivity 100.0% [98.5-1000%] vs 85.6% [80.7-89.4%], p<0.0001). Serum immunohistochemistry testing was more often in agreement with CBA with fixed cells (77 [71%] of 108) than with CBA with live cells (63 [58%] of 108, p=0.0056). In multivariable analysis, CSF and serum titres were higher in patients with poor outcome than in those with good outcome (CSF dilution 340 vs 129, difference 211, [95% CI 1-421], p=0.049; serum dilution 7370 vs 1243, difference 6127 [2369-9885], p=0.0025), and in patients with teratoma than in those without teratoma (CSF 395 vs 110, difference 285 [134-437], p=0.0079; serum 5515 vs 1644, difference 3870 [548-7193], p=0.024). Over time there was a decrease of antibody titres in the 35 patients with good or poor outcome and samples followed at three timepoints regardless of outcome (from diagnosis to last follow-up: CSF 614 to 76, difference 538 [288-788]; serum 5460 to 1564, difference 3896 [2428-5362]; both p<0.0001). Relapses were associated with a change in titre more often in CSF than in serum (14 of 19 vs seven of 16, p=0.037). After recovery, 24 of 28 CSF samples and 17 of 23 serum samples from patients remained antibody positive. Patients' antibodies targeted a main epitope region at GluN1 aminoacid 369; the epitope repertoire did not differ between patients with different outcomes, and did not change during relapses. INTERPRETATION: The sensitivity of NMDA receptor antibody testing is higher in CSF than in serum. Antibody titres in CSF and serum were higher in patients with poor outcome or teratoma than in patients with good outcome or no tumour. The titre change in CSF was more closely related with relapses than was that in serum. These findings emphasise the importance of including CSF in antibody studies, and that antibody titres can complement clinical assessments. FUNDING: Dutch Cancer Society, National Institutes of Health, McKnight Neuroscience of Brain Disorders award, the Fondo de Investigaciones Sanitarias, ErasmusMC fellowship, and Fundació la Marató de TV3.

Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study.

BACKGROUND: Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disorder in which the use of immunotherapy and the long-term outcome have not been defined. We aimed to assess the presentation of the disease, the spectrum of symptoms, immunotherapies used, timing of improvement, and long-term outcome. METHODS: In this multi-institutional observational study, we tested for the presence of NMDAR antibodies in serum or CSF samples of patients with encephalitis between Jan 1, 2007, and Jan 1, 2012. All patients who tested positive for NMDAR antibodies were included in the study; patients were assessed at symptom onset and at months 4, 8, 12, 18, and 24, by use of the modified Rankin scale (mRS). Treatment included first-line immunotherapy (steroids, intravenous immunoglobulin, plasmapheresis), second-line immunotherapy (rituximab, cyclophosphamide), and tumour removal. Predictors of outcome were determined at the Universities of Pennsylvania (PA, USA) and Barcelona (Spain) by use of a generalised linear mixed model with binary distribution. RESULTS: We enrolled 577 patients (median age 21 years, range 8 months to 85 years), 211 of whom were children (<18 years). Treatment effects and outcome were assessable in 501 (median follow-up 24 months, range 4-186): 472 (94%) underwent first-line immunotherapy or tumour removal, resulting in improvement within 4 weeks in 251 (53%). Of 221 patients who did not improve with first-line treatment, 125 (57%) received second-line immunotherapy that resulted in a better outcome (mRS 0-2) than those who did not (odds ratio [OR] 2·69, CI 1·24-5·80; p=0·012). During the first 24 months, 394 of 501 patients achieved a good outcome (mRS 0-2; median 6 months, IQR 2-12) and 30 died. At 24 months' follow-up, 203 (81%) of 252 patients had good outcome. Outcomes continued to improve for up to 18 months after symptom onset. Predictors of good outcome were early treatment (0·62, 0·50-0·76; p<0·0001) and no admission to an intensive care unit (0·12, 0·06-0·22; p<0·0001). 45 patients had one or multiple relapses (representing a 12% risk within 2 years); 46 (67%) of 69 relapses were less severe than initial episodes (p<0·0001). In 177 children, predictors of good outcome and the magnitude of effect of second-line immunotherapy were similar to those of the entire cohort. INTERPRETATION: Most patients with anti-NMDAR encephalitis respond to immunotherapy. Second-line immunotherapy is usually effective when first-line treatments fail. In this cohort, the recovery of some patients took up to 18 months. FUNDING: The Dutch Cancer Society, the National Institutes of Health, the McKnight Neuroscience of Brain Disorders award, The Fondo de Investigaciones Sanitarias, and Fundació la Marató de TV3.

Accuracy and reproducibility of lymphoscintigraphy for sentinel node detection in patients with cutaneous melanoma.

UNLABELLED: Lymphoscintigraphy is an important part of the mapping and identification of sentinel lymph nodes (SLNs). However, few studies report its reproducibility, and some concerns prevail. The aim of the study was to determine the reproducibility of lymphoscintigraphy performed by different team members following a strict protocol to assess lymphatic drainage and the location and number of SLNs. METHODS: Sixty-eight melanoma patients were included. All underwent 2 separate lymphoscintigraphy studies, which followed the same acquisition protocol. Discordance was defined as a change in localization or a failure to identify the SLN in one of the studies. RESULTS: All patients showed lymphatic drainage, and in all cases at least 1 sentinel node was identified. In 65 of 68 patients (96%), the findings of the first lymphoscintigraphy study were similar to those of the second. This similarity was also found in the number of sentinel nodes (171 in the first study and 173 in the second). Eighty percent of patients showed 1-3 SLNs in both lymphoscintigraphy studies. The 2 studies differed in 3 patients (4%): 2 melanomas were located on the trunk and 1 on the head and neck. Drainage was visualized to more than 1 lymphatic basin in 19 patients (28%) in the first study versus 18 patients in the second study. CONCLUSION: Lymphoscintigraphy is highly reproducible in the detection of sentinel nodes in melanoma patients. The classic protocol of radiotracer injection is reproducible and reliable enough to guarantee SLN identification, although a slight variation in isolated cases (especially when primary lesions are located on the trunk or the head and neck regions) is inevitable.

An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation.

BACKGROUND: Rotation thromboelastometry (TEM) has been proposed as a convenient alternative to standard coagulation tests in guiding the treatment of coagulopathy during orthotopic liver transplantation (OLT). This study was aimed at assessing the value of TEM in monitoring blood coagulation and guide transfusion support in OLT. STUDY DESIGN AND METHODS: Standard coagulation and TEM (EXTEM and FIBTEM) tests were performed at four preestablished intraoperative time points in 236 OLTs and prospectively recorded in a dedicated database together with the main operative and transfusion data. Transfusion thresholds were based on standard coagulation tests. Spearman's rank correlation (ρ), linear regression, and receiver operating characteristic curves were used when appropriate. RESULTS: EXTEM maximum clot firmness (MCF(EXTEM)) was the TEM variable that best correlated with the platelet (PLT) and fibrinogen levels (ρ = 0.62 and ρ = 0.69, respectively). MCF(FIBTEM) correlated with fibrinogen level (ρ = 0.70). EXTEM clot amplitude at 10 minutes (A10(EXTEM)) was a good linear predictor of MCF(EXTEM) (R(2) =0.93). The cutoff values that best predicted the transfusion threshold for PLTs and fibrinogen were A10(EXTEM) = 35 mm and A10(FIBTEM) = 8 mm. At these values, the negative and positive predictive accuracies of TEM to predict the transfusion thresholds were 95 and 27%, respectively. CONCLUSION: A10(EXTEM) is an adequate TEM variable to guide therapeutic decisions during OLT. Patients with A10(EXTEM) of greater than 35 mm are unlikely to bleed because of coagulation deficiencies, but using A10(EXTEM) of not more than 35 mm as the sole transfusion criterion can lead to unnecessary utilization of PLTs and fibrinogen-rich products.

Clinical trials during pregnancy: what has been done.

OBJECTIVE: We describe clinical trials conducted in pregnant women. METHODS: We searched PubMed database for articles related to clinical trials between 01/01/2000 and 31/12/2009 involving pregnant women by using the preferred terms "pregnancy", "human", and "clinical trials". RESULTS: Of 1,264 retrieved publications, 762 (60%) were excluded, leaving 502 for analysis: 53% were preventive studies in maternal or fetal conditions; 47% were therapeutic trials, mostly focused on acute obstetric diseases; 66% were assigned a pharmacological intervention. The studied drugs were 16% for labour induction and 15% for abortive procedures, followed by multivitamins and micronutrients, labour analgesia and anesthesia, antibiotics, tocolytics, and antimalarial drugs. The main objectives of the studies were focused on efficacy (54%) and efficacy and safety (26%); 81% of the studies were controlled, randomized and parallel-design trials; 19% were blinded. CONCLUSION: Clinical trials in pregnant women are mainly conducted with an efficacy objective regarding maternal-fetal prevention and in obstetric diseases to study labor induction and abortive measures. This is in line with the type of intervention and drugs involved.