Selection Of Transplant Candidates Research Articles

Enhancing regenerative potential: A comprehensive review of stem cell transplantation for sports-related neuronal injuries, with a focus on spinal cord injuries and peripheral nervous system damage

Neuronal injuries, as one of the consequences of sports-related incidents, exert a profound influence on the athletes' future, potentially leading to complete immobility and impeding their athletic pursuits. In cases of severe damage inflicted upon the spinal cord (SC) and peripheral nervous systems (PNS), the regenerative process is notably compromised, rendering it essentially inefficient. Among the pivotal therapeutic approaches for the enhancement and prevention of secondary SC injuries (SCI), stem cell transplantation (SCT) stands out prominently. Stem cells, whether directly involved in replacement and reconstruction or indirectly through modification and secretion of crucial bioenvironmental factors, engage in the intricate process of tissue regeneration. Stem cells, through the secretion of neurotrophic factors (NTFs) (aiming to modulate the immune system), reduction of inflammation, axonal growth stimulation, and myelin formation, endeavor to facilitate the regeneration of damaged SC tissue. The fundamental challenges of this approach encompass the proper selection of suitable stem cell candidates for transplantation and the establishment of an appropriate microenvironment conducive to SC repair. In this article, an attempt has been made to explore sports-related injuries, particularly SCI, to comprehensively review innovative methods for treating SCI, and to address the existing challenges. Additionally, some of the stem cells used in neural injuries and the process of their utilization have been discussed.

Role of biomarkers in the diagnosis and management of HCC.

For many cancers, biomarkers have served as an important tool across the cancer care continuum from risk stratification and early detection to diagnosis and treatment. Alpha fetoprotein (AFP) remains one of the few validated biomarkers for patients with hepatocellular carcinoma (HCC). Although AFP has shown potential for each of these steps, its performance when used alone has often been suboptimal. There continues to be discordant recommendations about AFP's value when combined with ultrasound for surveillance as well as its role in diagnostic algorithms. Conversely, high AFP levels are associated with aggressive tumor biology and survival, so it remains a key factor for selection of liver transplant candidates. There have been immense efforts to identify and validate additional biomarkers for each of these steps in the HCC care continuum. Indeed, biomarker panels have shown promising data for HCC risk stratification and surveillance among patients with cirrhosis, as well as prognostication and detection of minimal residual disease in patients undergoing HCC treatment. Several large prospective studies to evaluate the role of these emerging biomarkers in clinical practice are currently ongoing.

Liver Transplant for Hepatocellular Carcinoma in Post-Milan Criteria Era: A Long-Term Single-Center Experience.

We investigated the outcomes of liver transplant in patients with hepatocellular carcinoma. Prospectively, recipients of deceased donor liver transplants from 2007 to 2021 at Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran, were enrolled into the study. The Milan criteria were applied for selection of liver transplant candidates diagnosed with hepatocellular carcinoma. Patients with diagnosis of acute liver failure and who underwent secondary liver transplant were excluded. All patients diagnosed with hepatocellular carcinoma were given mechanistic target of rapamycin inhibitor with calcineurin inhibitor minimization 4 weeks after liver transplant. Patients were assigned to the experimental group (with hepatocellular carcinoma; n = 82) or the control group (without hepatocellular carcinoma; n = 1076). We recorded the etiologies of liver cirrhosis in the experimental group, demographic data from all patients, and postoperative complications. Of 1158 total patients, mean age was 44.15 ± 14.71 years (range, 1-73 years) and 712 were male patients (61.5%). In the experimental group (n = 82), there were 76 patients (92.68%) who were within the Milan criteria; others were excluded intraoperatively. All patients were followed for a median of 65.3 ± 40.8 months (range 10-197 months). Patient survival rates in the experimental group and control group at 3 months, 1 year, and 3 years were 89%, 80%, and 78% versus 84%, 81%, and 70%, respectively (P = .742). Hepatocellular carcinoma reoccurred in 6 patients (7.31%) at mean of 16.83 months postoperatively. Liver transplant for patients with hepatocellular carcinoma in the post-Milan criteria era is associated with acceptable outcomes.

Incidence, management and outcome of Hepatic Veno-Occlusive disease /Sinusoidal Obstruction Syndrome after hematopoietic stem cell transplant in Thalassemia major patients: A prospective study of Pakistani BMT.

Hepatic Veno occlusive disease (VOD), also known as sinusoidal obstruction syndrome (VOD/SOS), is a post-transplant life threatening complication. In this study, we aimed to discuss the incidence, management and outcome of VOD in post allogenic transplant patients of beta thalassemia major (BTM). A prospective study was conducted in Armed Forces Bone Marrow Transplant Center, between 2001-2022. A total of 385 fully Human Leucocyte Antigen (HLA) matched BTM patients, with Ursodeoxycholic acid for prophylaxis, were included in the study. Incidence of VOD was calculated through cumulative incidence estimates. Chi square test and Mann Whitney test were used to compare discrete and continuous variables respectively. VOD was diagnosed and graded according to European Society for Blood and Marrow Transplantation EBMT Pediatric diagnostic criteria. Risk factors for VOD were grouped as recipient, transplant and donor related. Univariate analysis was performed by log-rank test. All patients who developed VOD were managed primarily with fluid restriction and strict input output monitoring. Statistical analyses were performed using SPSS v 25.0. Out of 385 transplant patients, forty developed VOD. Median time from date of transplant till onset of VOD was 14 days (range 6-30). Cumulative incidence of all grade VOD was 10.39% (95% CI, 7-14). Eleven out of 40 patients who developed VOD died. Cumulative incidence of Transplant related mortality (TRM) for patients with and VOD was 20.5% (95% CI, 16.6-25.1) vs 27.5% (95% CI, 16.1-42) (p value 0.318) respectively. Among risk factors, age of recipient and fibrosis (p value of 0.04 and 0.000 respectively) were found to be significantly associated with VOD. Careful selection of transplant candidates before transplant can help reduce the incidence of VOD.

Incidence of Kidney Failure after Primary Organ Transplant.

Careful selection of multiorgan transplant candidates is required to avoid unintended consequences to patients waiting for kidney transplant alone. The need for a safety net among heart and lung transplant recipients is unknown. The objective of this study was to quantify the incidence of kidney failure after liver, heart, or lung transplantation and identify pre-transplant predictors of post-transplant kidney failure. A retrospective cross-sectional study of adults who received liver, heart, or lung transplant between January 1, 2008 and December 31, 2018 was conducted using data from the Scientific Registry of Transplant Recipient and the United States Renal Data System. Post-transplant renal failure was defined as (a) new start of dialysis; (b) estimated glomerular filtration rate of < 25 mL/min; (c) a new waitlisting for a kidney transplant; or (d) receipt of a kidney transplant. The final descriptive cohort 53,620 liver transplant recipients, 22,042 heart transplant recipients, and 10,688 lung transplant recipients. In the first-year post-transplant, the probability of ESKD was comparable among heart transplant recipients (0.036, 95% CI [0.033, 0.038]) and liver transplant recipients (0.033, 95% CI [0.031, 0.035]) but was markedly lower in lung transplant recipients (0.024, 95% CI [0.021, 0.027]). In the second-year post-transplant, the probability of ESKD was comparable among liver (0.016, 95% CI [0.015, 0.017]), lung (0.018, 95% CI [0.015, 0.021]), and heart transplant recipients (0.014, 95% CI [0.013, 0.016]). Candidates for thoracic transplant would likely benefit from a safety net policy similar to the one enacted in 2017 for liver transplant, so as to maintain judicious patient selection for simultaneous multi-organ transplant. National data sources do not currently collect sufficiently reliable follow up data to identify pre-transplant predictors of end stage kidney disease, pointing to a need for transplant centers to consistently report kidney impairment data to national databases.

The role of coronary artery disease in lung transplantation

Abstract Background Coronary artery disease (CAD) is a common comorbidity in patients suffering from terminal lung disease and a recurrent problem in pre-transplant evaluation. While historically, CAD has been treated as a contraindication for lung transplantation, data from multiple small studies suggests that CAD in well selected patients might not be associated with a worse outcome. In its 2020 consensus document for the selection of lung transplant candidates, the International Society for Heart and Lung Transplantation states that CAD should not be considered an absolute contraindication but a potential marker for an unfavourable phenotype. However, data backing up this decision is limited and in parts inconclusive. Purpose This study aims to provide solid data on the relevance of pre-existing CAD in the setting of lung transplantation. Furthermore, defining cardiovascular risk factors and their effect in this unique population is required to support evidence-based risk stratification. Methods 1003 patients receiving lung transplantation between January 2000 and August 2021 were included in this study. The median follow up was 3.24 years [1.30, 4.82]. Plaque formation in the coronary arteries was identified by coronary angiography in 230 patients. A relevant CAD defined by stenosis &amp;gt;50% or previous percutaneous coronary intervention/coronary artery bypass graft was present in 104 patients. Results Baseline characteristics of the CAD group differed significantly from the non-CAD group in terms of Age at Transplantation [y] (60.28 [56.71, 63.24] vs. 53.96 [44.45, 59.85], p&amp;lt;0.001), Sex [male] (74.0% vs. 52.3%, p&amp;lt;0.001) and BMI [kg/m2] (24.13 [21.25, 27.41] vs 22.22 [19.37, 25.62], p&amp;lt;0.001) as well as the abundance of cardiovascular risk factors including hypertension (67.3% vs 32.1%, p&amp;lt;0.001) and smoking (67.3% vs 40.9%, p&amp;lt;0.001). Therefore 1:1 propensity score matching was performed, resulting in 98 matched pairs. Matching variables, including demographics, cardiovascular risk factors, results from the right heart catheter and lung testing, were well balanced without significant differences between the groups. The primary endpoint overall survival was similar in the matched groups: HR=0.94, 95% CI 0.64-1.39, p=0.77. Graph 1 pictures the corresponding Kaplan – Meier curves. In addition, no significant differences in intrahospital mortality between patients with and without CAD (8.2% vs 5.1%, p=0.566) could be detected. Furthermore, there was no significant difference in the occurrence of myocardial infarction (6.1% vs 4.1%, p=0.745) or stroke (2.0% vs 5.1%, p=0.441) post transplantation. Conclusion The finding of this study provides further evidence indicating that CAD itself may not be associated with worse short – or long-term survival following lung transplantation. Careful evaluation and patient selection can allow patients suffering from CAD to successfully undergo lung transplantation without inferior survival.Survival Analysis

Alcohol Use in Liver Transplant Recipients With Alcohol-related Liver Disease: A Comparative Assessment of Relapse Prediction Models.

The selection of liver transplant (LT) candidates with alcohol-related liver disease (ALD) is influenced by the risk of alcohol relapse (AR), yet the ability to predict AR is limited. We evaluate psychosocial factors associated with post-LT AR and compare the performance of high-risk alcoholism risk (HRAR), sustained alcohol use post-LT (SALT), and the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) scores in predicting relapse. A retrospective analysis of ALD patients undergoing LT from 2015 to 2021 at a single US transplant center was performed. Risk factors associated with post-LT AR were evaluated and test characteristics of 3 prediction models were compared. Of 219 ALD LT recipients, 23 (11%) had AR during a median study follow-up of 37.5 mo. On multivariate analysis, comorbid psychiatric illness (odds ratio 5.22) and continued alcohol use after advice from a health care provider (odds ratio 3.8) were found to be significantly associated with post-LT AR. On sensitivity analysis, SIPAT of 30 was optimal on discriminating between ALD LT recipients with and without post-LT AR. SIPAT outperformed both the HRAR and SALT scores (c-statistic 0.67 versus 0.59 and 0.62, respectively) in identifying post-LT AR. However, all scores had poor positive predictive value (<25%). AR after LT is associated with comorbid psychiatric illness and lack of heeding health care provider advice to abstain from alcohol. Although SIPAT outperformed the HRAR and SALT scores in predicting AR, all are poor predictors. The current tools to predict post-LT AR should not be used to exclude LT candidacy.

Mechanisms and treatment approaches for ACLF.

Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by decompensation of cirrhosis, severe systemic inflammation and organ failures. ACLF is frequently triggered by intra- and/or extrahepatic insults, such as bacterial infections, alcohol-related hepatitis or flares of hepatic viruses. The imbalance between systemic inflammation and immune tolerance causes organ failures through the following mechanisms: (i) direct damage of immune cells/mediators; (ii) worsening of circulatory dysfunction resulting in organ hypoperfusion and (iii) metabolic alterations with prioritization of energetic substrates for inflammation and peripheral organ 'energetic crisis'. Currently, the management of ACLF includes the support of organ failures, the identification and treatment of precipitating factors and expedited assessment for liver transplantation (LT). Early LT should be considered in patients with ACLF grade 3, who are unlikely to recover with the available treatments and have a mortality rate > 70% at 28 days. However, the selection of transplant candidates and their prioritization on the LT waiting list need standardization. Future challenges in the ACLF field include a better understanding of pathophysiological mechanisms leading to inflammation and organ failures, the development of specific treatments for the disease and personalized treatment approaches. Herein, we reviewed the current knowledge and future perspectives on mechanisms and treatment of ACLF.

Assessment of HLA-DPB1 genetic variation using an HLA-DP tool and its implications in clinical transplantation.

HLA-DP is a classic transplantation antigen that mediates alloreactivity through T-cell epitope (TCE) diversity and expression levels. A current challenge is to integrate these functional features into the prospective selection of unrelated donor candidates for transplantation. Genetically, HLA-DPB1 exon 2 defines the permissive and nonpermissive TCE groups, and exons 2 and 3 (in linkage with rs9277534) indicate low- and high-expression allotypes. In this study, we analyzed 356 272 exon 2-exon 3-phased sequences from individuals across 5 self-identified race and ethnicity categories: White, Hispanic, Asian or Pacific Islander, Black or African American, and American Indian or Alaskan Native. This sequence data set revealed the complex relationship between TCE and expression models and the importance of exon 3 sequence data. We also studied archived donor search lists for 2545 patients who underwent transplantation from an HLA-11/12 unrelated donor mismatched for a single HLA-DPB1 allele. Depending on the order in which the TCE and expression criteria were considered, some patients had different TCE- and expression-favorable donors. In addition, this data set revealed that many expression-favorable alternatives existed in the search lists. To improve the selection of candidate donors, we provide, disseminate, and automate our findings through our multifaceted tool called Expression of HLA-DP Assessment Tool, consisting of a public web application, Python package, and analysis pipeline.

Lung Transplantation for Pulmonary Arterial Hypertension: Optimized Referral and Listing Based on an Evolving Disease Concept.

Pulmonary hypertension (PH) was once a devastating and fatal disease entity, the outlook of which has been significantly improved by the continued progress of medical treatment algorithms. However, some patients still ultimately fail to achieve an adequate clinical response despite receiving maximal medical treatment. Historically, lung transplantation (LTx) has been the only effective therapeutic option that could lead to satisfactory outcomes and save these advanced patients' lives. However, patients with PH tend to have the highest mortality rates on the transplant waiting list; especially after comprehensive medical treatment, they continue to deteriorate very rapidly, eventually missing optimal transplantation windows. Balancing optimized medical treatment with the appropriate timing of referral and listing has been highly controversial in LTx for patients with PH. The 2021 consensus document for the selection of lung transplant candidates from the International Society for Heart and Lung Transplantation (ISHLT) updated the specific recommendations for the LTx referral and listing time for patients with PH based on objective risk stratification. Herein, we review the evolving PH-related concepts and highlight the optimization of LTx referral and listing for patients with PH, as well as their management on the waiting list.

An international expert consensus statement focusing on pre and post hair transplantation care

AimTo achieve international expert consensus and give recommendations on best practices in hair transplantation surgery, focusing on pre- and post-transplantation care.MethodsA modified Delphi method was used to reach consensus. An international scientific committee developed an 81-statement questionnaire. A panel of 38 experts in hair transplantation from 17 countries across 4 continents assessed the questionnaire.ResultsTwo consensus rounds were carried out, with 59 out of 81 statements (73%) reaching consensus. Expert recommendations emphasize the correct selection of candidates for hair transplantation and the need for patients to have received adequate medical treatment for alopecia before transplant. Comorbidities should be assessed and considered while planning surgery, and an individualized plan for perioperative care should be drawn up before transplant. Certain medications associated with increased risk of bleeding should be withdrawn before surgery. Specific recommendations for post-transplantation care are given. After transplantation, patients should gradually resume their normal haircare regimen. Close follow-up should be carried out during the first year after transplant.ConclusionsThis study presents numerous consensus-based recommendations on general aspects of hair transplantation, including candidate selection, medical therapy prior to transplantation, anesthesia, and resuming haircare after transplantation.

Expanded extracorporeal membrane oxygenation bridge to heart and lung transplant candidate selection does not impact outcomes compared to traditional candidate selection criteria.

Extracorporeal membrane oxygenation is used as a bridge to transplant (ECMO-BTT) in selected patients. The objective of this study was to determine whether 1-year post-transplant and post-ECMO survival are impacted by traditional compared to expanded selection criteria. We performed a retrospective study of patients >17 years who received ECMO as bridge to transplant (BTT) or bridge to transplant decision for lung or combined heart and lung transplantation at the Mayo Clinic Florida and Rochester. Institutional protocol excludes patients >55 years, maintained on steroids, unable to participate in physical therapy, with body mass index >30 or <18.5 kg/m2, non-pulmonary end-organ dysfunction, or unmanageable infections from ECMO-BTT. For this study, adherence to this protocol was considered traditional whereas exceptions to the protocol were considered expanded selection criteria. A total of 45 patients received ECMO as bridge therapy. Out of those 29 patients (64%) received ECMO as bridge to transplant and 16 patients (36%) as bridge to transplant decision. The traditional criteria cohort consisted of 15 (33%) patients and expanded criteria cohort consisted of 30 (67%) patients. In the traditional cohort, 9 (60%) of 15 patients were successfully transplanted compared to 16 (53%) of 30 patients in the expanded criteria cohort. No difference in being delisted or dying on the waitlist (OR: 0.58, CI: 0.13-2.58), surviving to 1-year post-transplant (OR: 0.53, CI: 0.03-9.71) or 1-year post-ECMO (OR: 0.77, CI: 0.0.23-2.56) was observed between the traditional criteria and expanded criteria cohorts. At our institution, we did not see differences in odds of 1-year post-transplant and post-ECMO survival between those who met traditional criteria compared to those who did not. Multicenter, prospective studies are needed to evaluate the impact of ECMO-BTT selection criteria.

Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor.

Immune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. We investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs). The genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs. Our Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.

Cardiothoracic Transplant Anesthesia: Selected Highlights: Part I—Lung Transplantation

The Year in Cardiothoracic Transplant: Lung Transplantation in 2021 focuses on the recent research this year, including the assessment, optimization, and selection of candidates for lung transplantation (LTX), donor optimization, the use of organs from donation after circulatory death (DCD) donors, the use of ultrasound to assess donor lung function, and outcomes utilizing marginal donors, as well as recipient factors affecting LTX, including age, disease, the use of extracorporeal life support, and COVID-19. The remainder of the article focuses on the perioperative management of LTX, including antirejection strategies, as well as recent multi-organizational recommendations on the care of these patients.

AFP score and metroticket 2.0 perform similarly and could be used in a “within-ALL” clinical decision tool

Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model's original thresholds. This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell's adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model's original thresholds. During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p <0.0001). At last tumor reassessment before LT, c-statistics did not significantly differ between the two composite models, either as original or threshold versions, for recurrence (0.72 vs. 0.68; p= 0.06), HCC survival, and overall survival after LT. We observed predictive gaps and overlaps between the model's thresholds, and no significant gain on reclassification. Patients meeting both models ("within-ALL") at last tumor reassessment presented the lowest 5-year cumulative incidence of HCC recurrence (7.7%; 95% CI 5.1-11.5) and higher 5-year post-LT survival (70.0%; 95% CI 64.9-74.6). In this multicenter cohort, Metroticket 2.0 and the AFP score demonstrated a similar ability to predict HCC recurrence post-LT. The combination of these composite models might be a promising clinical approach. Composite models were recently proposed for the selection of liver transplant (LT) candidates among individuals with hepatocellular carcinoma (HCC). We found that both the AFP score and Metroticket 2.0 predicted post-LT HCC recurrence and survival better than Milan criteria; the Metroticket 2.0 did not result in better reclassification for transplant selection compared to the AFP score, with predictive gaps and overlaps between the two models; patients who met low-risk thresholds for both models had the lowest 5-year recurrence rate. We propose prospectively testing the combination of both models, to further optimize the LT selection process for candidates with HCC.

A Predictive Scoring System for Therapy Failure in Persons with Chronic Myeloid Leukemia Receiving Initial a Second-Generation Tyrosine Kinase Inhibitor Therapy

Purposes Develop and validate a predictive scoring system for therapy failure in persons with chronic phase chronic myeloid leukemia (CML) receiving initial a second-generation tyrosine kinase inhibitor (2G-TKI). Methods Data from 329 consecutive subjects with CML receiving initial 2G-TKI therapy at one centre (Beijing, China) in a training dataset were interrogated to develop a predictive model which was then validated in 1,083 subjects from 65 other centers in China. Therapy-failure was defined using the 2020 ELN criteria including progression to accelerated or blast phases or CML-related death. Fine-Gray model was used for uni- and multi-variable analyses (UVA and MVA) to identify co-variates significantly-associated with therapy-failure. Akaike information criterion (AIC) was used to select prognostic co-variate and determine the best model. 1000 bootstrap re-samplings, Fine-Gray test, the minimal p-value approach, Bonferroni correction and kernel density estimator were used to determine optimal cut-offs to classify subjects into risk cohorts. Time-dependent receiver-operator characteristic curves (ROC) were used to estimate prediction accuracy and calibration plots used to determine concordance between predicted and observed cumulative incidences. Decision curve analysis (DCA) was used to calculate the net benefit using the model. Results In the training dataset, 279 subjects (85%) initially received nilotinib; and 50 (15%), dasatinib. Median 2G-TKI therapy-duration was 36 months (interquartile range [IQR], 24-68 months). 75 subjects (23%) had therapy-failure at a median of 9 months (IQR 3-12 months) after therapy start. In MVA, increasing splenomegaly and a higher percentage blood blasts were significantly-associated with the higher cumulative incidences of therapy-failure. We used these data to develop a predictive scoring system: "2G-TKI failure risk score= 0.6405×[(spleen size below the costal margin in cm + 0.2)/10] + 0.1348×(blood blasts + 0.2)" which divided subjects into low- (score ≤ 0.3021; n = 89; 31%), intermediate- (0.3021 < score < 1.4508; n = 155; 54%) and high-risk (score ≥ 1.4508; n = 43; 15%) cohorts with 5-year cumulative incidences of therapy-failure of 3% (95% Confidence Interval [CI], 0, 5%), 26% (20, 32%) and 72% (56, 88%; p-value for trend < 0.001; Figure 1A). Hazard ratios (HRs) for therapy-failure (low-risk cohort as reference) were 4.8 (1.7, 13.6; p = 0.002) and 16.5 (5.7, 47.6; p < 0.001; p for trend < 0.001) for the intermediate- and high-risk cohorts. In the external validation dataset, subjects were classified into the low- (n = 433; 40%), intermediate- (n = 583; 54%) and high-risk (n = 67; 6%) cohorts using our scoring system. 5-year cumulative incidences of therapy failure were 8% (3, 13%), 18% (12, 25%) and 44% (29, 60%; p for trend < 0.001; Figure 1B). HRs (low-risk cohort as reference) were 2.7 (1.9, 3.6; p < 0.001) and 10.6 (5.8, 15.4; p < 0.001; p for trend < 0.001) for the intermediate- and high-risk cohorts. In the training dataset cohort time-dependent AUROC curves for therapy-failure at 1-, 3-, and 5-years in the model were 0.73-0.82 and 0.68-0.75 in the validation dataset. Calibration plots for the 1-, 3- and 5-years cumulative incidences of therapy-failure indicated good concordance between predicted and observed outcomes. DCA curves indicated net benefit from using the predictive scoring system in clinical settings. Conclusions We developed and externally validated a therapy-failure scoring system in persons with chronic phase CML receiving initial 2G-TKI. The model had high AUROCs and performed well in calibration plots and DCAs. Our model may help physicians decide appropriateness of initial the 2G-TKI therapy including possible selection of appropriate haematopoietic cell transplant candidates. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Indicaciones de trasplante pulmonar

In advanced stages of diffuse interstitial lung disease (DILD), the only treatment that may increase survival is lung transplantation. In Spain, 40% of all lung transplantations were performed in patients with DILD; it is the leading cause of transplantation in our country. The selection of candidates for lung transplantation continues to be a challenge for specialist physicians, especially due to ethical difficulties. In this protocol, we will analyze the criteria for referring patients with advanced interstitial lung disease to a lung transplantation center, the indications for their inclusion on the transplantation list, as well as the risk factors that we must take into account when evaluating this therapeutic measure and its contraindications in order to thus provide specific recommendations and optimize the management of these patients.

Patient Perspectives on the Use of Frailty, Cognitive Function, and Age in Kidney Transplant Evaluation

Background The allocation of scarce deceased donor kidneys is a complex process. Transplant providers are increasingly relying on constructs such as frailty and cognitive function to guide kidney transplant (KT) candidate selection. Patient views of the ethical issues surrounding the use of such constructs are unclear. We sought to assess KT candidates’ attitudes and beliefs about the use of frailty and cognitive function to guide waitlist selection. Methods KT candidates were randomly recruited from an ongoing single-center cohort study of frailty and cognitive function. Semi-structured interviews were conducted, and thematic analysis was performed. Inductively derived themes were mapped onto bioethics principles. Results Twenty interviews were conducted (65% contact rate, 100% participation rate) (60% male; 70% White). With respect to the use of frailty and cognitive function in waitlisting decisions, four themes emerged in which participants: (1) valued maximizing a scarce resource (utility); (2) prioritized equal access to all patients (equity); (3) appreciated a proportional approach to the use of equity and utility (precautionary utility); and (4) sought to weigh utility- and equity-based concerns regarding social support. While some participants believed frailty and cognitive function were useful constructs to maximize utility, others believed their use would jeopardize equity. Patients were uncomfortable with using single factors such as frailty or cognitive impairment to deny someone access to transplantation; participants instead encouraged using the constructs to identify opportunities for intervention to improve frailty and cognitive function prior to KT. Conclusions KT candidates’ values mirrored the current allocation strategy, seeking to balance equity and utility in a just manner, albeit with conflicting viewpoints on the appropriate use of frailty and cognitive impairment in waitlisting decisions.

Commentary: Put your back into it: Erector spinae muscle density and lung transplant survival

Current data indicate the median survival of patients after lung transplants to be 6.7 years.1 The selection of optimal transplant candidates remains challenging, with many models of patient evaluation currently employed. Indicators of frailty are frequently used to act as prognostic indicators for solid-organ transplant,2,3 with increased frailty having been demonstrated to be associated with prolonged ventilation and length of stay post-transplant.4 Generalized sarcopenia and muscle density have successfully been used as frailty indicators, with Hsu and colleagues5 demonstrating a significant association between psoas muscle sarcopenia and poor outcomes following lung transplantation.

Multiresistant organisms: bacteria and beyond

Infections with multiresistant organisms are an emerging problem, cause early mortality post lung transplantation and are sometimes associated with graft dysfunction. Frequently they raise questions about the selection of lung transplant candidates and therapeutic management post lung transplantation. There are no guidelines and management must be individualized. This review summarizes the available therapeutic options in cases of multidrug-resistant (MDR) organisms and outcomes after lung transplant. Improvements in diagnosis, new and more effective drugs and the experience gained in the management of these infections in lung transplantation, lead to a more optimistic horizon than that found a decade ago. Update on the management of Burkholderia cepacia complex, Mycobacterium abscessus complex, Aspergillus spp., Scedosporium spp. and Lomentospora prolificans infections. This review clarifies current posttransplant outcomes and adds a little hope in these scenarios.