Bioactive Self-Regulated Liquified Microcompartments to Bioengineer Bone-Like Microtissues.

Designing a microenvironment that drives autonomous stromal cell differentiation toward osteogenesis while recapitulating the complexity of bone tissue remains challenging. In the current study, bone-like microtissues are created using electrohydrodynamic atomization to form two distinct liquefied microcapsules (mCAPs): i) hydroxypyridinone (HOPO)-modified gelatin (GH mCAPs, 7.5% w/v), and ii) HOPO-modified gelatin and dopamine-modified gelatin (GH+GD mCAPs, 7.5%+1.5% w/v). The ability of HOPO to coordinate with iron ions at physiological pH allows the formation of a semipermeable micro-hydrogel shell. In turn, the dopamine affinity for calcium ions sets a bioactive milieu for bone-like microtissues. After 21 days post encapsulation, GH and GH+GD mCAPs potentiate autonomous osteogenic differentiation of mesenchymal stem cells accompanied by collagen type-I gene upregulation, increased alkaline phosphatase (ALP) expression, and formation of mineralized extracellular matrix. However, the GH+GD mCAPs show higher levels of osteogenic markers starting on day 14, translating into a more advanced and organized mineralized matrix. The GH+GD system also shows upregulation of the receptor activator of nuclear factor kappa-B ligand (RANK-L) gene, enabling the autonomous osteoclastic differentiation of monocytes. These catechol-based mCAPs offer a promising approach to designing multifunctional and autonomous bone-like microtissues to study in vitro bone-related processes at the cell-tissue interface, angiogenesis, and osteoclastogenesis.

Left bundle branch block cardiomyopathy (LBBB-CMP): from the not-so-benign finding of idiopathic LBBB to LBBB-CMP diagnosis and treatment.

Introduction Idiopathic left bundle branch block (iLBBB) is an uncommon finding. Its benignity has been increasingly questioned, though its natural history remains poorly clarified. Similarly, LBBB-cardiomyopathy (LBBB-CM) has been also increasingly recognized as a distinct entity, where electromechanical dyssynchrony seems to play a central role in left ventricular dysfunction (LVD) development. Still, it remains a scarcely studied topic. There is an urgent need for investigation and evidence reinforcement in these areas. OBJECTIVES: two main objectives: (1) to explore the natural history of "asymptomatic" iLBBB carriers; (2) to characterize the outcomes and therapeutic approach used in a "real-world" cohort of possible LBBB-CMP patients (pts). METHODS: tertiary care centre retrospective study of pts with iLBBB and possible LBBB-CMP, screened from a large hospital electrocardiographic database from 2011 to 2017 (LBBB = 347). To assign the 1st objective, only pts with left ventricular ejection fraction (LVEF) ≥ 50% and available follow-up (FU) data were included (n = 152). Regarding the 2nd objective, possible LBBB-CMP pts were selected and defined as iLBBB pts with LVD (LVEF < 50%) and no secondary causes for LVD (n = 53). Data were based on pts' careful review of medical records. RESULTS: focusing our 1st objective, 152 iLBBB carriers were identified. Median FU time were 8 years, and 61% were female. During FU, approximately 25% developed LVD, 20% needed ≥ 1 cardiovascular (CV) hospitalization, and 15% needed a cardiac device implantation. The majority (2/3) of pts with LVD on FU (n = 35) had no secondary causes for LVD, being classified as possible LBBB-CMP pts. Time-to-LVD analysis showed no differences between pts with a known cause for LVD vs LBBB-CMP pts (Log-rank = 0.713). Concerning the 2nd objective, 53 possible LBBB-CMP pts were identified. Median FU time were 10 years, and 51% were female. During the FU, 77% presented heart failure (HF) symptoms, and 42% needed ≥ 1 CV hospitalization, mainly due to HF. Half presented severe LVD at some point in time, and 55% needed a cardiac device, most of them a cardiac resynchronization therapy (CRT) device. Comparing CRT with non-CRT pts, no differences were found in terms of medical therapy, but better outcomes were observed in CRT group: LVEF improvement was higher (median LVEF improvement of 11% in non-CRT vs 27% in CRT; p < 0.001), and fully recovery from LVD was more frequent (50% of CRT vs 14% non-CRT; p = 0.028). CONCLUSION: our data strengthen current evidence on natural history of iLBBB, showing significant CV morbidity associated with the presence of iLBBB, and reinforces the need for a serial and proper FU of these carriers. Our data on "real-world" possible LBBB-CMP pts shows high rates of CV events, namely HF-related events, and supports the growing evidence pointing out CRT as this subgroup of pts' cornerstone of treatment. In conclusion, our work sheds additional light on these largely unknown topics and underlines the urgent need for larger and prospective studies addressing the identification of LVD development predictors in iLBBB carriers, as well as the establishment of diagnostic criteria and therapeutic approach for LBBB-CMP.

Authors' Response.

Dear Editor, We would like to thank Dr. Madias for his valuable comment on our original article entitled "QT interval prolongation in Takotsubo Syndrome: a frightening feature with no major prognostic impact" published in Monaldi Archives for Chest Disease on December 6, 2023...

QT interval prolongation in Takotsubo syndrome: a frightening feature with no major prognostic impact.

Despite the frequent and often severe repolarization abnormalities seen in Takotsubo syndrome (TTS), the underlying mechanism of life-threatening arrhythmias is incompletely understood, and the risk remains uncertain. TTS is considered a potential cause of acquired long QT syndrome; however, there is no robust evidence that QT prolongation has a major prognostic impact on these patients' outcomes. Our aim was to assess the prevalence and clinical implications of acquired long QT during TTS events and compare in-hospital and long-term outcomes between patients with and without corrected QT interval (QTc) prolongation. This is a retrospective cohort study that included 113 patients admitted to our tertiary care hospital with a diagnosis of TTS. The cohort was divided into two groups: a long QTc group (QTc≥460 milliseconds in any electrocardiogram at admission or during hospitalization) and a normal QTc group. Baseline characteristics, occurrences during hospitalization, and outcome data were obtained from the revision of medical registries and hospital visits. Of the 113 patients, 107 (94.7%) were female. The mean age was 67.6±11.7 years. QTc prolongation was found in 38%. Demographic characteristics, relevant chronic medication, prevalence of cardiovascular risk factors, and other comorbidities were similar between the groups, except for history of atrial fibrillation, which was more common in the long QTc group. Syncope was more prevalent in the long QTc group. In-hospital complications were not statistically different between patients with long and normal QTc (48.8% versus 44.2%, p=0.637), including ventricular arrhythmias and complete atrioventricular block (both 4.7% versus 1.4%, p=0.556). In-hospital mortality was 0.9%, corresponding to one patient in the long QTc group. The mean follow-up time was 4.8±3.8 years. 5-year all-cause mortality and the occurrence of the composite endpoint of major adverse cardiac and cerebrovascular events did not differ between the groups (p=0.511 and p=0.538, respectively). Our study found no association between prolonged QTc interval during TTS events and adverse prognosis, since in-hospital and long-term outcomes were similar between the groups. Our findings suggest that, although QT prolongation is usually a frightening feature on ECG, this repolarization abnormality during the acute phase has no major prognostic implications in the TTS population.

Emerging modulators for osteogenic differentiation: a combination of chemical and topographical cues for bone microenvironment engineering.

Bone presents an intrinsic ability for self-regeneration and repair, however critical defects and large fractures require invasive and time-consuming clinical interventions. As an alternative to current therapy, bone tissue engineering (BTE) has primarily aimed to recreate the bone microenvironment by delivering key biomolecules and/or by modification of scaffolds to guide cell fate towards the osteogenic lineage or other phenotypes that may benefit the bone regeneration mechanism. Considering that bone cells communicate, in their native microenvironment, through biochemical and physical signals, most strategies fail when considering only chemical, geometrical or mechanical cues. This is not representative of the physiological conditions, where the cells are simultaneously in contact and stimulated by several cues. Therefore, this review explores the synergistic effect of biochemical/physical cues in regulating cellular events, namely cell adhesion, proliferation, osteogenic differentiation, and mineralization, highlighting the importance of the combined modifications for the development of innovative bone regenerative therapies.

Valorization of Fly Ashes and Sands Wastes from Biomass Boilers in One-Part Geopolymers.

Fly ash (FA) and exhausted bed sands (sands wastes) that are generated in biomass burners for energy production are two of the wastes generated in the pulp and paper industry. The worldwide production of FA biomass is estimated at 10 million tons/year and is expected to increase. In this context, the present work aims to develop one-part alkali-activated materials with biomass FA (0-100 wt.% of the binder) and sands wastes (100 wt.% of the aggregate). FA from two different boilers, CA and CT, was characterized and the mortar's properties, in the fresh and hardened conditions, were evaluated. Overall, the incorporation of FA decreases the compressive strength of the specimens. However, values higher than 30 MPa are reached with 50 wt.% of FA incorporation. For CA and CT, the compressive strength of mortars with 28 days of curing was 59.2 MPa (0 wt.%), 56.9 and 57.0 MPa (25 wt.%), 34.9 and 46.8 MPa (50 wt.%), 20.5 and 13.5 MPa (75 wt.%), and 9.2 and 0.2 MPa (100 wt.%), respectively. The other evaluated characteristics (density, water absorption, leached components and freeze-thaw resistance) showed no significant differences, except for the specimen with 100 wt.% of CA. Therefore, this work proved that one-part geopolymeric materials with up to 90 wt.% of pulp and paper industrial residues (FA and sand) can be produced, thus reducing the carbon footprint associated with the construction sector.

Brain topography beyond parcellations: Local gradients of functional maps.

Functional neuroimaging provides the unique opportunity to characterize brain regions based on their response to tasks or ongoing activity. As such, it holds the premise to capture brain spatial organization. Yet, the conceptual framework to describe this organization has remained elusive: on the one hand, parcellations build implicitly on a piecewise constant organization, i.e. flat regions separated by sharp boundaries; on the other hand, the recently popularized concept of functional gradient hints instead at a smooth structure. Noting that both views converge to a topographic scheme that pieces together local variations of functional features, we perform a quantitative assessment of local gradient-based models. Using as a driving case the prediction of functional Magnetic Resonance Imaging (fMRI) data -concretely, the prediction of task-fMRI from rest-fMRI maps across subjects- we develop a parcel-wise linear regression model based on a dictionary of reference topographies. Our method uses multiple random parcellations -as opposed to a single fixed parcellation- and aggregates estimates across these parcellations to predict functional features in left-out subjects. Our experiments demonstrate the existence of an optimal cardinality of the parcellation to capture local gradients of functional maps.

Subject-specific segregation of functional territories based on deep phenotyping.

Functional magnetic resonance imaging (fMRI) has opened the possibility to investigate how brain activity is modulated by behavior. Most studies so far are bound to one single task, in which functional responses to a handful of contrasts are analyzed and reported as a group average brain map. Contrariwise, recent data-collection efforts have started to target a systematic spatial representation of multiple mental functions. In this paper, we leverage the Individual Brain Charting (IBC) dataset-a high-resolution task-fMRI dataset acquired in a fixed environment-in order to study the feasibility of individual mapping. First, we verify that the IBC brain maps reproduce those obtained from previous, large-scale datasets using the same tasks. Second, we confirm that the elementary spatial components, inferred across all tasks, are consistently mapped within and, to a lesser extent, across participants. Third, we demonstrate the relevance of the topographic information of the individual contrast maps, showing that contrasts from one task can be predicted by contrasts from other tasks. At last, we showcase the benefit of contrast accumulation for the fine functional characterization of brain regions within a prespecified network. To this end, we analyze the cognitive profile of functional territories pertaining to the language network and prove that these profiles generalize across participants.

Unrecognized Fibrinogen A α-Chain Amyloidosis: Results From Targeted Genetic Testing.

BACKGROUND: Fibrinogen A α-chain (AFib) amyloidosis results from autosomal-dominant mutations in the gene encoding AFib (FGA). Patients with this disorder typically present with proteinuria. Isolated cases of AFib amyloidosis, carrying the FGA p.Glu545Val variant, were identified in the district of Braga, in northwest Portugal. This observation led us to hypothesize that this disorder might be an unrecognized cause of kidney disease in that region and prompted us to carry out targeted genetic testing for the p.Glu545Val variant in the local hemodialysis population and family members of identified cases. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 3 groups of participants: (1) kidney biopsy registry, n=4; (2) hemodialysis facility, n=122 of 267 patients; and (3) genetically at-risk individuals; n=69 of 167 family members. OUTCOMES: Kidney disease, kidney disease progression, and survival. RESULTS: The p.Glu545Val variant was identified in all 4 patients of the biopsy registry, 12 of 122 (9.8%) hemodialysis patients tested, and 34 of 69 (49%) relatives tested. These 50 cases belonged to 13 unrelated families with kidney disease or amyloidosis identified in 61% of probands. 35 individuals presented with hypertension at a mean of 51.0±10.4 years. Of these, 30 developed kidney disease at a mean of 56.7±12.0 years, and 21 initiated dialysis therapy at a mean of 61.4±11.3 years. Heart, liver, spleen, colon, and ileum were involved along the progression of the disease. Kidney disease was formerly attributed to hypertension in 25% of patients with AFib amyloidosis undergoing hemodialysis. LIMITATIONS: Retrospective data collection for patients with amyloidosis previously diagnosed. CONCLUSIONS: AFib amyloidosis appears to be an under-recognized disorder in Braga, Portugal, where we found a high frequency of the FGA p.Glu545Val variant. Due to the nonspecific nature of its major clinical features, the diagnosis of AFib amyloidosis should have a high index of suspicion, particularly in populations in which hypertension is prevalent.

Addressing a Paradox: Dual Strategies for Creative Performance in Introspective and Extrospective Networks.

Neuroimaging studies of internally generated behaviors have shown seemingly paradoxical results regarding the dorsolateral prefrontal cortex (DLPFC), which has been found to activate, not activate or even deactivate relative to control conditions. On the one hand, the DLPFC has been argued to exert top-down control over generative thought by inhibiting habitual responses; on the other hand, a deactivation and concomitant decrease in monitoring and focused attention has been suggested to facilitate spontaneous associations and novel insights. Here, we demonstrate that prefrontal engagement in creative cognition depends dramatically on experimental conditions, that is, the goal of the task. We instructed professional pianists to perform improvisations on a piano keyboard during fMRI and play, either with a certain emotional content (happy/fearful), or using certain keys (tonal/atonal pitch-sets). We found lower activity in primarily the right DLPFC, dorsal premotor cortex and inferior parietal cortex during emotional conditions compared with pitch-set conditions. Furthermore, the DLPFC was functionally connected to the default mode network during emotional conditions and to the premotor network during pitch-set conditions. The results thus support the notion of two broad cognitive strategies for creative problem solving, relying on extrospective and introspective neural circuits, respectively.

CONJUNCTIVAL BACTERIAL FLORA, ANTIBIOGRAM, AND LACRIMAL PRODUCTION TESTS OF COLLARED ANTEATER (TAMANDUA TETRADACTYLA).

The collared anteater ( Tamandua tetradactyla ) is adapted to a variety of habitats. It is a solitary species for which no reference values for ophthalmic tests have been established. Eight animals ranging from 1 to 4 yr of age, two males and six females, were manually restrained for assessment. Ophthalmic tests included evaluation of tear production by Schirmer tear test 1 (STT1), endodontic absorbent paper point tear test (EAPPTT), palpebral fissure length (PFL), culture of the conjunctival bacterial flora, and antimicrobial susceptibility test. Median ± semi-interquartile range (S-IQR) STT1, EAPPTT, and PFL were 8.50 ± 4.13 mm/min, 14.13 ± 3.24 mm/min, and 15.91 ± 2.51 mm, respectively. Bacterial growth was present in 100% of the samples, with predominance of Gram-positive bacteria (70.27%). Staphylococcus spp. was the most frequently isolated genus. Antimicrobial susceptibility test showed sensitivity of Staphylococcus epidermidis and Staphylococcus spp. to neomycin, tobramycin, and gentamicin. The results in this study can benefit the determination of reference values for different diagnostic techniques, and may be used as a guide for diagnosis and treatment of ocular diseases in collared anteaters.

Connecting to create: expertise in musical improvisation is associated with increased functional connectivity between premotor and prefrontal areas.

Musicians have been used extensively to study neural correlates of long-term practice, but no studies have investigated the specific effects of training musical creativity. Here, we used human functional MRI to measure brain activity during improvisation in a sample of 39 professional pianists with varying backgrounds in classical and jazz piano playing. We found total hours of improvisation experience to be negatively associated with activity in frontoparietal executive cortical areas. In contrast, improvisation training was positively associated with functional connectivity of the bilateral dorsolateral prefrontal cortices, dorsal premotor cortices, and presupplementary areas. The effects were significant when controlling for hours of classical piano practice and age. These results indicate that even neural mechanisms involved in creative behaviors, which require a flexible online generation of novel and meaningful output, can be automated by training. Second, improvisational musical training can influence functional brain properties at a network level. We show that the greater functional connectivity seen in experienced improvisers may reflect a more efficient exchange of information within associative networks of importance for musical creativity.

Should one go for individual- or group-level brain parcellations? A deep-phenotyping benchmark.

The analysis and understanding of brain characteristics often require considering region-level information rather than voxel-sampled data. Subject-specific parcellations have been put forward in recent years, as they can adapt to individual brain organization and thus offer more accurate individual summaries than standard atlases. However, the price to pay for adaptability is the lack of group-level consistency of the data representation. Here, we investigate whether the good representations brought by individualized models are merely an effect of circular analysis, in which individual brain features are better represented by subject-specific summaries, or whether this carries over to new individuals, i.e., whether one can actually adapt an existing parcellation to new individuals and still obtain good summaries in these individuals. For this, we adapt a dictionary-learning method to produce brain parcellations. We use it on a deep-phenotyping dataset to assess quantitatively the patterns of activity obtained under naturalistic and controlled-task-based settings. We show that the benefits of individual parcellations are substantial, but that they vary a lot across brain systems.

A hierarchical atlas of the human cerebellum for functional precision mapping.

The human cerebellum is activated by a wide variety of cognitive and motor tasks. Previous functional atlases have relied on single task-based or resting-state fMRI datasets. Here, we present a functional atlas that integrates information from 7 large-scale datasets, outperforming existing group atlasses. The new atlas has three further advantages: First, the atlas allows for precision mapping in individuals: The integration of the probabilistic group atlas with an individual localizer scan results in a marked improvement in prediction of individual boundaries. Second, we provide both asymmetric and symmetric versions of the atlas. The symmetric version, which is obtained by constraining the boundaries to be the same across hemispheres, is especially useful in studying functional lateralization. Finally, the regions are hierarchically organized across 3 levels, allowing analyses at the appropriate level of granularity. Overall, the new atlas is an important resource for the study of the interdigitated functional organization of the human cerebellum in health and disease.

Long-term prognosis of idiopathic ventricular fibrillation: An eighteen-year experience from a tertiary center.

INTRODUCTION AND OBJECTIVES: Idiopathic ventricular fibrillation (IVF) is diagnosed in patients who survive sudden cardiac arrest (SCA), preferably with documented ventricular fibrillation (VF), without any identifiable structural or electrical abnormality. Current evidence provides limited guidance on the diagnosis and follow-up of these patients. Our aim was to assess the clinical outcomes of survivors of an aborted SCA attributed to IVF. METHODS: We retrospectively collected clinical data from all patients who survived SCA and implanted a cardiac defibrillator (ICD) between 2005 and 2023. RESULTS: A total of 38 patients, 36.8% female, with a mean age of 44±14 years old were included. Median follow-up time was 8.7 years (interquartile range (IQR) 4.7-14.7 years). All patients underwent a comprehensive diagnostic evaluation that excluded structural and coronary disease. During follow-up, underlying diagnoses were established in 34.2% of the whole cohort. Genetic testing, performed in 37.2%, revealed underlying diagnoses in 57.1% of those tested, compared to only 26.3% of patients who did not undergo genetic testing [p=0.035, OR=5.1 (95% confidence interval (CI) 1.2-21.5)]. Mortality was 10.5% (due to non-arrhythmic causes) and 36.8% patients received appropriate therapies with a median time to first ICD therapy of 39 [5.4-47.3] months. CONCLUSION(S): Etiological diagnosis and recurrence prediction in patients with IVF remains challenging, even with extensive diagnostic evaluation and long-term follow-up. In our study, genetic testing enhanced diagnostic yield. Consistent with previous findings, our cohort experienced a notable arrhythmic recurrence, with no cardiac deaths, underlining the pivotal role of ICD implantation in these patients.

Initial Validation of the Coach-Athlete Relationship Questionnaire in a Sample of Portuguese Athletes.

Our primary objectives in this study were to translate and provide psychometric support for the Coach Athlete Relationship Questionnaire (CART-Q) Portuguese version, assess its invariance across sex, and explore its nomological validity in relation to enjoyment. Our sample participants were 470 athletes (226 females, 244 males) aged between 16 to 39 years from various individual and team sports. We found that the translated Portuguese version of the CART-Q exhibited satisfactory test-retest reliability and can serve as a reliable tool for evaluating the core constructs of the coach-athlete relationship - closeness, commitment, and complementarity. Moreover, this instrument showed evidence of nomological validity through significant positive correlations between its underlying factors and athletes' enjoyment with their sport. The proposed model for explaining item variance was also found to be invariant between male and female respondents. We recommend further use of this instrument in research and practical applications.

Analysis of the costs of teleconsultation for the treatment of diabetes mellitus in the SUS.

OBJECTIVE: To present the results of a cost analysis of remote consultations (teleconsultations) compared to in-person consultations for patients with type 2 diabetes, in the Brazilian public healthcare system (SUS) in the city of Joinville, Santa Catarina (SC). In addition to the costs from the local manager's perspective, the article also presents estimates from the patient's perspective, based on the transportation costs associated with each type of consultation. METHOD: Data were collected from 246 consultations, both remote and in-person, between 2021 and 2023, in the context of a randomized clinical trial on the impact of teleconsultation carried out in the city of Joinville, SC. Teleconsultations were carried out at Primary Health Units (PHU) and in-person consultations at the Specialized Health Center. The consultation costs were calculate by the method time and activity-based costing (TDABC), and for the estimate of transportation costs data was collected directly from the research participants . The mean costs and time required to carry out each type of consultation in different scenarios and perspectives were analyzed and compared descriptively. RESULTS: Considering only the local SUS manager's perspective, the costs for carrying out a teleconsultation were 4.5% higher than for an in-person consultation. However, when considering the transportation costs associated with each patient, the estimated value of the in-person consultation becomes 7.7% higher and, in the case of consultations in other municipalities, 15% higher than the teleconsultation. CONCLUSION: The results demonstrate that the incorporation of teleconsultation within the SUS can bring economic advantages depending on the perspective and scenario considered, in addition to being a strategy with the potential to increase access to specialized care in the public network.

Designing of a Multifunctional 3D-Printed Biomimetic Theragenerative Aerogel Scaffold via Mussel-Inspired Chemistry: Bioactive Glass Nanofiber-Incorporated Self-Assembled Silk Fibroin with Antibacterial, Antiosteosarcoma, and Osteoinductive Properties.

Biomaterial-mediated bone tissue engineering (BTE) offers an alternative, interesting approach for the restoration of damaged bone tissues in postsurgery osteosarcoma treatment. This study focused on synthesizing innovative composite inks, integrating self-assembled silk fibroin (SF), tannic acids (TA), and electrospun bioactive glass nanofibers 70SiO2-25CaO-5P2O5 (BGNF). By synergistically combining the unique characteristics of these three components through self-assembly and microextrusion-based three-dimensional (3D) printing, our goal was to produce durable and versatile aerogel-based 3D composite scaffolds. These scaffolds were designed to exhibit hierarchical porosity along with antibacterial, antiosteosarcoma, and bone regeneration properties. Taking inspiration from mussel foot protein attachment chemistry involving the coordination of dihydroxyphenylalanine (DOPA) amino acids with ferric ions (Fe3+), we synthesized a tris-complex catecholate-iron self-assembled composite gel. This gel formation occurred through the coordination of oxidized SF (SFO) with TA and polydopamine-modified BGNF (BGNF-PDA). The dynamic nature of the coordination ligand-metal bonds within the self-assembled SFO matrix provided excellent shear-thinning properties, allowing the SFO-TA-BGNF complex gel to be extruded through a nozzle, facilitating 3D printing into scaffolds with outstanding shape fidelity. Moreover, the developed composite aerogels exhibited multifaceted features, including NIR-triggered photothermal antibacterial and in vitro photothermal antiosteosarcoma properties. In vitro studies showcased their excellent biocompatibility and osteogenic features as seeded cells successfully differentiated into osteoblasts, promoting bone regeneration in 21 days. Through comprehensive characterizations and biological validations, our antibacterial scaffold demonstrated promise as an exceptional platform for concurrent bone regeneration and bone cancer therapy, setting the stage for their potential clinical application.

Repeated human leukocyte antigens eplets, importance of typing the partner.

INTRODUCTION: Antibody-mediated rejection (AMR) is the most common cause of immune-mediated allograft failure after kidney transplant and impacts allograft survival. Previous sensitization is a major risk factor for development of donor specific antibodies (DSA). AMR can have a wide range of clinical features such as impaired kidney function, proteinuria/hypertension or can be subclinical. HLA molecules have specific regions of antigens binding antibodies called epitopes and eplets are considered essential components responsible for immune recognition. We present a patient with subclinical AMR 1 week post transplantation. CASE REPORT: A 48-year-old, caucasian woman with end-stage kidney disease (ESKD) secondary to autosomal dominant polycystic kidney disease (ADPKD) on peritoneal dialysis was registered in deceased donor waitlist. She was a hypersensitized patient from 3 prior pregnancies with a calculated panel reactive antibody of 93,48%. She was transplanted through kidney paired exchange donation with no evidence of DSA pre transplantation. Surgery and post-op were unremarkable with excellent and immediate graft function. Per protocol DSA levels on the 5th day was DR1 of 3300 MFI, with an increase in MFI by day 13 with 7820 MFI and a new B41 1979MFI. Allograft kidney biopsy findings were diagnostic of AMR and she was treated with immunoglobulin and plasmapheresis. As early onset AMR post transplantation was observed an anamnestic response was hypothesized from a previous exposure to allo-HLA. We decided to type her husband, her son's father, which was presented with DSA. Mismatch eplet analysis revealed a shared 41 T and 67LQ eplets between the donor and husband, responsible for the reactivity and new HLA class I B41 and HLA class II DR1 DSA, respectively. DISCUSSION: Shared eplets between the patient husband and donor was responsible for the alloimmune response and early development of DSAs. This case highlights the importance of early monitoring DSA levels in highly sensitized patients after transplant in order to promptly address and lower inflammatory damage. Mismatch eplet analysis can provide a thorough and precise evaluation of immune compatibility providing a useful technique to immune risk stratification, donor selection and post-transplant immunosuppressive therapy and monitoring.