A novel scoring system proposal to guide surgical treatment indications for high grade gliomas in elderly patients: DAK-75.

High-grade gliomas are the most prevalent neurooncological desease in adults, their incidence increases with age, peaking in the seventh decade. This paper aims to address how to select patients for surgical resection by identifying pre-surgical predictors of 12-month mortality in newly diagnosed HGG patients aged ≥ 75 years. A prognostic score will be proposed to guide surgical decisions based on expected survival. Retrospective observational single-center cohort study was carried out at the "Città della Salute e della Scienza-Molinette" University Hospital in Turin, Italy. All consecutive patients aged ≥ 75 years newly diagnosed with HGG were included, regardless of whether they underwent surgical resection. Clinical, radiological, histological and molecular data were collected.Variables potentially available at the time of diagnosis were considered to develop a multivariable logistic regression predictive model, with 12-months overall survival as the dependent variable. 102 patients aged 75 years or older received a new diagnosis of high-grade glioma, of whom 68 underwent surgical resection. Patients undergoing surgery were slightly younger (76.9 vs 79.0 years, p = 0.007) and had better performance status (median KPS 80 vs 70). Most tumors undergoing surgery were localized in cortical or subcortical non-motor areas (p < 0.001) and less frequently deep-seated (p = 0.023) or multifocal (p < 0.001). A predictive model, the DAK-75 score, was developed: the AUROC of the final model was 0.822 (95% CI 0.741-0.902). The score includes clinical presentation, tumor location, and KPS, ranging from 0 to 20, categorizing risk scores into low-risk and high-risk groups (< or > 8). Higher scores corresponded to fewer surgical patients and higher one-year mortality rates (92.2% vs 47.1%, p < 0.001). DAK-75 score may represent a valuable tool in the decision-making process for neurosurgical intervention in elderly patients diagnosed with HGG. Further studies are needed to externally and prospectively validate the scoring system.

Does presbygeusia really exist? An updated narrative review.

This review critically assessed the existence of presbygeusia, i.e., the impairment in taste perception occurring in the elderly, as a natural part of the aging process and its potential clinical implications. Several factors might contribute to age-related taste alterations (TAs), including structural changes in taste buds, alterations in saliva composition, central nervous system changes, and oral microbiota dysbiosis. A comprehensive literature review was conducted to disentangle the effects of age from those of the several age-related diseases or conditions promoting TAs. Most of the included studies reported TAs in healthy elderly people, suggesting that presbygeusia is a relatively frequent condition associated with age-related changes in the absence of pathological conditions. However, the impact of TAs on dietary preferences and food choices among the elderly seems to be less relevant when compared to other factors, such as cultural, psychological, and social influences. In conclusion, presbygeusia exists even in the absence of comorbidities or drug side effects, but its impact on dietary choices in the elderly is likely modest.

Predictors of non-adherence to an early in-hospital rehabilitation program after surgery for hip fracture in a co-managed orthogeriatric unit.

BACKGROUND: Hip fracture is a common event in older adults, leading to an increased risk of mortality, disability, and higher healthcare costs. Early in-hospital rehabilitation after surgery within orthogeriatric units may improve outcomes with limited incident complications even in the oldest old. We aimed to determine the prevalence and predictors of non-adherence to early rehabilitation in the orthogeriatric unit of an Italian tertiary hospital and its impact on outcomes and setting at discharge. METHODS: Retrospective observational single-centered cohort study. Patients aged ≥ 65 years admitted to the orthogeriatric unit for hip fracture who underwent surgery between April 2019 and October 2020 were considered eligible if able to walk autonomously or with assistance and independent in at least 2 Basic Activities of Daily Living. Along with sociodemographic and geriatric variables, characteristics of surgery and rehabilitation, in-hospital complications and functional outcomes at discharge were collected. The primary outcome was non-adherence to the early in-hospital rehabilitation program. RESULTS: Among 283 older patients (mean age 82.7 years, 28.6% male), non-compliance with physical therapy was assessed in 49 cases (17.3%), characterized by worse pre-fracture clinical, cognitive, and functional status and showing worse outcomes in terms of mobilization at discharge. After multivariable analysis, non-adherence was independently associated with the onset of delirium (OR 5.26, 95%CI 2.46-11.26; p < 0.001) or infections after surgery (OR 3.26, 95%CI 1.54-6.89; p < 0.001) and a systolic blood pressure at admission < 120 mmHg (OR 4.52, 95%CI 1.96-10.43, p < 0.001). CONCLUSIONS: Pre-fracture poor cognitive and functional status, along with lower systolic blood pressure, seem to make some patients more vulnerable to in-hospital complications (mainly delirium and infections) and negatively affect the adherence to physical therapy and, by consequence, clinical outcomes of rehabilitation.

Short-term mortality and associated factors among older hospitalized patients: A narrative retrospective analysis of end-of-life care in an acute geriatric unit.

OBJECTIVES: To explore short-term mortality and its predictors among older patients hospitalized in a acute geriatric ward (AGW) in Northwestern Italy. DESIGN: Retrospective observational single-center cohort study. MATERIAL AND METHODS: Patients consecutively admitted for any reason between June 2021 and May 2022 were included in the analysis. Along with sociodemographic, clinical, and functional variables, prognosis estimation (Palliative Prognostic Index; PPI) at the time of admission was registered. Short-term all-cause mortality (in-hospital and within 3 months of discharge) was the primary outcome. RESULTS: About one-third of the total sample died in the short-term (32.4 %). Along with PPI score (OR 1.115, 95 %CI 1.034-1.202), short-term mortality was independently associated with functional dependency (OR 1.278, 95 %CI 1.170-1.395). CONCLUSIONS: The high short-term mortality in our sample should call for the inclusion of palliative prognostic tools within the in-hospital comprehensive geriatric assessment to better recognize and appropriately manage older patients at the end of life.

Clinical outcomes and temporal trends of immunological and non-immunological rare diseases in adult kidney transplant.

BACKGROUND: Rare diseases (RDs) encompass many difficult-to-treat conditions with different characteristics often associated with end-stage renal disease (ESRD). However, data about transplant outcomes in adult patients are still lacking and limited to case reports/case series without differentiation between immunological/non-immunological RDs. METHODS: Retrospective analysis among all adult kidney transplanted patients (KTs) with RDs (RDsKT group) performed in our high-volume transplantation center between 2005 and 2016. RDs were classified according to the Orphanet code system differentiating between immunological and non-immunological diseases, also comparing clinical outcomes and temporal trends to a control population without RDs (nRDsKT). RESULTS: Among 1381 KTs, 350 patients (25.3%) were affected by RDs (RDsKTs). During a f/up > 5 years [median 7.9 years (4.8-11.1)], kidney function and graft/patient survival did not differ from nRDsKTs. Considering all post-transplant complications, RDsKTs (including, by definition, patients with primary glomerulopathy except on IgA nephropathy) have more recurrent and de-novo glomerulonephritis (14.6% vs. 9.6% in nRDsKTs; p = 0.05), similar rates of de-novo cancers, post-transplant diabetes, dysmetabolism, hematologic disorders, urologic/vascular problems, and lower infectious episodes than nRDsKTs (63.7% vs 72.7%; p = 0.013). Additional stratification for immunological and non-immunological RDsKTs or transplantation periods (before/after 2010) showed no differences or temporal trends between groups. CONCLUSIONS: Kidney transplant centers are deeply involved in RDs management. Despite their high-complex profile, both immunological and non-immunological RDsKTs experienced favorable patients' and graft survival.

Early effects of first-line treatment with anti-interleukin-6 receptor antibody tocilizumab for chronic active antibody-mediated rejection in kidney transplantation.

INTRODUCTION: Chronic active antibody-mediated rejection (cAMR) is a major determinant of late allograft failure. Rituximab/immunoglobulins (IVIg) + plasma exchange (PLEX) showed controversial results in cAMR treatment. Tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, has been recently used as rescue therapy in patients non-responsive to rituximab/IVIg/PLEX with favorable outcomes. Whether TCZ acts "per se" or requires a priming effect from previous treatments is currently unknown. METHODS: Fifteen patients with cAMR were treated with TCZ as a first-line therapy and followed for a median time of 20.7 months. RESULTS: Despite the majority of patients experiencing advanced transplant glomerulopathy (TG) at diagnosis (60% with cg3), glomerular filtration rate and proteinuria stabilized during the follow-up, with a significant reduction in donor-specific antibodies. Protocol biopsies after 6 months demonstrated significant amelioration of microvascular inflammation and no TG, C4d deposition, or IF/TA progression. Gene-expression and immunofluorescence analysis showed upregulation of three genes (TJP-1, AKR1C3, and CASK) involved in podocyte, mesangial, and tubular restoration. CONCLUSION: Tocilizumab adopted as a first-line approach in cAMR was associated with early serological and histological improvements and functional stabilization even in advanced TG, suggesting a role for the use of TCZ alone with the avoidance of unnecessary previous immunosuppressants.

[Guidelines, heart failure and the elderly]. / Linee guida, scompenso cardiaco e anziani.

Heart failure (HF) guidelines have recently introduced several innovations in pharmacological therapeutic options. Specifically, for HF with reduced ejection fraction, an intensive therapeutic strategy of early initiation and rapid up-titration of guideline-directed medical therapy is now recommended in all patients to reduce the risk of HF rehospitalization or death. In clinical practice, however, this approach is not always feasible in the elderly population due to the coexistence of multiple geriatric conditions such as frailty, comorbidities in addition to the risk of adverse drug effects, general prescribing inertia and the unmet need for close follow-up during drug up-titration. As for HF with preserved ejection fraction, sodium-glucose cotransporter 2 inhibitors have been shown to significantly reduce the composite outcome of HF hospitalization and cardiovascular mortality. However, these drugs have not yet been proven effective in some cardiomyopathies, as these were not included in clinical trials. This review aims to provide a critical analysis of current HF guidelines, illustrating their limits in real-world applicability through a cardio-geriatric lens reinterpretation of recent evidence.

Nutritional screening on hospital admission and one-year clinical outcomes in a prospective cohort of older patients.

BACKGROUND & AIMS: Malnutrition negatively affects the prognosis and quality of life of hospitalized patients. However, there are several gaps between evidence-based knowledge and current clinical practice. Our primary aim was to describe the prevalence of malnutrition risk in a cohort of in a cohort of older inpatients; secondly, we explored its predictors and its independent impact on 12-month survival. METHODS: Prospective study focused on patients aged 65 years and older consecutively admitted for any reason to the acute geriatric and general medical units of an Italian university hospital. Comprehensive geriatric assessment data, including the short form of the Mini Nutritional Assessment (MNA-SF), were collected within 48 hours of admission. The prevalence of malnutrition and risk of malnutrition according to the MNA-SF represented the main outcome. Correlations among clinical variables, nutritional status, and one-year survival were analyzed using multivariable and Cox models. RESULTS: Among 594 patients (median age: 84 years, 49.5 % female), mostly living at home with moderate functional autonomy, 82.3 % were identified as probably malnourished or at risk of malnutrition according to MNA-SF (39.9 % and 42.4 %, respectively). Malnutrition and the risk of malnutrition were positively associated with living alone at home (OR 2.803, 95%CI 1.567-5.177, p < 0.001), and negatively associated with autonomy in IADL (OR 0.765, 95%CI 0.688-0.846, p < 0.001) and the best performance at HST (OR 0.901, 95%CI 0.865-0.936; p < 0.001). After 12 months, 31.8 % of patients was dead and mortality was positively correlated with malnutrition according to MNA-SF (OR 2.493, 95%CI 1.345-4.751, p = 0.004), institutionalization (OR 2.815, 95%CI 1.423-5.693, p = 0.003) and severe cognitive impairment (OR 1.701, 95%CI 1.031-2.803, p = 0.036). CONCLUSION: Malnutrition is common among older inpatients upon admission, primarily influenced by their functional and cognitive status, and it is linked to a worse prognosis. Early incorporation of thorough nutritional and functional assessments into clinical practice is crucial to improve prognosis prediction and enable timely, focused interventions targeting modifiable causal factors in a patient-centered approach.

Predictors and Outcomes of Oral Anticoagulant Deprescribing in Geriatric Inpatients With Atrial Fibrillation: A Retrospective Multicenter Cohort Study.

OBJECTIVE: To investigate prevalence and predictors of oral anticoagulant therapy (OAT) deprescribing in older inpatients with atrial fibrillation (AF), and its association with 1-year incidence of major clinical outcomes. DESIGN: Multicenter retrospective cohort study. SETTING AND PARTICIPANTS: Inpatients aged ≥75 years with known AF on OAT at admission discharged from 3 Italian acute geriatric wards between January 2014 and July 2018. METHODS: Data from a routine Comprehensive Geriatric Assessment (CGA), along with OAT status at discharge were recorded. One-year incidence of all-cause death, stroke or systemic embolism (SSE), and major and clinically relevant nonmajor bleeding (MB/CRNMB) were retrieved from administrative databases. Associations were explored through multilevel analysis. RESULTS: Among 1578 patients (median age 86 years, 56.3% female), OAT deprescription (341 patients, 21.6%) was associated with bleeding risk, functional dependence and cognitive impairment, and inversely, with previous SSE and chronic AF. Incidences of death, SSE, and MB/CRNMB were 56.6%, 1.5%, and 4.1%, respectively, in OAT-deprescribed patients, and 37.6%, 2.9%, and 4.9%, respectively, in OAT-continued patients, without significant differences between groups. OAT deprescription was associated with all-cause mortality [adjusted odds ratio (aOR) 1.41, 95% CI 1.68-1.85], along with older age, comorbidity burden, cognitive impairment, and functional dependence, but with neither SSE nor MB/CRNMB incidence, as opposed to being alive and free from SSE and MB/CNRMB, respectively (aOR 0.68, 95% CI 0.25-1.82, and aOR 0.95 95% CI 0.49-1.85, respectively). Conversely, OAT deprescription was associated with higher odds of being dead than alive both in patients free from SSE and in those free from MB/CRNMB. CONCLUSIONS AND IMPLICATIONS: CGA-based OAT deprescribing is common in acute geriatric wards and is not associated with increased SSE. The net clinical benefit of OAT in geriatric patients is strongly related with the competing risk of death, suggesting that functional and cognitive status, as well as residual life expectancy, should be considered in clinical decision making in this population.

Absence of IL-6 Receptor Blockade Effect on the Outcomes of Transplant Glomerulopathy in the Absence of Anti-HLA Donor-specific Antibodies.

Background: Transplant glomerulopathy (TG) is the hallmark of chronic antibody-mediated rejection but often occurs without anti-HLA donor-specific antibodies (DSAs) in the assumption that other DSAs may be the effectors of the tissue injury. Recently, we reported a positive effect of interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ) in TG/DSA+. In the present study, we investigate the effect of TCZ in a cohort of TG cases without detectable anti-HLA DSAs. Methods: Single-center retrospective analysis of TG cases without anti-HLA DSAs (TG/DSA) treated with TCZ for chronic antibody-mediated rejection as first-line therapy evaluated through clinical, protocol biopsies, and gene expression analyses was included. Results: Differently from TG/DSA+, TG/DSA- showed a progressive reduction in the estimated glomerular filtration rate at 12 mo and after that with no significant modification in microvascular inflammation or C4d+. No upregulation in tight junction protein-1, aldo-keto reductase family 1 member C3, and calcium/calmodulin-dependent serine protein kinase, documented in TG/DSA+, was noted in post-TCZ biopsies. The reduction of microvascular inflammation was associated with natural killer-cell reduction in TG/DSA+, whereas TG/DSA- tends to maintain or increase periglomerular/interstitial infiltration. Conclusions: In the absence of anti-HLA DSAs, TG behavior seems not to be modified by IL-6 receptor blockade. These results are at variance with observational studies and previous trials with IL-6 inhibitors in TG associated with anti-HLA DSAs. These data may fuel the hypothesis of different mechanisms underlying TGs (including the potentially different roles of natural killer cells) and suggest carefully selecting patients with TG for clinical trials or off-label treatment based on their antidonor serologic status.

A Comprehensive Geriatric Workup and Frailty Assessment in Older Patients with Severe Aortic Stenosis.

Aortic stenosis (AS) represents a notable paradigm for cardiovascular (CV) and geriatric disorders owing to comorbidity. Transcatheter aortic valve replacement (TAVR) was initially considered a therapeutic strategy in elderly individuals deemed unsuitable for or at high risk of surgical valve replacement. The progressive improvement in TAVR technology has led to the need to refine older patients' stratification, progressively incorporating the concept of frailty and other geriatric vulnerabilities. Recognizing the intricate nature of the aging process, reliance exclusively on chronological age for stratification resulted in an initial but inadequate tool to assess both CV and non-CV risks effectively. A comprehensive geriatric evaluation should be performed before TAVR procedures, taking into account both physical and cognitive capabilities and post-procedural outcomes through a multidisciplinary framework. This review adopts a multidisciplinary perspective to delve into the diagnosis and holistic management of AS in elderly populations in order to facilitate decision-making, thereby optimizing outcomes centered around patient well-being.

Predictors of In-Hospital Mortality in Older Inpatients with Suspected Infection.

OBJECTIVES: To determine the rate and predictors of death in older individuals with suspected infection at any time during hospital stay in a geriatric acute ward and the prognostic ability of different tools [quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA), Modified and National Early Warning Scores (MEWS) and (NEWS)] in such population. DESIGN: Prospective observational single-center cohort study. SETTING AND PARTICIPANTS: Among patients admitted to an acute geriatric unit of an Italian University Hospital with at least 1 sepsis risk factor, all subjects with suspected infection at admission or during hospital stay (defined as antibiotic prescription and associated culture test) were considered. METHODS: A geriatric assessment including comorbidity and social, functional, and cognitive status was performed for each patient. Clinical parameters were evaluated at least twice daily throughout hospital stay; qSOFA, MEWS, and NEWS were derived, with positive cutoffs set at ≥2, ≥5, and ≥7, respectively. RESULTS: Among 305 older inpatients (median age 86.0 years, 49.2% female), 21% died during hospital stay. Sepsis was diagnosed in 31.8% of the overall sample and in 64.1% of deceased patients. Deceased patients showed a significantly higher prevalence of prior institutionalization, functional dependence, cognitive impairment, and multimorbidity. The prognostic accuracy of the qSOFA score at infection onset was only fair (area under the receiver operating characteristic curve 0.72; 95% CI, 0.65-0.79, P < .001) and comparable with that of MEWS and NEWS. After multivariable analysis, in-hospital death was positively associated with male sex [odds ratio (OR), 2.11; 95% CI, 1.01-4.44; P = .048] and abnormal white blood cells count (OR, 4.93; 95% CI, 2.36-10.29; P < .001), platelet count (OR, 2.61; 95% CI, 1.10-6.16; P = .029) and serum creatinine (OR, 2.70; 95% CI, 1.30-5.61; P = .008), along with any of the score considered, and negatively associated with autonomy in instrumental activities (OR, 0.78; 95% CI, 0.68-0.90; P < .001). CONCLUSIONS: Prognosis in older inpatients with infection or sepsis appears to be determined both by the geriatric characteristics and by the severity of the acute event, expressed by recommended tools and blood test results.

Impact of frailty models on the prescription of oral anticoagulants and on the incidence of stroke, bleeding, and mortality in older patients with atrial fibrillation: a systematic review.

BACKGROUND: Frailty is common in older patients with atrial fibrillation (AF). Current guidelines recommend oral anticoagulant therapy (OAT) except in case of severe frailty or reduced life expectancy, but definitive evidence on which "frailty" tools may help to identify older AF patients expected to derive little or no benefit from OAT is still lacking. Some persistent uncertainties may derive from the different clinical implications that the two major models of frailty, namely the frail phenotype (FP) and the deficit accumulation model (DAM), underlie. We thus conducted a systematic review of published studies to examine the association of the presence of frailty, categorized according to the FP and DAM, with 1) OAT prescription and 2) incidence of clinical outcomes (all-cause mortality, stroke and/or systemic embolism and major or clinically relevant non-major bleeding) in patients receiving OAT. METHODS: Embase and MEDLINE were searched from inception until May 31st, 2022, for studies using a validated tool to identify frailty in subjects aged 65 years or older with a diagnosis of non-valvular AF; only studies on patients prescribed an OAT were considered eligible for the analyses involving clinical outcomes. The protocols for each review question have been registered in PROSPERO database (CRD42022308623 and CRD42022308628). FINDINGS: Twenty-three studies exploring the association between frailty and OAT prescription on a total of 504 719 subjects were included. Patients with increasing severity of DAM frailty showed consistently lower OAT prescription rates than non-frail patients, whereas use of OAT did not significantly differ between patients with the FP compared with non-frail subjects. Eleven studies exploring the association between frailty and clinical outcomes on a total of 41 985 individuals receiving oral anticoagulation were included. Compared with non-frail subjects, a higher risk of all-cause mortality and clinical outcomes could be observed for AF patients prescribed with OAT with severe frailty according to the DAM, with inconclusive findings for the FP. High levels of heterogeneity were observed in both groups of studies; therefore, a meta-analysis was not performed. CONCLUSIONS: Due to the great heterogeneity among different validated frailty measures, indiscriminately relying on "frailty" should not be regarded as the gold standard for clinical decision-making about stroke prevention in older AF patients. Present findings suggest that severe frailty according to the DAM is associated with less use of OAT and increased risk of all-cause mortality, thereby representing at the moment the most reasonable tool to efficiently recognize patients with limited life expectancy and for whom there is so far scant, if any, evidence of a clinical benefit of OAT.

Recipient pre-existing chronic hypotension is associated with delayed graft function and inferior graft survival in kidney transplantation from elderly donors.

BACKGROUND: Pre-existing chronic hypotension affects a percentage of kidney transplanted patients (KTs). Although a relationship with delayed graft function (DGF) has been hypothesized, available data are still scarce and inconclusive. METHODS: A monocentric retrospective observational study was performed on 1127 consecutive KTs from brain death donors over 11 years (2003-2013), classified according to their pre-transplant Mean Blood Pressure (MBP) as hypotensive (MBP < 80 mmHg) or normal-hypertensive (MBP ≥ 80 mmHg, with or without effective antihypertensive therapy). RESULTS: Univariate analysis showed that a pre-existing hypotension is associated to DGF occurrence (p<0.01; OR for KTs with MBP < 80 mmHg, 4.5; 95% confidence interval [CI], 2.7 to 7.5). Chronic hypotension remained a major predictive factor for DGF development in the logistic regression model adjusted for all DGF determinants. Adjunctive evaluations on paired grafts performed in two different recipients (one hypotensive and the other one normal-hypertensive) confirmed this assumption. Although graft survival was only associated with DGF but not with chronic hypotension in the overall population, stratification according to donor age revealed that death-censored graft survival was significantly lower in hypotensive patients who received a KT from >50 years old donor. CONCLUSIONS: Our findings suggest that pre-existing recipient hypotension, and the subsequent hypotension-related DGF, could be considered a significant detrimental factor, especially when elderly donors are involved in the transplant procedure.

Prevalence, determinants and practical implications of inappropriate hospitalizations in older subjects: A prospective observational study.

In a context of high demand for hospital services among older people, we aimed to assess the rate and determinants of inappropriate hospitalizations of older patients, and to what extent they were associated with inappropriate hospital stay. This prospective observational multicentre study evaluated a random sample of consecutive patients aged ≥ 70 years accessing the Emergency Department (ED) of two Italian tertiary hospitals. A standardized comprehensive geriatric assessment was carried out in each patient, including the Blaylock Risk Assessment Screen Scale (BRASS) for identification of patients at risk of difficult discharge. Inappropriate hospitalization was defined by the ED physician when patients did not necessitate hospital-provided procedures but was due to social reasons or lack of an alternative care-setting. Among 1877 patients (median age 80.7 years, 50.1% male), with a high prevalence of functional dependence and social isolation (around 30% and 25%, respectively), 767 (40.9%) were hospitalized. Incidence of inappropriate hospitalization was 14.6% (95% CI 12.1%-17.1%) and was associated with moderate-high risk of difficult discharge at BRASS (OR = 1.98, 95% CI 1.16-3.39, p = 0.013) and the presence of dementia with behavioural disorders (OR = 1.79, 95% CI 1.10-2.91, p = 0.020). Compared with patients appropriately admitted, inappropriate hospitalizations had shorter length of hospital stay but accounted for 1059/9154 days of stay (11.6%). Inappropriate hospitalizations occurred in less than 15% of cases, mainly accounted for by patients no longer manageable at home, but contributed to the greatest proportion of inappropriate hospital stay. These findings highlight the need of implementing appropriate home-care services and ensuring rapid access to suitable care-facilities for community-dwelling frail older patients.

Prevention of acute rejection after rescue with Belatacept by association of low-dose Tacrolimus maintenance in medically complex kidney transplant recipients with early or late graft dysfunction.

BACKGROUND: Increased acute rejection risk in rescue protocols with Belatacept may limit its use particularly in medically complex patients where preexisting increased risk of rejection couples with CNI toxicity. METHODS: Retrospective analysis was performed in 19 KTs shifted to a Belatacept-based immunosuppression with low-dose Tacrolimus (2-3 ng/mL) after evidence of allograft disfunction, including patients with primary non-function (PNF), chronic-active antibody-mediated rejection (cAMR), history of previous KTs and/or other concomitant transplants (liver, pancreas). Evaluation of CD28+ CD4+ effector memory T cell (TEM) before conversion was performed in 10/19. RESULTS: Kidney function significantly improved (median eGFR 16.5 ml/min/1.73m2 before vs 25 ml/min after; p = 0.001) at a median time after conversion of 12.5 months (9.1-17.8). Overall graft and patient survival were 89.5% and 100% respectively. Definitive weaning from dialysis in 5/5 KTs with PNF was observed, whereas 7/8 patients lost their graft within first year in a control group. eGFR significantly ameliorated in re-trasplants (p = 0.001) and stabilized in KTs with other organ transplants or cAMR. No acute rejection episodes occurred, despite the significant risk suggested by high frequency of CD28+ CD4+ TEM in most patients. Opportunistic infections were limited and most common in early vs late-converted. CONCLUSIONS: Rescue association of Belatacept with low-dose Tacrolimus in medically complex KTs is a feasible option that allows prevention of acute rejection and amelioration of graft function.