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 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.

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.

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.

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.

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.

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.

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.