Longevity Matching for Living Donor Renal Transplantation.

INTRODUCTION: This study identifies the effect of individual donor and recipient characteristics on graft survival in living-donor kidney transplantation (LDKT) using a recently described novel measure, kidney life years (KLYs). MATERIALS AND METHODS: The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify first-time kidney-only LDKT recipients between 1987 and 2020 who did not experience death with a functioning graft (DWFG) and were not missing relevant information (n = 87,290). Patient characteristics were evaluated using Cox and multiple regression analyses, with the dependent variable being KLYs. An equation for expected KLYs based on patient characteristics was created using regression coefficients. The equation was validated using bootstrapped Pearson correlations and then applied to the DWFG group for comparison. RESULTS: Based on statistical significance from Cox and multiple linear regression analyses, 9 of the original 18 variables were selected for inclusion in the equation. Variables with notable impact included HLA match points (0.021 KLYs; 95% CI: [0.019,0.024]; P ≤ .001), Donor Age (-0.030 KLYs; 95% CI: [-0.035,-0.025]; P ≤ .001), and Donor African American Ethnicity (-2.356 KLYs; 95% CI: [-2.552,-2.159]; P ≤ .001). Equation validation was supported, given a negative correlation (r = -0.071; P ≤ .001) between expected KLY change and observed graft failure. Expected KLY change was found to be greater in those who eventually DWFG when compared with all other LDKTs (t = -5.735, P ≤ .001). CONCLUSIONS: Increasing HLA match points may be more beneficial for graft longevity than minimizing donor age in comparisons using realistic between-donor differences. Additionally, greater average expected KLYs in those who ultimately DWFG may illustrate an opportunity for improved donor-recipient matching.

Deciphering the True Immunologic Risk in Renal Transplantation in Patients With HIV.

Since 1995, rates of end-stage renal disease have risen dramatically in patients living with HIV infection. However, given the concern for higher rates of acute rejection in this patient population, the immunologic threat posed by HIV infection is a specter clinicians must continually confront. Living donor transplantation may negate this risk; this study aims to assess the benefit of living donor transplantation in this population and to ascertain the immunologic risk faced by patients who are HIV-infected. The 2021 UNOS database was queried, and all HIV-infected kidney transplant recipients since 1987 were identified. Recipients were stratified based on deceased (DDKT) vs living (LDKT) donor status. Overall survival, allograft survival, acute rejection, panel reactive antibody (PRA) percentage, and crossmatch positivity were compared between groups. One thousand two hundred twenty-six patients underwent DDKT, and 304 patients underwent LDKT. Living donor kidney transplantation demonstrated greater overall survival (P = .045) and graft survival (P < .001). However, no difference in acute rejection was noted between the cohorts, and no difference in overall or graft survival was evident based on PRA percentage. Crossmatch positive status did not negatively affect graft survival. Patients with HIV undergoing LDKT fared better than those undergoing DDKT. Nevertheless, patients at higher immunologic risk-elevated PRA% and crossmatch positivity-did not experience graft loss at a higher rate than patients at lower immunologic risk. These results were valid in both DDKT and LDKT cohorts. These findings suggest that infection with HIV does not overtly increase patients' immunologic risk, and concerns surrounding transplantation in this population may be overestimated.

Effect of an educational intervention to increase stroke awareness among Italian high school students: A prospective study in Tuscany.

INTRODUCTION: Stroke in young people shares traditional modifiable risk factors with older groups, and greatly affects quality of life. However, evidence on the effectiveness of educational interventions in young populations, aiming at spreading stroke knowledge and enhancing prevention, is still scarce. We evaluated baseline knowledge of stroke and possible improvements after an educational intervention among Italian high school students, also considering differences related to sex and type of school. SUBJECTS AND METHODS: Using a mixed educational strategy, a prospective evaluation of stroke knowledge was performed in five humanities and sciences (lyceums) and five vocational high schools of Tuscany (students of the 12th and 13th grade). A baseline assessment with a structured questionnaire (21 questions) was followed by a standardized oral presentation, using audiovisual materials. After 3 months, the same questionnaire was re-administered to evaluate the long-term impact of the educational intervention. RESULTS: Overall, 573 students (50.8% males; age range, 17-19 years) were enrolled; 288 (50.3%) were from lyceums and 285 (49.7%) from vocational schools. Follow-up participation was 97.2%. Baseline performances were comparable between groups for most variables examined. At 3 months, all groups showed a significant improvement from baseline regarding reaction to a stroke event, identification of stroke risk factors, such as smoking (from 62.9% to 83.7%; p < 0.001) and alcohol abuse (from 49.6% to 67.2%; p < 0.001), and symptoms. Knowledge of the existence of stroke units and thrombolysis increased from 25.4% to 60.7% (p < 0.001) and from 35.8% to 84.0% (p < 0.001), respectively. CONCLUSIONS: Our educational intervention improved stroke awareness in high school students. The effects persisted after 3 months. Improved knowledge in young populations may reduce stroke burden in adult life, increase timely access to therapies, and spread knowledge across families.

Benefit of Kidney Transplantation for Post Lung Transplantation Renal Failure.

INTRODUCTION: Nephrotoxicity is a significant side effect of thoracic transplantation. Many lung transplant patients will require subsequent renal transplantation (KAL). Recently, simultaneous lung/kidney transplants (SLuK) have become an attractive option for patients with end-stage renal disease at the time of lung transplantation. This article explores SLuK outcomes compared to conventional KAL, as well as outcomes among KAL patients against those were KAL listed but never transplanted. MATERIALS AND METHODS: The United Network for Organ Sharing/the Organ Procurement and Transportation Network database was used to identify SLuK patients (n = 74), KAL transplants (n = 456), and patients who were listed for KAL but were never transplanted (n = 626). Significance was determined by chi2, Wilcoxon rank sum test, or independent t-tests. Death-censored graft survival for subgroups was estimated using Kaplan-Meier with log-rank for significance. Analyses were completed using SPSS Statistics 28. RESULTS: The SLuK cohort was older (P = 0.04), more likely diabetic (P < 0.001), and had shorter life expectancies (P < 0.001) than KAL patients. Of those SLuK transplants within 5 y, 84% of patients were alive 1 y post transplant and 82% were alive 3 y post-transplant (compared to 74.6% and 60.3% of overall SLuK). Patients who did undergo KAL were younger and had a lower body mass index (both P < 0.001) compared to those who did not. Those who received a kidney had increased survival times compared to WL patients (P < 0.001). CONCLUSIONS: Conventional KAL transplants are still favorable for average lung recipients. However, recent improvements have made SLuK an option for patients with renal dysfunction. Those patients who were able to receive KAL transplants were better surgical candidates than those who remained on the waitlist.

Frailty Prevalence, Incidence, and Association with Incident Disability in the Italian Longitudinal Study on Aging.

INTRODUCTION: Data on frailty frequency are heterogeneous and mostly based on cross-sectional studies. Little is known about frailty development and progression over time. Our aim was to conduct a systematic analysis of frailty prevalence and incidence in a large cohort of older adults and to evaluate the association with incident disability, in order to tackle the current paucity and fragmentation of longitudinal data on frailty. METHODS: As secondary analysis of the Italian Longitudinal Study on Aging (ILSA) population-based cohort (n = 5,632, 65-84), frailty status was operationalized according to Fried criteria (n = 2,457). Weighted prevalence and incidence rates were calculated at each ILSA wave (T0 1992-1993, T1 1995-1996, T2 2000-2001). The association with incident disability in Activities of Daily Living (ADL) or Instrumental Activities of Daily Living (IADL) was investigated through Cox proportional hazard models, controlling for possible confounders. RESULTS: Prevalence of frailty and pre-frailty at baseline (mean age 71.6 years; women 58.9%) were 4.0% (95% confidence interval [CI]: 3.4-4.6) and 44.6% (95% CI: 43.1-46.1), respectively. Incidence rates per 1,000 person-years for the T0-T1 interval were 7.3 (95% CI: 5.2-9.3) for frailty and 83.7 (95% CI: 73.6-93.8) for pre-frailty. Prevalence and incidence of frailty, and to a lesser degree of pre-frailty, were overall higher for women and increased with age, yet no increasing trend with advancing age was detected for pre-frailty incidence. Frailty incidence rates were significantly higher among pre-frail than non-frail individuals at follow-up entry. After full adjustment, being frail markedly increased the risk of incident disability in ADL (hazard ratio [HR] 3.58, 95% CI: 1.97-6.52) and IADL (HR 2.56, 95% CI: 1.58-4.16) over a 4-year period. DISCUSSION/CONCLUSION: According to our findings, frailty is common among older people and is a strong and independent predictor of disability. Further research on factors and characteristics related to frailty progression, and especially remission, over time is crucial to calibrate effective public health preventive measures.

Renal Cell Carcinoma in End-Stage Kidney Disease and the Role of Transplantation.

Kidney transplant patients have a higher risk of renal cell carcinoma (RCC) compared to non-transplanted end-stage kidney disease (ESKD) patients. This increased risk has largely been associated with the use of immunosuppression; however, recent genetic research highlights the significance of tissue specificity in cancer driver genes. The implication of tissue specificity becomes more obscure when addressing transplant patients, as two distinct metabolic environments are present within one individual. The oncogenic potential of donor renal tissue is largely unknown but assumed to pose minimal risk to the kidney transplant recipient (KTR). Our review challenges this notion by examining how donor and recipient microenvironments impact a transplant recipient's associated risk of renal cell carcinoma. In doing so, we attempt to encapsulate how ESKD-RCC and KTR-RCC differ in their incidence, pathogenesis, outcome, and approach to management.

Dosing strategies for de novo once-daily extended release tacrolimus in kidney transplant recipients based on CYP3A5 genotype.

BACKGROUND: Tacrolimus extended-release tablets have been Food and Drug Administration-approved for use in the de novo kidney transplant population. Dosing requi rements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression. Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus, but this has not been established for tacrolimus extended-release tablets in the de novo setting. AIM: To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype. METHODS: Single-arm, prospective, single-center, open-label, observational study (ClinicalTrials.gov: NCT037 13645). Life cycle pharma tacrolimus (LCPT) orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight. If weight is more than 120% of ideal body weight, an adjusted body weight was used. LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL. Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion. RESULTS: Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (6 d vs 13.5 d vs 4.5 d; P = 0.025). Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers (16 mg vs 16 mg vs 12 mg; P = 0.010) (0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg; P = 0.018). CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers (7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL; P = 0 0.008). No differences were identified with regards to kidney graft function at 30-d post-transplant. Serious adverse events were reported for 13 (36%) patients. CONCLUSION: Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacro limus to achieve target trough concentrations. We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.

Influence of atrial fibrillation subtypes on anticoagulant therapy in a high-risk older population: the FAI project.

BACKGROUND AND AIM: Benefits of oral anticoagulants (OAC) in atrial fibrillation (AF) patients with moderate-to-high risk of stroke are independent of AF pattern. We evaluated whether AF clinical subtype influenced OAC use in a representative sample of the Italian older population. METHODS: A cross-sectional examination of all subjects aged 65 + years from three general practices in northern, central, and southern Italy started in 2016. A double-screening procedure was followed by clinical and ECG confirmation. Patients were categorized as having paroxysmal, persistent, or permanent AF. OAC use was evaluated in confirmed AF patients. RESULTS: The sample included 6016 subjects. Excluding 235 non-eligible, participation was 78.3%, which left 4528 participants (mean age 74.5 ± 6.8 years, 47.2% men). Overall, 319 AF cases were identified: 43.0% had paroxysmal, 21.3% persistent, and 35.7% permanent AF. Frequency of OAC therapy was 91.2% in permanent, 85.3% in persistent, and only 43.0% in paroxysmal AF (P < 0.001). In multivariate analysis, controlled for baseline variables and risk scales, persistent and permanent AF were associated with a significant increase in the likelihood of receiving OAC compared with paroxysmal AF (P < 0.001). This was confirmed for permanent AF also in multivariate analyses considering separately vitamin K antagonists or direct-acting oral anticoagulants (OR, 4.37, 95% CI, 2.43-7.85; and 1.92, 95% CI, 1.07-3.42, respectively) and for persistent AF and direct-acting oral anticoagulants (OR, 4.33, 95% CI, 2.30-8.15). CONCLUSIONS: In a population-based survey, AF pattern was an independent predictor of OAC treatment. Paroxysmal AF is still perceived as carrying a lower risk of vascular events.

Simple Prediction Score for Developing Surgical Site Infection after Clean Neck Operation.

Background: Clean neck operations (thyroidectomies, parathyroidectomies, and lymph node resection) are among the most common procedures performed in the United States. Surgical site infections (SSIs) after clean neck operations are rare, but the consequences are devastating and often life-threatening. The aim of this study was to develop a score that will identify patients at high risk for developing a SSI after a clean neck procedure. Materials and Methods: Patients with either thyroidectomies, parathyroidectomies, or lymph node resection of the neck were identified from the 2016 and 2017 databases of the American College of Surgeons National Surgical Quality Improvement Program and were used for this analysis. Our primary goal was to build a scoring system with which we will be able to identify patients at high risk for SSI after a clean neck operation. Results: Of a total of 99,877 patients, 72,719 patients had a thyroidectomy, 22,043 patients had parathyroidectomy, and 5,115 patients had lymph node resection of the neck. Multivariable logistic regression identified the following independent risk factors associated with post-operative SSI: male gender (adjusted odds ratio [aOR], 1.25; 95% confidence interval [CI], 1.03-1.51), diabetes mellitus (aOR, 1.34; 95% CI, 1.07-1.67), smoking (aOR, 1.66; 95% CI, 1.36-2.04), pre-operative steroid use (aOR, 1.75; 95% CI, 1.21-2.53), cancer diagnosis (aOR, 1.44; 95% CI, 1.17-1.77), radical lymphadenectomies (aOR, 2.94; 95% CI, 2.16-4), and total operative time ≥198 minutes (aOR, 2.25; 95% CI, 1.82-2.78). Afterward, we developed a prognostic score for calculating the odds of having post-operative SSI. One point was allotted for each of the aforementioned factors, except lymphadenectomies where two points were allotted, and operative time was excluded. Our score was associated with a stepwise higher risk of post-operative SSI after a clean neck operation. Conclusions: Pre-operative and intra-operative factors can predict which patients undergoing a clean neck surgery may develop SSI. Our prognostic score may help guide surgeons identify patients at high-risk for SSI after clean neck surgery and these patients might benefit from prophylactic use of antibiotic agents.

Myocardial GRK2 Reduces Fatty Acid Metabolism and ß-Adrenergic Receptor-Mediated Mitochondrial Responses.

G-protein coupled receptor (GPCR) kinase 2 (GRK2) is upregulated in heart failure (HF) patients and mouse models of cardiac disease. GRK2 is a regulator of ß-adrenergic receptors (ßARs), a GPCR involved in ionotropic and chronotropic responses. We and others have recently reported GRK2 to be localized in the mitochondria, although its function in the mitochondria and/or metabolism remain not clearly defined. We hypothesized that upregulation of GRK2 reduced mitochondrial respiratory function and responses to ßAR activation. Utilizing isolated mouse primary adult cardiomyocytes (ACMs), we investigated the role of glucose, palmitate, ketone bodies, and BCAAs in mediating cell survival. Our results showed that myocyte upregulation of GRK2 promotes palmitate-induced cell death. Isotopologue labeling and mass spectrometry showed that the upregulation of GRK2 reduces ß-hydroxybutyryl CoA generation. Next, using isoproterenol (ISO), a non-selective ßAR-agonist, we determined mitochondrial function in mouse and human primary ACMs. Upregulation of GRK2 impaired ISO-mediated mitochondrial functional responses, which we propose is important for metabolic adaptations in pathological conditions. Increased cardiac levels of GRK2 reduced fatty acid-specific catabolic pathways and impaired ISO-stimulated mitochondrial function. Our data support the notion that GRK2 participates in bioenergetic remodeling and may be an important avenue for the development of novel pharmacological strategies in HF.

Frailty Predicts Morbidity and Mortality After Laparoscopic Cholecystectomy for Acute Cholecystitis: An ACS-NSQIP Cohort Analysis.

BACKGROUND: Current guidelines recommend laparoscopic cholecystectomy be offered for patients with acute cholecystitis except those deemed as high risk. Few studies have examined the impact of frailty on outcomes for patients undergoing laparoscopic cholecystectomy. Therefore, the aim of this study was to determine the association of frailty with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis. METHODS: Patients undergoing laparoscopic cholecystectomy for acute cholecystectomy were identified from 2005 to 2010 in the American College of Surgeons National Surgical Quality Improvement Project (NSQIP). The Modified Frailty Index (mFI) was used a surrogate for frailty, and patients were stratified as non-frail (mFI 0), low frailty (mFI 1-2), intermediate frailty (mFI 3-4) and high frailty (mFI ≥ 5). Univariable and multivariable analyses were performed. Receiver operator curves (ROC) and an area under the curve (AUC) were generated to determine accuracy of mFI in predicting postoperative morbidity and mortality. RESULTS: Of the 6898 patients undergoing laparoscopic cholecystectomy, 3245 (47%) patients were non-frail. There were 2913 (42%) patients with low-frailty, 649 (9%) patients with intermediate frailty, and 91 (2%) with high frailty. Clavien IV complications were higher for intermediate frail patients (OR 1.81, 95% CI 1.00-3.28, p = 0.050) and high-frail patients (OR 4.59, 95% CI 1.98-10.7, p < 0.001). Additionally, mortality was higher for patients with intermediate frailty (OR 4.69, 95% CI 1.37-16.0, p = 0.014) and high frailty (OR 12.2, 95% CI 2.67-55.5, p = 0.001). The mFI had excellent accuracy for mortality (AUC = 0.83) and Clavien IV complications (AUC = 0.73). CONCLUSION: Frailty is associated with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis.

Fatty liver: The metabolic syndrome increases major hepatectomy mortality.

BACKGROUND: As the obesity epidemic worsens, the prevalence of fatty liver disease has increased. However, minimal data exist on the impact of combined fatty liver and metabolic syndrome on hepatectomy outcomes. Therefore, the aim of this analysis is to measure the outcomes of patients who do and do not have a fatty liver undergoing hepatectomy in the presence and absence of the metabolic syndrome. METHODS: Patients with fatty and normal livers undergoing major hepatectomy (≥3 segments) were identified in the 2014 to 2018 American College of Surgeon National Surgical Quality Improvement Program database. Patients undergoing partial hepatectomy and those with missing liver texture data were excluded. Propensity matching was used and adjusted for multiple variables. A subgroup analysis stratified by the metabolic syndrome (body mass index ≥30 kg/m2, hypertension and diabetes) was performed. Demographics and outcomes were compared by χ2 and Mann-Whitney tests. RESULTS: Of 2,927 hepatectomies, 30% of patients (N = 863) had a fatty liver. The median body mass index was 28.6, and the metabolic syndrome was present in 6.3% of patients (N = 184). After propensity matching, 863 patients with fatty and 863 with normal livers were compared. Multiple outcomes were significantly worse in patients with fatty livers (P <.05), including serious morbidity (32% vs 24%), postoperative invasive biliary procedures (15% vs 10%), organ space infections (11% vs 7.8%), and pulmonary complications. Patients with fatty livers and the metabolic syndrome had significantly increased postoperative cardiac arrests, pulmonary embolisms, and mortality (P < .05). CONCLUSION: Fatty liver disease is associated with significantly worse outcomes after major hepatectomy. The metabolic syndrome confers an increased risk of postoperative mortality.

Liver Ischemia Reperfusion Injury, Enhanced by Trained Immunity, Is Attenuated in Caspase 1/Caspase 11 Double Gene Knockout Mice.

Ischemia reperfusion injury (IRI) during liver transplantation increases morbidity and contributes to allograft dysfunction. There are no therapeutic strategies to mitigate IRI. We examined a novel hypothesis: caspase 1 and caspase 11 serve as danger-associated molecular pattern (DAMPs) sensors in IRI. By performing microarray analysis and using caspase 1/caspase 11 double-knockout (Casp DKO) mice, we show that the canonical and non-canonical inflammasome regulators are upregulated in mouse liver IRI. Ischemic pre (IPC)- and post-conditioning (IPO) induce upregulation of the canonical and non-canonical inflammasome regulators. Trained immunity (TI) regulators are upregulated in IPC and IPO. Furthermore, caspase 1 is activated during liver IRI, and Casp DKO attenuates liver IRI. Casp DKO maintained normal liver histology via decreased DNA damage. Finally, the decreased TUNEL assay-detected DNA damage is the underlying histopathological and molecular mechanisms of attenuated liver pyroptosis and IRI. In summary, liver IRI induces the upregulation of canonical and non-canonical inflammasomes and TI enzyme pathways. Casp DKO attenuate liver IRI. Development of novel therapeutics targeting caspase 1/caspase 11 and TI may help mitigate injury secondary to IRI. Our findings have provided novel insights on the roles of caspase 1, caspase 11, and inflammasome in sensing IRI derived DAMPs and TI-promoted IRI-induced liver injury.

Liver fibrosis score, physical frailty, and the risk of dementia in older adults: The Italian Longitudinal Study on Aging.

INTRODUCTION: Liver fibrosis increases progressively with aging and has been associated with poorer cognitive performance in middle-aged and older adults. We investigated the relationships between a non-invasive score for advanced liver fibrosis (non-alcoholic fatty liver disease [NAFLD] fibrosis score [NFS]) and dementia risk. We also assessed physical frailty, a common geriatric condition which is associated to dementia. We tested the joint effects of physical frailty and fibrosis on dementia incidence. METHODS: A total of 1061 older adults (65 to 84 years), from the Italian Longitudinal Study on Aging, were prospectively evaluated for the risk of dementia in a period between 1992 and 2001. Liver fibrosis was defined according to the NFS. Physical frailty was assessed according to the Fried's criteria. Cox proportional hazards models were used to estimate the short- and long-term risk of overall dementia, associated to the NFS, testing the effect modifier of physical frailty status. RESULTS: Older adults with only high NFS (F3-F4) did not exhibit a significant increased risk of overall dementia. Over 8 years of follow-up, frail older adults with high NFS had an increased risk of overall dementia (hazard ratio [HR]: 4.23; 95% confidence interval [CI]: 1.22 to 14.70, P = .023). Finally, physically frail older adults with low albumin serum levels (albumin < 4.3 g/dL) and with advanced liver fibrosis (F3-F4 NFS) compared to those with lower liver fibrosis score (F0-F2 NFS) were more likely to have a higher risk of overall dementia in a long term-period (HR: 16.42; 95% CI: 1.44 to 187.67, P = .024). DISCUSSION: Advanced liver fibrosis (F3-F4 NFS) could be a long-term predictor for overall dementia in people with physical frailty. These findings should encourage a typical geriatric, multidisciplinary assessment which accounts also for the possible co-presence of frail condition in older adults with chronic liver disease and liver fibrosis.

Prevalence of Atrial Fibrillation Subtypes in Italy and Projections to 2060 for Italy and Europe.

BACKGROUND/OBJECTIVES: Atrial fibrillation (AF) subtypes may carry different cardiovascular risk profiles, but information on their frequency from population-based studies is lacking. We estimated prevalence of AF subtypes in a representative sample of the Italian older population, projecting figures for Italy and the European Union. DESIGN: Cross-sectional study. SETTING: Three primary care practices in northern, central, and southern Italy. PARTICIPANTS: All individuals aged 65 years or older, for a total sample of 6,016 subjects. Excluding 235 noneligible, participation was 78.3%, which left 4,528 participants. MEASUREMENTS: A double systematic and opportunistic screening procedure identified possible AF cases, followed by clinical and electrocardiogram confirmation. Patients were categorized with paroxysmal, persistent, or permanent AF. Prevalence was calculated by sex and 5-year age groups. Prevalence figures were applied to population projections for all 28 European Union states to estimate AF subtypes expected in future decades. RESULTS: In the 4,528 participants (mean age = 74.5 ± 6.8 years; 47.2% men), 331 AF cases were identified: 140 (42.3%) paroxysmal, 77 (23.3%) persistent, and 114 (34.4%) permanent. Prevalence was 3.1% (95% confidence interval (CI) = 2.6%-3.6%) for paroxysmal, 1.7% (95% CI = 1.4%-2.1%) for persistent, and 2.5% (95% CI = 2.1%-3.0%) for permanent AF. Italian older persons having AF in 2016 were estimated at approximately 449,000 for paroxysmal, approximately 240,000 for persistent, and approximately 391,000 for permanent AF, projected to increase in 2060 to approximately 785,000, approximately 358,000, and approximately 748,000, respectively. European Union older persons having AF in 2016 were estimated at approximately 3,185,000 for paroxysmal, approximately 1,722,000 for persistent, and approximately 2,710,000 for permanent AF, projected to increase in 2060 to approximately 5,989,000, approximately 2,833,000, and approximately 5,579,000, respectively. CONCLUSION: We provided first projections of AF subtypes for Italy and Europe. The worse cardiovascular risk profile of persistent and permanent forms indicates an increased burden in future decades.

Biopsychosocial frailty and the risk of incident dementia: The Italian longitudinal study on aging.

INTRODUCTION: Frailty is a critical intermediate status of the aging process including physical, cognitive, and psychosocial domains/phenotypes. We operationalized a new biopsychosocial frailty (BF) construct, estimating its impact on the risk of incident dementia and its subtypes. METHODS: In 2171 older individuals from the population-based Italian Longitudinal Study on Aging (ILSA), we identified by latent class procedures the BF construct as the physical frail status plus at least one of the two items of the 30-item Geriatric Depression Scale impaired (items 3/10). RESULTS: Over a 3.5-year follow-up, participants with BF showed an increased risk of overall dementia (hazard ratio [HR]: 2.16, 95% confidence interval [CI]:1.07-4.37), particularly vascular dementia (VaD) (HR: 3.21, 95% CI: 1.05-9.75). Similarly, over a 7-year follow-up, an increased risk of overall dementia (HR: 1.84, 95% CI: 1.06-3.20), particularly VaD (HR: 2.53, 95% CI: 1.08-5.91), was also observed. DISCUSSION: In a large cohort of Italian older individuals without cognitive impairment at baseline, a BF model was a short- and long-term predictor of overall dementia, particularly VaD.

Prevalence of atrial fibrillation in the Italian elderly population and projections from 2020 to 2060 for Italy and the European Union: the FAI Project.

AIMS: To estimate prevalence of atrial fibrillation (AF) in a representative sample of the Italian elderly population, projecting figures for Italy and the European Union. METHODS AND RESULTS: A cross-sectional examination of all subjects aged 65+ years from three general practices in Northern, Central, and Southern Italy started in 2016. Participants were administered a systematic and an opportunistic screening, followed by clinical and electrocardiogram confirmation. The study sample included 6016 subjects. Excluding 235 non-eligible, among the remaining 5781 participation was 78.3%, which left 4528 participants (mean age 74.5 ± 6.8 years, 47.2% men). Prevalence of AF was 7.3% [95% confidence intervals (CI) 6.6-8.1], higher in men and with advancing age (6.6% from systematic plus 0.7% from opportunistic screening). Using prevalence figures, Italian elderly having AF in 2016 were estimated at ∼1 081 000 (95% CI 786 000-1 482 000). Considering stable prevalence, this number will increase by 75% to ∼1 892 000 in 2060 (95% CI 1 378 000-2 579 000). European Union elderly having AF in 2016 were estimated at ∼7 617 000 (95% CI 5 530 000-10 460 000), increasing by 89% to ∼14 401 000 in 2060 (95% CI 10 489 000-19 647 000). In 2016, subjects aged 80+ years represented 53.5% of cases in Italy and 51.2% in the European Union; in 2060, 69.6% and 65.2%, respectively. CONCLUSIONS: Our findings indicate a high burden of AF in coming decades, especially among the oldest-old, who carry the higher AF-related risk of stroke and medical complications.

Endovascular intervention for iliac vein thrombosis after simultaneous kidney-pancreas transplant.

May-Thurner syndrome (MTS) is an anatomic variant where the overlying right common iliac artery compresses and chronically obstructs the left common iliac vein, leading to thrombosis. Interventions for symptomatic MTS include endovascular thrombectomy and stenting. Occluding venous thrombus can be fatal to transplanted allografts. No guidelines exist for patients with MTS after simultaneous kidney-pancreas transplant. A 57-year-old female with ESRD and diabetes mellitus underwent a kidney-pancreas transplant. Post-operative imaging revealed a compressed left CIV with an occlusive thrombus threatening the renal graft. Thrombectomy with stent placement was performed, maintaining patency of both allograft venous outflows. Post-intervention the patient has demonstrated preserved kidney and pancreas allograft function through 1 year of follow-up. Interventions for MTS in patients after transplant are challenging given the complex allograft vascular reconstruction. We present a case which demonstrates that angiographic interventions for MTS can be safely performed after simultaneous kidney-pancreas transplant.

Characterization of a rare variant (c.2635-2A>G) of the MSH2 gene in a family with Lynch syndrome.

INTRODUCTION: Lynch syndrome is caused by germline mutations in one of the mismatch repair genes ( MLH1, MSH2, MSH6, and PMS2) or in the EPCAM gene. Lynch syndrome is defined on the basis of clinical, pathological, and genetic findings. Accordingly, the identification of predisposing genes allows for accurate risk assessment and tailored screening protocols. CASE DESCRIPTION: Here, we report a family case with three family members manifesting the Lynch syndrome phenotype, all of which harbor the rare variant c.2635-2A>G affecting the splice site consensus sequence of intron 15 of the MSH2 gene. This mutation was previously described only in one family with Lynch syndrome, in which mismatch repair protein expression in tumor tissues was not assessed. In this study, we report for the first time the molecular characterization of the MSH2 c.2635-2A>G variant through in silico prediction analysis, microsatellite instability, and mismatch repair protein expression experiments on tumor tissues of Lynch syndrome patients. The potential effect of the splice site variant was revealed by three splicing prediction bioinformatics tools, which suggested the generation of a new cryptic splicing site. The potential pathogenic role of this variant was also revealed by the presence of microsatellite instability and the absence of MSH2/MSH6 heterodimer protein expression in the tumor cells of cancer tissues of the affected family members. CONCLUSIONS: We provide compelling evidence in favor of the pathogenic role of the MSH2 variant c.2635-2A>G, which could induce an alteration of the canonical splice site and consequently an aberrant form of the protein product (MSH2).

Administrative data underestimate acute ischemic stroke events and thrombolysis treatments: Data from a multicenter validation survey in Italy.

BACKGROUND: Informing health systems and monitoring hospital performances using administrative data sets, mainly hospital discharge data coded according to International-Classification-Diseases-9edition-Clinical-Modifiers (ICD9-CM), is now commonplace in several countries, but the reliability of diagnostic coding of acute ischemic stroke in the routine practice is uncertain. This study aimed at estimating accuracy of ICD9-CM codes for the identification of acute ischemic stroke and the use of thrombolysis treatment comparing hospital discharge data with medical record review in all the six hospitals of the Florence Area, Italy, through 2015. METHODS: We reviewed the medical records of all the 3915 potential acute stroke events during 2015 across the six hospitals of the Florence Area, Italy. We then estimated sensitivity and Positive Predictive Value of ICD9-CM code-groups 433*1, 434*1 and thrombolysis code 99.10 against medical record review with clinical adjudication. For each false-positive case we obtained the actual diagnosis. For each false-negative case we obtained the primary and secondary ICD9-CM diagnoses. RESULTS: The medical record review identified 1273 acute ischemic stroke events. The hospital discharge records identified 898 among those (true-positive cases),but missed 375 events (false-negative cases), and identified 104 events that were not eventually confirmed as acute ischemic events (false-positive cases). Code-group specific Positive Predictive Value was 85.7% (95%CI,74.6-93.3) for 433*1 and 89.9% (95%CI, 87.8-91.7) for 434*1 codes. Thrombolysis treatment, as identified by ICD9-CM code 99.10, was only documented in 6.0% of acute ischemic stroke events, but was 13.6% in medical record review. CONCLUSIONS: Hospital discharge data were found to be fairly specific but insensitive in the reporting of acute ischemic stroke and thrombolysis, providing misleading indications about both quantity and quality of acute ischemic stroke hospital care. Efforts to improve coding accuracy should precede the use of hospital discharge data to measure hospital performances in acute ischemic stroke care.