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Clinical case We describe a case of a 62–y–old man, affected by hypertension, insulin–dependent diabetes mellitus, advanced liver cirrhosis. After screeing, the patient was listed for liver transplantation. On September 2022, the patient was admitted to our Emergency Room due to HF in class NYHA III. The transthoracic echocardiogram showed a severe aortic regurgitation with mobile vegetations, the largest of which is more than 10 mm on the right aortic cusp. Normal biventricular function was observed with sPAP of 45 mmHg. Thus, we concluded for post–endocarditis severe aortic regurgitation. We discussed tha case in our Department Heart Team with the concomitant presence of the Liver Team. We considered the patient at high surgical risk, mostly due to the risk of postoperative hepatic insufficiency. So, we decided for a TAVI off–label. So, we impantanted a Sapien 3 Ultra 26 mm through transfemoral access. To reduce the risk of cerebral embolization, we used Triguard 3 system, while to prevent coronary embolization we used a closed stent into the right coronary ostia, ready to be opened. The patient was discharged in the fourth postoperative day, without conduction disturbances. The postoperative echo showed normal valvular function and absence of paravalvular leakages. Conclusions Patients with advanced liver cirrhosis are at risk of organ failure following use of extracorporeal circulation. In selected patients, TAVI may be a valid alternative. The peculiarity of the specific case was due to the use of the TAVI in an off–label procedure of aortic insufficiency with the simultaneous presence of mobile vegetation at high embolic risk.

The Tower of London (ToL) is a problem-solving task, which is a valuable tool for the neuropsychological examination of a patient with a possible cognitive decline. The aim of the present study was to evaluate the ToL in comparison to the Mini Mental State Examination (MMSE) in a group of older people with or without dementia.Seventy outpatients of both sexes, 30 with low-moderate dementia and 40 with apparently normal cognition were evaluated with the MMSE and the ToL task in the same day. The ToL score was calculated according to the Krikorian method and also the execution time was measured. The differences between groups were assessed with the unpaired t-test, and the relationship between two parameters was assessed with the analysis of the coefficient of linear regression. The results were adjusted for age and education.The evaluation of cognitive impairment by MMSE showed a significant difference in the two groups (p0.001). The mean scores (p0.001) and execution times (p0.05) of the ToL, resulted significantly lower in the patients affected by dementia. However, seven participants with dementia had a normal score in the ToL test, indicating that the executive neuropsychological tasks could be preserved notwithstanding the cognitive decline and nine participants with normal MMSE obtained a low ToL score, suggestive of the higher sensibility of the ToL for the executive task that reveals an unknown cognitive deficit.The correlation between MMSE and ToL is good, but ToL test provides complementary information to the MMSE and vice versa.

Kidney function is assessed in clinical practice to screen for kidney disease, to adapt dosage of medications for renal clearance, and to follow the evolution of known kidney disease. Because renal disease has different clinical presentations and patients are often asymptomatic, it is important to assess kidney function as accurately as possible, especially in older adults, since there is a progressive decline in renal function with age. Glomerular filtration rate (GFR) is the best quantification of kidney function,1 but because it cannot be measured directly, it is estimated from serum concentration or urinary clearance of a filtration marker. Exogenous filtration markers such as inulin, which is the criterion standard filtration marker, give accurate estimates of GFR,2 but determining them is complex and expensive, has potential complications, and is inappropriate for general use. Currently, serum creatinine is the most widely used method of assessing renal function in clinical practice, although it has been well established that serum creatinine alone may not be well correlated with true GFR.3,4 Indeed, as renal function declines, tubular creatinine secretion increases, leading to a blunted and delayed rise in serum creatinine concentration, which reaches the abnormal range only when more than half of the total filtration rate is lost.3 Furthermore, because creatinine is derived from the metabolism of creatine in the muscle and from dietary meat intake, factors related to reduced muscle mass, a potential problem in old age, and low dietary meat intake have a strong effect on serum creatinine concentration.4 To account for muscle mass, different estimation equations of GFR adjust serum creatinine concentration for different demographic characteristics and body composition variables. These include the Cockcroft–Gault equation5 or the Modification of Diet in Renal Disease (MDRD) Study equation.6 Despite the fact that serum creatinine is well known to be poorly correlated with GFR, and despite availability of different estimation equations, many clinicians continue to rely solely on serum creatinine as a measure of renal function and interpret a normal serum creatinine as indicating normal renal function. But how many patients with impaired kidney function are missed when relying on serum creatinine alone? Do women have the same risk of misclassification as men? Does this risk change according to body mass index (BMI)? The purpose of this article is to estimate the magnitude of renal function misclassification in a community-dwelling elderly population with normal serum creatinine values and to describe the participant characteristics related to misclassification.

Hydroxyurea is a cytotoxic agent widely used in the treatment of myeloproliferative disorders. It is considered a-well-tolerated antineoplastic drug, with a dose-related bone marrow suppression as main adverse effect. This report describes a patient with essential thrombocythemia who developed an interstitial pneumonitis and respiratory failure within 4 years from beginning therapy with hydroxyurea (HU). After discontinuing of HU. both clinical and radiological resolution of pneumonitis occurred. In conclusion, HU-induced pulmonary toxicity is a potentially life-threatening side effect.

It is well established that during sea-ice formation, crystals aggregate into a solid matrix, and dissolved sea-water constituents, including inorganic nutrients, are rejected from the ice matrix. However, the behaviour of dissolved organic matter (DOM) during ice formation and growth has not been studied to date. DOM is the primary energetic substrate for microbial heterotrophic activity in sea water and sea ice, and therefore it is at the base of the trophic fluxes within the microbial food web. The aim of our study was to compare the behaviour of DOM and inorganic nutrients during formation and growth of sea ice. Experiments were conducted in a large indoor ice-tank facility (Hamburg Ship Model Basin, Germany) at −15°C. Three 1 m3 tanks, to which synthetic sea water, nutrients and dissolved organic compounds (diatom-extracted DOM) had been added, were sampled over a period of 5 days during sea-ice formation. Samples were collected throughout the experiment from water underlying the ice, and at the end from the ice as well. Brine was obtained from the ice by centrifuging ice cores. Inorganic nutrients (nitrate and phosphate) were substantially enriched in brine in comparison to water and ice phases, consistent with the processes of ice formation and brine rejection. Dissolved organic carbon (DOC) was also enriched in brine but was more variable and enriched in comparison to a dilution line. No difference in bacteria numbers was observed between water, ice and brine. No bacteria growth was measured, and this therefore had no influence on the measurable DOC levels. We conclude that the incorporation of dissolved organic compounds in newly forming ice is conservative. However, since the proportions of DOC in the brine were partially higher than those of the inorganic nutrients, concentrating effects of DOC in brine might be different compared to salts.

Background Compliance to immunosuppressive therapy is critical to prevent organ rejection and possible graft loss. A once-daily Tacrolimus formulation that may improve adherence-to-therapy while allowing the same patient care strategies, total daily dose and monitoring techniques that have been recently approved. The present study was sought to evaluate the feasibility of this formulation among liver transplantation patients (OLT). Materials and Methods Patients transplanted for at least 6 months were enrolled if they had stable doses of Tacrolimus over the last 3 months. Conversion from a twice to a once-daily regimen was based on a 1 mg:1 mg proportion. Tacrolimus blood levels were assessed at 0, 15, 30, 60, 90 days as well and 6 months after conversion. We recorded liver and renal function as well as adverse events. Results Among twenty-eight patients enrolled in the study including 23 males and 5 females the overall mean age was 59 ± 8 years and the mean distance from OLT was 39 ± 22. 32% of patients did not require any dose adjustment. In contrast, 43% required an increase (+0.6 ± 0.3 mg/d), while 25%, a decrease (−0.5 ± 0.0 mg/d) in the drug dose to maintain the same tacrolimus blood concentrations as at baseline. Ninety percent of patients stabilized blood levels within 45 days. None of the patients experienced adverse events or alterations in liver function. Conclusions Our study confirmed that once-daily Tacrolimus is a useful therapeutic option for OLT patients; however dose adjustments are frequently needed in the short term. The drug is safe and may improve patient compliance.

STUDY HYPOTHESIS: The Identification of Senior At Risk (ISAR) and the Triage Risk Stratification Tool (TRST) are the two most studied screening tools to detect high-risk patients for unplanned readmission after an emergency department (ED)-visit. Since their performance was unclear among ED-patients over 75 years, we evaluated their capacities to predict readmission at 1, 3, 6 and 12 months as well as their usefulness in avoiding unnecessary further comprehensive geriatric assessment (CGA) in negative screened patients. METHODS: Historical cohort study with systematic routine data collection of functional status, comorbid conditions and readmission rate of patients released home after an ED-visit between 2007 and 2009 at the Geneva University Hospitals. RESULTS: 345 patients were included (mean age 84y; 63% female). Readmission rates were 25%, 38%, 49%, and 60% at 1, 3, 6, and 12 months, respectively. Positive ISAR (>/=2/6) and TRST (>/=2/5) predicted modestly unplanned readmission at each time point (AUC range: 0.607-0.664). Prediction of readmission with ISAR or TRST was not modified after adjustment for variables significantly associated with readmission (being male, having poor functional or comorbid scores). In case of negative ISAR or TRST, their high negative predictive values (NPV) would safely allow avoiding 64 useless CGA (ISAR

Detection of subjects with early chronic kidney disease (CKD) is important because some will progress up to stage 5 CKD, and most are at high risk of cardiovascular morbidity and mortality. While validity and precision of estimated glomerular filtration rate (eGFR) equations in tracking true GFR have been repeatedly investigated, their prognostic performance for mortality has not been hitherto compared. This is especially relevant in an elderly population in whom the risk of death is far more common than progression.We analysed data of participants in the InCHIANTI study, a community-based cohort study of older adults. Twenty-four-hour creatinine clearance (Ccr), Cockcroft-Gault (C-G) and Modification of Diet in Renal Disease (MDRD)-derived equations (six and four input variables) were calculated at enrolment (1998-2000), and all-cause mortality and cardiovascular mortality were prospectively ascertained by Cox regression over a 6-year follow-up.Of the 1270 participants, 942 (mean age 75 years) had complete data for this study. The mean renal function ranged from 77 ml/min/1.73 m(2) by Ccr to 64 ml/min/1.73 m(2) by C-G. Comparisons among equations using K/DOQI staging highlight relevant mismatches, with a prevalence of CKD ranging from 22% (MDRD-4) to 40% (C-G). Reduced renal function was a strong independent predictor of death. In a Cox model--adjusted for demographics, physical activity, comorbidities, proteinuria and inflammatory parameters-participants with Ccr 60-90 ml/min/1.73 m(2) and Ccr60 ml/min/1.73 m(2) were, respectively, 1.70 (95% CI: 1.02-2.83) and 1.91 (95% CI: 1.11-3.29) times more likely to die over the follow-up compared to those with Ccr90 ml/min/1.73 m(2). For the C-G, the group with values60 ml/min/1.73 m(2) had a significant higher all-cause mortality compared to those with values90 ml/min/1.73 m(2) (HR 2.59, 95% CI: 1.13-5.91). The classification based on the MDRD formulae did not provide any significant prognostic information. The adjusted risk of all-cause mortality followed a similar pattern when Ccr and estimating equations were introduced as continuous variables or dichotomized as higher or lower than 60 ml/min. C-G was the best prognostic indicator of cardiovascular mortality. Possibly, Ccr and C-G are better prognostic indicators than MDRD-derived equations because they incorporate a stronger effect of age.In a South-European elderly population, the prevalence of CKD is high and varies widely according to the method adopted to estimate GFR. Researchers and clinicians who want to capture the prognostic information on mortality related to kidney function should use the Ccr or C-G formula and not MDRD equations. These results highlight the importance of strategies for early detection and clinical management of CKD in elderly subjects.

Summary Introduction Depression has been hypothesized to be associated with metabolic abnormalities which increase the risk of cardiovascular disease (CVD) and diabetes. Such a link could be due to increased HPA-axis activity. This study investigates the cross-sectional relationship between depression, urinary cortisol and metabolic syndrome in an older population. Methods Data are from 867 participants of the InChianti Study, aged ⩾65 years. Depressive symptoms were assessed using the CES-D scale; cortisol levels were determined in 24-h urine samples. Metabolic syndrome was defined as three or more of the following: abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure, and high fasting glucose. Results Clinically relevant depressed mood (CES-D⩾20) was present in 20.6% of the sample, and 24.5% had the metabolic syndrome. After adjustment for sociodemographics and health indicators, depression score (per SD increase: OR=1.20, 95% CI=1.02–1.41) and urinary cortisol level (per SD increase: OR=1.23, 95% CI=1.01–1.51) were significantly associated with presence of metabolic syndrome. There was, however, a significant interaction ( p = 0.003 ) between depressed mood and urinary cortisol in the probability of having metabolic syndrome. The odds of metabolic syndrome in persons with both depressed mood and urinary cortisol excretion in the highest tertile was 1.84 (95% CI=1.02–3.34) compared to persons with neither condition. Discussion This study suggests a synergistic relationship between depression, cortisol and metabolic syndrome. Hypercortisolemic depression may constitute a specific risk group for the metabolic syndrome.

A woman noted vesicles and papules on her left upper extremity fifteen years after she underwent mastectomy and received radiation treatment for left breast carcinoma. The vesicles showed clinical and pathologic features of acquired lymphangiectasis. The skin lesions were successfully treated with shave excision followed by electrodesiccation and sequential peristaltic compressions twice daily.

It has been hypothesized that there are significant dissolved organic matter (DOM) pools in sea-ice systems, although measurements of DOM in sea ice have only rarely been made. The significance of DOM for ice-based productivity and carbon turnover therefore remains highly speculative. DOM within sea ice from the Amundsen and Bellingshausen Seas, Antarctica, in 1994 and the Weddell Sea, Antarctica, in 1992 and 1997 was investigated. Measurements were made on melted sea-ice sections in 1994 and 1997 and in sea-ice brines in 1992. Dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) concentrations in melted ice cores were up to 1.8 and 0.78 mM, respectively, or 30 and 8 times higher than those in surface water concentrations, respectively. However, when concentrations within the brine channel/pore space were calculated from estimated brine volumes, actual concentrations of DOC in brines were up to 23.3 mM and DON up to 2.2 mM, although mean values were 1.8 and 0.15 mM, respectively. There were higher concentrations of DOM in warm, porous summer second-year sea ice compared with colder autumn first-year ice, consistent with the different biological activity supported within the various ice types. However, in general there was poor correlation between DOC and DON with algal biomass and numbers of bacteria within the ice. The mean DOC/DON ratio was 11, although again values were highly variable, ranging from 3 to highly carbon-enriched samples of 95. Measurements made on a limited dataset showed that carbohydrates constitute on average 35% of the DOC pool, with highly variable contributions of 1−99%.

Background The recurrence of hepatitis C viral infection is common after liver transplant, and achieving a sustained virological response to antiviral treatment is desirable for reducing the risk of graft loss and improving patients’ survival. Aim To investigate the long-term maintenance of sustained virological response in liver transplant recipients with hepatitis C recurrence. Methods 436 Liver transplant recipients (74.1% genotype 1) who underwent combined antiviral therapy for hepatitis C recurrence were retrospectively evaluated. Results The overall sustained virological response rate was 40% (173/436 patients), and the mean follow-up after liver transplantation was 11 ± 3.5 years (range, 5–24). Patients with a sustained virological response demonstrated a 5-year survival rate of 97% and a 10-year survival rate of 93%; all but 6 (3%) patients remained hepatitis C virus RNA-negative during follow-up. Genotype non-1 (p = 0.007), treatment duration >80% of the scheduled period (p = 0.027), and early virological response (p = 0.002), were associated with the maintenance of sustained virological response as indicated by univariate analysis. Early virological response was the only independent predictor of sustained virological response maintenance (p = 0.008). Conclusions Sustained virological response achieved after combined antiviral treatment is maintained in liver transplant patients with recurrent hepatitis C and is associated with an excellent 5-year survival.