Late diagnosis of Fabry disease caused by a de novo mutation in a patient with end stage renal disease.

BACKGROUND: We present the case of a white 35-year-old male with a diagnosis of Fabry disease and negative family history. CASE PRESENTATION: At the age of 31, he underwent a renal biopsy with a diagnosis of hypertension-induced nephroangiosclerosis. At the age of 35, he was referred to our hospital and started dialysis: the unusual finding of left ventricular hypertrophy with a normal ejection fraction and of myocardial fibrosis at the cardiac magnetic resonance suggested a diagnosis of Fabry disease, although there was no apparent family history—so extensive tests were subsequently undertaken. The patient had low plasma levels of α-galactosidase A and the genetic analysis showed a single nucleotide point mutation in hemizygosis at nucleotide c.901 C>T in exon 6 of the GLA gene, confirming the diagnosis of Fabry disease. We extended the genetic analysis to all family members of the patient (mother, sister and brothers) and none of them had any alteration in the GLA gene, suggesting a de novo mutation in the patient. CONCLUSIONS: In a family, it is rare to find only one Fabry disease affected subject with a de novo mutation. These findings emphasize the importance of early diagnosis, genetic counseling and studying the genealogical tree of suspicious patients, even in absence of a typical family history

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Evaluation of the predictive ability of the in situ concrete strength through core drilling and its effects on the capacity of the RC columns

Assessment of seismic performance of existing RC buildings is a difficult work. The concrete mechanical characteristics have a crucial role on the seismic performance of the buildings during a strong earthquake. The core test has become the most effective method to estimate directly the in situ compressive strength of concrete. Then, some Non-Destructive Tests (NDT) can be effectively used by setting reliable relationships with the core test results. In the past years, the core drilling has been widely studied. Many design codes or guidelines provide useful indication about the operative procedures in order to get no damaged samples. On the contrary, poor reference are available about the effects of core drilling on RC structure capacity. It should be remembered that, due to the increasing demand of utilization and rehabilitation of existing RC buildings, procedures in the evaluation and experimental tests on the constituent materials of these buildings should be improved. In fact, in poor quality concrete, the use of coring test method should take into account the potential negative impact on the safety of these structures. The peculiarities of this work are two: (1) the selection of samples and (2) the type of test. RC columns extracted from an existing old structure designed only for gravity loads have been considered and loading-unloading compression tests have been carried out on specimens. To this end, a wide description of the samples and their characterization has been considered as a fundamental step in order to properly design the experimental campaign. Non-destructive tests, core drilling and subsequent test have been carried out on RC columns extracted from an existing building. Monotonic loading-unloading compression tests on column specimens have been carried out. Comparison of test results highlights the effect on the strength of structural elements of core drilling and subsequent restoration

Cyclic Tests on External RC Beam-Column Joints: Role of Seismic Design Level and Axial Load Value on the Ultimate Capacity

A wide experimental program on beam-column RC joints carried out in the framework of the DPC-Reluis Project (DPC: Department of Civil Protection, Reluis: Network of University Laboratories of Earthquake Engineering) is presented. All the experimental tests were performed at the Laboratory of Structures of the University of Basilicata, Potenza (Italy). The main objective of the experimental campaign is to study and compare the post-elastic behaviour of beam-column joints with different earthquake resistant design levels, indicating the role of some structural parameters such as the axial load value acting on the column, the beam dimensions, and the steel type, on the joint performances and failure mechanism. The analyses have mainly been devoted to improving the assessment procedures regarding existing buildings but also to verifying the prediction capability of the capacity models relevant to beam-column joints contained in literature and in the new seismic codes. Following a short description of the experimental methodologies used in other campaigns, the experimental program is presented, providing a detailed description of the specimens and of the testing set-up. This is followed by a report of the main results of the cyclic tests performed on the beam-column specimens which highlight the role played by axial load and seismic design level in determining the failure mechanism and the global response of the joints

Experimental Evaluation of The Ultimate Capacity of External RC Beam-Column Joints

Some results of a wide experimental program carried out on beam-column RC joints are presented. All the experimental tests were performed at the Laboratory of Structures of the University of Basilicata, Italy. Current assessment procedures on existing buildings usually neglect the variations of joint stiffness due to axial load variations. Main objective of the paper is to show how the axial load value on the columns can affect both ultimate capacity and stiffness of joints. To this purpose, the behaviour of three identical specimens tested under different axial load values is analysed and compared in terms of ultimate capacity and deformation behaviour. Results show significant variations of the joint stiffness at increasing drift values and, moreover, that the main source of deformability moves from the beam to the joint panel when the axial load decreases. The increase in joints’ deformability is mainly due to early cracking of the joint panel as a consequence of the stress state determined by low axial load values