The resistive and pulsatility indices of the dorsal metatarsal artery for the screening of peripheral lower artery disease in patients with and without diabetes.

BACKGROUND: In lower extremity peripheral artery disease (PAD), the ankle-brachial index (ABI) is an easily reproducible diagnostic tool for PAD, but it loses reliability when > 1.4 due to calcification of the vessel wall. Patients with diabetes are at higher risk for wall calcification. In order to overcome the limitation and reliability of ABI, particularly in patients with diabetes, we decided to assess resistive (RI) and pulsatility index (PI) by ultrasound doppler of the dorsal metatarsal artery (DMA). RESULTS: We therefore analyzed 51 legs (32 patients), evaluating the correlation between PI, RI, and ABI. Patients with diabetes were 21 (65.6 %), accounting for 33 legs (64.7 %). Out of 51 legs assessed, 37 (72.5 %) cases had compressible arteries, whereas in 14 legs (27.5 %) ABI was not calculable due to wall calcification. PAD was significantly associated with lower both RI and PI of the DMA (both p < 0.000). RI, but not PI, showed a significant correlation (r = 0.535) with ABI, when ABI was less than 1.4, but not when ABI > 1.4. When analyzed separately, patients with diabetes showed a similar figure in comparison with those without diabetes (r = 0.600), RI, but not PI, showed a significant correlation with ABI. CONCLUSION: Dorsal metatarsal artery resistive index (MARI) showed a significant inverse correlation with PAD, similarly to ABI, irrespective of the presence of diabetes. MARI seems to be an effective screening tool for PAD even in patients with wall calcification. Further studies are needed for confirming the results of the present pilot study.

Hemophagocytic syndrome related by EBV infection: case report.

A 34-year-old woman of Asian origin with diffuse lymphadenopathy and hepatosplenomegaly in hemophagocytic syndrome induced by Epstein Barr Virus (EBV) infection. The rapidity of progression of clinical manifestations lead to early orotracheal intubation and death due to multiple organ failure (MOF).

A Multinational Survey Investigating the Unmet Needs and Patient Perspectives Concerning Proton Pump Inhibitors in Systemic Sclerosis.

OBJECTIVE: Proton pump inhibitors (PPIs) are widely prescribed to treat gastroesophageal reflux disease (GERD) in Systemic Sclerosis (SSc). However, not all patients adequately respond to the treatment, and there are frequent concerns about the safety of long-term use of PPIs. Our aim was to identify the main problems/complaints of SSc patients on PPIs, as well as understand their unmet needs. METHODS: SSc patients treated with PPIs were invited through international patient associations and social media to participate in an online survey. RESULTS: We gathered 301 valid responses from 14 countries (United Kingdom 19.3% and United States 70.4%). Multiple PPIs use (two: 30% and three: 21% in series) was common. The majority (89%) reported improvement in gastrointestinal symptoms from receiving PPIs. Side effects attributed to receiving PPIs were uncommon (19%); however, most (79%) were potentially concerned. Around half (58%) had received lifestyle information, and most (85%) had searched online for information about PPIs. Only in the minority (12%) had a surgical approach been discussed; however, half (46%) indicated that they would be willing to undergo surgery to resolve their GERD symptoms but had important concerns. CONCLUSION: Despite the frequent use of PPIs in patients with SSc, there is significant heterogeneity in prescription, and combination therapy (PPIs plus other medication for acid reflux) is not uncommon (approximately 40%). Patients have significant concerns about PPIs side effects. Education about PPIs is often neglected, and patients very frequently use online sources to obtain information on drug treatment. A surgical approach is infrequently discussed, and patients fear this potential therapeutic approach.

Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort).

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Impact of implementing a Choosing Wisely educational intervention into clinical practice: The CW-SIMI study (a multicenter-controlled study).

OBJECTIVES: To evaluate the impact of an educational intervention based on the Italian Society of Internal Medicine Choosing Wisely (CW-SIMI) recommendations. DESIGN: Multicenter, interventional, controlled study. SETTING: Twenty-three acute-care hospital wards in Italy. PARTICIPANTS: 303 Physicians working in internal medicine wards. INTERVENTION: An online educational course. MAIN OUTCOMES: The rate of proton pump inhibitor (PPI) prescriptions, the number of days of central venous catheter (CVC) usage, and the duration of intravenous (IV) antibiotic prescriptions evaluated at one month (T1) and at six months (T2) after course completion. Patients admitted and discharged during a 30-day period before the educational intervention (T0, one year before T2) were considered the comparison group. RESULTS: A total of 232 physicians completed the course, while 71 did not attend the course. Data from 608, 662, and 555 patients were analyzed at T0, T1, and T2, respectively. The rate of PPI prescriptions declined at one month (RR: 0.67, 95% CI: 0.52-0.87, p = 0.0005) and at six months (RR: 0.62, 95% CI: 0.46-0.84, p = 0.003), and the number of days of CVC usage was reduced at six months (9.13 days at T0 vs. 5.52 days at T2, p = 0.007). The duration of IV antibiotic prescriptions displayed a decreasing trend (7.94 days at T0 vs. 7.42 days at T2, p = 0.081). CONCLUSIONS: A simple online educational intervention based on the CW-SIMI recommendations was associated with a clinically relevant reduction in the usage of PPIs and CVCs. Further studies are needed to confirm these findings and a possible benefit on patients' outcomes.

Acute heart failure in the elderly: setting related differences in clinical features and management.

BACKGROUND: Administrative data show that acute heart failure (HF) patients are older than those enrolled in clinical registries and frequently admitted to non-cardiological settings of care. The purpose of this study was to describe clinical characteristics of old patients hospitalised for acute HF in Cardiology, Internal Medicine or Geriatrics wards. METHODS: Data came from ATHENA (AcuTe Heart failurE in advaNced Age) registry which included elderly patients (≥ 65 years) admitted to the above mentioned settings of care from December 1, 2014 to December 1, 2015. RESULTS: We enrolled 396 patients, 15.4% assigned to Cardiology, 69.7% to Internal Medicine, and 14.9% to a Geriatrics ward. Mean age was 83.5 ± 7.6 years (51.8% of patients ≥ 85 years) and was higher in patients admitted to Geriatrics (P < 0.001); more than half were females. Medical treatments did not differ significantly among settings of care (in a context of a low prescription rate of renin-angiotensin-aldosterone system inhibitors) whereas significant differences were observed in comorbidity patterns and management guidelines recommendation adherence for decongestion evaluation with comparison of weight and N-terminal pro-B-type natriuretic peptide levels on admission and at discharge (both P = 0.035 and P < 0.001), echocardiographic evaluation ( P < 0.001) and follow-up visits planning ( P < 0.001), all higher in Cardiology. Mean in-hospital length of stay was 9 ± 5.9 days, significantly higher in Geriatrics (13.7 ± 6.5 days) and Cardiology (9.9 ± 6.7 days) compared to Internal Medicine (8 ± 5.2 days), P < 0.001. In-hospital mortality was 9.3%, resulting higher in Geriatrics (18.6%) and Cardiology (16.4%) than Internal Medicine (5.8%), P = 0.001. CONCLUSIONS: In elderly patients hospitalised for acute HF, clinical characteristics and management differ significantly according to the setting of admission.

Use of the FebriDx point-of-care test for the exclusion of SARS-CoV-2 diagnosis in a population with acute respiratory infection during the second (COVID-19) wave in Italy.

OBJECTIVE: Evaluate the real-world accuracy of Myxovirus resistance protein A (MxA) detected by the rapid, point-of-care FebriDx test during the second-wave pandemic in Italy in patients with acute respiratory infection (ARI) and a clinical suspicion of COVID-19. DESIGN AND METHODS: Prospective, observational, diagnostic accuracy study whereby hospitalized patients with ARI were consecutively enrolled in a single tertiary care center in Italy from August 1, 2020 to January 31, 2021. RESULTS: COVID-19 was diagnosed in 136/200 (68.0%) patients and Non-COVID-19 was diagnosed in 64/200 (32.0%) patients. COVID-19 patients were younger and had a lower Charlson comorbidity index compared to Non-COVID-19 patients (p < 0.001). Concordance between FebriDx, MxA and rt-PCR for SARS-CoV-2 (gold standard) was good (k 0.93, 95% CI 0.87-0.99). Overall sensitivity and specificity were 97.8% [95% CI 93.7-99.5] and 95.3% [95% CI 86.9%-99.0%], respectively. FebriDx demonstrated a negative predictive value of 95.3% (95% CI 86.9-99.0) for an observed disease prevalence of 68%. CONCLUSIONS: FebriDx MxA showed high diagnostic accuracy to identify COVID-19 and could be considered as a real-time triage tool to streamline the management of suspected COVID-19 patients. FebriDx also detected bacterial etiology in Non-COVID-19 patients suggesting good performance to distinguish bacterial from viral respiratory infection.

Association of the New Variant Tyr424Asp at TBK1 Gene with Amyotrophic Lateral Sclerosis and Cognitive Decline.

A new risk gene associated with amyotrophic lateral sclerosis (ALS) has recently been identified: the Tank-binding kinase 1 (TBK1) gene. Up to now, 90 TBK1 variants have been described in ALS patients with or without frontotemporal dementia (FTD), thus making TBK1 the third or fourth most frequent genetic cause of ALS and FTD. A point mutation analysis in a cohort of 69 Italian ALS patients was performed in order to analyze the frequency of TBK1 mutations and the correlation with clinical phenotypes. The analysis identified the novel variant p.Tyr424Asp in a patient with a rapid progression of the disease. Our data supports the implication of TBK1 in ALS pathogenesis in Italy.

The classification of hospitalized patients with hyperglycemia and its implication on outcome: results from a prospective observational study in Internal Medicine.

The relevance of classifying hyperglycemic hospitalized subjects (HS) as known diabetes (D), newly discovered diabetes (ND), and stress hyperglycemia (SH) is unclear. The aim of this study was to determine the prevalence, in-hospital mortality, and length of stay (LOS) of three different phenotypes of HS. Fasting glucose ≥126 mg/dL (7 mmol/L) or random blood glucose ≥200 mg/dL (11.1 mmol/L) defined HS who were categorized into three groups: D; ND (no history of diabetes and HbA1c ≥48 mmol/mol); SH (no history of diabetes and HbA1c <48 mmol/mol). The end points of the study were in-hospital mortality and LOS. Of 1447 consecutive enrolled subjects, the prevalence of HS was 28.6 % (415/1447), of these 71.6 % had D, 21.2 % SH, and 7.2 % ND, respectively. In-hospital death was 3.9 % in normoglycemic and 6.0 % in hyperglycemic subjects. Individuals with SH had an increased risk of in-hospital death (7.9 %) (HR 2.17, 95 % CI 1.18-4.9; p = 0.039), while this was not observed for D and ND patients. The mean LOS was greater in ND and SH subjects. Hyperglycemia is common, and is associated with an increased risk of in-hospital mortality and extension of hospital stay. HbA1c along with clinical history is a useful tool to identify subgroups of hyperglycemic hospitalized subjects. Individuals with SH have a longer LOS, and a double risk of in-hospital mortality. Additionally, identifying previously unknown diabetes represents a remarkable opportunity for prevention of diabetes-related acute and chronic complications.

Biohumoral markers as predictor of right ventricular dysfunction in AL Amyloidosis.

AIM: In AL amyloidosis, the importance of right ventricle (RV) involvement has recently been underlined and its role in predicting prognosis has been emphasized. Little is known about the relationship between RV involvement, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin levels. Aim of our study was to clarify the relationship between NT-proBNP and troponin and RV involvement and analyze their independent value as predictors of RV dysfunction. METHODS AND RESULTS: We examined 76 consecutive patients with biopsy-proven AL amyloidosis. Each patient received complete clinical evaluation, troponin I, NT-proBNP assay and comprehensive echocardiographic evaluation. Considering a tricuspidal annulus plane systolic excursion (TAPSE) value <16 mm, 23 patients (30%) presented RV systolic dysfunction, whereas 53 (70%) did not. Patient with reduced TAPSE had thicker left ventricle (LV) walls and RV free walls, reduced LV fractional shortening, impaired LV diastolic function and worse LV and RV myocardial performance index. For RV dysfunction the best predictive value for NT-proBNP was identified as 2977 ng/l with sensitivity and specificity of 87% and 84%, respectively; best cut-off for troponin I was identified as 0.085 ng/l, with sensitivity and specificity of 85% and 90% respectively. At multivariable logistic regression analysis, both NT-proBNP and troponin I emerged as independent predictors of RV dysfunction presence but troponin appears to have a higher predictive power. CONCLUSION: Our study demonstrated that cut-off values of 2977 ng/ml for NT-proBNP and 0.085 ng/l for troponin were able to identify a subgroup of AL patients with RV dysfunction. Troponin I is more accurate and seems to be the best biohumoral marker of RV dysfunction.

Incidence and characteristics of asymptomatic distal deep vein thrombosis unexpectedly found at admission in an Internal Medicine setting.

INTRODUCTION: Lower limb deep vein thrombosis (DVT) is the most frequent clinical manifestation of venous thromboembolism (VTE) and can involve proximal or distal veins. Distal DVT (dDVT) is often asymptomatic and data about its incidence and prognosis are scanty, especially in high risk medical inpatients. Therefore, no consensus exists on the value of detecting and treating dDVTs. Aim of study was to evaluate incidence and characteristics of asymptomatic isolated dDVT at admission in an Internal Medicine department. MATERIALS AND METHODS: Consecutive patients hospitalized for acute medical illnesses, in whom VTE was not the admission diagnosis, underwent Doppler Ultrasonography. For all patients with dDVT standard treatment with therapeutic doses of low molecular weight heparin or fondaparinux was proposed. Follow-up visits were scheduled at 1, 6 and 12weeks. RESULTS: One-hundred-fifty-four patients were enrolled. In 4.5% a proximal DVT and in 16.2% an asymptomatic dDVT were found. Female sex, elevated age and renal and electrolyte abnormalities were significantly associated to dDVT (p=0.014, p=0.009 and p=0.046, respectively). Only low degree of mobility (LDM) was independently associated to dDVT [OR 7.97 (95%CI 2.42-26.27), p=0.001)]. A high mortality rate, not for VTE-related causes, was found, especially in the first week, among dDVT patients. CONCLUSIONS: We found a high incidence of clinically silent dDVTs. LDM evaluation could be useful to select patients at high risk in whom to perform a search for dDVT.

Melatonin is a safe and effective treatment for chronic pulmonary and extrapulmonary sarcoidosis.

Chronic sarcoidosis (CS) is often unresponsive to usual treatments. Melatonin, an immunoregulatory drug, was employed in CS patients in whom usual treatments were ineffective or induced severe side effects. Melatonin was given for 2 yr (20 mg/day in the first year, 10 mg/day in the second year) to 18 CS patients. Pulmonary function tests, chest X rays, pulmonary computed tomography, Ga(67) scintigraphy and angiotensin-converting enzyme (ACE) were assayed at baseline and in the follow-up. Normalization of ACE, improvement of pulmonary parameters and resolution of skin involvement were found in the patients given melatonin. After 24 months of melatonin therapy, hylar adenopathy completely resolved in eight patients and parenchymal lesions were markedly improved in all patients; in the five patients with reduced diffusion capacity of the lung for carbon monoxide, the values normalized after 6 months of therapy and remained stable until month 24. After 24 months, Ga(67) pulmonary and extra-pulmonary uptake was totally normalized in seven patients and, at month 12 months, ACE was normalized in six patients in which the values were high at the baseline. Skin lesions, present in three patients, completely disappeared at month 24 months. No side effects were experienced and no disease relapse was observed during melatonin treatment. Melatonin may be an effective and safe therapy for CS when other treatments fail or cause side effects.

Hemorheologic profile in systemic sclerosis: role of NOS3 -786T > C and 894G >T polymorphisms in modulating both the hemorheologic parameters and the susceptibility to the disease.

OBJECTIVE: Microvascular disorders are relevant in systemic sclerosis (SSc). Hyperviscosity, due to alterations of blood cells and plasma components, may play a role in the pathogenesis of microcirculatory disorders. An impaired availability of nitric oxide, related to polymorphisms in NOS3, the gene for endothelial cell nitric oxide synthase, might influence erythrocyte deformability. We undertook this study to investigate the hemorheologic profile in SSc and the role of NOS3 polymorphisms in modulating the hemorheologic status of SSc patients. METHODS: We studied 113 consecutive SSc patients (75 with limited cutaneous SSc [lcSSc] and 38 with diffuse cutaneous SSc [dcSSc]) and 113 healthy controls. The hemorheologic profile was obtained by assessing whole blood viscosity (WBV; at shear rates of 0.512 and 94.5 seconds(-1)), plasma viscosity (PLV; at a shear rate of 94.5 seconds(-1)), and erythrocyte deformability index (DI). We determined NOS3 polymorphisms by molecular analysis. RESULTS: A marked alteration of hemorheologic parameters was found both in patients with lcSSc and in those with dcSSc compared with controls (P < 0.0001). In multivariate analysis, rheologic variables were significantly associated with the disease (for WBV at a shear rate of 94.5 seconds(-1), odds ratio [OR] 5.4, 95% confidence interval [95% CI] 1.4-19.9, P = 0.01; for PLV, OR 2.8, 95% CI 1.2-6.5, P = 0.01; for DI, OR 3.9, 95% CI 1.4-10.8, P = 0.007), and NOS3 -786C and 894T alleles significantly affected the DI (for -786C allele, OR 2.3, 95% CI 1.01-5.4, P = 0.04; for 894T allele, OR 2.2, 95% CI 1.01-4.8, P = 0.04). The simultaneous presence of the -786C and 894T alleles represented a susceptibility factor for SSc (OR 2.8, 95% CI 1.4-5.7, P = 0.004). CONCLUSION: Our findings document an altered rheologic profile in SSc and demonstrate a relationship between this alteration and NOS3 polymorphisms, thus shedding light on a potential novel mechanism influencing the microcirculation in this disease.