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.

Ultrasound evaluation of bowel vasculopathy in systemic sclerosis.

BACKGROUND: Gastrointestinal (GI) manifestations are frequent in systemic sclerosis (SSc) with an impact on quality of life and morbidity. Bowel vasculopathy is a key pathogenetic factor responsible for GI involvement. OBJECTIVES: To compare abdominal ultrasound (US) and Color Doppler Ultrasonography (CDU) features of splanchnic vessels of SSc patients with healthy controls. METHODS: The charts of SSc patients who underwent an abdominal US and CDU study were retrospectively analyzed. For Superior Mesenteric Artery (SMA) and Inferior Mesenteric Artery (IMA) caliber, Peak Systolic Velocity (PSV), Reverse Velocity (RV), End-Diastolic Velocity (EDV), Mean Velocity (mV), Blood-flow, Resistive Index (RI) and Pulsatility Index (PI) were recorded. RESULTS: 28 SSc patients and 28 controls were enrolled. In SSc, caliber of SMA was significantly smaller than in controls (5.75 ± 0.62 mm vs. 6.45 ± 0.60 mm, p < 0.0001 - p adj =0.0002). The flow study of SMA and IMA showed a significant reduction of RV (SMA: 7.25 ± 6.37 cm/s vs. 18.52 ± 6.16 cm/s, p < 0.0001 - p adj <0.0001; IMA: 2.69 ± 6.10 cm/s vs. 17.06 ± 5.75 cm/s, p < 0.0001 - p adj <0.0001) and PI (SMA: 3.33 ± 0.75 vs. 4.53 ± 1.03, p < 0.0001 - p adj =0.0002; IMA: 3.54 ± 0.95 vs. 6.08 ± 1.53, p < 0.0001 - p adj <0.0001) in SSc patients than controls. CONCLUSION: involvement of splanchnic vessels in SSc may be non-invasively investigated with abdominal US and CDU. Morphological and functional changes of Doppler parameters observed in SMA and IMA clearly demonstrate that these vessels are affected by SSc vasculopathy.

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.

Dural Metastasis without Subdural Hematoma or Subdural Fluid Collection in a Patient with Signet Ring Cell Gastric Adenocarcinoma.

BACKGROUND Signet ring cell (SRC) gastric adenocarcinoma is an aggressive histotype associated with poor prognosis, especially in advanced gastric cancer. Dural metastasis is rarely described in the literature, and clinical manifestations are generally related to subdural hematoma. Here we present a case of advanced SRC gastric cancer with dural neoplastic involvement in the absence of subdural hematoma or subdural fluid collection. CASE REPORT A 39-year-old woman presented with multiple episodes of confusion and headache. She had a history of SRC gastric adenocarcinoma that had been treated with neoadjuvant chemotherapy and total gastrectomy without evidence of disease relapse at follow-up. During hospitalization, she experienced persistent drowsiness and frequent generalized seizures that were nonresponsive to antiepileptic drugs. Brain computed tomography showed a dural right parafalcine nodular lesion suggestive of metastasis, and an SRC presence was detected in a cerebrospinal fluid sample. Cerebral magnetic resonance imaging showed isolated diffuse dural neoplastic involvement without evidence of subdural hematoma or subdural fluid collection. We considered palliative treatment with intrathecal chemotherapy, but it was not carried out because of clinical worsening and subsequent death. CONCLUSIONS In the very few case reports in the literature, dural metastasis in advanced gastric cancer is mainly associated with subdural hematoma. In our case, the absence of any subdural effusion, which is an even rarer condition, along with an unusual clinical presentation dominated by generalized seizures represented a diagnostic challenge. Given the aggressive course of the disease, a rapid diagnosis could allow a faster specific treatment to relieve a patient's symptoms.

Different NT-proBNP circulating levels for different types of cardiac amyloidosis.

AIM: Several studies suggest that the N-terminal fragment of pro-brain natriuretic peptide levels are quite different in wild-type transthyretin (TTR)-related amyloidosis (ATTRwt) and mutated TTR-related amyloidosis (ATTRm) compared with immunoglobulin light-chain cardiac amyloidosis. Our aim was to test this hypothesis in a cohort of patients with different types of cardiac amyloidosis. PATIENTS AND METHODS: Seventy patients with ATTRwt, ATTRm, and light-chain cardiac amyloidosis matched for left ventricular (LV) mass index were studied by standard echocardiography, tissue Doppler imaging, and plasmatic cardiac biomarkers. RESULTS: Despite similar LV mass and renal function, patients with ATTR cardiac amyloidosis showed lower levels of N-terminal fragment of pro-brain natriuretic peptide than do light-chain amyloidosis ones, especially when expressed as a function of LV mass index. CONCLUSION: Amyloidogenic light-chain-derived fibrils induce more severe myocardial dysfunction in light-chain amyloidosis than in ATTR, despite similar myocardial infiltration. Thus, the degree of cardiac dysfunction may be related not only to the amount of amyloid deposited, but also to qualitative differences among fibrils.

Comparison of carotid artery blood velocity measurements by vector and standard Doppler approaches.

Although severely affected by the angle dependency, carotid artery peak systolic velocity measurements are widely used for assessment of stenosis. In this study, blood peak systolic velocities in the common and internal carotid arteries of both healthy volunteers and patients with internal carotid artery stenosis were measured by two vector Doppler (VD) methods and compared with measurements obtained with the conventional spectral Doppler approach. Although the two VD techniques were completely different (using the transmission of focused beams and plane waves, respectively), the measurement results indicate that these techniques are nearly equivalent. The peak systolic velocities measured in 22 healthy common carotid arteries by the two VD techniques were very close (according to Bland-Altman analysis, the average difference was 3.2%, with limits of agreement of ± 8.6%). Application of Bland-Altman analysis to comparison of either VD technique with the spectral Doppler method provided a 21%-25% average difference with ± 13%-15% limits of agreement. Analysis of the results obtained from 15 internal carotid arteries led to similar conclusions, indicating significant overestimation of peak systolic velocity with the spectral Doppler method. Inter- and intra-operator repeatability measurements performed in a group of 8 healthy volunteers provided equivalent results for all of the methods (coefficients of variability in the range 2.7%-6.9%), even though the sonographers were not familiar with the VD methods. The results of this study suggest that the introduction of vector Doppler methods in commercial machines may finally be considered mature and capable of overcoming the angle-dependent overestimation typical of the standard spectral Doppler approach.

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.

A case of persistent hiccup after laparoscopic cholecystectomy.

A 79-year-old man, with history of recent laparoscopic cholecystectomy, came to our attention for persistent hiccup, dysphonia, and dysphagia. Noninvasive imaging studies showed a nodular lesion in the right hepatic lobe with transdiaphragmatic infiltration and increased tracer uptake on positron emission tomography. Suspecting a malignant lesion and given the difficulty of performing a percutaneous transthoracic biopsy, the patient underwent surgery. Histological analysis of surgical specimen showed biliary gallstones surrounded by exudative inflammation, resulting from gallbladder rupture and gallstones spillage as a complication of the previous surgical intervention. This case highlights the importance of considering such rare complication after laparoscopic cholecystectomy.

Cardiac amyloidosis: the heart of the matter.

Amyloidosis comprises a unique group of diseases that share in common the extracellular deposition of insoluble fibrillar proteins in organs and tissue including the heart. Cardiac amyloidosis could be primary a part of systemic acquired amyloidosis, or a result of heredofamilial amyloidosis. Although the infiltration of the heart from different types of amyloid results in restrictive cardiomyopathy that manifests with refractory congestive heart failure and conduction abnormalities, unequivocal identification of the deposited amyloidogenic protein is mandatory in order to avoid misdiagnosis and inappropriate treatment. Recent developments in imaging techniques and extracardiac tissue biopsy have minimized the need for invasive endomyocardial biopsy for amyloidosis. Despite advances in treatment, the prognosis of a patient with amyloidosis is still poor and depends upon the underlying disease, and the type and degree of dysfunction of the involved organs. Thus, early diagnosis is mandatory because patients with advanced disease are usually too ill for intensive therapy. This review outlines current approaches to diagnosis, assessment of disease severity, and treatment of cardiac amyloidosis.

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.

The thrombophilic pattern of different clinical manifestations of venous thromboembolism: a survey of 443 cases of venous thromboembolism.

Although pulmonary embolism (PE) and deep vein thrombosis (DVT) share many risk factors, it is uncertain whether thrombophilic abnormalities may impact differently on the development of these two clinical manifestations of venous thromboembolism (VTE). To give further insight into this issue, we estimated the association of PE with different types of thrombophilia and evaluated whether these abnormalities have a different prevalence in patients presenting with PE, alone or associated with DVT, as compared with those with isolated DVT. In this study 443 consecutive patients with a first episode of VTE and 304 matched healthy controls underwent laboratory screening for thrombophilia, including natural anticoagulants, factor V Leiden and prothrombin G20210A polymorphisms, antiphospholipid antibodies, homocysteine, factor VIII, and lipoprotein(a). Of the 443 patients, 224 patients had isolated DVT, 144 had combined DVT/PE, and 75 had isolated PE. At least one thrombophilic abnormality was detected in 72.8% of DVT, 66% of DVT/EP, and 60% of isolated PE patients. A high prevalence of hyperhomocysteinemia and elevated lipoprotein(a) levels was found in all patients with no significant differences among the three groups. The prevalence of prothrombin G20210A polymorphism and of elevated factor VIII levels was significantly higher in patients with DVT and DVT/PE than in controls, but not in those with isolated PE, whereas factor V Leiden polymorphism was associated with isolated DVT but not with DVT/PE or isolated PE. In conclusion, the thrombophilic burden seems different in isolated PE versus DVT with or without PE, suggesting that PE may encompass a different pathophysiological process of thrombosis to DVT.

[Severe recurrent intrahepatic cholestasis in systemic AL amyloidosis without obvious liver involvement: unexplained hepatic toxicity or a case of misdiagnosed liver amyloidosis?]. / Colestasi intraepatica in corso di amiloidosi sistemica AL senza evidenza istologica di un coinvolgimento epatico: un caso di epatopatia tossica o una mancata diagnosi di amiloidosi epatica?

We report the case of a 50-year-old woman who was admitted to the hospital for acute abdominal pain with nephrotic proteinuria, rapidly progressive renal failure, and moderate anemia. Laboratory tests showed mild Bence Jones (λ) proteinuria with negative serum immunofixation and a mild increase in λ free light chains. A bone marrow biopsy and a fat tissue aspirate showed multiple myeloma and amyloidosis. Because of the end-stage renal disease, the patient began regular dialysis treatment and was started on bortezomib 1.3 mg/m2 plus dexamethasone 40 mg on days 1, 4, 8 and 11 of 21-day cycles. Ten days later she complained of a new episode of abdominal pain with jaundice. A CT scan and an MRI scan ruled out all secondary causes of cholangitis including cancer. Acute intrahepatic cholestasis due to amyloid deposition was then hypothesized. After 4 well tolerated cycles of bortezomib and dexamethasone, blood tests showed a complete hematological response with full reversal of cholestasis. After three months, a new episode of abdominal pain occurred and this time the patient was operated on and found to have an intestinal volvulus. Because of the jaundice, a transjugular liver biopsy was performed showing no evidence of amyloid deposits. Two months later the patient died of septic shock. Although no autopsy was performed and the ultimate cause of the cholestasis could not be ascertained, amyloidosis remains the major culprit in this unfortunate case.

Lack of activation of renal functional reserve predicts the risk of significant renal involvement in systemic sclerosis.

OBJECTIVE: To evaluate if defective activation of renal functional reserve (RFR) in systemic sclerosis (SSc) without clinical signs of renal involvement predicts the risk of developing clinically relevant renal damage. METHODS: Twenty-eight normotensive SSc patients with normal renal function and no urinary abnormalities were submitted to an intravenous amino acid load to activate RFR. Nineteen patients (six with diffuse cutaneous SSc (dcSSc)) had an RFR activation defect, while nine (two with dcSSc) showed normal RFR. All patients were followed up for 5 years, with periodic evaluation of renal function, urinary protein excretion and systemic blood pressure (BP). RESULTS: At admission, patients with normal RFR had lower BP than those with abnormal RFR; no age, disease duration or creatinine clearance (CCr) differences were found. Five years later, patients with abnormal RFR showed, with respect to basal values, a significantly higher CCr reduction than patients with normal RFR (mean percent decrease 15.4 ± 9.5 vs 2.6 ± 3.8, p<0.001). Among patients with abnormal RFR, 13 (68.4%) showed a CCr reduction of ≥ 2 ml/min/year, with a final CCr of ≤ 70 ml/min in eight cases; two patients developed microalbuminuria and 10 grade 1 or 2 systemic hypertension. Significant CCr reduction rates were found in eight patients with high BP and in five patients who remained normotensive. No patient with normal RFR had proteinuria or high BP during follow-up. CONCLUSIONS: Lack of RFR activation is an early sign of renal involvement in SSc, and is a harbinger of an increased risk of developing renal insufficiency and systemic hypertension.