Impact of different chemotherapy regimens on intestinal mucosal injury assessed with bedside ultrasound: a study in 213 AML patients.

Introduction: Neutropenic enterocolitis (NEC) is a life-threatening complication reported in patients with acute myeloid leukemia (AML) following chemotherapy (CHT). Intensive induction and consolidation CHT may damage intestinal mucosa leading to a NEC episode (NECe). NEC reported mortality may be up to 30-60%. Early US-guided bed-side diagnosis and prompt treatment may substantially improve the survival. An emerging worldwide concern is the intestinal colonization by multi-drug-resistant bacteria especially when patients are exposed to chemotherapy regimens potentially correlated to mucosal damage. Methods: In our study we prospectively enrolled all AML patients admitted in our leukemia unit to receive intensive induction and consolidation chemotherapy and experiencing chemotherapy-induced-neutropenia (CHTN). Results and discussion: Overall, we enrolled N=213 patients from 2007 to March 2023. We recorded N=465 CHTN, and N=42 NECe (9.0% incidence). The aim of our study was to assess which chemotherapy regimens are more associated with NEC. We found that ALM1310, followed by 7 + 3 (daunorubicin), 7 + 3 (idarubicin), 5 + 3 + 3 (cytarabine, etoposide, idarubicin), and AML1310 (consolidation) were associated with a statistically higher incidence of NEC. We did not detect NEC episodes in patients treated with CPX-351, 5 + 2 (cytarabine, idarubicine), and high-dose cytarabine. Thus, we found that cytarabine could determine mucosal damage when associated with an anthracycline but not if delivered either alone or as dual-drug liposomal encapsulation of daunorubicin/cytarabine. We also describe NEC mortality, symptoms at diagnosis, intestinal sites involvement, and prognostic significance of bowel wall thickening.

Naturalistic follow-up in bipolar patients after successful electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for acute depression, mania and mixed states. We evaluated the long-term outcome of patients with bipolar depression or mixed state, responsive to ECT. METHODS: this observational follow-up study was conducted in 70 patients with Bipolar Disorder: 36 patients met DSM-IV-TR criteria for a major depressive episode (MDE) and 34 for a mixed episode (MXE). During the follow-up after ECT, the relapse rates and the duration of response and remission periods were recorded. RESULTS: the mean duration of the follow-up was 57 weeks. 93% of the patients maintained at least a partial therapeutic response for more than 90% of the follow-up period. 73% of patients fulfilled the criteria for a full remission, 33% showed a depressive relapse and 10% a mixed relapse. No manic relapses occurred but almost 1/3 of the sample presented hypomanic episodes. MDE patients presented higher rates of remission compared to MXE ones. Patients with anxiety disorders reported earlier relapses than those without this comorbidity. Relapsed-patients showed higher functional impairment at baseline evaluation, compared to non-relapsed ones. LIMITATIONS: nonrandom allocation, limited sample size, possible influence of psychopharmacological treatment. CONCLUSIONS: Given several methodological limitations, this study cannot draw definite conclusions but could suggest that in treatment-resistant bipolar patients with severe depression or mixed state, ECT may represent a useful treatment option. Patients with mixed features, comorbid anxiety disorders and higher functional impairment present less favorable outcome. Future research on long-term efficacy of ECT and on clinical predictors of relapse is needed.

Electroconvulsive therapy in 197 patients with a severe, drug-resistant bipolar mixed state: treatment outcome and predictors of response.

OBJECTIVE: We prospectively evaluated the short-term outcome and the predictors of response to electroconvulsive therapy (ECT) in a large sample of patients with a bipolar mixed state. METHOD: From January 2006 to May 2011, we performed an analysis using data obtained from 197 of 203 consecutive patients with a bipolar mixed state, according to DSM-IV-TR diagnostic criteria, who were treated with ECT at the Department of Psychiatry of the University of Pisa. All patients were evaluated prior to and after the ECT course using the Hamilton Depression Rating Scale-17 (HDRS-17), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impressions (CGI) scale. The CGI subscale "global improvement" and final HDRS-17 and YMRS total scores were used to identify nonresponder, responder, and remitter groups. RESULTS: At the end of the ECT course, 55 patients (27.9%) were considered nonresponders, 82 responders (41.6%), and 60 remitters (30.5%). As expected, at the end of the ECT trial, the CGI-Severity scale (CGI-S; P < .0001), HDRS-17 (P < .0001), and BPRS (P < .0001) scores were significantly lower in remitters than in responders and nonresponders. Using backward stepwise logistic regression, the length of current episode, lifetime comorbidity of obsessive-compulsive disorder, and baseline YMRS total mean score were statistically significant predictors of nonresponse versus remission (P < .0001). CONCLUSIONS: Less than 30% of the patients included in the study were nonresponders to ECT. Long-lasting mixed episode with excitatory symptoms and lifetime comorbidity of obsessive-compulsive disorder significantly predicted a lack of complete remission.

Predictors of remission in 208 drug-resistant depressive patients treated with electroconvulsive therapy.

OBJECTIVES: This study aimed to explore predictors of remission to electroconvulsive therapy (ECT) in a sample of depressive patients resistant to pharmacological treatments. METHODS: Two hundred eight patients, 31 of whom had major depressive disorder, 101 had bipolar disorder II (BP II), and 76 had bipolar disorder I (BP I), diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria were treated with bilateral ECT on a twice-a-week schedule. All patients included were undergoing a depressive episode, excluding patients with mixed and manic episodes. Patients were assessed before (baseline) and a week after the ECT course (final score) using the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Young Mania Rating Scale (YMRS), the Brief Psychiatric Rating Scale, and the Clinical Global Impression-Improvement (CGI-I). RESULTS: At the end of the ECT course, 56 patients (26.9%) were considered nonresponders, and 80 patients (38.4%) were considered responders (HAM-D score of at least 50% and CGI-I subscale rating of 2, "much improved") and 72 remitters (34.6%) (HAM-D scores ≤8 and a CGI-I subscale rating of 1). On backward stepwise logistic regression length of current episode, Bipolar Disorder and baseline YMRS total mean scores were statistically significant predictors of nonresponders versus remitters. Among the YMRS items at basal evaluation 8 (thought content), 10 (appearance), and 11 (insight), the mean scores were significantly lower in the remitters than in the responders and nonresponders. CONCLUSION: Major depressive disorder, short duration of the current episode, absence of psychotic symptoms, preserved insight, and adequate personal care are associated with complete remission in our sample of drug-resistant depressive patients treated with ECT.

The intracavitary ECG method for positioning the tip of central venous catheters: results of an Italian multicenter study.

PURPOSE: The aim of this multicenter study was to assess the feasibility, safety, and accuracy of the intracavitary ECG method for real-time positioning of the tip of different types of central venous catheters. METHODS: A total of 1444 catheter insertions in adult patients were studied in eight Italian centers (539 ports, 245 PICCs, 325 tunneled CVCs, 335 non-tunneled CVCs). Patients with no visible P wave at the standard baseline ECG were excluded. Depending on the type of catheter and its purpose, the target was to position the tip either (a) at the cavo-atrial junction, or (b) in the lower third of the superior vena cava, or (c) in the upper part of the atrium. The final position was verified by a post-procedural chest x-ray. RESULTS: The method was feasible in 99.3% of all cases. There were no complications potentially related to the method itself. At the final x-ray control, 83% of all tips were positioned exactly at the target; 12.4% were positioned within 1-2 cm from the target, but still in a correct central position; only 3.8% were malpositioned. The mismatch between intra-procedural ECG method and post-procedural x-ray was significantly lower when the x-ray was taken in supine position. CONCLUSIONS: Our multicenter study confirms that the intracavitary ECG method for real time verification of tip position is accurate, safe, feasible in all adult patients and applicable to any type of short-term or long-term central venous access device.

Transthoracic Doppler echocardiography of mammary artery grafts to assess graft function.

BACKGROUND: Transthoracic Doppler echocardiography of internal mammary artery grafts (MAGs) has been tested by the supraclavicular approach, but little information is available about the parasternal approach. OBJECTIVE: To evaluate the usefulness of parasternal transthoracic Doppler echocardiography to assess the patency of left and right MAGs. PATIENTS AND METHODS: Forty-eight patients with previous MAGs were divided into two groups on the basis of coronary angiography: 42 patients had patent MAGs and six patients had severe MAG stenosis. Doppler echocardiography of MAGs was performed on all patients, both at baseline and after low-dose dipyridamole infusion. Systolic and diastolic time-velocity integrals and their ratios were obtained, and MAG flow reserve was calculated. RESULTS: Patients with patent MAGs had a predominant diastolic flow, while a prominent systolic pattern was found in the presence of MAG stenosis. In patients with stenosis, baseline Doppler analysis showed a lower diastolic peak velocity (DPV) (P<0.01), diastolic time-velocity integral (P<0.05), and diastolic and systolic time-velocity integral ratios (both P<0.005), and a reduced MAG flow reserve (P<0.001). In the overall population, when adjusting for clinical variables, a multilinear regression analyis underscored MAG flow reserve (beta=0.38, P<0.01) and baseline DPV (beta=0.29, P<0.05) as independent determinants of MAG stenosis (cumulative R2=0.25, P<0.005). CONCLUSIONS: Doppler echocardiographic evaluation of MAGs is a reliable, noninvasive tool to assess MAG patency and functional status of the vessel. MAG blood flow reserve and baseline DPV are independent determinants of MAG stenosis.

Coronary flow reserve in hypertensive patients with appropriate or inappropriate left ventricular mass.

OBJECTIVE: To assess the association between coronary flow reserve (CFR) and levels of left ventricular mass (LVM) exceeding the compensatory needs in arterial hypertension. DESIGN, SETTINGS AND PATIENTS: The association between the excess of LV mass and CFR was assessed in a population of 40 consecutive hypertensive outpatients free of coronary heart disease, 22 with appropriate and 17 with inappropriately high LVM (i.e. LVM exceeding 128% of the value predicted by sex, stroke work and height in m(2.7)). The CFR (the ratio between dipyridamole and basal diastolic peak velocity) of the distal left anterior descending artery was measured by transthoracic Doppler echocardiography. RESULTS: Patients with inappropriate LVM had similar age, body mass index (BMI), baseline blood pressure (BP) and coronary velocities, but lower LV systolic function, post-dipyridamole diastolic peak velocities (P < 0.05) and lower CFR (P < 0.002) than patients with appropriate LVM. CFR was negatively related to the extent of the excess of LVM (beta = -0.44, P < 0.005), independently of potential combined effect of age, BMI and post-dipyridamole diastolic BP. Impairment of CFR (i.e. < 2) was better discriminated by identification of clear-cut inappropriate LVM (P < 0.004) than by the presence of LV hypertrophy (i.e. LV mass index > or = 51 g/m(2.7); P = 0.057). CONCLUSIONS: In hypertensive patients free of coronary artery disease, the degree of reduction in CFR is associated with the excess of LVM beyond the values compensatory for individual haemodynamic load. This relation is also independent of the presence of LV hypertrophy.

Noninvasive assessment of left and right internal mammary artery graft patency using transthoracic color Doppler echocardiography.

BACKGROUND: The aim of this study was to evaluate the patency of left and right internal mammary artery grafts respectively on the left anterior descending and right coronary artery by noninvasive transthoracic color Doppler echocardiography. METHODS: Thirty eight patients (34 males, 4 females, mean age 59 +/- 2 years), with a history of coronary artery bypass grafting for a total of 42 mammary artery grafts, were studied by means of color Doppler echocardiography at baseline and after vasodilation with dipyridamole infusion (0.56 mg/kg i.v. over 4 min). The evaluated echocardiographic parameters included: systolic (SPV) and diastolic peak velocities (DPV), systolic (SVI) and diastolic velocity-time integrals (DVI), and the DPV/SPV and DVI/SVI ratios. We also calculated the dipyridamole infusion to baseline ratio of the diastolic peak velocities (DPVdip/DPVbaseline), the index of internal mammary artery graft blood flow reserve and the percent DPV increment as an index of graft stenosis. RESULTS: On the basis of coronary angiography, two groups were selected: group A (36 mammary grafts) with patent grafts and group B (6 mammary grafts) with moderate or severe stenosis of the grafts. Group A had a predominant diastolic pattern with a DPV of 0.24 +/- 0.13 m/s, whereas group B had a predominant systolic pattern with a reduced DPV of 0.12 +/- 0.03 m/s (p < 0.01). Dipyridamole induced an increase in the DPV respectively of 86.8 +/- 64.4% in group A and 13.8 +/- 15.9% in group B (p < 0.001). Statistical analysis (Mann-Whitney test) revealed a significant difference between the two groups for the baseline DPV (p < 0.01), DVI (p < 0.05), DPV/SPV ratio (p < 0.005), DVI/SVI ratio (p < 0.05), and for the after dipyridamole infusion values: DPV (p < 0.0001), DVI (p < 0.005), DPV/SPV ratio (p < 0.001), and DVI/SVI ratio (p < 0.05). Multivariate analysis showed that the percent DPV increment, the DPVdip/DPVbaseline ratio and the baseline DPV were independent determinants of the stenosis as evaluated at angiography (beta = -0.38, p < 0.01; beta = -0.37, p < 0.01, and beta = -0.33, p < 0.05, respectively; cumulative r2 = 0.25, standard error 0.30 m/s, p < 0.005). CONCLUSIONS: The echocardiographic evaluation of the mammary grafts is a simple, noninvasive method for the assessment of the graft patency and of the functional status of the vessel. The percent DPV increment and baseline DPV were independent determinants of mammary graft stenosis.

Is the time course of clozapine response correlated to the time course of clozapine plasma levels? A one-year prospective study in drug-resistant patients with schizophrenia.

The relationship between the time course of clinical response to clozapine and the time course of clozapine plasma levels has never been investigated. In the present study, we assessed prospectively the clinical response to clozapine and the plasma levels of the drug and its major metabolites in 32 drug-resistant patients with schizophrenia kept on a fixed dose of 600 mg/day for 1 year Four of the patients met response criteria at week 4 of treatment. At weeks 8, 12, and 24, new responders were 7, 6, and 6, respectively. Nine patients never achieved clinical response. In responders at week 4, clozapine and clozapine-N-oxide plasma levels were significantly higher than in both new responders at weeks 8, 12, and 24 and nonresponders. In new responders at weeks 8, 12, and 24, in spite of a fixed clozapine daily dose, mean drug plasma levels progressively rose up to when clinical response occurred; then, the levels remained stable over time. Nonresponders exhibited mean clozapine plasma levels constantly below the value of 260 ng/ml, with N-demethylation as the preferred metabolic route. The present findings show, for the first time, that the time course of the clinical response to clozapine may be linked to the time course of plasma levels of clozapine and its major metabolites.

Coronary flow reserve and myocardial diastolic dysfunction in arterial hypertension.

The aim of this study was to assess the relation between coronary blood flow and left ventricular (LV) myocardial diastolic dysfunction in arterial hypertension. The study population included 30 hypertensive patients who were free of coronary artery disease and pharmacologic therapies. They underwent standard Doppler echocardiography and color tissue Doppler of the middle posterior septum at baseline and with high-dose dobutamine, and second-harmonic Doppler flow analysis of the distal left anterior descending coronary artery at baseline and after vasodilation by dipyridamole (0.56 mg/kg IV in 4'). Coronary flow reserve (CFR) was estimated as the ratio of hyperemic and baseline diastolic flow velocities. According to CFR, hypertensives were divided into 2 groups: 15 patients with normal CFR (>/=2) and 15 patients with reduced CFR (<2). The 2 groups were comparable for sex, age, body mass index, baseline heart rate, and blood pressure. LV mass index was greater in hypertensives with reduced CFR (p <0.01). By color tissue Doppler, baseline and high-dose dobutamine septal systolic velocities did not differ between the 2 groups. The ratio between myocardial velocities in early diastole and at atrial contraction (E(m)/A(m) ratio) was lower in patients with reduced CFR, both at baseline (p <0.05) and with high-dose dobutamine (p <0.00001). After adjusting for age, body mass index, LV mass index, and both high-dose dobutamine diastolic blood rate and heart rate by a multiple linear regression analysis, E(m)/A(m) ratio at high-dose dobutamine was independently associated with CFR in the overall population (beta 0.62, p <0.0005) (cumulative R(2) 0.38, p <0.0005). In conclusion, this study provides evidence of an independent association between CFR and myocardial diastolic function. In hypertensive patients without coronary artery stenosis, CFR alteration may be a determinant of myocardial diastolic dysfunction or diastolic impairment that should be taken into account as possibly contributing to coronary flow reduction.

Positive association between circulating free insulin-like growth factor-1 levels and coronary flow reserve in arterial systemic hypertension.

BACKGROUND: The reduction of coronary flow reserve (CFR) found in arterial hypertension may be due to changes in afterload, left ventricular (LV) structure, and metabolic factors. Also, insulin-like growth factor-1 (IGF-1) may be associated with the magnitude of CFR in relation to its modulating action on cardiac and endothelial function. METHODS: A total of 44 newly diagnosed, untreated hypertensive patients, who were free of diabetes mellitus and coronary artery disease, underwent M-mode analysis, second-harmonic Doppler echocardiographic assessment of CFR (dipyridamole infusion 0.56 mg/kg intravenously in four patients), determination of circulating free IGF-1, and insulin resistance. Based on CFR levels, hypertensive subjects were divided into two groups: 18 with normal CFR (> or = 2) and 26 with impaired CFR (<2). RESULTS: Patients with normal CFR had lower diastolic blood pressure, heart rate, and LV mass index but higher free circulating IGF-I than patients with reduced CFR (P < .001). Insulin resistance was not significantly different between the two groups. In a first multilinear regression analysis that included demographic and echocardiographic variables, insulin resistance was independently associated with CFR (standardized beta coefficient = -0.31, P < .05) in the overall population. However, in a subsequent model which included also IGF-1, the relationship between insulin resistance and CFR disappeared, whereas IGF-1 was the main independent determinant of CFR (beta = 0.51, P < .0002). CONCLUSIONS: Free IGF-1 circulating levels are independently associated with CFR in hypertensive individuals free of overt coronary artery disease. A possible beneficial effect exerted by IGF-1 on coronary blood flow may be supposed in arterial hypertension.

[Mitral stenosis: echocardiographic evaluation]. / Stenosi mitralica: valutazione ecocardiografica.

The diagnostic tools available for the evaluation of mitral stenosis are two-dimensional and Doppler echocardiography, which are able to identify morphologic and flow changes. Two-dimensional echocardiography can be used to assess the morphological appearance of the mitral valve apparatus, including its mobility and thickness and the presence of calcified leaflets and subvalvular fusion. Wilkins'score permits evaluation of each variable which, on the basis of its severity, is scored according to a point system ranging from 1 to 4. In patients with severe mitral stenosis, a low total score (< 8) and elastic symmetric commissures suggest valvuloplasty. A total score > 10 and the presence of more than mild mitral regurgitation or of calcification of both commissures suggest valvular replacement. The left atrial and ventricular chamber sizes and other associated valvular diseases can also be assessed at two-dimensional or Doppler echocardiography. The severity of obstruction can be assessed using two-dimensional and Doppler echocardiographic area (pressure half-time, proximal isovelocity surface area, continuity equation) and with the mean transmitral gradient measured using a continuous wave Doppler signal across the mitral valve. Valvuloplasty can also be performed in patients with a high score when surgery is contraindicated. During follow-up it is necessary to evaluate the area, the mean gradient, the right ventricular systolic pressure and the presence of a residual atrial septal defect and mitral regurgitation. Restenosis is diagnosed when the valve area decreases to 50% of that achieved during valvuloplasty or surgery.