Dose-dense CHOP plus rituximab (R-CHOP14) for the treatment of elderly patients with high-risk diffuse large B cell lymphoma: a pilot study

BACKGROUND: Aggressive non-Hodgkin's lymphomas (NHL) require intensive therapies which seemed impracticable in elderly patients. Dose reduction and therapy attenuation reduced treatment-related toxicity, but also decreased therapeutic efficacy. In elderly patients too, the achievement of complete remission is the most important prognostic factor affecting outcome. Therefore, we have treated elderly patients with a dose-intensified protocol. Aim of the study was to verify the feasibility of this scheme in a subset of patients with high-risk aggressive lymphomas. METHODS: Between June 2002 and June 2004, 26 patients over the age of 60 years with a diagnosis of aggressive NHL and an intermediate-high or high International Prognostic Index were treated with biweekly CHOP plus rituximab with the support of granulocyte colony-stimulating factors (G-CSF). RESULTS: Seventeen patients (65%) regularly kept the interval between cycles. Haematological and extrahaematological toxicities were moderate in all the patients. Twenty (77%) patients achieved complete remissions, 6 (23%) partial remissions with an overall response rate of 100%. After a median follow-up of 23 months, the overall survival was 79%; after a median follow-up of 17 months, the disease-free survival was 70%. CONCLUSION: These results confirm that a dose-dense CHOP programme can be administered safely and effectively in a subset of elderly patients with high-risk aggressive NHL. The addition of rituximab could increase the response rate without adding toxicity.     

Relation of patient age to outcome of percutaneous mitral valvuloplasty

The aim of this study was to evaluate the impact of age on immediate- and long-term outcomes of percutaneous mitral balloon valvuloplasty (PMV). PMV is the first-line treatment for patients with symptomatic mitral stenosis. However, long-term results in large series of patients from Europe and the United States have been found less favorable than those from Asia and South America involving younger patients. Six hundred ten patients who underwent 626 PMV procedures were prospectively followed for 6.1 +/- 4.10 years using clinical and echocardiographic evaluation. Patients were divided in quartiles according to age: < or =41 years (n = 163), 42 to 53 years (n = 163), 54 to 63 years (n = 142), and >63 years (n = 158). The success of PMV was defined as valve area > or =1.5 cm(2) without severe regurgitation; restenosis was defined as a loss > or =50% of initial gain, with a valve area of <1.5 cm(2). PMV success was significantly more prevalent in younger patients: 95.7% in group 1, 91.4% in group 2, 86.4% in group 3, and 83.4% in group 4 (p = 0.002). No significant differences in complications were found among all age groups, including death, cardiac tamponade, emergency mitral replacement, and any embolic events (p = NS). Event-free survival was greater in younger patients (p <0.0001), but on multivariate analysis, age was not an independent predictor of events (p = NS). Restenosis occurred in 27.9% of patients, throughout all groups (p = NS). In conclusion, PMV may be safely and effectively performed in younger and older patients. Although event-free survival was greater in younger groups, multivariate analysis did not find that age was an independent predictor of events.     

Influence of transmurality, infarct size, and severe microvascular obstruction on left ventricular remodeling and function after primary coronary angioplasty

Infarct size has been considered an established marker of left ventricular (LV) remodeling. We assessed the predictive value of myocardial/microvascular injury assessed by delayed enhanced magnetic resonance imaging (MRI) on LV remodeling and LV ejection fraction after primary coronary intervention (PCI) compared with peak troponin levels, an established index of myocardial infarct size. We performed MRI in 76 patients with first acute myocardial infarction 6 +/- 2 days after successful PCI. Necrosis was judged as transmural when delayed enhancement was extended to >or=75% of LV segment thickness. Severe microvascular obstruction was identified as areas of late hypoenhancement surrounded by delayed enhancement. Infarct size was expressed as an index by dividing the total percentage of delayed enhancement involvement by the number of LV segments. LV end-diastolic volume index and function were quantified by 2-dimensional echocardiography at 6 +/- 1 months after acute myocardial infarction. Remodeling was evaluated as a change in LV end-diastolic volume index at follow-up compared with baseline. At univariate analyses, transmural necrosis, severe microvascular obstruction, infarct size, and troponin level were correlated directly with remodeling and inversely with LV function at follow-up (p <0.001). At multiple regression, only transmural necrosis and troponin level remained independent predictors of LV remodeling and function. With respect to troponin, transmural necrosis improved the predictive power of LV remodeling (R2 for change = 0.19) and function (R2 for change = 0.16). In conclusion, in patients with acute myocardial infarction undergoing PCI, the amount of transmural necrosis as assessed by MRI is a major determinant of LV remodeling and function, with significant additional predictive value to infarct size and severe microvascular obstruction.     

Partial surgical removal of growth hormone-secreting pituitary tumors enhances the response to somatostatin analogs in acromegaly

CONTEXT: Surgery is a cornerstone in the treatment of acromegaly, but its efficacy in large, invasive tumors is scant. OBJECTIVE: The objective of this study was to investigate whether partial surgical removal of GH-secreting pituitary tumors enhances the response rate to somatostatin analogs (SSA; sc octreotide, slow-release octreotide, and lanreotide). DESIGN: This was a multicenter, open, retrospective study. SETTING: The study was performed at university hospitals. SUBJECTS AND METHODS: Eighty-six patients (42 women and 44 men; age, 42 +/- 14 yr) with acromegaly were studied. INTERVENTIONS: Patients underwent two courses of octreotide, lanreotide, or slow-release octreotide treatments before and after surgery of at least 6 months. MAIN OUTCOME MEASURE: The main outcome measure was normal IGF-I levels for age. RESULTS: Presurgical SSA treatment significantly decreased GH and IGF-I levels in all patients. GH levels were less than 2.5 microg/liter in 12 patients (14%); IGF-I levels normalized in nine (10%). After surgery, GH and IGF-I levels further decreased in all patients; tumor removal was greater than 75% in 50 (58%), 50.1-75% in 21 (24%), 25.1-50% in 10 (12%), and less than 25% in five patients (6%). Preoperatively, pituitary function was impaired in 12 patients (14%). Postsurgical SSA treatment lowered GH levels to less than 2.5 microg/liter in 49 (56%) and normalized IGF-I levels in 48 patients (55%). The success rate was significantly increased compared with that before surgery (P < 0.0001). GH (r = -0.48; P < 0.0001) and IGF-I levels (r = -0.38; P = 0.0003) after postsurgery SSA treatment correlated with the amount of tumor surgically removed. After surgery, pituitary function was impaired in 28 patients (32.6%) and was improved in 12 patients (13.9%). The cumulative prevalence of pituitary deficiency did not change during the study (normal function from 40 to 42%; deficiency from 60 to 58%). CONCLUSIONS: Surgical tumor removal (>75%) enhances the response to SSAs without impairing pituitary function. Our data indicate that surgical debulking has a significant place in the treatment algorithm of acromegaly.     

Primary treatment of acromegaly with octreotide LAR: a long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage

CONTEXT: Neurosurgery is regarded as the first-line treatment of acromegaly. Because of its low cure rate in macro and invasive adenoma, the role of primary medical treatment is debated. OBJECTIVE: Our objective was to evaluate primary pharmacological treatment in acromegaly. DESIGN AND SETTING: We conducted an open prospective study at two Italian tertiary level centers. PATIENTS: We studied 67 consecutive patients (36 women; age, 54.9 +/- 14.2 yr; 72% bearing macroadenoma). Intervention: Individually tailored octreotide LAR (OCLAR) was administered. MAIN OUTCOME MEASURES: Outcomes included safe GH (<2.5 mug/liter), normal age-matched IGF-I levels, and tumor shrinkage. RESULTS: After a median follow-up of 48 months (range, 6-108 months), safe GH levels and normal age-matched IGF-I values were obtained by 68.7 and 70.1% of patients, respectively. Hormonal endpoints were achieved regardless of basal levels, and early results were predictive of outcome. Tumor shrank in 82.1% of patients by 62 +/- 31% (range, 0-100%), decreasing from 2101 +/- 2912 to 1010 +/- 2196 mm(3) (P < 0.0001). The higher the basal GH values and the greater the GH/IGF-I changes on treatment, the greater the tumor shrinkage. Tumor disappeared in three patients and was progressively reduced to empty sella in five patients; apparent magnetic resonance imaging cavernous sinus invasion disappeared in three. In males, testosterone increased, restoring eugonadism in 64% of hypogonadal patients. CONCLUSIONS: The efficacy on GH/IGF-I levels in unselected patients and the outstanding volumetric control indicate that treatment with OCLAR may be the first therapeutic approach to all acromegalic patients not amenable to surgical cure. Tumor shrinkage might also encourage the evaluation of primary OCLAR adoption in patients with initial visual field defects.     

Stent explantation from an arteriovenous fistula for hemodialysis: a case report

Percutaneous transluminal angioplasty is the first treatment of a dysfunctional vascular access for hemodialysis. A case of stenting of a native arteriovenous hemodialysis fistula is reported that was treated with a stent placement at the anastomosis level, with explantation of the stent after complete thrombosis of the fistula 48 hours after the procedure. It is preferable to treat arteriovenous fistulas with simple balloon dilatation, avoiding stenting of the fistula, especially in the anastomosis site.     

Functional dyspepsia and depression as an associated factor

AIM: To assess the association between depression and functional dyspepsia. PATIENTS AND METHODS: Three hundred and forty eight dyspeptic patients were included in a cross-sectional study in the gastroenterology outpatient clinic of a University Hospital in southern Brazil (Pelotas, RS) within a 1-year period (from March, 2001 to March, 2002). The assessment of depression occurred after the diagnosis of dyspepsia. The presence (or not) of depression was verified in both functional and organic dyspeptic patients. In a second moment, the results were compared, an univariate analysis was used to describe the frequencies of the interest variables and a chi-square for the comparison between proportions of the categorical variables. The logistic regression technique was used to establish the odd of functional dyspeptic patients to present depression and to control the effect of other variables in the outcome variable RESULTS: Showed greater prevalence of depression among functional dyspepsia patients (30,4%), when compared to organic dyspepsia patients (11,2%). Women showed greater risk to present functional dyspepsia (OR: 1,74, IC 95%, 1,05-2,89) and in terms of age, the group with ages between 31 to 50 years (OR: 0,28 IC 95%, 0,13-0,54) and 51 to 60 years (OR: 0,41, IC 95%, 0,17-0,96) showed protection effect (subjects within this age groups have minor risk to present functional dyspepsia). After the multivariate analysis depressed patients showed three times greater comorbidity with functional dyspepsia when compared to non-depressed patients (OR 3, 13; IC 95%; 1, 71-5, 74). DISCUSSION: The adjustment for the gender, age and marital status variables confirmed the association between functional dyspepsia and depression. Results point the need to assess the presence of depression in functional dyspepsia patients and to establish specific treatment strategies for these patients.     

A recombinant probiotic for treatment and prevention of cholera

BACKGROUND & AIMS: We have developed a therapeutic strategy based on molecular mimicry of host receptors for bacterial toxins on the surface of harmless gut bacteria. In the present study, this has been applied to the development of a recombinant probiotic for treatment and prevention of cholera, caused by Vibrio cholerae. METHODS: We expressed glycosyltransferase genes from Neisseria gonorrhoeae and Campylobacter jejuni in a harmless Escherichia coli strain, resulting in production of a chimeric lipopolysaccharide terminating in a mimic of the ganglioside GM(1). RESULTS: The recombinant bacterium was capable of binding cholera toxin, a sine qua non of virulence, with high avidity; when tested with purified cholera toxin, it was capable of adsorbing >5% of its own weight of toxin in vitro. Administration of the GM(1)-expressing probiotic also protected infant mice against challenge with virulent V cholerae, even when treatment was delayed until after establishment of infection. When treatment commenced 1 hour after challenge, 12 of 12 mice given the probiotic survived, compared with only 1 of 12 for control mice (P < .00001). CONCLUSIONS: Toxin-binding probiotics such as that described here have considerable potential for prophylaxis and treatment of cholera in humans.