Effective cryoablation of a lateral accessory pathway within the distal coronary sinus

Limited information is available on the efficacy of cryoablation in the coronary venous system in humans. A patient with a lateral accessory pathway was referred to our center after several unsuccessful endocardial and epicardial (within the coronary sinus) attempts using standard radiofrequency energy. Ablation was subsequently performed successfully by applying cryoenergy distally into the coronary sinus, using a temperature of -50 degrees C and a freezing application time of 45 s. There were no complications. Angiography of the left coronary circumflex artery and coronary venous system was performed at 12 months follow-up using cardiac multislice computed tomography, and no coronary stenosis or anatomic anomaly was found. Neither pre-excitation or any arrhythmia recurred during follow-up. This experience suggests that ablating in the distal coronary sinus can be safely performed using cryoenergy.     

Predictors and Clinical Impact of Prosthesis-Patient Mismatch After Self-Expandable TAVR in Small Annuli

ObjectivesThe aim of this study was to define predictors of prosthesis-patient mismatch (PPM) and its impact on mortality after transcatheter aortic valve replacement (TAVR) with self-expandable valves (SEVs) in patients with small annuli.BackgroundTAVR seems to reduce the risk for PPM compared with surgical aortic valve replacement, especially in patients with small aortic annuli. Nevertheless, predictors and impact of PPM in this population have not been clarified yet.MethodsPredictors of PPM and all-cause mortality were investigated using multivariable logistic regression analysis from the cohort of the TAVI-SMALL (International Multicenter Registry to Evaluate the Performance of Self-Expandable Valves in Small Aortic Annuli) registry, which included patients with severe aortic stenosis and small annuli (annular perimeter <72 mm or area <400 mm² on computed tomography) treated with transcatheter SEVs: 445 patients with (n = 129) and without (n = 316) PPM were enrolled.ResultsIntra-annular valves conferred increased risk for PPM (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.16 to 4.81), while post-dilation (OR: 0.46; 95% CI: 0.25–0.84) and valve oversizing (OR: 0.53; 95% CI: 0.28–1.00) seemed to protect against PPM occurrence. At a median follow-up of 354 days, patients with severe PPM, but not those with moderate PPM, had a higher all-cause mortality rate compared with those without PPM (log-rank p = 0.008). Multivariable Cox regression confirmed severe PPM as an independent predictor of all-cause mortality (hazard ratio: 4.27; 95% CI: 1.34 to 13.6).ConclusionsAmong patients with aortic stenosis and small aortic annuli undergoing transcatheter SEV implantation, use of intra-annular valves yielded higher risk for PPM; conversely, post-dilation and valve oversizing protected against PPM occurrence. Severe PPM was independently associated with all-cause mortality.     

Inflammatory carcinoma of the breast. Clinical review and summary of the Vanderbilt experience with multi-modality therapy

Inflammatory breast cancer is a distinct clinicopathologic entity that accounts for 1 percent of all cases of breast cancer. The diagnosis should be strongly suspected on the basis of the distinctive clinical findings, which include edema of the breast, inflammation, wheals, and a typical reddish-purple color of the overlying skin. Pathologic examination usually shows infiltration of the dermal lymphatics with carcinoma. Evidence of distant metastatic spread is more frequent than with other types of breast cancer and is seen in approximately 30 percent of patients. The five-year disease-free survival rate is less than 5 percent when local therapy alone (mastectomy and/or local radiotherapy) is used. The addition of combination chemotherapy to high-dose local radiotherapy has improved the five-year survival rate to approximately 30 percent. The potential for long-term survival is limited to the subgroup of patients with only local-regional disease at the time of diagnosis. Patients with inflammatory breast cancer should be treated with combined-modality therapy using combination chemotherapy and high-dose radiotherapy to the breast, since this approach is potentially curative. The fatalism formerly associated with this diagnosis is no longer warranted, particularly in patients with local-regional disease. Failure to employ intensive combined-modality treatment will deny some patients a chance for long-term survival.     

Cardiac damage in hypertensive patients with inverse white coat hypertension. Hospitalet study

BACKGROUND: Few studies have assessed the relationship between ambulatory blood pressure (BP) and cardiac damage in essential hypertensive patients with inverse white coat hypertension (IWCH). OBJECTIVES: To determine the frequency of IWCH in untreated grade 1-2 hypertension and to assess possible differences in cardiac damage among patients with IWCH, white coat hypertension (WCH) and the rest of patients with grade 1-2 hypertension. PATIENTS AND METHODS: Two hundred and eleven patients with grade 1-2 hypertension were sequentially included. A good quality 24-h ambulatory BP monitoring was obtained in 204 patients (age: 41 +/- 12 years, 56% males). IWCH was defined as a daytime systolic and/or diastolic BP higher than diagnostic office systolic and/or diastolic BP, respectively. WCH was defined as a daytime BP < 135/85 mmHg. A good quality echocardiogram was obtained in 174 patients. We considered left ventricular hypertrophy a left ventricular mass index (LVMI) > or = 125 g/m2. RESULTS: We found IWCH in 29 subjects (14%), and WCH in 68 (33%). Office BP in patients with IWCH was in an intermediate position between WCH and the rest of grade 1-2 hypertension patients. The IWCH patients showed 24-h, daytime and night-time BP higher than the other groups. Left ventricular mass was significantly greater in patients with IWCH than in the other grade 1-2 hypertension patients after adjusting for age, gender, body mass index, smoking and office BP (regression coefficient 28.14, 95%CI: 7.36-48.91). CONCLUSION: IWCH is independently associated with higher values of left ventricular mass in patients with grade 1-2 hypertension.     

Urinary incontinence in the elderly: relation to cognitive and motor function

Urinary incontinence is a common problem in older subjects, very often wrongfully accepted as a normal part of the aging process. A total of 520 subjects (208 males and 312 females; mean age 74.8 +/- 11.8 years), from both private- and nursing-home dwelling populations, were included in this study aimed to estimate the incidence of urinary incontinence and identify factors associated with condition, in aged subjects. The incidence and type of urinary incontinence (stress, urge or mixed incontinence) were assessed by structured questionnaires and diagnosis was confirmed by a seven-day consecutive voiding diary. Assessment of physical, cognitive and emotional functions was performed on each subject using the Mini Mental State Examination (MMSE), Instrumental Activities of Daily Living Scale (IADL), Tinetti Scale (gait), Tinetti Scale (balance) and Geriatric Depression Scale (GDS) instruments. In the total population sample the incidence of urinary incontinence was 47.9%. The incontinence cases were classified, according to the different types, as: stress incontinence (males: 3.4%; females: 8.7%; males+females: 6.5%); urge incontinence (males: 27.4%; females: 31.4%; males+females: 29.8%); mixed incontinence (males: 20.2%; females: 5.8%; males+females: 11.5%). In the total population sample, no significant relationship was found between age and prevalence of urinary incontinence. In the elderly female group, age significantly correlated in a direct manner with urge incontinence (P<0.01) and inversely with stress incontinence (P<0.001). Only in the male sex group age significantly correlated with mixed incontinence (P<0.005). Multiple linear regression analysis showed that the dependent variable 'incontinence' could be predicted by MMSE (P<0.001) in the male sex group and by the Tinetti Scale (gait) (P<0.001) in the female sex group.     

Chromogranin 'A' in normal subjects,essential hypertensives and adrenalectomized patients

OBJECTIVE: Chromogranin A (CgA) is an acidic glycoprotein co-stored in vesicles and co-released with catecholamines. Although currently used as a humoral marker of endocrine tumours, several aspects of CgA secretion still need to be clarified in humans. PATIENTS: Fifty-four controls, 83 essential hypertensive and six adrenalectomized patients were studied. DESIGN: In the controls and hypertensive patients, CgA and catecholamines were measured before (supine position) and after changes in posture (2' upright position), insulin-induced hypoglycaemia (0.15 IU/kg i.v.) and glucagon injection (1 mg i.v.). In addition, blood samples were taken in the morning (0800 h) and in the afternoon (1800 h), and every 5 h for 24 h. In the adrenalectomized patients, blood samples were obtained in the morning and in the afternoon. MEASUREMENTS: CgA was measured by an immunoradiometric assay, and noradrenaline and adrenaline by high-performance liquid chromatography. RESULTS: In controls, posture slightly increased plasma catecholamines without affecting CgA levels. Hypoglycaemia evoked a rise in noradrenaline (P < 0.04), adrenaline (P < 0.01) and CgA (79.6 +/- 11.8 vs. 46.1 +/- 10.1 microg/l, P < 0.03). Glucagon injection increased plasma adrenaline (P < 0.01) but not noradrenaline or CgA levels. At variance with blood pressure and catecholamines, CgA increased significantly in the afternoon (51.1 +/- 4.0 vs. 45.0 +/- 3.9 microg/l, P < 0.05); it also had a circadian rhythm, with peak values during the night (at 2300 h, 65.4 +/- 9.0 microg/l) and a nadir in the morning (at 0800 h, 43.1 +/- 6.6 microg/l). In hypertensives, basal and stimulated CgA levels as well as diurnal/circadian variations of this peptide were similar to those in normal subjects. In adrenalectomized patients plasma CgA in the morning (34.3 +/- 6.5 microg/l) was lower (P < 0.03) than in all controls and hypertensives studied, but also showed an afternoon increment (46.4 +/- 6.6 microg/l, P < 0.003). No correlation was found between CgA and catecholamines or blood pressure in all subjects or in the subgroups. CONCLUSIONS: In normal humans, chromogranin A and catecholamines are not always co-secreted, and co-secretion occurs only for marked exocytotic adrenergic stimuli, such as hypoglycaemic stress. In addition, chromogranin A has a circadian rhythm unrelated to plasma catecholamines. Basal plasma concentrations and the secretory pattern of chromogranin A in hypertensives do not differ from the findings in controls. Finally, the adrenal glands contribute partially to circulating chromogranin A and are not involved in the circadian rhythm of this peptide in humans.     

Step‐down approach using either cyclosporin A or methotrexate as maintenance therapy in early rheumatoid arthritis

Objective

To evaluate the feasibility and outcome of the step‐down approach using either cyclosporin A (CSA) or methotrexate (MTX) as maintenance therapy following 6 months treatment with these 2 agents in combination in early, nonerosive rheumatoid arthritis (RA).

Methods

Fifty‐seven patients younger than 65 years with early, nonerosive RA were first treated with CSA and MTX in combination for 6 months. They were then randomly stepped down to single‐agent maintenance treatment for another 18 months. Safety, clinical efficacy, survival on treatment, and radiographic progression were evaluated.

Results

When being treated with combination therapy, 7 of the 57 patients (12.3%) withdrew because of adverse events. Of the remaining 50 patients, 42 (84.0%) were American College of Rheumatology (ACR) 20% responders, 30 (60.0%) were ACR 50% responders, and 23 (46.0%) were ACR 70% responders. At month 6, 22 patients were randomized to CSA and 27 to MTX. During this trial period, the treatment was discontinued by 16 patients taking CSA (mainly because of loss of efficacy) and by 4 taking MTX. At month 24, the probability (± SEM) of survival on treatment was 0.273 ± 0.09 for CSA and 0.852 ± 0.07 for MTX. Of the 6 CSA patients who completed the trial, 4 (66.7%) were ACR 20% responders, and 3 (50%) were both ACR 50% and ACR 70% responders. Of the 23 completers in the MTX arm, 21 (91.3%) were ACR 20% responders, 18 (78.3%) were ACR 50%, and 10 (43.5%) were ACR 70% responders. The treatment was not responsible for severe adverse events. Radiography showed a slow progression in the damage score and number of eroded joints in both treatment groups.

Conclusion

Stepping down to single agent maintenance therapy following 6 months of combination treatment with CSA and MTX in early RA was only successful with MTX. Because this treatment did not prevent some radiographic progression, other approaches (e.g., step‐up approach) may be more appropriate in early RA.

     

Cuidados paliativos en la enfermedad pulmonar intersticial difusa: resultados de una encuesta de ámbito nacional

Introduction

Interstitial lung diseases (ILD) and, in particular, idiopathic pulmonary fibrosis, may have a significant impact on patient survival. Recent studies highlight the need for palliative care (PC) in the management of ILD patients. The aim of this study was to determine the current situation of PC in patients in Spain.

Toward the development of a test for growth hormone (GH) abuse: a study of extreme physiological ranges of GH-dependent markers in 813 elite athletes in the postcompetition setting

There is a need to develop a test to detect GH abuse by elite athletes. Measured levels of GH in blood or urine, however, provide little information on the GH-IGF-I axis. Previous studies have identified a series of indirect markers of GH action that are markedly altered by the administration of GH, but to a lesser degree by acute exercise. This study was undertaken to determine the physiological range of these GH-dependent variables in elite athletes after a competitive event to determine whether such values differ from resting values in normal and athletic subjects and to establish whether any adjustments to this range are required on the basis of age, gender, demographic characteristics, or the nature of the exercise performed. Serum samples were collected from 813 elite athletes (537 males and 276 females; age range, 17-64 yr) from 15 sporting disciplines within 2 h of completion of a major competitive event. IGF-I, IGF-binding protein 2 (IGFBP-2), IGFBP-3, acid-labile subunit, and the bone and soft tissue markers, osteocalcin, carboxyl-terminal propeptide of type I procollagen, carboxyl-terminal cross-linked telopeptide of type I collagen, and procollagen type III were measured. Sporting category, gender, age, height, weight, body mass index (BMI), and racial group of the athlete were documented, and results were compared both to normative data and to values obtained from elite athletes under resting conditions. Forty-one percent of IGF-I values in male athletes and 41% of values in female athletes were above the upper limits of 99% reference ranges derived from resting values in a normal population. Postcompetition levels of all variables except carboxyl-terminal propeptide of type I procollagen and carboxyl-terminal cross-linked telopeptide of type I collagen differed from resting values. There was a consistent age-dependent fall in measured levels of all variables (P < 0.0001) with the exception of IGFBP-2, which increased with age (P < 0.0001). BMI, but not height, exerted a small, but significant, influence on several variables. After adjustment for age, there were no significant differences in the levels of any of the measured variables between sporting categories. IGFBP-2 and IGFBP-3 were lower in 35 black athletes compared with those in 35 white athletes matched for age, gender, height, BMI, and sporting category. We have demonstrated that there are predictable age-dependent levels of GH-dependent markers in elite athletes that are consistent even at the extremes of physical exertion and that these are independent of sporting category. Normative data applicable to white athletes are provided. This provides important groundwork for the development of a test for GH abuse, although these values may be specific for the reagents and assays used.