Heart transplantation experiences: a phenomenological approach

Aim. The aim of this study was to understand the heart transplantation experience based on patients` descriptions. Background. To patients with heart failure, heart transplantation represents a possibility to survive and improve their quality of life. Studies have shown that more quality of life is related to patients` increasing awareness and participation in the work of the healthcare team in the post-transplantation period. Deficient relationships between patients and healthcare providers result in lower compliance with the postoperative regimen. Method. A phenomenological approach was used to interview 26 patients who were heart transplant recipients. Patients were interviewed individually and asked this single question: What does the experience of being heart transplanted mean? Participants` descriptions were analysed using phenomenological reduction, analysis and interpretation. Results. Three categories emerged from data analysis: (i) the time lived by the heart recipient; (ii) donors, family and caregivers and (iii) reflections on the experience lived. Living after heart transplant means living in a complex situation: recipients are confronted with lifelong immunosuppressive therapy associated with many side-effects. Some felt healthy whereas others reported persistence of complications as well as the onset of other pathologies. However, all participants celebrated an improvement in quality of life. Health caregivers, their social and family support had been essential for their struggle. Participants realised that life after heart transplantation was a continuing process demanding support and structured follow-up for the rest of their lives. Conclusion. The findings suggest that each individual has unique experiences of the heart transplantation process. To go on living participants had to accept changes and adapt: to the organ change, to complications resulting from rejection of the organ, to lots of pills and food restrictions. Relevance to clinical practice. Stimulating a heart transplant patients spontaneous expression about what they are experiencing and granting them the actual status of the main character in their own story is important to their care.

Continuous positive airway pressure increases inspiratory capacity of COPD patients

Background and objective: Hyperinflation with a decrease in inspiratory capacity (IC) is a common presentation for both unstable and stable COPD patients. As CPAP can reduce inspiratory load, possibly secondary to a reduction in hyperinflation, this study examined whether CPAP would increase IC in stable COPD patients. Methods: Twenty-one stable COPD patients (nine emphysema, 12 chronic bronchitis) received a trial of CPAP for 5 min at 4, 7 and 11 cmH(2)O. Fast and slow VC (SVC) were measured before and after each CPAP trial. In patients in whom all three CPAP levels resulted in a decreased IC, an additional trial of CPAP at 2 cmH(2)O was conducted. For each patient, a `best CPAP` level was defined as the one associated with the greatest IC. This pressure was then applied for an additional 10 min followed by spirometry. Results: Following application of the `best CPAP`, the IC and SVC increased in 15 patients (nine emphysema, six chronic bronchitis). The mean change in IC was 159 mL (95% CI: 80-237 mL) and the mean change in SVC was 240 mL (95% CI: 97-386 mL). Among these patients, those with emphysema demonstrated a mean increase in IC of 216 mL (95% CI: 94-337 mL). Six patients (all with chronic bronchitis) did not demonstrate any improvement in IC. Conclusions: The best individualized CPAP can increase inspiratory capacity in patients with stable COPD, especially in those with emphysema.

Double-blind, Randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: Results from EFECT

Purpose The third-generation nonsteroidal aromatase inhibitors (AIs) are increasingly used as adjuvant and first-line advanced therapy for postmenopausal, hormone receptor-positive (HR +) breast cancer. Because many patients subsequently experience progression or relapse, it is important to identify agents with efficacy after AI failure. Materials and Methods Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) is a randomized, double-blind, placebo controlled, multicenter phase III trial of fulvestrant versus exemestane in postmenopausal women with HR + advanced breast cancer (ABC) progressing or recurring after nonsteroidal AI. The primary end point was time to progression (TTP). A fulvestrant loading-dose (LD) regimen was used: 500 mg intramuscularly on day 0, 250 mg on days 14, 28, and 250 mg every 28 days thereafter. Exemestane 25 mg orally was administered once daily. Results A total of 693 women were randomly assigned to fulvestrant (n = 351) or exemestane ( n = 342). Approximately 60% of patients had received at least two prior endocrine therapies. Median TTP was 3.7 months in both groups ( hazard ratio = 0.963; 95% CI, 0.819 to 1.133; P = .6531). The overall response rate ( 7.4% v 6.7%; P = .736) and clinical benefit rate ( 32.2% v 31.5%; P = .853) were similar between fulvestrant and exemestane respectively. Median duration of clinical benefit was 9.3 and 8.3 months, respectively. Both treatments were well tolerated, with no significant differences in the incidence of adverse events or quality of life. Pharmacokinetic data confirm that steady-state was reached within 1 month with the LD schedule of fulvestrant. Conclusion Fulvestrant LD and exemestane are equally active and well-tolerated in a meaningful proportion of postmenopausal women with ABC who have experienced progression or recurrence during treatment with a nonsteroidal AI.

Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial

Background Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant (HERA) trial. Methods The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant, adjuvant chemotherapy, or both in patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. After a positive first interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation, event-free patients in the observation group were allowed to cross over to receive trastuzumab. We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48.4 months (IQR 42.0-56.5) and assess the effect of the extensive crossover to trastuzumab. Our analysis was by intention-to-treat. The HERA trial is registered with the European Clinical Trials Database, number 2005-002385-11. Findings The HERA trial population comprised 1698 patients randomly assigned to the observation group and 1703 to the 1-year trastuzumab group. Intention-to-treat analysis of disease-free survival showed a significant benefit in favour of patients in the 1-year trastuzumab group (4-year disease-free survival 78.6%) compared with the observation group (4-year disease-free survival 72.2%; hazard ratio [HR] 0.76; 95% CI 0.66-0.87; p<0.0001). Intention-to-treat analysis of overall survival showed no significant difference in the risk of death (4-year overall survival 89.3% vs 87.7%, respectively; HR 0.85; 95% CI 0.70-1.04; p=0.11). Overall, 885 patients (52%) of the 1698 patients in the observation group crossed over to receive trastuzumab, and began treatment at median 22.8 months (range 4.5-52.7) from randomisation. In a non-randomised comparison, patients in the selective-crossover cohort had fewer disease-free survival events than patients remaining in the observation group (adjusted HR 0.68; 95% CI 0.51-0.90; p=0.0077). Higher incidences of grade 3-4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group. The most common grade 3 or 4 adverse events, each in less than 1% of patients, were congestive cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhoea. Interpretation Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with significant clinical benefit at 4-year median follow-up. The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort.

Entecavir Treatment for up to 5 Years in Patients with Hepatitis B e Antigen-Positive Chronic Hepatitis B

Sustained virologic suppression is a primary goal of therapy for chronic hepatitis B (CHB). In study entecavir (ETV)-022, 48 weeks of entecavir 0.5 mg was superior to lamivudine for virologic suppression for hepatitis B e antigen (HBeAg)-positive CHB. A total of 183 entecavir-treated patients from ETV-022 subsequently enrolled in study ETV-901. We present the results after up to 5 years (240 weeks) of continuous entecavir therapy. The entecavir long-term cohort consists of patients who received >= 1 year of entecavir 0.5 mg in ETV-022 and then entered ETV-901 with a treatment gap <= 35 days. In ETV-901 the entecavir dose was 1.0 mg daily. For patients with samples available at Year 5, proportions with hepatitis B virus (HBV) DNA <300 copies/mL, normal alanine aminotransferase (ALT) levels, HBeAg loss, and HBeAg seroconversion were determined. In all, 146 patients met criteria for inclusion in the entecavir long-term cohort. At Year 5, 94% (88/94) had HBV DNA <300 copies/mL and 80% (78/98) had normal ALT levels. In addition to patients who achieved serologic responses during study ETV-022, 23% (33/141) achieved HBeAg seroconversion and 1.4% (2/145) lost hepatitis B surface antigen (HBsAg) during study ETV-901. Through 5 years, entecavir resistance emerged in one patient. The safety profile of entecavir was consistent with previous reports. Conclusion: Extended therapy with entecavir through 5 years maintained or increased rates of HBV DNA suppression and ALT normalization. Additional patients also achieved HBeAg loss and seroconversion. Entecavir provides sustained viral suppression with minimal resistance during long-term treatment of HBeAg-positive CHB. (HEPATOLOGY 2010;51:422-430.)

Major histocompatibility complex (MHC) class II-positive dendritic cells in the rat iris - In situ development from MHC class II-negative precursors

Purpose. To examine the postnatal development of major histocompatibility complex (MHC) class II-positive dendritic cells (DC) in the iris of the normal rat eye. Methods. Single-and double-color immunomorphologic studies were performed on whole mounts prepared from rat iris taken at selected postnatal ages (2 to 3 days to 78 weeks). Immunopositive cells were enumerated, using a quantitative light microscope, and MHC class II expression on individual cells was assessed by microdensitometric analysis. Results. Major histocompatibility class II-positive DCs in the iris developed in an age-dependent manner and reached adult-equivalent density and structure at approximately 10 weeks of age, considerably later than previously described in other DC populations in the rat. In contrast, the anti-rat DC monoclonal antibody OX62 revealed a population of cells present at adult-equivalent levels as early as 3 weeks after birth. Dual-color immunostaining and microdensitometric analysis demonstrated that during postnatal growth, development of the network of MHC class II-positive DCs was a consequence of the progressive increase in expression of MHC class II antigen by OX62-positive cells. Conclusions. During postnatal growth, the DC population of the iris develops initially as an OX62-positive-MHC class II-negative population, which then develops increasing MHC class II expression in situ and finally resembles classic DC populations in other tissue sites. Maturation of the iris DC population is temporally delayed compared with time to maturation in other tissue sites in the rat.

Acute increase in urinary 6-sulfatoximelatonin after clomipramine, as a predictive measure for emotional improvement

Nocturnal melatonin pineal output is triggered by sympathetic outflow. Antidepressants that block norepinephrine neuronal uptake should increase pineal function. This can be monitored by measuring 6-sulfatoximelatonin (aMT6s), the main melatonin metabolite, in the urine. In this study, we compared the excretion of aMT6s before (baseline), one, and 21 days after administration of clomipramine to healthy subjects (n = 32). At the end of treatment, subjects were divided into responders (n = 12) and non-responders (n = 20) according to the improvement in their emotional state in three out of four domains (interpersonal tolerance, efficiency, well-being and feeling different from the usual self). There was no difference in aMT6s before clomipramine between responders and non-responders in any of the time intervals analysed (06:00-12:00, 12:00-18:00, 18:00-24:00 and 24:00-06:00 hours). At day one, but not at day 21, the fraction of aMT6s excreted during the time interval 24:00-06:00, relative to the total amount excreted by each subject per day, was significantly higher (P = 0.0287) than baseline (0.57 +/- 0.04) in responders. No significant difference was observed in non-responders. The increase in pineal function induced by clomipramine was restricted to day one, indicating that long-lasting adaptation restores pineal function. In addition, the day one increase in aMT6s was significantly increased only in the responders group, raising the possibility that the blocking of neuronal uptake is predictive of emotional improvement.

Pulmonary lesion induced by low and high positive end-expiratory pressure levels during protective ventilation in experimental acute lung injury

Objective: To investigate the effects of low and high levels of positive end-expiratory pressure (PEEP), without recruitment maneuvers, during lung protective ventilation in an experimental model of acute lung injury (ALI). Design: Prospective, randomized, and controlled experimental study. Setting: University research laboratory. Subjects: Wistar rats were randomly assigned to control (C) [saline (0.1 ml), intraperitoneally] and ALI [paraquat (15 mg/kg), intra peritoneally] groups. Measurements and Main Results: After 24 hours, each group was further randomized into four groups (six rats each) at different PEEP levels = 1.5, 3, 4.5, or 6 cm H(2)O and ventilated with a constant tidal volume (6 mL/kg) and open thorax. Lung mechanics [static elastance (Est, L) and viscoelastic pressure (Delta P2, L)] and arterial blood gases were measured before (Pre) and at the end of 1-hour mechanical ventilation (Post). Pulmonary histology (light and electron microscopy) and type III procollagen (PCIII) messenger RNA (mRNA) expression were measured after 1 hour of mechanical ventilation. In ALI group, low and high PEEP levels induced a greater percentage of increase in Est, L (44% and 50%) and Delta P2, L (56% and 36%) in Post values related to Pre. Low PEEP yielded alveolar collapse whereas high PEEP caused overdistension and atelectasis, with both levels worsening oxygenation and increasing PCIII mRNA expression. Conclusions: In the present nonrecruited ALI model, protective mechanical ventilation with lower and higher PEEP levels than required for better oxygenation increased Est, L and Delta P2, L, the amount of atelectasis, and PCIII mRNA expression. PEEP selection titrated for a minimum elastance and maximum oxygenation may prevent lung injury while deviation from these settings may be harmful. (Crit Care Med 2009; 37:1011-1017)

The Effects of Continuous Positive Airway Pressure on Prehypertension and Masked Hypertension in Men With Severe Obstructive Sleep Apnea

Obstructive sleep apnea and hypertension are common conditions that frequently coexist. Continuous positive airway pressure (CPAP) reduces blood pressure in patients with obstructive sleep apnea and sustained hypertension. However, the impact of CPAP on patients with obstructive sleep apnea and prehypertension and masked hypertension, conditions associated with increased cardiovascular risk, is unknown. Thirty-six male patients (age, 43 +/- 7 years; body mass index, 28.8 +/- 3.0 kg/m(2)) with untreated severe obstructive sleep apnea (apnea-hypopnea index, 56 +/- 22 events/hr on polysomnography) with diagnostic criteria for prehypertension and/or masked hypertension, based on office and 24-hour ambulatory blood pressure monitoring, respectively, were studied. The patients randomized to no treatment (control; n=18) or CPAP (n=18) for 3 months had similar frequency of prehypertension and masked hypertension at study entry. There were no significant changes in blood pressure in patients randomized to the control group. In contrast, patients randomized to CPAP presented significant reduction in office systolic (from 126 +/- 5 to 121 +/- 7 mm Hg; P=0.001) and a trend for diastolic blood pressure (from 75 +/- 7 to 73 +/- 8 mm Hg; P=0.08) as well as a significant decrease in daytime and nighttime systolic and diastolic blood pressure (P < 0.05 for each comparison). There was a significant reduction in the frequency of prehypertension (from 94% to 55%; P=0.02) and masked hypertension (from 39% to 5%; P=0.04) only in the CPAP group. In conclusion, effective CPAP therapy promotes significant reduction in the frequency of prehypertension and masked hypertension by promoting significant blood pressure reductions in patients with severe obstructive sleep apnea. (Hypertension. 2011;57[part 2]:549-555.)

Cardiopulmonary Effects of Matching Positive End-Expiratory Pressure to Abdominal Pressure in Concomitant Abdominal Hypertension and Acute Lung Injury

Background: To evaluate the cardiopulmonary effects of positive end-expiratory pressure (PEEP) equalization to intra-abdominal pressure (IAP) in an experimental model of intra-abdominal hypertension (IAH) and acute lung injury (ALI). Methods: Eight anesthetized pigs were submitted to IAH of 20 mm Hg with a carbon dioxide insufflator for 30 minutes and then submitted to lung lavage with saline and Tween (2.5%). Pressure x volume curves of the respiratory system were performed by a low flow method during IAH and ALI, and PEEP was subsequently adjusted to 27 cm center dot H(2)O for 30 minutes. Results: IAH decreases pulmonary and respiratory system static compliances and increases airway resistance, alveolar-arterial oxygen gradient, and respiratory dead space. The presence of concomitant ALI exacerbates these findings. PEEP identical to AP moderately improved oxygenation and respiratory mechanics; however, an important decline in stroke index and right ventricle ejection fraction was observed. Conclusions: Simultaneous IAH and ALI produce important impairments in the respiratory physiology. PEEP equalization to AP may improve the respiratory performance, nevertheless with a secondary hemodynamic derangement.

Predictive Factors for Positive Surgical Margins and Their Locations After Robot-Assisted Laparoscopic Radical Prostatectomy

Background: Positive surgical margin (PSM) after radical prostatectomy (RP) has been shown to be an independent predictive factor for cancer recurrence. Several investigations have correlated clinical and histopathologic findings with surgical margin status after open RP. However, few studies have addressed the predictive factors for PSM after robot-assisted laparoscopic RP (RARP). Objective: We sought to identify predictive factors for PSMs and their locations after RARP. Design, setting, and participants: We prospectively analyzed 876 consecutive patients who underwent RARP from January 2008 to May 2009. Intervention: All patients underwent RARP performed by a single surgeon with previous experience of > 1500 cases. Measurements: Stepwise logistic regression was used to identify potential predictive factors for PSM. Three logistic regression models were built: (1) one using preoperative variables only, (2) another using all variables (preoperative, intraoperative, and postoperative) combined, and (3) one created to identify potential predictive factors for PSM location. Preoperative variables entered into the models included age, body mass index (BMI), prostate-specific antigen, clinical stage, number of positive cores, percentage of positive cores, and American Urological Association symptom score. Intra-and postoperative variables analyzed were type of nerve sparing, presence of median lobe, percentage of tumor in the surgical specimen, gland size, histopathologic findings, pathologic stage, and pathologic Gleason grade. Results and limitations: In the multivariable analysis including preoperative variables, clinical stage was the only independent predictive factor for PSM, with a higher PSM rate for T3 versus T1c (odds ratio [OR]: 10.7; 95% confidence interval [CI], 2.6-43.8) and for T2 versus T1c (OR: 2.9; 95% CI, 1.9-4.6). Considering pre-, intra-, and postoperative variables combined, percentage of tumor, pathologic stage, and pathologic Gleason score were associated with increased risk of PSM in the univariable analysis (p < 0.001 for all variables). However, in the multivariable analysis, pathologic stage (pT2 vs pT1; OR: 2.9; 95% CI, 1.9-4.6) and percentage of tumor in the surgical specimen (OR: 8.7; 95% CI, 2.2-34.5; p = 0.0022) were the only independent predictive factors for PSM. Finally, BMI was shown to be an independent predictive factor(OR: 1.1; 95% CI, 1.0-1.3; p = 0.0119) for apical PSMs, with increasing BMI predicting higher incidence of apex location. Because most of our patients were referred from other centers, the biopsy technique and the number of cores were not standardized in our series. Conclusions: Clinical stage was the only preoperative variable independently associated with PSM after RARP. Pathologic stage and percentage of tumor in the surgical specimen were identified as independent predictive factors for PSMs when analyzing pre-, intra-, and postoperative variables combined. BMI was shown to be an independent predictive factor for apical PSMs. (C) 2010 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Estrogen receptor-positive breast carcinomas in younger women are different from those of older women: A pathological and immunohistochemical study

The higher frequency of triple-negative and HER-2-positive tumors detected in younger patients has been suggested as an explanation for the more aggressive tumor types observed in this age group. However, estrogen receptor (ER)-positive tumors are the most frequent subtype of breast carcinomas identified, even in younger patients. In this retrospective study, the morphological and immunohistochemical profiles of ER-positive breast carcinomas from women 35 yrs and younger that were diagnosed between 1997 and 2007 were evaluated. From these cases, 213 were selected based on the availability of pathology reports and paraffin blocks. For comparison, 117 consecutive cases of breast carcinomas diagnosed in patients >60 yrs from 2006 were included. Paraffin-embedded tumors were stained for expression of ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2). Ki-67 antigen, epidermal growth factor receptor (EGFR), cytokeratin 5/6, p53, vimentin, CD117, and p63 using tissue microarrays. ER-positive carcinomas were diagnosed in 120 (56.1%) samples of the younger patient group and in 92 (78.6%) samples of the older patient group. Of these ER-positive carcinomas, 48 (40%) from the younger patient group presented the subtype luminal A, compared with 53 (57.6%) from the older patient group (p=0.01). Tumors from the younger patient group were also associated with increased vascular involvement, co-expression of HER-2, and decreased expression of CD117. These results highlight differences in expression markers and the pathology of ER-positive tumors detected in younger women, with a notable characteristic being co-expression of HER-2. (C) 2010 Elsevier Ltd. All rights reserved.