Effect of a sequential education and monitoring programme on quality-of-life components in heart failure

Aims Trials of disease management programmes (DMP) in heart failure (HF) have shown controversial results regarding quality of life. We hypothesized that a DMP applied over the long-term could produce different effects on each of the quality-of-life components. Methods and results We extended the prospective, randomized REMADHE Trial, which studied a DMP in HF patients. We analysed changes in Minnesota Living with Heart Failure Questionnaire components in 412 patients, 60.5% male, age 50.2 +/- 11.4 years, left ventricular ejection fraction 34.7 +/- 10.5%. During a mean follow-up of 3.6 +/- 2.2 years, 6.3% of patients underwent heart transplantation and 31.8% died. Global quality-of-life scores improved in the DMP intervention group, compared with controls, respectively: 57.5 +/- 3.1 vs. 52.6 +/- 4.3 at baseline, 32.7 +/- 3.9 vs. 40.2 +/- 6.3 at 6 months, 31.9 +/- 4.3 vs. 41.5 +/- 7.4 at 12 months, 26.8 +/- 3.1 vs. 47.0 +/- 5.3 at the final assessment; P<0.01. Similarly, the physical component (23.7 +/- 1.4 vs. 21.1 +/- 2.2 at baseline, 16.2 +/- 2.9 vs. 18.0 +/- 3.3 at 6 months, 17.3 +/- 2.9 vs. 23.1 +/- 5.7 at 12 months, 11.4 +/- 1.6 vs. 19.9 +/- 2.4 final; P<0.01), the emotional component (13.2 +/- 1.0 vs. 12.1 +/- 1.4 at baseline, 11.7 +/- 2.7 vs. 12.3 +/- 3.1 at 6 months, 12.4 +/- 2.9 vs. 16.8 +/- 5.9 at 12 months, 6.7 +/- 1.0 vs. 10.6 +/- 1.4 final; P<0.01) and the additional questions (20.8 +/- 1.2 vs. 19.3 +/- 1.8 at baseline, 14.3 +/- 2.7 vs. 17.3 +/- 3.1 at 6 months, 12.4 +/- 2.9 vs. 21.0 +/- 5.5 at 12 months, 6.7 +/- 1.4 vs. 17.3 +/- 2.2 final; P<0.01) were better (lower) in the intervention group. The emotional component improved earlier than the others. Post-randomization quality of life was not associated with events. Conclusion Components of the quality-of-life assessment responded differently to DMP. These results indicate the need for individualized DMP strategies in patients with HF. Trial registration information www.clincaltrials.gov NCT00505050-REMADHE.

Conventional Versus Biventricular Pacing in Heart Failure and Bradyarrhythmia: The COMBAT Study

Background: Worsening in clinical and cardiac status has been noted after chronic right ventricular pacing, but it is uncertain whether atriobiventricular (BiVP) is preferable to atrio-right ventricular pacing (RVP). Conventional versus Multisite Pacing for BradyArrhythmia Therapy study (COMBAT) sought to compare BiVP versus RVP in patients with symptomatic heart failure (HF) and atrioventricular (AV) block. Methods and Results: COMBAT is a prospective multicenter randomized double blind crossover study. Patients with New York Heart Association functional class (FC) II-IV, left ventricular ejection fraction (LVEF) <40%, and AV block as an indication for pacing were enrolled. All patients underwent biventricular system implantation and then were randomized to receive successively (group A) RVP-BiVP-RVP, or (group B) BiVP-RVP-BiVP. At the end of each 3-month crossover period, patients were evaluated according to Quality of Life (QoL), FC, echocardiographic parameters, 6-Minute Walk Test (6MWT), and peak oxygen consumption (VO(2max)). Sixty patients were enrolled, and the mean follow-up period was 17.5 +/- 10.7 months. There were significant improvements in QoL, FC, LVEF, and left ventricular end-systolic volume with BiVP compared with RVP. The effects of pacing mode on 6MWT and VO(2max) were not significantly different. Death occurred more frequently with RVP. Conclusion: In patients with systolic HF and AV block requiring permanent ventricular pacing, BiVP is superior to RVP and should be considered the preferred pacing mode. (J Cardiac Fail 2010;16:293-300)

Endoscopic features in a model of multivisceral xenotransplantation

Introduction: Xenotransplantation and multivisceral transplantation are advanced therapeutic methods that still require a scientific basis. There are no experimental models of multivisceral transplantation available, particularly not the monitoring by endoscopy. Here, we describe the endoscopic features in a model of multivisceral xenotransplantation. Methods: The distal esophagus, stomach, intestine, colon, liver, pancreas, and the kidneys with a common vascular pedicle were harvested from rabbits and implanted in swine (group I, n = 9) or in rabbits (group II, n = 4). Endoscopy was performed in the stomach, jejunum, and ascending colon at four consecutive time points (immediate after surgery and 10, 90, and 180 min after reperfusion). Lesions were macroscopically graded as mild, moderate, and severe. Biopsies were taken following sacrifice at 180 min after reperfusion. Results: In group I, the stomach, jejunum, and colon manifested a progression of lesions with predominance of mild lesions after 10 min, mild to moderate lesions after 90 min, and moderate to severe lesions after 180 min. In animals from group II, endoscopy showed normal features at all time points after reperfusion. Histopathologic analysis confirmed the diagnosis of hyperacute rejection in group I. Grafts from group II animals presented normal or mild ischemic/reperfusion injury. Conclusion: All animals subjected to multivisceral xenotransplantation showed a progression of endoscopic lesions with time after transplantation, while animals subjected to allotransplantation showed no aberrations in endoscopy. We conclude that endoscopy is a useful tool in the assessment of hyperacute rejection of a xenograft.

Small Airway Remodeling in Idiopathic Interstitial Pneumonias: A Pathological Study

Background: Few studies have addressed small airway (SA) histopathological changes and their possible role in the remodeling process in idiopathic interstitial pneumonias. Objectives: To study morphological, morphometrical and immunohistochemical features of SA in idiopathic pulmonary fibrosis (usual interstitial pneumonia, UIP) and nonspecific interstitial pneumonia (NSIP). Methods: We analyzed SA pathology in lung biopsies from 29 patients with UIP and 8 with NSIP. Biopsies were compared with lung tissue from 13 patients with constrictive bronchiolitis (CB) as positive controls and 10 normal autopsied control lungs. We semi-quantitatively analyzed SA structure, inflammation, architectural features and the bronchiolar epithelial immunohistochemical expression of TGF-beta, MMP-2, 7, 9, and their tissue inhibitors (TIMP-1, 2). Results: Compared to controls, patients with UIP, NSIP and CB presented increased bronchiolar inflammation, peribronchiolar inflammation and fibrosis and decreased luminal areas. UIP patients had thicker walls due to an increase in most airway compartments. NSIP patients presented increased epithelial areas, whereas patients with CB had larger inner wall areas. All of the groups studied presented increased bronchiolar expression of MMP-7 and MMP-9, compared to the controls. Conclusion: We conclude that SAs are pathologically altered and may take part in the lung-remodeling process in idiopathic interstitial pneumonias. Copyright (C) 2009 S. Karger AG, Basel

Adverse mucocutaneous reactions to chemotherapeutic agents - Part I

The local and systemic treatment of tumors can cause changes in the skin, mucous membranes, hair and nails. Accurate diagnosis and appropriate treatment of side effects require knowledge about the patterns of the most common adverse reactions to drugs the patient may be using. The dermatologist must be familiar with the manifestations of certain soft tissue neoplasms, as well as with the adverse mucocutaneous forms of cancer treatment.

The Incapacity of the Surgeon to Identify NASH in Bariatric Surgery Makes Biopsy Mandatory

Nonalcoholic steatohepatitis (NASH) is a morbid condition highly related to obesity. It is unclear if the macroscopic liver appearance correlates with the histopathologic findings. The goal of this prospective study was to determine the relationship between the intraoperative liver appearance and the histopathologic diagnosis of NASH in morbidly obese subjects undergoing bariatric surgery. We also aimed to determine variables that could predict NASH preoperatively. Consecutive 51 subjects undergoing bariatric surgery without evidence of other liver disease underwent intraoperative liver biopsy. An intraoperative liver visual (macroscopic and tactile examination) was recorded. The liver aspect was compared with the liver histologic findings. Histological assessment was categorized into two groups: NASH and non-NASH (including normal histology and simple steatosis). Clinical and biochemical parameters were obtained from the patient databases and were compared between groups to identify preoperatively predictive factors of NASH. From 51 patients, only one presented totally normal histology. Forty-three (86.2%) presented simple steatosis, and seven (13.7%) were classified as NASH. Clinical parameters were not different between groups. At biochemical analysis, only VLDL cholesterol level was significantly higher in the NASH group (p = 0.037) but yet within the normal range. Association between macroscopic liver appearance and the presence of histological NASH is poor (sensitivity of 14%, specificity of 56%, positive predictive value of 5%, and negative predictive value of 80%). No predictor of NASH was found. Surgeons` evaluation could not identify NASH individuals. Routine liver biopsy during bariatric operations is mandatory to differentiate NASH and nonalcoholic fatty liver disease.

Prevention of Venous Thrombosis by Warfarin after Permanent Transvenous Leads Implantation in High-Risk Patients

Background: The incidence of venous lesions following transvenous cardiac device implantation is high. Previous implantation of temporary leads ipsilateral to the permanent devices, and a depressed left ventricular ejection fraction have been associated with an increased risk of venous lesions, though the effects of preventive strategies remain controversial. This randomized trial examined the effects of warfarin in the prevention of these complications in high-risk patients. Method: Between February 2004 and September 2007, we studied 101 adults who underwent a first cardiac device implantation, and who had a left ventricular ejection fraction <= 0.40, or a temporary pacing system ipsilateral to the permanent implant, or both. After device implantation, the patients were randomly assigned to warfarin to a target international normalized ratio of 2.0-3.5, or to placebo. Clinical and laboratory evaluations were performed regularly up to 6 months postimplant. Venous lesions were detected at 6 months by digital subtraction venography. Results: Venous obstructions of various degrees were observed in 46 of the 92 patients (50.0%) who underwent venography. The frequency of venous obstructions was 60.4% in the placebo, versus 38.6% in the warfarin group (P = 0.018), corresponding to an absolute risk reduction of 22% (relative risk = 0.63; 95% confidence interval = 0.013-0.42). Conclusions: Warfarin prophylaxis lowered the frequency of venous lesions after transvenous devices implantation in high-risk patients. (PACE 2009; 32:S247-S251)

The epidemiology of acute respiratory failure in hospitalized patients: A Brazilian prospective cohort study

Purpose: The purpose of this study was to assess risk factors associated with the development of acute respiratory failure (ARF) and death in a general intensive care unit (ICU). Materials and Methods: Adults who were hospitalized at 12 surgical and nonsurgical ICUs were prospectively followed up. Multivariable analyses were realized to determine the risk factors for ARF and point out the prognostic factors for mortality in these patients. Results: A total of 1732 patients were evaluated, with an ARF prevalence of 57%. Of the 889 patients who were admitted without ARF, 141 (16%) developed this syndrome in the ICU. The independent risk factors for developing ARF were 64 years of age or older, longer time between hospital and ICU admission, unscheduled surgical or clinical reason for ICU admission, and severity of illness. Of the 984 patients with ARF, 475 (48%) died during the ICU stay. Independent prognostic factors for death were age older than 64 years, time between hospital and ICU admission of more than 4 days, history of hematologic malignancy or AIDS, the development of ARF in ICU, acute lung injury, and severity of illness. Conclusions: Acute respiratory failure represents a large percentage of all ICU patients, and the high mortality is related to some preventable factors such as the time to ICU admission. (C) 2011 Elsevier Inc. All rights reserved.

Infectious diseases in paediatric pathology: experience from a developing country

Infectious and parasitic diseases have always challenged man. Although many of them are typically seen in some areas of the world and can be adequately managed by just improving socioeconomic status and sanitary conditions, they are still quite prevalent and may sometimes be seen outside their original geographical areas. Human migration due to different reasons, tourism, blood transfusion and solid organ transplantation has created new concerns for health professionals all over the world. If not for diagnostic purposes, at least these tropical and infectious diseases should be largely known because their epidemiology, pathogenesis, host/parasite interaction, inflammatory and reparative responses are quite interesting and teach us about human biology. Curiosity is inherent to pathology practice and so we are compelled to look for things other than tumours or degenerative diseases. This review focuses on infectious and parasitic diseases found in a developing country and brings up-to-date information on diseases caused by viruses (dengue, yellow fever), bacteria (typhoid fever, leprosy), parasites (Chagas` disease, cutaneous and visceral leishmaniasis, amoebiasis, Capillaria hepatica, schistosomiasis, cysticercosis) and caused by fungi (paracoccidioidomycosis, cryptococcosis, histoplasmosis) that may be useful for pathologists when facing somewhat strange cases from developing countries.

Apoptosis induction by (+)alpha-tocopheryl succinate in the absence or presence of all-trans retinoic acid and arsenic trioxide in NB4, NB4-R2 and primary APL cells

We analyzed the effect of (+)alpha-tocopheryl succinate (alpha-TOS) alone or associated with arsenic trioxide (ATO) or all-trans retinoid acid (ATRA) in acute promyelocytic leukemia (APL). alpha-TOS-induced apoptosis in APL clinical samples and in ATRA-sensitive (NB4) and ATRA-resistant (NB4-R2) APL cell lines. The effective dose 50% (ED-50) was calculated to be 71 and 58 mu M, for NB4 and NB4-R2, respectively. a-TOS neither induced nor modified ATRA-induced differentiation of APL cells, and did not affect the proliferation and differentiation of normal CD34(+) hematopoietic progenitors in methylcellulose assays. alpha-TOS exerted a moderate antagonistic effect to ATO-induced apoptosis when treatment was done simultaneously but when alpha-TOS was added 24 h after ATO, an additive effect was observed. Our results support the concept of alpha-TOS as an anti-leukemic compound which spares normal hematopoiesis. (C) 2008 Elsevier Ltd. All rights reserved.

Antibody-targeted horseradish peroxidase associated with indole-3-acetic acid induces apoptosis in vitro in hematological malignancies

Indole-3-acetic acid (IAA), when oxidized by horseradish peroxidase (HRP), is transformed into cytotoxic molecules capable of inducing cell injury. The aim of this study was to test if, by targeting hematopoietic tumors with HRP-conjugated antibodies in association with IAA treatment, there is induction of apoptosis. We used two lineages of hematologic tumors: NB4, derived from acute promyelocytic leukemia (APL) and Granta-519 from mantle cell lymphoma (MCL). We also tested cells from 12 patients with acute myeloid leukemia (AML) and from 10 patients with chronic lymphocytic leukemia (CLL). HRP targeting was performed with anti-CD33 or anti-CD19 antibodies (depending on the origin of the cell), followed by incubation with goat anti-mouse antibody conjugated with HRP. Eight experimental groups were analyzed: control, HRP targeted, HRP targeted and incubated with 1, 5 and 10 mM IAA, and cells not HRP targeted but incubated with 1, 5 and 10 mM IAA. Apoptosis was analyzed by flow cytometry using annexin V-FITC and propidium iodide labeling. Results showed that apoptosis was dependent on the dose of IAA utilized, the duration of exposure to the prodrug and the origin of the neoplasia. Targeting HRP with antibodies was efficient in activating IAA and inducing apoptosis. (C) 2010 Elsevier Ltd. All rights reserved.

Hydrogen Sulfide Prevents Ethanol-Induced Gastric Damage in Mice: Role of ATP-Sensitive Potassium Channels and Capsaicin-Sensitive Primary Afferent Neurons

The aim of this study was to evaluate the protective effect of hydrogen sulfide (H(2)S) on ethanol-induced gastric lesions in mice and the influence of ATP-sensitive potassium (K(ATP)) channels, capsaicin-sensitive sensory afferent neurons, and transient receptor potential vanilloid (TRPV) 1 receptors on such an effect. Saline and L-cysteine alone or with propargylglycine, sodium hydrogen sulfide (NaHS), or Lawesson`s reagent were administrated for testing purposes. For other experiments, mice were pretreated with glibenclamide, neurotoxic doses of capsaicin, or capsazepine. Afterward, mice received L-cysteine, NaHS, or Lawesson`s reagent. After 30 min, 50% ethanol was administrated by gavage. After 1 h, mice were sacrificed, and gastric damage was evaluated by macroscopic and microscopic analyses. L-Cysteine, NaHS, and Lawesson`s reagent treatment prevented ethanol-induced macroscopic and microscopic gastric damage in a dose-dependent manner. Administration of propargylglycine, an inhibitor of endogenous H(2)S synthesis, reversed gastric protection induced by L-cysteine. Glibenclamide reversed L-cysteine, NaHS, or Lawesson`s reagent gastroprotective effects against ethanol-induced macroscopic damage in a dose-dependent manner. Chemical ablation of sensory afferent neurons by capsaicin reversed gastroprotective effects of L-cysteine or H(2)S donors (NaHS or Lawesson`s reagent) in ethanol-induced macroscopic gastric damage. Likewise, in the presence of the TRPV1 antagonist capsazepine, the gastroprotective effects of L-cysteine, NaHS, or Lawesson`s reagent were also abolished. Our results suggest that H(2)S prevents ethanol-induced gastric damage. Although there are many mechanisms through which this effect can occur, our data support the hypothesis that the activation of K(ATP) channels and afferent neurons/TRPV1 receptors is of primary importance.

Comparison of Preoperative Nd:YAG Laser Anterior Capsulotomy Versus Two-Stage Curvilinear Capsulorhexis in Phacoemulsification of White Intumescent Cataracts

BACKGROUND AND OBJECTIVE: To compare the results of preoperative Nd:YAG laser anterior capsulotomy versus two-stage continuous curvilinear capsulorhexis (CCC) in phacoemulsification of eyes with white intumescent cataracts and liquefied cortex. PATIENTS AND METHODS: Twenty-three eyes with white intumescent cataract were consecutively randomized for phacoemulsification with preoperative Nd:YAG laser anterior capsulotomy (group 1, n = 11) or two-stage CCC (group 2, n = 12) procedures. Intraoperative findings and postoperative outcomes were compared using the nonparametric tests. RESULTS: Postoperative Visual acuity, mean surgical time, mean effective phacoemulsification time, and frequency of complications were not significantly different between the two groups (P > .05). Two cases in each group were converted to the extracapsular technique. Excluding these four patients, surgical time was shorter In group 1 (P = .017). CONCLUSION: Preoperative Nd:YAG laser anterior capsulotomy is a safe technique in decompressing the capsular bag before phacoemulsification of white intumescent cataracts with liquefied cortex.

Secondary PSF/TFE3-associated renal cell carcinoma in a child treated for genitourinary rhabdomyosarcoma

Xp11.2 translocation-associated renal cell carcinoma (RCC) is a rare tumor that accounts for at least one-third of childhood RCC. Different reports have emphasized that previous radio/chemotherapy might be involved in its pathogenesis. We describe a child who developed a t(X;1) (p11.2;p34) associated RCC after previous treatment for genitourinary rhabdomyosarcoma in infancy. The presence of the PSF-TFE3 fusion has only been described in a very limited number of cases. Our report expands the spectrum of tumors in which RCC can arise in the pediatric age group after chemotherapy.