bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Kisspeptin and RFamide‐Related Peptide‐3 Neurones in the Circadian‐Timed Preovulatory Luteinising Hormone Surge
Authors: Khan A. R. , Kauffman A. S.
Published: May 2011

Many aspects of female reproduction often require intricate timing, ranging from the temporal regulation of reproductive hormone secretion to the precise timing of sexual behaviour. In particular, in rodents and other species, ovulation is triggered by a surge in pituitary luteinising hormone (LH) secretion that is governed by a complex interaction between circadian signals arising in the hypothalamus and ovarian‐derived oestradiol signals acting on multiple brain circuitries. These circadian and hormonal pathways converge to stimulate a precisely‐timed surge in gonadotropin‐releasing hormone (GnRH) release (i.e. positive‐feedback), thereby triggering the preovulatory LH surge. Reflecting its control by afferent circadian signals, the preovulatory LH surge occurs at a specific time of day, typically late afternoon in nocturnal rodents. Although the specific mechanisms mediating the hormonal and circadian regulation of GnRH/LH release have remained poorly understood, recent findings now suggest that oestradiol and circadian signals govern specific reproductive neuropeptide circuits in the hypothalamus, including the newly‐identified kisspeptin and RFamide‐related peptide (RFRP)‐3 neuronal populations. Neurones producing kisspeptin, the protein product of the Kiss1 gene, and RFRP‐3 have been shown to provide excitatory and inhibitory input to GnRH neurones, respectively, and are also influenced by sex steroid and circadian signals. In the present review, we integrate classic and recent findings to form a new working model for the neuroendocrine regulation of the circadian‐timed preovulatory LH surge in rodents. This model proposes kisspeptin and RFRP‐3 neuronal populations as key nodal points for integrating and transducing circadian and hormonal signals to the reproductive axis, thereby governing the precisely‐timed LH surge.
Spatial stratification of host‐seeking Diptera in boreal forests of northern Europe
Authors: SWANSON D. A. , ADLER P. H. , MALMQVIST B.
Published: May 2011

The stratification of haematophagous Diptera was assessed in two boreal forests in northern Sweden by placing traps baited with carbon dioxide at 1.5 m, 5.0 m and 10.0 m above the ground. More than 40 000 specimens were captured, including 617 biting midges (Ceratopogonidae), 4029 mosquitoes (Culicidae) and 36 092 black flies (Simuliidae). Catches at the various trap heights reflected the general vertical distribution of the preferred hosts, with mammalophilic flies predominating (68.6%) in catches at 1.5 m and ornithophilic flies (42.4%) in catches at 10.0 m; however, most flies that use host birds at ground level were caught in the lowest traps (e.g. 85.1% of Simulium annulus were collected at 1.5 m). Within‐species variation in vertical patterns between forests suggests plasticity in responses to environmental factors such as vegetative structure.
Tumour‐loaded α‐type 1‐polarized Dendritic Cells from Patients with Chronic Lymphocytic Leukaemia Produce a Superior NK‐, NKT‐ and CD8+ T Cell‐attracting Chemokine Profile
Authors: Gustafsson Karin , Junevik Katarina , Werlenius Olle , Holmgren Sandra , Karlsson‐Parra Alex , Andersson Per‐Ola
Published: May 2011

Tumour‐loaded dendritic cells (DCs) from patients with chronic lymphocytic leukaemia (CLL) matured using an α‐type 1‐polarized DC cocktail (IL‐1β/TNF‐α/IFN‐α/IFN‐γ/poly‐I:C;αDC1) were recently shown to induce more functional CD8+ T cells against autologous tumour cells in vitro than DCs matured with the ‘standard’ cocktail (IL‐1β/TNF‐α/IL‐6/PGE2;PGE2DCs). However, the ability of vaccine DCs to induce a type 1‐polarized immune response in vivo probably relies on additional features, including their ability to induce a CXCR3‐dependent recruitment of NK cells into vaccine‐draining lymph nodes. Moreover, their guiding of rare tumour‐specific CD8+ T cells to sites of DC–CD4+ T cell interactions by secretion of CCL3 and CCL4 is needed. We therefore analysed the chemokine profile and the lymphocyte‐attracting ability in vitro of monocyte‐derived PGE2DCs and αDC1s from patients with CLL. αDC1s produced much higher levels of CXCR3 ligands (CXCL9/CXCL10/CXCL11) than PGE2DCs. Functional studies further demonstrated that αDC1s were superior recruiters of both NK and NKT cells. Moreover, αDC1s produced higher levels of CCL3/CCL4 upon CD40 ligation. These findings suggest that functional αDC1s, derived from patients with CLL, produce a desirable NK‐, NKT‐ and CD8+ T cell‐attracting chemokine profile which may favour a guided and Th1‐deviated priming of CD8+ T cells, supporting the idea that αDC1‐based vaccines have a higher immunotherapeutic potential than PGE2DCs.
Tuberculosis treatment default among HIV‐TB co‐infected patients in urban Uganda
Authors: Elbireer Sawsan , Guwatudde David , Mudiope Peter , Nabbuye‐Sekandi Juliet , Manabe Yukari C.
Published: May 2011

Objective  To identify health facility and patient‐specific factors associated with TB treatment default in HIV‐infected patients, in a TB clinic on the campus of Mulago National Referral Hospital in Kampala, Uganda.

Methods  Unmatched case–control study between March and May 2009. Cases were TB patients known to have defaulted on their anti‐TB treatment, defined as a TB patient who had documented discontinuation of TB medication for two or more consecutive months due to reasons other than physician’s advice and who did not access care at another facility. Controls were TB patients who completed 8 months of anti‐TB treatment without interruption of two or more months. Data on health facility‐specific factors and individual characteristics were collected using semi‐structured questionnaires.

Results  Factors associated with defaulting from TB treatment were: distance from home to clinic (OR 2.22; 1.21–4.06); long waiting time at the clinic (OR 4.18; 2.18–8.02); poor drug availability (OR 4.75; 2.29–9.84); conduct of staff (OR 2.72; 1.02–7.25); lack of opportunity to express feelings (OR 3.47; 1.67–7.21). Other patient‐related factors were lack of health education, i.e. not being aware of the duration of treatment or the risk of discontinuing it (OR 5.31; 1.94–14.57); not knowing that TB can be cured (OR 44.11; 13.66–142.41); length of TB treatment (OR 10.77; 5.18–22.41), and side effects of treatment OR 5.53 (2.25–13.61).

Conclusions  Defaulting is influenced by health systems, staff factors, and patient misinformation. Health education on TB directed at patients combined with staff sensitization could help to improve adherence to TB treatment.
Risk stratification of kidneys from donation after cardiac death donors and the utility of machine perfusion
Authors: Cantafio A.W. , Dick A.A.S. , Halldorson J.B. , Bakthavatsalam R. , Reyes J.D. , Perkins J.D.
Published: May 2011

Cantafio AW, Dick AAS, Halldorson JB, Bakthavatsalam R, Reyes JD, Perkins JD. Risk stratification of kidneys from donation after cardiac death donors and the utility of machine perfusion. Clin Transplant 2011: 25: E530–E540. © 2011 John Wiley & Sons A/S.

Abstract:  There has been a dramatic increase in the utilization of kidneys from donors after cardiac death (DCD). While these organs represent an opportunity to expand the donor pool, the assessment of risk and optimal perioperative management remains unclear. Our primary aim was to identify risk factors for objective outcomes, and secondarily, we sought to determine what impact pulsatile machine perfusion (PMP) had on these outcomes. From 1993 to November 2008, 6057 DCD kidney transplants were reported to the Organ Procurement and Transplantation Network database, with complete endpoints for delayed graft function (DGF) and graft survival (GS). Risk factors were identified using a multivariable regression analysis adjusted for recipient factors. Age (50 yr) [OR 1.81, p < 0.0001] and cold ischemia time (CIT) (>30 h) [OR 3.22, p < 0.0001] were the strongest predictors of DGF. The use of PMP decreased the incidence of DGF only when donor age was >60 yr and improved long‐term graft survival when donor age was >50 yr. Donor warm ischemia time >20 min was also found to correlate with increased DGF. While the incidence of DGF in DCD kidneys is significantly higher, the only factors the transplant surgeon can control are CIT and the use of PMP. The data suggest that the use of PMP in DCD kidneys <50 yr old provides little clinical benefit and may increase CIT.
Are informed consent forms for organ transplantation and donation too difficult to read?
Authors: Gordon Elisa J. , Bergeron Ashley , McNatt Gwen , Friedewald John , Abecassis Michael M. , Wolf Michael S.
Published: May 2011

Gordon EJ, Bergeron A, McNatt G, Friedewald J, Abecassis MM, Wolf MS. Are informed consent forms for organ transplantation and donation too difficult to read?  Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01480.x.  © 2011 John Wiley & Sons A/S.

Abstract:  Informed consent for organ transplantation and donation is an ethical obligation, legally required, and considered as part of the Patient’s Rights Condition of Medicare Participation for hospitals. National policy‐makers recommend that informed consent forms and patient education materials be written at a low reading level (5th–8th grade level) to facilitate patient comprehension. We assessed reading levels of informed consent forms (CFs) for adult organ transplant recipients and living organ donors across US transplant centers. CFs were analyzed using three measures of reading level: Lexile Measure, Flesch–Kincaid Grade Level, and the Gunning Fog Index. Of active transplant centers contacted (N = 209), 75 (36%) sent a total of 332 CFs. CFs were written, on average, at the college level, which is a considerably higher reading level than the standards set by policy‐makers. CF reading levels were negatively correlated with transplant center volume (r = −0.119; p < 0.03). CFs for intestine transplantation and for evaluation/listing were the easiest to read, while consent forms for liver transplantation/donation and pre‐transplant agreements were the most difficult to read. Reducing CFs’ reading level may help to increase patient comprehension for adequate informed consent.
Lung transplantation after hematopoietic stem cell transplantation
Authors: Whitson Bryan A. , Shelstad Ryan C. , Hertz Marshall I. , Kelly Rosemary F. , D’Cunha Jonathan , Shumway Sara J.
Published: May 2011

Whitson BA, Shelstad RC, Hertz MI, Kelly RF, D’Cunha J, Shumway SJ. Lung transplantation after hematopoietic stem cell transplantation.  Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01482.x.  © 2011 John Wiley & Sons A/S.

Abstract:  Introduction:  Pulmonary insufficiency following bone marrow transplant (BMT) is common and has significant associated mortality. Lung transplantation (LTX) is the only viable treatment for patients with end‐stage pulmonary disease, but LTX after BMT is an uncommon event given the medical candidacy of the potential recipients. We sought to evaluate the short‐ and long‐term outcomes of LTX in BMT recipients.

Methods:  We performed a retrospective evaluation of our institution’s longitudinal LTX and BMT databases. Demographic and outcomes variables were collected.

Results:  We identified 639 LTX from January 1, 1988, through December 31, 2009, and 5525 BMT from program inception, March 21, 1974, through December 31, 2009. From the cross‐referenced cohort, we identified four patients who had BMT followed by LTX. Our series was composed of two men and two women, with a mean age of 32.3 yr (range, 20–59 yr). Single LTX were performed in two recipients (50%). All patients had significant and expected morbidities related to their transplant immunosuppression. Three patients (75%) required cardiopulmonary bypass at the time of LTX. The two recipients who underwent bilateral LTX required open chest management and subsequent tracheostomy. All patients are still alive at follow‐up (range, 19–119 months, median 39.5).

Conclusion:  Our study demonstrates that LTX in the setting of BMT is a high‐risk operation with the potential for a tumultuous perioperative course. Despite this, good outcomes and survival are obtainable in carefully selected patients. Selection factors include clinically stable patients without active sepsis and preoperative optimization of nutrition in anticipation of a prolonged recovery. An experienced multidisciplinary team approach and a protocol‐driven management plan are paramount for successful outcomes in this challenging population.
LabMELD‐based organ allocation increases total costs of liver transplantation: a single‐center experience
Authors: Bruns Helge , Hillebrand Norbert , Schneider Tobias , Hinz Ulf , Fischer Lars , Schmidt Jan , Goldschmidt Andreas J.W. , Schemmer Peter
Published: May 2011

Bruns H, Hillebrand N, Schneider T, Hinz U, Fischer L, Schmidt J, Goldschmidt AJW, Schemmer P. LabMELD‐based organ allocation increases total costs of liver transplantation: a single‐center experience. Clin Transplant 2011: 25: E558–E565. © 2011 John Wiley & Sons A/S.

Abstract:  Introduction:  In 2006, model for end‐stage liver disease (MELD)‐based allocation was implemented in the Eurotransplant (ET) region. Sick patients, who in general require more resources, are prioritized. In this analysis, the effect of MELD on costs for liver transplantation (LTx) was assessed.

Methods:  Total costs for LTx before and after implementation of MELD were identified in 256 patients from January 2005–December 2007. Forty‐nine patients (Re‐LTx, HU listings, and 30‐d mortality) were excluded from further analysis. The costs of LTx in 207 patients have been correlated with their corresponding labMELD; 84 and 123 LTx before and after implementation of MELD were compared, and patient survival was monitored.

Results:  A positive correlation exists between labMELD and costs (r2 = 0.28; p < 0.05). Only nominal correlation existed between the Child–Pugh classification and costs. The labMELD scores can be stratified into four groups (I: 6–10, II: 11–18, III: 19–24, and IV: >24), with an increase of €15.672 ± 2.233 between each group (p < 0.05). Recipients’ labMELD at the time of LTx increased significantly in the MELD‐based allocation system. Costs increased by €11.650/patient (p < 0.05), while median survival decreased from 1219 to 869 d (p < 0.05).

Conclusion:  LabMELD‐based allocation increased total costs of LTx. In accordance with other studies, the sickest patients need the most resources.
Pharmacokinetics, pharmacodynamics, safety, and tolerability of single‐dose fingolimod (FTY720) in adolescents with stable renal transplants
Authors: Ettenger R. , Schmouder R. , Kovarik J. M. , Bastien M. C. , Hoyer P. F.
Published: May 2011

Ettenger R, Schmouder R, Kovarik JM, Bastien MC, Hoyer PF. Pharmacokinetics, pharmacodynamics, safety, and tolerability of single‐dose fingolimod (FTY720) in adolescents with stable renal transplants. Pediatr Transplantation 2011: 15: 406–413. © 2011 John Wiley & Sons A/S.

Abstract:  Oral fingolimod signals the sphingosine 1‐phosphate receptor and this in turn mediates immunomodulatory activity. No data of fingolimod in any pediatric population existed before this study. We put our study results in perspective against data from adult renal transplant patients. We investigated pharmacokinetics and pharmacodynamics of single‐dose fingolimod (0.07 mg/kg) and its effects on lymphocytes and heart rate in seven adolescents (14.1 ± 1.6 yr) with stable renal transplants. Blood samples for pharmacokinetics and lymphocytes were collected at screening, baseline, and up to 28 days post‐dosing. Cardiac monitoring included 12‐lead ECG, 24‐h Holter monitoring, and echocardiography. A fingolimod dose of 0.07 mg/kg resulted in mean AUC of 731 ± 240 ng·h/mL and Cmax of 3.6 ± 0.6 ng/mL. Drug exposure was nearly identical to adults receiving the same dose. Absolute lymphocyte count decreased 85% from baseline; average nadir occurred by six h post‐dose. Heart rate decreased from 74 bpm (predose mean) to 53 bpm (nadir) three h post‐dose. Mean heart rates recovered by Day 14 (75 bpm). Weight‐adjusted doses of fingolimod in adolescents resulted in drug exposure similar to adults. Adolescents and adults shared comparable negative chronotropic effects and decreased lymphocyte count. Recovery trajectories of these parameters back to baseline were similar between age groups.
Long‐term follow‐up in adult living donors for combined liver/bowel transplant in pediatric recipients: A single center experience
Authors: Ghafari Jamie L. , Bhati Chandra , John Eunice , Tzvetanov Ivo G. , Testa Giuliano , Jeon Hoonbae , Oberholzer Jose , Benedetti Enrico
Published: May 2011

Ghafari JL, Bhati C, John E, Tzvetanov IG, Testa G, Jeon H, Oberholzer J, Benedetti E. Long‐term follow‐up in adult living donors for combined liver/bowel transplant in pediatric recipients: A single center experience. Pediatr Transplantation 2011: 15: 425–429. © 2011 John Wiley & Sons A/S.

Abstract:  Pediatric candidates for combined liver/bowel transplant (LBTx) experience a very high mortality on the cadaver waiting list. Our transplant center has successfully used adult living donors to treat pediatric candidates for LBTx. We report the long‐term follow‐up of this unique cohort of organ donors. The charts of six adult donors for LBTx performed between 2004 and 2007 were reviewed. All the pertinent clinical data were carefully reviewed and integrated with phone interviews of all donors. A total of six children (average age 13.5 months) received living donor LBTx. Average follow‐up for the donors was 42 months (range 29–51). The donors’ median age was 25 yr (19–32); five women and one man. The average median hospital stay was nine days. There were no peri‐operative complications. At present all donors remain in good health. Three of the five mothers became pregnant after donation. Five of the six children are currently alive and well whereas one died with functioning grafts six months post‐transplant due to plasmoblastic lymphoma. Living donor LBTx is an effective therapy for combined hepatic and intestinal failure in children less than five yr. The donor operation can be performed with minimal morbidity.
Laparoendoscopic single‐site (LESS) bilateral nephrectomy in the pretransplant pediatric population
Authors: Marietti Sarah , Holmes Nicholas , Chiang George
Published: May 2011

Marietti S, Holmes N, Chiang G. Laparoendoscopic single‐site (LESS) bilateral nephrectomy in the pretransplant pediatric population. Pediatr Transplantation 2011: 15: 396–399. © 2011 John Wiley & Sons A/S.

Abstract:  End‐stage renal failure management in children may require bilateral kidney removal prior to transplantation secondary to recurrent urinary tract infections, renin‐dependent hypertension, vesicoureteral reflux, proteinuria, risk of malignancy (Denys‐Drash), or high output renal failure. Conventional laparoscopy or open nephrectomy has been employed to date. However, we present our method of bilateral nephrectomy in four patients via the SILS Covidien © system. Patient age ranged from 18 months to 18 years. Operative time ranged from 308 to 370 minutes. Estimated blood loss was minimal, all cases were completed via the single incision and no cases were converted to open. Laparoendoscopic single‐site bilateral nephrectomy is safe and feasible in children and well‐suited for the pre‐transplant population.
Plasticity in the development and dedifferentiation of Dictyostelium discoideum
Authors: Roberge‐White Emily , Katoh‐Kurasawa Mariko
Published: May 2011

Dictyostelium discoideum has served as a model for development and differentiation for over 70 years. Also regulated in Dictyostelium is the process of dedifferentiation, which consists of multiple cellular events that are separately regulated, providing an excellent model system for studying the return of partially differentiated cells to a more pluripotent state. An interesting aspect of Dictyostelium development is the plasticity between growth and development. Reversibility of the processes of differentiation and dedifferentiation exist, allowing Dictyostelium to adjust to changing conditions by reverting to the growth phase during differentiation or reinitiating development during dedifferentiation. This ability of cells to respond to environmental cues is mediated by the checkpoint‐like events “commitment” and “erasure,” which occur during differentiation and dedifferentiation, respectively. Our review will discuss the current state of knowledge regarding dedifferentiation and the plasticity of the developmental process in both the forward and reverse directions.
Cell migration in multicellular environments
Authors: Tsujioka Masatsune
Published: May 2011

Most experiments observing cell migration use planar plastic or glass surfaces despite these conditions being considerably different from physiological ones. On such planar surfaces, cells take a dorsal‐ventral polarity to move two‐dimensionally. Cells in tissues, however, interact with surrounding cells and the extracellular matrix such that they transverse three‐dimensionally. For this reason, three‐dimensional matrices have become more and more popular for cell migration experiments. In addition, recent developments in imaging techniques have enabled high resolution observations of in vivo cell migration. The combination of three‐dimensional matrices and such imaging techniques has revealed motile mechanisms in tissues not observable in studies using planar surfaces. Regarding models for such cell migration studies, the cellular slime mould Dictyostelium discoideum is ideal. Single amoeboid cells aggregate into hemispherical mound structures upon starvation to begin a multicellular morphogenesis. These tiny and simple multicellular bodies are suitable for observing the behaviors of individual cells in multicellular structures. Furthermore, the unique life cycle can be exploited to identify which genes are involved in cell migration in multicellular environments. Since mutants lacking such genes are expected to fail to undergo morphogenesis, easy and systematic gene screening is possible by isolating mutants whose developments arrest around the mound stage, which is the case for several mutants lacking specific cytoskeletal proteins. In this article, I discuss the basic elements required for cell migration in multicellular environments and how Dictyostelium can be used to elucidate them.
Non‐genetic heterogeneity and cell fate choice in Dictyostelium discoideum
Authors: Chattwood Alex , Thompson Christopher R. L.
Published: May 2011

From microbes to metazoans, it is now clear that fluctuations in the abundance of mRNA transcripts and protein molecules enable genetically identical cells to oscillate between several distinct states (Kaern et al. 2005). Since this cell–cell variability does not derive from physical differences in the genetic code it is termed non‐genetic heterogeneity. Non‐genetic heterogeneity endows cell populations with useful capabilities they could never achieve if each cell were the same as its neighbors (Raj & van Oudenaarden 2008; Eldar & Elowitz 2010). One such example is seen during multicellular development and “salt and pepper” cell type differentiation. In this review, we will first examine the importance of non‐genetic heterogeneity in initiating “salt and pepper” pattern formation during Dictyostelium discoideum development. Second, we will discuss the various ways in which non‐genetic heterogeneity might be generated, as well as recent advances in understanding the molecular basis of heterogeneity in this system.
Management of cancer risk in Barrett's esophagus
Authors: Tan Alyisha , Macrae Finlay
Published: May 2011

The importance of Barrett's esophagus (BE) lies in its potential to give rise to esophageal adenocarcinoma (EAC), postulated to be through a series of progressive degrees of dysplasia; from intestinal metaplasia to low‐grade dysplasia, high‐grade dysplasia, and subsequently, to cancer. The management strategies for the detection and treatment of dysplasia and early esophageal cancer on a background of BE have changed significantly in the last few decades, with the emergence of newer and less invasive non‐operative alternatives. This review aims to outline BE and its relation to EAC, the rationale and cost‐effectiveness of both screening and surveillance programs, methods of diagnosing and identifying dysplasia and early cancer in Barrett's, and approaches to individualizing their endoscopic and surgical management based on best‐available staging techniques.
Dihydrolipoyl histidinate zinc complex, a new antioxidant, attenuates hepatic ischemia‐reperfusion injury in rats
Authors: Masuda Takashi , Iwashita Yukio , Hagiwara Satoshi , Ohta Masayuki , Inomata Masafumi , Noguchi Takayuki , Kitano Seigo
Published: May 2011

Background and Aims:  Ischemia/reperfusion (I/R) injury is characterized by significant oxidative stress, which induces characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. The aim of this study was to evaluate the protective effect of dihydrolipoyl histidinate zinc complex (DHLHZn) on oxidative damage after severe hepatic I/R injury.

Methods:  Thirty male Wistar rats were subjected to 45 min of hepatic ischemia by clamping of the hepatic artery and portal vein, followed by a 6‐h reperfusion period. DHLHZn (10 mg/kg) (I/R + DHLHZn group) or saline (I/R group) was administered intraperitoneally twice, 30 min before ischemia and at the beginning of the reperfusion. Sham‐operated animals (sham group) received equal amounts of saline. The rats were killed at the end of the reperfusion period. Serum levels of aspartate aminotransferase and alanine aminotransferase were determined, and histological examination and oxidative stress were evaluated in liver tissues. In addition, antimycin A‐stimulated RAW264.7 cells (murine macrophage‐like cells) were treated with DHLHZn to estimate its antioxidant effect.

Results:  Serum aspartate aminotransferase and alanine aminotransferase levels were increased in the I/R group, but these increases were significantly inhibited in the I/R + DHLHZn group. Similarly, liver tissue damage observed in the I/R group was attenuated in the I/R + DHLHZn group. Cells treated in vitro with both DHLHZn and antimycin A showed reduced reactive oxygen species activity compared to cells treated with antimycin A alone.

Conclusion:  The new antioxidant DHLHZn may have potential for therapeutic application in liver I/R injury, although this is a limited animal study.
Complex non‐invasive fibrosis models are more accurate than simple models in non‐alcoholic fatty liver disease
Authors: Adams Leon A , George Jacob , Bugianesi Elisabetta , Rossi Enrico , De Boer W Bastiaan , van der Poorten David , Ching Helena L I , Bulsara Max , Jeffrey Gary P
Published: May 2011

Background and Aim:  Significant hepatic fibrosis is prognostic of liver morbidity and mortality in non‐alcoholic fatty liver disease (NAFLD); however, it remains unclear whether non‐invasive fibrosis models can determine this end‐point. We therefore compared the accuracy of simple bedside versus complex fibrosis models across a range of fibrosis in a multi‐centre NAFLD cohort.

Methods:  Simple (APRI, BARD) and complex (Hepascore, Fibrotest, FIB4) fibrosis models were calculated in 242 NAFLD subjects undergoing liver biopsy. Significant (F2‐4) and advanced fibrosis (F3,4) were defined using Kleiner criteria. Models were compared using area under the receiver operator characteristic curves (AUC). Cut‐offs were determined by Youden Index or 90% predictive values.

Results:  For significant fibrosis, non‐invasive fibrosis models had modest accuracy (AUC 0.707–0.743) with BARD being least accurate (AUC 0.609, P < 0.05 vs others). Using single cut‐offs, sensitivities and predictive values were < 80%; using two cut‐offs, > 75% of subjects fell within indeterminate ranges. Simple models had significantly more subjects within indeterminate ranges than complex models (99.1–100% vs 82.1–84.4% respectively, P < 0.05 for all). For advanced fibrosis, complex models were more accurate than BARD (AUC 0.802–0.858 vs 0.701, P < 0.05). Using two cut‐offs, complex models had fewer individuals within indeterminate ranges than BARD (11.1–32.3% vs 70.7%, P < 0.01 for all). For cirrhosis, complex models had higher AUC values than simple models.

Conclusions:  In NAFLD subjects, non‐invasive models have modest accuracy for determining significant fibrosis and have predictive values less than 90% in the majority of subjects. Complex models are more accurate than simple bedside models across a range of fibrosis.
Outcomes after curative treatment for cryptogenic cirrhosis‐associated hepatocellular carcinoma satisfying the Milan criteria
Authors: Takuma Yoshitaka , Nouso Kazuhiro , Makino Yasuhiro , Gotoh Tomoyuki , Toshikuni Nobuyuki , Morimoto Youichi , Shimomura Hiroyuki , Yamamoto Hiroshi
Published: May 2011

Background and Aim:  The prognosis of cryptogenic cirrhosis‐associated hepatocellular carcinoma (CC‐HCC) was reported to be poor because many of them were discovered at the advanced stage. The aim of this study is to reveal the clinical features of early CC‐HCC.

Methods:  Consecutive 36 curatively treated CC‐HCC patients satisfying the Milan Criteria were compared with corresponding 211 HCV‐associated HCC (HCV‐HCC) patients. The clinical background, tumor recurrence rate, overall survival rate, and prognostic values of the patients were assessed.

Results:  The size of CC‐HCCs was larger than that of HCV‐HCCs (P = 0.01). The respective tumor recurrence rates at 1, 3, and 5 years were 11%, 32%, and 46% in the CC‐HCC, and 21%, 59%, and 81% in the HCV‐HCC. The respective overall survival rates at 1, 3, and 5 years were 94%, 85%, and 80% in the CC‐HCC, and 98%, 81%, and 61% in the HCV‐HCC. CC‐HCC patients had a lower tumor recurrence rate and a higher survival rate compared to the HCV‐HCC patients (P = 0.001 and P = 0.02, respectively). Via multivariate analysis, significant factors for high recurrence rate were number of HCCs (P = 0.02) and serum alpha fetoprotein levels (P = 0.03) in CC‐HCC, whereas multiple tumors (P < 0.001), large tumor size (P = 0.01), and high alanine aminotransferase (P = 0.04) in HCV‐HCC. The factor for survival was albumin in both groups.

Conclusion:  The size of CC‐HCC was larger than that of HCV‐HCC even in patients who received curative treatment; however, the risk for recurrence and the mortality of the patients with CC‐HCC was lower than those with HCV‐HCC.
Suppressive effects of entecavir on hepatitis B virus and hepatocellular carcinoma
Authors: Jin Young‐Joo , Shim Ju Hyun , Lee Han Chu , Yoo Dong‐Jun , Kim Kang Mo , Lim Young‐Suk , Suh Dong Jin
Published: May 2011

Background and Aim:  We investigated the efficacy and effectiveness of entecavir in hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) patients.

Methods:  We enrolled 231 nucleoside‐naïve chronic hepatitis B (CHB) patients primarily treated with entecavir 0.5 mg/day for at least 6 months in our institution. Of these, 71 patients had HCC at the start of entecavir treatment (HCC group) and 160 did not (non‐HCC group). We compared antiviral responses to entecavir in the two groups, and evaluated the effects of entecavir on the clinical outcomes of curatively‐treated HCC patients.

Results:  The HCC and non‐HCC groups had similar cumulative rates of HBV‐DNA negativity, alanine aminotransferase normalization, and hepatitis e antigen loss in year 2 (100% vs 95.4%, 94.7% vs 97.3%, and 40.8% vs 41.8%, respectively; P > 0.05). Entecavir treatment for 12 months decreased mean Model for End‐Stage Liver Disease scores in patients with cirrhosis and HCC (7.2 vs 5.6, P < 0.001). Of the 71 HCC patients, 16 underwent curative therapies concurrently with entecavir; hepatectomy in six and radiofrequency ablation in 10, and the 55 remaining patients received transarterial chemoembolization or conservative treatment. In a subgroup of 16 HCC patients receiving curative treatments, patients who became serum HBV DNA negative by week 24 had better overall survival (P = 0.039), but not recurrence‐free survival (P = 0.961), than those who did not.

Conclusions:  First‐line entecavir monotherapy is comparably effective in CHB patients with and without HCC, and improves hepatic function in HBV‐related HCC patients. An early virological response to entecavir is prognostic of improved survival following curative therapy against HBV‐related HCC.
Negative hepatitis B envelope antigen predicts intrahepatic recurrence in hepatitis B virus‐related hepatocellular carcinoma after ablation therapy
Authors: Chung Goh Eun , Kim Won , Lee Jeong‐Hoon , Kim Yoon Jun , Yoon Jung‐Hwan , Lee Jeong Min , Lee Jae Young , Kim Se Hyung , Kim Donghee , Lee Hyo‐Suk
Published: May 2011

Background and Aim:  Patients with persistently active hepatitis B virus (HBV) replication are at high risk for progression to liver cirrhosis and hepatocellular carcinoma (HCC). The influence of the viral load of HBV on intrahepatic recurrence after local ablation therapy in patients with HBV‐related HCC has not been elucidated. We aimed to evaluate predictors of intrahepatic recurrence and clarify the correlation between viral load and intrahepatic recurrence after percutaneous ablation.

Methods:  Patients with HBV‐related, solitary HCC undergoing radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), between October 2004 and December 2008 were prospectively enrolled. Statistical analyses were performed using the Kaplan–Meier method and Cox regression model to identify risk factors for intrahepatic recurrence.

Results:  A total of 145 patients (male, 81.4%; mean age, 55.3 years) were included. Ninety patients (62.1%) had serum HBV DNA ≥ 2000 IU/mL. The median follow‐up duration was 28.9 months (range, 12.0–57.0) and 63 patients (43.4%) experienced intrahepatic tumor recurrence. Multivariate analysis indicated that seropositivity for hepatitis B envelope antigen (HBeAg) was an independent negative predictor of intrahepatic recurrence (hazard ratio, 0.473; P = 0.026) and late (≥ 1 year) recurrence (HR, 0.288; P = 0.012). The serum alpha fetoprotein (AFP) level also significantly predicted late recurrence (HR, 1.001; P = 0.005). However, neither the ablation method nor serum HBV DNA titers were correlated with intrahepatic recurrence.

Conclusions:  These findings show that HBeAg‐negativity and serum AFP levels were associated with late intrahepatic recurrence of HCC, implicating HBeAg‐negativity as a risk factor for de novo recurrence after percutaneous ablation in HBV‐related HCC.
Portal venous invasion: The single most independent risk factor for immediate postoperative recurrence of hepatocellular carcinoma
Authors: Choi Kang Kook , Kim Sung Hoon , Choi Sae Byeol , Lim Jin Hong , Choi Gi Hong , Choi Jin Sub , Kim Kyung Sik
Published: May 2011

Background and Aim:  Despite improvements of treatment in hepatocellular carcinoma (HCC), the recurrence rate after curative hepatic resection still remains remarkably high. An immediate recurrence of HCC after surgery is frustrating. We tried to clarify risks of immediate postoperative recurrence of HCC; that is, within 4 months after curative hepatic resection.

Methods:  A total of 167 patients with HCC underwent hepatic resection; 60 had immediate postoperative recurrences (IPR group), and 107 had disease‐free survival for more than 5 years (DFS group). Variables were compared between the two groups.

Results:  Univariate analysis showed the following variables were significant risk factors for immediate postoperative recurrence of HCC: male sex, elevated serum aspartate aminotransferase level, greater amount of blood loss, longer operation time, worse tumor differentiation, higher tumor node metastasis stage, and presence of any of the following: intrahepatic metastasis, tumor‐rupture, portal venous invasion, or microvascular invasion. In multivariate analysis, only portal venous invasion was a significant risk factor (odds ratio = 3.2, P = 0.03, standard error = 0.5, Logistic regression analysis).

Conclusions:  Portal venous invasion may be the most significant risk factor for immediate postoperative recurrence of HCC. However, accurate assessment of this risk factor may require histological examination, limiting its utility as a preoperative predictor. Further research is necessary to definitively identify preoperative predictors.
Sudden cardiac death: the perspectives of Spanish survivors
Authors: Palacios‐Ceña Domingo , Losa‐Iglesias Marta Elena , Salvadores‐Fuentes Paloma , Fernández‐de‐las‐Peñas Cesar
Published: May 2011

Sudden cardiac death is an episode of sudden death from cardiac causes in previously healthy patients. The aim of this study was to investigate the life experiences of patients who were resuscitated successfully following a sudden cardiac death. Purposeful sampling was used to recruit the nine participants through the snowball technique. Unstructured interviews were carried out until data saturation was reached. The Giorgi method of analysis, which seeks to reduce the participant's experience to minimal thematic units, common thematic groups, and essential themes in order to describe it, was used. Four essential themes were found: “facing fear”; “the search for meaning”; “feeling death up close and personal”; and “loneliness and estrangement”. Nurses must integrate the lifestyle changes of patients who survive a cardiac death in order to provide adequate care following hospital discharge. Patients should undertake follow‐up programs in order to receive counseling from health professionals. As a result, the creation of interdisciplinary support groups and the implementation of follow‐up programs after hospital discharge are fundamental. Survivors' experiences can inform the development of nursing programs and hospital follow‐up services that address the survival of cardiac death.
Factor analysis on oral health care for acute hospitalized patients in Japan
Authors: Kuramoto Chika , Watanabe Yutaka , Tonogi Morio , Hirata Soichiro , Sugihara Naoki , Ishii Takuo , Yamane Gen‐yuki
Published: May 2011

Aim:  We conducted a survey to investigate the status regarding the implementation of oral health care for inpatients aged 65 years and older who were in the acute stages of stroke and to examine the factors related to the details of excellent model hospitals.

Methods:  We sent a questionnaire on oral health care targeting all 8089 hospitals in Japan. On the basis of the responses obtained from the hospitals, we conducted a survey to analyze the factors defining what are known to be excellent model hospitals. We then conducted a logistic regression analysis using a stepwise procedure.

Results:  Replies were received from 2444 of the 8089 hospitals (30.2%): 91.8% of the hospitals reported that oral health care was a part of the daily nursing routine while 91.2% of the hospitals considered that aspiration pneumonia could be prevented by appropriate oral health care. Only 30% of the nurses had undergone oral hygiene training. Among the factors involved in excellent model hospitals, we observed a strong correlation with a sense of the necessity for oral health care, oral hygiene training for nurses and a large number of hospital beds.

Conclusion:  Large scale hospitals tend to be more interested in oral health care than smaller hospitals. Providing oral health care is already common in acute hospitals in Japan. There is a great demand for oral hygiene training and obtaining information from dental professionals. It is important to promote the cooperation between dental and nursing personnel within hospitals regarding oral hygiene training. Geriatr Gerontol Int 2011; 11: 460–466.
Evaluation of delirium in elderly: A hospital‐based study
Authors: Khurana Vishal , Gambhir Indrajeet Singh , Kishore Dhiraj
Published: May 2011

Aim:  The study aimed to study the prevalence, etiologies, clinical profile and outcome of delirium in hospitalized elderly in medicine wards.

Methods:  Four hundred elderly patients of more than 60 years of age admitted with delirium in the emergency and medicine wards of Sir Sunderlal Hospital Varanasi, India, were evaluated and managed. The Hindi version of the Mini‐Mental Status Examinations, a vernacular (Hindi) version of the Mini‐Mental State Examination, was used for evaluation of cognitive function status of patients and Confusion Assessment Method (CAM), a screening instrument based on the third edition of the Diagnostic and Statistical Manual of Mental Disorders was used for diagnosis of delirium.

Results:  A total of 400 hospitalized elderly delirious patients were included in the study aged 61–105 years. The mean age of the subjects was 70.87 ± 9.26 years and 70.81 ± 8.4 years amongst males and females, respectively. The mortality rate was 14.75%. Out of nine CAM features, all the cases had all three essential features, 78.75% had four features, 58.5% had five features, 44.5% had six features and 9.25% had all nine features. There was a high prevalence of hypoactive delirium (65%) as compared to hyperactive (25%) or mixed (10%). Most common etiologies were sepsis followed by metabolic abnormalities. 70% had 2 or more etiologies.

Conclusion:  Sepsis and metabolic abnormalities were the most common etiologies of delirium in this study. The maximum patients had more than one etiology and this emphasizes the multifactorial nature of delirium and need for thorough evaluation to unravel them. Most of the causes were treatable and have favorable outcome (83% recovered). Geriatr Gerontol Int 2011; 11: 467–473.
Modified evisceration technique in a golden eagle (Aquila chrysaetos)
Authors: Dees D. Dustin , Knollinger Amy M. , MacLaren Nicole E.
Published: May 2011

Two different modified techniques have been described for enucleation in raptors, including the transaural approach and the globe‐collapsing procedure. This case report describes an alternative, modified evisceration procedure in a mature female Golden Eagle (Aquila chrysaetos). The advantages of this procedure are decreased anesthetic time, ease of procedure, decreased risk of excessive traction of the optic nerve, decreased intraoperative orbital trauma, and preservation of the natural symmetry of the head. The major disadvantage of this procedure is that it does not allow complete histologic examination of the globe. Patients with intraocular infection or neoplasia, or significant orbital disease may be poor candidates for this technique.
Infective complications after transrectal ultrasound‐guided prostate biopsy following a new protocol for antibiotic prophylaxis aimed at reducing hospital‐acquired infections
Authors: Madden Thomas , Doble Andrew , Aliyu Sani H. , Neal David E.
Published: May 2011

Study Type – Therapy (case series)

Level of Evidence 4

What’s known on the subject? and What does the study add?

Clostridium Difficile infections have been a serious problem throughout the NHS and have forced clinicians to change the types of antibiotics they routinely prescribe.

Ciprofloxacin is a good choice of prophylactic agent for TRUSP Bx.

Co‐amoxiclav and gentamicin have never been studied in combinations as prophylaxis for TRUSP Bx.

Co‐amoxiclav and gentamicin in combination are an inferior choice of prophylactic agent compared to Ciprofloxacin.

Development of Clostridium Difficile infection does not appear to be a concern when using Ciprofloxacin as prophylaxis for TRUSP Bx.

Any change in antibiotic usage should take into account local knowledge of antiobiotic resitance as well as published evidence.

OBJECTIVE

• To compare the infective complications between two different antibiotic regimens used as prophylaxis for transrectal ultrasound‐guided prostate biopsy (TRUSP Bx).

PATIENTS AND METHODS

• The records of 709 consecutive patients undergoing TRUSP Bx over a period of 20 months at a UK teaching hospital were examined retrospectively.

• All clinic letters, microbiology reports and admission records were examined for each patient.

RESULTS

• Within the study period a total of 454 patients received prophylaxis with ciprofloxacin; 11 of these patients (2.4%) developed an infective complication within 4 weeks of the TRUSP Bx.

• A total of 255 patients received prophylaxis with co‐amoxiclav and gentamicin; 33 patients (12.9%) in this group had an infective complication.

• No cases of Clostridium difficile infection were recorded for any of these patients within 1 month of receiving antibiotics.

• Re‐introduction of the original regimen led to a fall in infective complications.

CONCLUSION

• Understandable concerns about the development of hospital‐acquired infection led to a new protocol for antibiotic prophylaxis which in turn led to a number of patients being put at increased risk of potentially serious infective complications. Antibiotic prophylaxis must reflect tissue penetration, the organisms encountered and their susceptibilities, as well as being based on objective evidence.
Non‐inferiority of silodosin to tamsulosin in treating patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH)
Authors: Yu Hong‐Jeng , Lin Alex Tong‐Long , Yang Stephen Shei‐Dei , Tsui Ke‐Hung , Wu Hsi‐Chin , Cheng Chen‐Li , Cheng Hong‐Lin , Wu Tony T. , Chiang Po‐Hui
Published: May 2011

Study Type – Therapy (RCT)

Level of Evidence 1b

What’s known on the subject? and What does the study add?

Silodosin administered by 4 mg twice daily is as effective as tamsulosin 0.2 mg daily in treating patients with LUTS associated with BPH.

Relative to tamsulosin, silodosin has less cardiovascular side effects as judged by the minimal changes of blood pressure and pulse rats after treatment.

OBJECTIVE

• To test the hypothesis that the efficacy of silodosin would not be inferior to tamsulosin in treating patients with lower urinary tract symptoms associated with benign prostate hyperplasia (BPH).

PATIENTS AND METHODS

• At nine medical centres, 209 patients with an International Prostate Symptom Score (IPSS) of ≥13 were randomized to silodosin (4 mg twice daily) or tamsulosin (0.2 mg once daily) for 12 weeks.

• The primary efficacy measure was the mean change from baseline to endpoint in IPSS.

• The non‐inferiority margin of the IPSS change was set at 1.0.

• Secondary efficacy measures included change in maximal urinary flow rate (Qmax) and health‐related quality of life (HRQL) score.

RESULTS

• Of the 170 (81.3%) patients who completed the study, 86.2% in the silodosin group vs 81.9% in the tamsulosin group achieved a ≥25% decrease in IPSS (P= 0.53).

• The mean difference (silodosin minus tamsulosin) in IPSS change from baseline was −0.60 (95% confidence interval −2.15, 0.95), inferring the non‐inferiority of silodosin to tamsulosin.

• The mean changes in the Qmax and HRQL score from baseline were comparable between the groups (both, P > 0.05). Although patients receiving silodosin had a significantly higher incidence of abnormal ejaculation (9.7% vs tamsulosin 1.0%, P= 0.009), only 1.9% discontinued treatment.

• Tamsulosin treatment resulted in a significant reduction in mean systolic blood pressure (−4.2 mmHg, within‐group P= 0.004) relative to the negligible change of silodosin (−0.1 mmHg, within‐group P= 0.96)

CONCLUSION

• The trial shows the non‐inferiority of silodosin 4 mg twice daily to tamsulosin 0.2 mg once daily in patients with symptoms of BPH.