Quality of life after hepatic resection.

BACKGROUND: Long-term quality of life (QoL) after liver resection is becoming increasingly important, as improvements in operative methods and perioperative care have decreased morbidity and mortality rates. In this study, postoperative QoL after resection of benign or malignant liver tumours was evaluated. METHODS: In this single-centre study, QoL was evaluated prospectively using the European Organisation for Research and Treatment of Cancer QLQ-C30 and the liver-specific QLQ-LMC21 module before, and 1, 3, 6 and 12 months after open or laparoscopic liver surgery. RESULTS: Between June 2007 and January 2013, 188 patients (130 with malignant and 58 with benign tumours) requiring major liver resection were included. Global health status was no different between the two groups before and 1 month after liver resection. All patients showed an improvement in global health status at 3, 6 and 12 months after surgery. Patients with benign tumours had better global health status than those with malignant tumours at these time points (P < 0·001, P = 0·002 and P = 0·006 respectively). Patients with benign disease had better physical function scores (P = 0·011, P = 0·025 and P = 0·041) and lower fatigue scores (P = 0·001, P = 0·002 and P = 0·002) at 3, 6 and 12 months than those with malignant disease. CONCLUSION: This study confirmed overall good QoL in patients undergoing liver resection for benign or malignant tumours, which improved after surgery. Benign diseases were associated with better short- and long-term QoL scores.

Obstacles to reduction in infantile developmental dysplasia of the hip.

PURPOSE: Identification of anatomical structures that block -reduction in developmental dysplasia of the hip (DDH) is -important for the management of this challenging condition. Obstacles to reduction seen on arthrogram are well-known. However, despite the increasing use of MRI in the assessment of adequacy of reduction in DDH, the interpretation of MRI patho-anatomy is ill-defined with a lack of relevant literature to guide clinicians. METHOD: This is a retrospective analysis of the MRI of patients with DDH treated by closed reduction over a five-year period (between 2009 and 2014). Neuromuscular and genetic disorders were excluded. Each MRI was analysed by two orthopaedic surgeons and a paediatric musculoskeletal radiologist to identify the ligamentum teres, pulvinar, transverse acetabular ligament (TAL), capsule, labrum and acetabular roof cartilage hypertrophy. Inter- and intraobserver reliability was calculated. The minimum follow-up was 12 months. RESULTS: A total of 29 patients (38 hips) underwent closed reduction for treatment of DDH. Eight hips showed persistent subluxation on post-operative MRI. Only three of these eight hips showed an abnormality on arthrogram. The pulvinar was frequently interpreted as 'abnormal' on MRI. The main obstacles identified on MRI were the ligamentum teres (15.8%), labrum (13.1%) and acetabular roof cartilage hypertrophy (13.2%). The inter-rater reliability was good for TAL, capsule and pulvinar; moderate for ligamentum teres and labrum; and poor for hypertrophied cartilage. CONCLUSION: The labrum, ligamentum teres and acetabular roof cartilage hypertrophy are the most important structures seen on MRI preventing complete reduction of DDH. Focused interpretation of these structures may assist in the management of DDH.

MR-FLIP: a new method that combines a functional lumen imaging probe with anatomical information for spatial compliance assessment of the anal sphincter muscles.

AIM: Continence results from a complex interplay between anal canal (AC) muscles and sensorimotor feedback mechanisms. The passive ability of the AC to withstand opening pressure - its compliance - has recently been shown to correlate with continence. A functional lumen imaging probe (FLIP) is used to assess AC compliance, although it provides no anatomical information. Therefore, assessment of the compliance specific anatomical structures has not been possible, and the anatomical position of critical functional zones remains unknown. In addition, the FLIP technique assumes a circular orifice cross-section, which has not been shown for the AC. To address these shortcomings, a technique combining FLIP with a medical imaging modality is needed. METHOD: We implemented a new research method (MR-FLIP) that combines FLIP with MR imaging. Twenty healthy volunteers underwent MR-FLIP and conventional FLIP assessment. MR-FLIP was validated by comparison with FLIP results. Anatomical markers were identified, and the cross-sectional shape of the orifice was investigated. RESULTS: MR-FLIP provides compliance measurements identical to those obtained by conventional FLIP. Anatomical analysis revealed that the least compliant AC zone was located at the proximal end of the external anal sphincter (EAS). The cross-sectional shape of the AC was found to deviate only slightly from circularity in healthy volunteers. CONCLUSION: The proposed method is equivalent to classical FLIP. It establishes for the first time direct mapping between local tissue compliance and anatomical structure, which is key to gaining novel insights into (in)continence. In addition, MR-FLIP provides a tool for better understanding conventional FLIP measurements in the AC by quantifying its limitations and assumptions.

Significant lethality following liver resection in A20 heterozygous knockout mice uncovers a key role for A20 in liver regeneration.

Hepatic expression of A20, including in hepatocytes, increases in response to injury, inflammation and resection. This increase likely serves a hepatoprotective purpose. The characteristic unfettered liver inflammation and necrosis in A20 knockout mice established physiologic upregulation of A20 as integral to the anti-inflammatory and anti-apoptotic armamentarium of hepatocytes. However, the implication of physiologic upregulation of A20 in modulating hepatocytes' proliferative responses following liver resection remains controversial. To resolve the impact of A20 on hepatocyte proliferation and the liver's regenerative capacity, we examined whether decreased A20 expression, as in A20 heterozygous knockout mice, affects outcome following two-third partial hepatectomy. A20 heterozygous mice do not demonstrate a striking liver phenotype, indicating that their A20 expression levels are still sufficient to contain inflammation and cell death at baseline. However, usually benign partial hepatectomy provoked a staggering lethality (>40%) in these mice, uncovering an unsuspected phenotype. Heightened lethality in A20 heterozygous mice following partial hepatectomy resulted from impaired hepatocyte proliferation due to heightened levels of cyclin-dependent kinase inhibitor, p21, and deficient upregulation of cyclins D1, E and A, in the context of worsened liver steatosis. A20 heterozygous knockout minimally affected baseline liver transcriptome, mostly circadian rhythm genes. Nevertheless, this caused differential expression of >1000 genes post hepatectomy, hindering lipid metabolism, bile acid biosynthesis, insulin signaling and cell cycle, all critical cellular processes for liver regeneration. These results demonstrate that mere reduction of A20 levels causes worse outcome post hepatectomy than full knockout of bona fide liver pro-regenerative players such as IL-6, clearly ascertaining A20's primordial role in enabling liver regeneration. Clinical implications of these data are of utmost importance as they caution safety of extensive hepatectomy for donation or tumor in carriers of A20/TNFAIP3 single nucleotide polymorphisms alleles that decrease A20 expression or function, and prompt the development of A20-based liver pro-regenerative therapies.

Molecular epidemiology of tuberculosis in Cambodian children.

SUMMARY We analysed Mycobacterium tuberculosis strains from children, hospitalized from January 2004 to July 2008 in the largest paediatric hospital complex in Cambodia. Specimens were tested for drug susceptibility and genotypes. From the 260 children, 161 strains were available. The East African-Indian genotype family was the most common (59.0%), increasing in frequency with distance from the Phnom Penh area, while the frequency of the Beijing genotype family strains decreased. The drug resistance pattern showed a similar geographical gradient: lowest in the northwest (4.6%), intermediate in the central (17.1%), and highest in the southeastern (30.8%) parts of the country. Three children (1.9%) had multidrug-resistant tuberculosis. The Beijing genotype and streptomycin resistance were significantly associated (P < 0.001). As tuberculosis in children reflects recent transmission patterns in the community, multidrug resistance levels inform about the current quality of the tuberculosis programme.

Orthogeriatric care pathway: a prospective survey of impact on length of stay, mortality and institutionalisation.

INTRODUCTION: Care pathways for elderly hip fracture patients are increasingly implemented but there has been only limited evaluation of their use. Our objective was to investigate the impact of such a care pathway on the use of healthcare resources and on patients' outcomes. MATERIALS AND METHODS: The prospective survey covered 493 hip fracture patients 65 years of age or older that were treated either before "Usual Care = (UC)" or after "Co-Managed-Care = (CMC)" implementation of the care pathway. Primary outcome was length of stay (LoS). Secondary outcomes were 1-year mortality and change in residential status from prefracture baseline to 1-year after surgery. Data were analysed by descriptive and interferential statistics and adjustment for baseline differences amongst the two patient groups was done. RESULTS: Patients in the CMC sample had more preexisting comorbidities (CCI 2.5 versus 2.1). Prior to the fracture, a larger proportion amongst them needed help in ADL (49 versus 26%), and they were more likely to reside in a nursing home (36 versus 29%). Prefracture mobility status was equal in both samples. In the CMC sample LoS was significantly shorter (LoS 8.6 versus 11.3 days, p < 0.01) and patients were less likely to experience a complication (59 vs 73%, p < 0.01) while being in the hospital. There was no significant difference in 1-year mortality or in change of residential status. CONCLUSIONS: A care pathway for elderly hip fracture patients allowed decreased LoS without affecting mortality or change of residential status 1 year after fracture compared to prefracture baseline.

Gadoxetate uptake as a possible marker of hepatocyte damage after liver resection-preliminary data.

AIM: To determine the feasibility of evaluating surgically induced hepatocyte damage using gadoxetate disodium (Gd-EOB-DTPA) as a marker for viable hepatocytes at magnetic resonance imaging (MRI) after liver resection. MATERIAL AND METHODS: Fifteen patients were prospectively enrolled in this institutional review board-approved study prior to elective liver resection after informed consent. Three Tesla MRI was performed 3-7 days after surgery. Three-dimensional (3D) T1-weighted (W) volumetric interpolated breath-hold gradient echo (VIBE) sequences covering the liver were acquired before and 20 min after Gd-EOB-DTPA administration. The signal-to-noise ratio (SNR) was used to compare the uptake of Gd-EOB-DTPA in healthy liver tissue and in liver tissue adjacent to the resection border applying paired Student's t-test. Correlations with potential influencing factors (blood loss, duration of intervention, age, pre-existing liver diseases, postoperative change of resection surface) were calculated using Pearson's correlation coefficient. RESULTS: Before Gd-EOB-DTPA administration the SNR did not differ significantly (p = 0.052) between healthy liver tissue adjacent to untouched liver borders [59.55 ± 25.46 (SD)] and the liver tissue compartment close to the resection surface (63.31 ± 27.24). During the hepatocyte-specific phase, the surgical site showed a significantly (p = 0.04) lower SNR (69.44 ± 24.23) compared to the healthy site (78.45 ± 27.71). Dynamic analyses revealed a significantly lower increase (p = 0.008) in signal intensity in the healthy tissue compared to the resection border compartment. CONCLUSION: EOB-DTPA-enhanced MRI may have the potential to be an effective non-invasive tool for detecting hepatocyte damage after liver resection.

Quantum engineering at the silicon surface using dangling bonds.

Individual atoms and ions are now routinely manipulated using scanning tunnelling microscopes or electromagnetic traps for the creation and control of artificial quantum states. For applications such as quantum information processing, the ability to introduce multiple atomic-scale defects deterministically in a semiconductor is highly desirable. Here we use a scanning tunnelling microscope to fabricate interacting chains of dangling bond defects on the hydrogen-passivated silicon (001) surface. We image both the ground-state and the excited-state probability distributions of the resulting artificial molecular orbitals, using the scanning tunnelling microscope tip bias and tip-sample separation as gates to control which states contribute to the image. Our results demonstrate that atomically precise quantum states can be fabricated on silicon, and suggest a general model of quantum-state fabrication using other chemically passivated semiconductor surfaces where single-atom depassivation can be achieved using scanning tunnelling microscopy.

Perspective on the evolution of cell-based bone tissue engineering strategies.

Despite the compelling clinical needs in enhancing bone regeneration and the potential offered by the field of tissue engineering, the adoption of cell-based bone graft substitutes in clinical practice is limited to date. In fact, no study has yet convincingly demonstrated reproducible clinical performance of tissue-engineered implants and at least equivalent cost-effectiveness compared to the current treatment standards. Here, we propose and discuss how tissue engineering strategies could be evolved towards more efficient solutions, depicting three different experimental paradigms: (i) bioreactor-based production; (ii) intraoperative manufacturing, and (iii) developmental engineering. The described approaches reflect the need to streamline graft manufacturing processes while maintaining the potency of osteoprogenitors and recapitulating the sequence of biological steps occurring during bone development, including vascularization. The need to combine the assessment of efficacy of the different strategies with the understanding of their mechanisms of action in the target regenerative processes is highlighted. This will be crucial to identify the necessary and sufficient set of signals that need to be delivered at the injury or defect site and should thus form the basis to define release criteria for reproducibly effective engineered bone graft substitutes.

Laboratory diagnosis of tuberculosis in a large pediatric hospital in Cambodia.

SETTING: Tuberculosis laboratory in the Jayavarman VII Children's Hospital in Siem Reap, part of the Kantha Bopha Hospitals, the largest pediatric hospital complex in Cambodia. OBJECTIVE: To determine the efficiency of on-site microscopy and rRNA amplification in children with a clinical diagnosis of tuberculosis (TB) and specimen sampling for culture. RESULTS: From 1 July 2005 to 31 March 2006, 52,400 children were admitted to the hospital. Among these, 405 children had tuberculosis, including 91 (22.5%) laboratory-confirmed cases, or respectively 7.7 and 1.7 per 1000 admissions. Among cases confirmed by microscopy or rRNA assay, rRNA identified 91.2%. Among all culture-confirmed cases, rRNA identified 90.5%. Culture alone contributed 7.1% to all laboratory confirmed cases. The yield of culture from preserved specimens was not affected by shipment delay. For 97.4% of the children, the maximum turnaround time for the on-site laboratory result was 48 h. CONCLUSION: Implementation of a mycobacteriology service in a referral hospital is feasible, as the molecular technique is highly efficient. Storage of specimen aliquots allows subsequent culture without loss of viability due to shipment delay.

[Open stabilization and primary hip arthroplasty in geriatric patients with acetabular fractures: combination of minimally invasive techniques]. / Offene Stabilisierung und Endoprothetik bei geriatrischen Patienten mit acetabulären Frakturen: Kombination minimal-invasiver Operationstechniken.

Fractures of the acetabulum after low-energy trauma in geriatric patients suffering from osteoporosis are increasing in number and significance due to demographic changes. The results of current therapeutic principles though tend to be poor in this population, while risk and treatment-related morbidity of surgical or conservative approaches are substantial.The treatment of geriatric patients can be challenging, not only because of their often complex medical history. They essentially need rapid functional restoration and return to their familiar environment to avoid general decline unlike younger patients for whom rather the long-term perspective is crucial. This article critically discusses the current literature and reports on first experiences with a new surgical concept in six geriatric patients aged 82-91 years: the combination of an anterior minimally invasive approach for open reduction and internal fixation of the acetabulum combined with an anterior minimally invasive (AMIS®) approach to the hip for total hip arthroplasty with promising short-term results.

Recent aspects on outcomes in geriatric fracture patients.

As the population ages, the number of fragility fractures is expected to increase dramatically. These injuries are frequently associated with less than satisfactory outcomes. Many of the patients experience adverse events or death, and few regain their pre-injury functional status. Many also lose their independence as a result of their fracture. This manuscript will explore problems and some potential solutions to evaluate the outcomes of geriatric fracture care. Specific, system-wide, and societal concerns will be discussed. Limited suggestions will be made for future steps to improve outcomes assessments.

Quantum-to-classical transition in cavity quantum electrodynamics.

The quantum properties of electromagnetic, mechanical or other harmonic oscillators can be revealed by investigating their strong coherent coupling to a single quantum two level system in an approach known as cavity quantum electrodynamics (QED). At temperatures much lower than the characteristic energy level spacing the observation of vacuum Rabi oscillations or mode splittings with one or a few quanta asserts the quantum nature of the oscillator. Here, we study how the classical response of a cavity QED system emerges from the quantum one when its thermal occupation-or effective temperature-is raised gradually over 5 orders of magnitude. In this way we explore in detail the continuous quantum-to-classical crossover and demonstrate how to extract effective cavity field temperatures from both spectroscopic and time-resolved vacuum Rabi measurements.

Lymphatic microvessel density and lymphovascular invasion assessed by anti-podoplanin immunostaining in human breast cancer.

BACKGROUND: The development of an antibody against podoplanin has enabled us to selectively stain lymphatic vessels in breast cancer samples for the first time. MATERIALS AND METHODS: We investigated lymphatic vessels in 45 specimens of invasive breast cancer by immunostaining for podoplanin. Lymphatic microvessel density (LMVD) was correlated with various clinical and histopathological parameters. LMVD was also compared to blood microvessel density (BMVD), assessed by CD34 -immunostaining. RESULTS: LMVD as well as lymphovascular invasion (LVI) correlated significantly with the lymph node status (p=0.001/ p=0.035). Logistic regression revealed that LVI was the more important factor for development of lymph node metastasis (p=0.043). There was no significant association between various clinical and histopathological parameters and LMVD or LVI, nor was a correlation found between LMVD and BMVD (p=0.121). CONCLUSION: High LMVD and the presence of LVI are strongly associated with lymph node metastasis in breast cancer.

Myocardial infarction during a football game: empiric estimation of the contribution of skeletal muscle damage to the serum creatine kinase activity.

A 40-year-old untrained participant of a competitive football game experienced chest pain after 20 minutes of playing time. An acute anterior myocardial infarction was diagnosed by electrocardiographic criteria and the creatine kinase rose to its maximum of 3900 U/l (normal range less than 125 U/l) by 24 h with a CK-MB fraction of 6.1%. In order to estimate the contribution of skeletal muscular work to CK activity, the course of CK activity was prospectively measured in 11 untrained participants of a competitive football game, who had normal electrocardiographic findings on exercise testing. Individual peak values of CK correlated positively (p less than 0.01) with the time spent in play. Based on this observation we could estimate that, at most, 14% of the total CK was contributed by skeletal muscle damage in our patient. When total CK was elevated above 125 U/l, the percentage of CK-MB activity did not exceed 6% of total CK in any case. 3-methylhistidine, methylhistidine, an indicator of contractile protein turnover and creatinine were prospectively determined in spot urine samples before the game and for up to 48 h after the game. 3-methylhistidine/creatinine ratios did not change from baseline after the game and no correlation with CK was found. Urine 3-methylhistidine/creatinine, measured within 48 h after a football game, does not contribute to the quantification of skeletal muscle damage.

[Large bladder diverticulum or double bladder--diagnosis and differential diagnosis]. / Grosses Blasendivertikel oder Doppelblase--Diagnose und Differentialdiagnose.

We report a case of a 13 year old boy with trisomy 21 syndrome who presented with recurrent urinary tract infections. A duplication of the urinary bladder was diagnosed by echography and x-ray examination with each portion of the duplicated bladder having its own uretral opening: Surgery and histology showed however the lesion to be a large diverticulum of the urinary bladder with the right uretral orifice being located in the wall of the diverticulum.

[Vascular diseases in 534 Swiss diabetics within the scope of a multinational study]. / Vaskuläre Erkrankungen bei 534 Schweizer Diabetikern im Rahmen einer multinationalen Studie.

In Switzerland 278 diabetic men and 256 women in the age group 35 to 54 were examined for the presence of angiopathic lesions, according to a standardized protocol of a multinational study comprising 6,695 diabetics from 14 countries. The diabetics were distributed according to sex, age, and duration of the disease into groups of equal size. Macro-angiopathy, as the sum of coronary heart disease, stroke, and vascular disease of the legs was found in 28% of men and in 29% of women in the Swiss group. The prevalence of myocardial infarction alone was 6.8% in men and 5.5% in women. These rates did not differ from those found in the other national groups. Micro-angiopathy was found in the form of retinopathy in 35% and as nephropathy in 32% of the Swiss diabetics. These rates were not different from those of all groups. Severe retinopathy was found more frequently in Swiss diabetics than in the whole study. Micro-angiopathy was strongly related to duration, hypertension, and type of treatment in all centres. Japanese diabetics showed a higher frequency of micro-angiopathy, although macrovascular disease was found at a low rate. Systolic blood pressure (BP) in the Swiss diabetics did not differ from the results of the whole group. In 14% of the Swiss diabetic men and in 18% of the women, systolic BP was over 160 mmHg. These rates were remarkably higher than in an age- and sex-matched sample of a randomly selected sample of a Swiss population (3.2% in men, 2.4% in women). Cholesterol was high in the Swiss diabetic groups, whereas body mass index was in the intermediate range. Of the Swiss diabetic men 38% smoked regularly. The frequency of coronary heart disease in Swiss men and women was similar. This is different from the lower rate usually found in non-diabetic women. Age, and not duration of the disease was the most important factor relating to macro-angiopathy. The different rates of macro- and microvascular complications in various populations, selected according to the same protocol, suggests that the risk factors for macrovascular disease differ from those of microvascular complications. Race, nutrition, treatment, exercise, and hypertension may further influence the prevalence of angiopathy in diabetics of same sex, age, and duration of the disease.

In vitro and in vivo studies on glucagonoma tissue.

A 66 year old patient with diabetes had a necrolytic migratory erythema, weight loss and anaemia. Plasma immunoreactive glucagon (IRG) of 2465 pmoles/l (normal 35 +/- 5 SEM pmoles/l) suggested the existence of a glucagonoma which was confirmed by arteriography and subsequently removed by surgery. Although plasma IRG returned to normal, glucose tolerance and insulin secretion remained pathological. Plasma amino acid levels had been reduced but were corrected by surgery. Pancreatic polypeptide, however, 298 pmoles/l before was still 206 pmoles/l after the operation (normal 12-48 pmoles per litre). Column chromatography of plasma and tumor extracts showed quantitatively important IRG fractions with molecular weights above 9000 daltons, possibly precursors of glucagon. Beside a 50-fold IRG excess, the tumour concentrations of insulin and somatostatin were 4 to 150 times increased. By contrast, pancreatic polypeptide was present in normal amounts. Electron microscopic examination showed atypical A-cell granula and unusual abundance of mitochondria.