Non-metastatic castrate-resistant prostate cancer: a call for improved guidance on clinical management.

BACKGROUND Guidelines on the clinical management of non-metastatic castrate-resistant prostate cancer (nmCRPC) generally focus on the need to continue androgen deprivation therapy and enrol patients into clinical trials of investigational agents. This guidance reflects the lack of clinical trial data with established agents in the nmCRPC patient population and the need for trials of new agents. AIM To review the evidence base and consider ways of improving the management of nmCRPC. CONCLUSION Upon the development of castrate resistance, it is essential to rule out the presence of metastases or micrometastases by optimising the use of bone scans and possibly newer procedures and techniques. When nmCRPC is established, management decisions should be individualised according to risk, but risk stratification in this diverse population is poorly defined. Currently, prostate-specific antigen (PSA) levels and PSA doubling time remain the best method of assessing the risk of progression and response to treatment in nmCRPC. However, optimising imaging protocols can also help assess the changing metastatic burden in patients with CRPC. Clinical trials of novel agents in nmCRPC are limited and have problems with enrolment, and therefore, improved risk stratification and imaging may be crucial to the improved management. The statements presented in this paper, reflecting the views of the authors, provide a discussion of the most recent evidence in nmCRPC and provide some advice on how to ensure these patients receive the best management available. However, there is an urgent need for more data on the management of nmCRPC.

500 ml of blood loss does not decrease non-invasive tissue oxygen saturation (StO2) as measured by near infrared spectroscopy - A hypothesis generating pilot study in healthy adult women

Background The goal when resuscitating trauma patients is to achieve adequate tissue perfusion. One parameter of tissue perfusion is tissue oxygen saturation (StO2), as measured by near infrared spectroscopy. Using a commercially available device, we investigated whether clinically relevant blood loss of 500 ml in healthy volunteers can be detected by changes in StO2 after a standardized ischemic event. Methods We performed occlusion of the brachial artery for 3 minutes in 20 healthy female blood donors before and after blood donation. StO2 and total oxygenated tissue hemoglobin (O2Hb) were measured continuously at the thenar eminence. 10 healthy volunteers were assessed in the same way, to examine whether repeated vascular occlusion without blood donation exhibits time dependent effects. Results Blood donation caused a substantial decrease in systolic blood pressure, but did not affect resting StO2 and O2Hb values. No changes were measured in the blood donor group in the reaction to the vascular occlusion test, but in the control group there was an increase in the O2Hb rate of recovery during the reperfusion phase. Conclusion StO2 measured at the thenar eminence seems to be insensitive to blood loss of 500 ml in this setting. Probably blood loss greater than this might lead to detectable changes guiding the treating physician. The exact cut off for detectable changes and the time effect on repeated vascular occlusion tests should be explored further. Until now no such data exist.

Dialysis and Renal Transplantation in HIV-Infected Patients: a European Survey

OBJECTIVES:: To determine prevalence and characteristics of end-stage renal diseases (ESRD) [dialysis and renal transplantation (RT)] among European HIV-infected patients. METHODS:: Cross-sectional multicenter survey of EuroSIDA clinics during 2008. RESULTS:: Prevalence of ESRD was 0.5%. Of 122 patients with ESRD 96 were on dialysis and 26 had received a RT. Median age was 47 years, 73% were males and 43% were black. Median duration of HIV infection was 11 years. Thirty-three percent had prior AIDS; 91% were receiving antiretrovirals; and 88% had undetectable viral load. Median CD4T-cell count was 341 cells per cubic millimetre; 20.5% had hepatitis C coinfection. Most frequent causes of ESRD were HIV-associated nephropathy (46%) and other glomerulonephritis (28%). Hemodialysis (93%) was the most common dialysis modality; 34% of patients were on the RT waiting list. A poor HIV control was the reason for exclusion from RT waiting list in 22.4% of cases. All the RT recipients were all alive at the time of the survey. Acute rejection was reported in 8 patients (30%). Functioning graft was present in 21 (80%). CONCLUSIONS:: This is the first multinational cross-sectional study of ESRD among European HIV population. Low prevalence of ESRD was found. Two-thirds of patients were excluded from RT for non-HIV/AIDS-related pathologies. Most patients had a functioning graft despite a high acute rejection rate.

Effects of the two production programs 'Naturafarm' and 'conventional' on the prevalence of non-perforating abomasal lesions in Swiss veal calves at slaughter

Non-perforating abomasal lesions are a considerable problem affecting more than half the population of veal calves. The objective of the present study was to assess the prevalence of pyloric and fundic abomasal lesions in Swiss veal calves at slaughter and to compare the occurrence of non-perforating abomasal lesions between two different production programs ('Naturafarm' and 'conventional'). 'Conventional'-production settings met the minimal standards as defined by the Swiss animal welfare legislation, whereas 'Naturafarm' production complied with increased animal welfare requirements. In order to identify risk factors for the development of abomasal lesions, information on management, housing, and feeding was obtained by a questionnaire. A total of 125 abomasa were randomly selected in one large abattoir. They were examined macroscopically, and the occurence of lesions in either the fundic or pyloric region of the abomasum was recorded separately. Animals raised in the 'conventional'-production setting revealed a significantly higher prevalence of lesions in the fundic part. Factors significantly affecting the prevalence of non-perforating lesions in the fundic part were the 'conventional'-production environment, including missing access to an outside pen, missing access to water and straw as the only roughage, feeding by bucket and the liquid milk by-product Protofit in combination with the powder Sprayfit.

ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS)

Cardiovascular disease (CVD) due to atherosclerosis of the arterial vessel wall and to thrombosis is the foremost cause of premature mortality and of disability-adjusted life years (DALYs) in Europe, and is also increasingly common in developing countries.1 In the European Union, the economic cost of CVD represents annually E192 billion1 in direct and indirect healthcare costs. The main clinical entities are coronary artery disease (CAD), ischaemic stroke, and peripheral arterial disease (PAD). The causes of these CVDs are multifactorial. Some of these factors relate to lifestyles, such as tobacco smoking, lack of physical activity, and dietary habits, and are thus modifiable. Other risk factors are also modifiable, such as elevated blood pressure, type 2 diabetes, and dyslipidaemias, or non-modifiable, such as age and male gender. These guidelines deal with the management of dyslipidaemias as an essential and integral part of CVD prevention. Prevention and treatment of dyslipidaemias should always be considered within the broader framework of CVD prevention, which is addressed in guidelines of the Joint European Societies’ Task forces on CVD prevention in clinical practice.2 – 5 The latest version of these guidelines was published in 20075; an update will become available in 2012. These Joint ESC/European Atherosclerosis Society (EAS) guidelines on the management of dyslipidaemias are complementary to the guidelines on CVD prevention in clinical practice and address not only physicians [e.g. general practitioners (GPs) and cardiologists] interested in CVD prevention, but also specialists from lipid clinics or metabolic units who are dealing with dyslipidaemias that are more difficult to classify and treat.

Biomarkers for Hepatocellular Apoptosis in the Management of Liver Diseases

Apoptosis is a rare event in normal hepatocytes. However, multiple signals can trigger apoptosis in hepatocytes and it plays a role in the pathogenesis of many liver diseases. This review summarizes the mechanisms of hepatocellular apoptosis and the importance of apoptosis in the pathological processes of liver disease. The potential for non-invasive biomarkers of apoptosis to gauge the extent and follow the evolution of clinical disease is emphasized.

Alternating one lung ventilation using a double lumen endobronchial tube and providing CPAP to the non-ventilated lung in a dog

INTRODUCTION: This case report describes the anaesthetic management of exploratory thoracoscopy and alternating one lung ventilation (OLV) in a dog with a pulmonary bulla, and the application of continuous positive airway pressure (CPAP) to the non-ventilated lung for preventing and treating hypoxia. CASE HISTORY: A 6-year-old, male castrated Border collie was scheduled for exploratory thoracoscopy to investigate spontaneous pnemothorax that had not resolved with repeated suction. Specific requirements for the thoracoscopy were alternating OLV to allow the surgical access to the right middle lobe and its removal, and the examination of the left hemithorax to rule out the presence of other lesions. DIAGNOSIS AND MANAGEMENT: Selective lung ventilation was performed with a double lumen endobronchial tube (DLT), inserted under endoscopic guidance. After a short period of two lung ventilation during preparation of the surgical field, alternating OLV was performed, combining CPAP, provided to the non-ventilated lung via a Mapleson D breathing system, and positive end-expiratory pressure (PEEP) applied to the ventilated lung. Left OLV occurred first and resection of the right middle pulmonary lobe was successfully performed; right OLV followed to allow the examination of the left hemithorax. DISCUSSION AND CONCLUSIONS: The combination of CPAP and PEEP resulted in a satisfactory intra-operative management of hypoxemia. Alternating OLV can be performed successfully by using a DLT. CPAP, commonly employed in human medicine, should be considered an important tool in the anaesthetic management of OLV in small animals.

Consensus Document of the International Union of Angiology (IUA)-2013. Current concept on the management of arterio-venous management

Arterio-venous malformations (AVMs) are congenital vascular malformations (CVMs) that result from birth defects involving the vessels of both arterial and venous origins, resulting in direct communications between the different size vessels or a meshwork of primitive reticular networks of dysplastic minute vessels which have failed to mature to become 'capillary' vessels termed "nidus". These lesions are defined by shunting of high velocity, low resistance flow from the arterial vasculature into the venous system in a variety of fistulous conditions. A systematic classification system developed by various groups of experts (Hamburg classification, ISSVA classification, Schobinger classification, angiographic classification of AVMs,) has resulted in a better understanding of the biology and natural history of these lesions and improved management of CVMs and AVMs. The Hamburg classification, based on the embryological differentiation between extratruncular and truncular type of lesions, allows the determination of the potential of progression and recurrence of these lesions. The majority of all AVMs are extra-truncular lesions with persistent proliferative potential, whereas truncular AVM lesions are exceedingly rare. Regardless of the type, AV shunting may ultimately result in significant anatomical, pathophysiological and hemodynamic consequences. Therefore, despite their relative rarity (10-20% of all CVMs), AVMs remain the most challenging and potentially limb or life-threatening form of vascular anomalies. The initial diagnosis and assessment may be facilitated by non- to minimally invasive investigations such as duplex ultrasound, magnetic resonance imaging (MRI), MR angiography (MRA), computerized tomography (CT) and CT angiography (CTA). Arteriography remains the diagnostic gold standard, and is required for planning subsequent treatment. A multidisciplinary team approach should be utilized to integrate surgical and non-surgical interventions for optimum care. Currently available treatments are associated with significant risk of complications and morbidity. However, an early aggressive approach to elimiate the nidus (if present) may be undertaken if the benefits exceed the risks. Trans-arterial coil embolization or ligation of feeding arteries where the nidus is left intact, are incorrect approaches and may result in proliferation of the lesion. Furthermore, such procedures would prevent future endovascular access to the lesions via the arterial route. Surgically inaccessible, infiltrating, extra-truncular AVMs can be treated with endovascular therapy as an independent modality. Among various embolo-sclerotherapy agents, ethanol sclerotherapy produces the best long term outcomes with minimum recurrence. However, this procedure requires extensive training and sufficient experience to minimize complications and associated morbidity. For the surgically accessible lesions, surgical resection may be the treatment of choice with a chance of optimal control. Preoperative sclerotherapy or embolization may supplement the subsequent surgical excision by reducing the morbidity (e.g. operative bleeding) and defining the lesion borders. Such a combined approach may provide an excellent potential for a curative result. Conclusion. AVMs are high flow congenital vascular malformations that may occur in any part of the body. The clinical presentation depends on the extent and size of the lesion and can range from an asymptomatic birthmark to congestive heart failure. Detailed investigations including duplex ultrasound, MRI/MRA and CT/CTA are required to develop an appropriate treatment plan. Appropriate management is best achieved via a multi-disciplinary approach and interventions should be undertaken by appropriately trained physicians.

Pain management and the effect of guidelines in neonatal units in Austria, Germany and Switzerland

BACKGROUND: Painful invasive procedures are frequently performed on preterm infants admitted to a neonatal intensive care unit (NICU). The aim of the present study was to investigate current pain management in Austrian, German and Swiss NICU and to identify factors associated with improved pain management in preterm infants. METHODS: A questionnaire was sent to all Austrian, German and Swiss pediatric hospitals with an NICU (n = 370). Pain assessment and documentation, use of analgesics for 13 painful procedures, presence of written guidelines for pain management and the use of 12 analgesics and sedatives were examined. RESULTS: A total of 225 units responded (61%). Pain assessment and documentation and frequent analgesic therapy for painful procedures were performed more often in units using written guidelines for pain management and in those treating >50 preterm infants at <32 weeks of gestation per year. This was also the case for the use of opioid analgesics and sucrose solution. Non-opioid analgesics were used more often in smaller units and in units with written guidelines. There was a broad variation in dosage of analgesics and sedatives within all groups. CONCLUSION: Pain assessment, documentation of pain and analgesic therapy are more frequently performed in NICU with written guidelines for pain management and in larger units with more than 50 preterm infants at <32 weeks of gestation per year.

Moving from sustainable management to sustainable governance of natural resources: The role of social learning processes in rural India, Bolivia and Mali

The present paper discusses a conceptual, methodological and practical framework within which the limitations of the conventional notion of natural resource management (NRM) can be overcome. NRM is understood as the application of scientific ecological knowledge to resource management. By including a consideration of the normative imperatives that arise from scientific ecological knowledge and submitting them to public scrutiny, ‘sustainable management of natural resources’ can be recontextualised as ‘sustainable governance of natural resources’. This in turn makes it possible to place the politically neutralising discourse of ‘management’ in a space for wider societal debate, in which the different actors involved can deliberate and negotiate the norms, rules and power relations related to natural resource use and sustainable development. The transformation of sustainable management into sustainable governance of natural resources can be conceptualised as a social learning process involving scientists, experts, politicians and local actors, and their corresponding scientific and non-scientific knowledges. The social learning process is the result of what Habermas has described as ‘communicative action’, in contrast to ‘strategic action’. Sustainable governance of natural resources thus requires a new space for communicative action aiming at shared, intersubjectively validated definitions of actual situations and the goals and means required for transforming current norms, rules and power relations in order to achieve sustainable development. Case studies from rural India, Bolivia and Mali explore the potentials and limitations for broadening communicative action through an intensification of social learning processes at the interface of local and external knowledge. Key factors that enable or hinder the transformation of sustainable management into sustainable governance of natural resources through social learning processes and communicative action are discussed.

Acute coronary syndromes: management and secondary prevention

Acute coronary syndromes represent a broad spectrum of ischemic myocardial events including unstable angina, non-ST elevation myocardial infarction and acute ST elevation myocardial infarction, which are associated with high morbidity and mortality. They constitute the most frequent cause of hospital admission related to cardiac disease. Early diagnosis and risk stratification are essential for initiation of optimal medical and invasive management. Therapeutic measures comprise aggressive antiplatelet, antithrombotic, and anti-ischemic agents. In addition, patients with high-risk features, notably positive troponin, ST segment changes and diabetes, benefit from an early invasive as compared to a conservative strategy. Importantly, lifestyle interventions, modification of the risk factor profile, and long-term medical treatment are of pivotal importance in reducing the long-term risk of recurrence.

PET-CT-guided interventions in the management of FDG-positive lesions in patients suffering from solid malignancies: initial experiences

Positron emission tomography-computed tomography (PET-CT) has gained widespread acceptance as a staging investigation in the diagnostic workup of malignant tumours and may be used to visualize metabolic changes before the evolution of morphological changes. To make histology of PET findings without distinctive structural changes available for treatment decisions, we developed a protocol for multimodal image-guided interventions using an integrated PET-CT machine. We report our first experience in 12 patients admitted for staging and restaging of breast cancer, non-small cell lung cancer, cervical cancer, soft tissue sarcoma, and osteosarcoma. Patients were repositioned according to the findings in PET-CT and intervention was planned based on a subsequent single-bed PET-CT acquisition of the region concerned. The needle was introduced under CT guidance in a step-by-step technique and correct needle position in the centre of the FDG avid lesion was assured by repetition of a single-bed PET-CT acquisition before sampling. The metabolically active part of lesions was accurately targeted in all patients and representative samples were obtained in 92%. No major adverse effects occurred. We conclude that PET-CT guidance for interventions is feasible and may be promising to optimize the diagnostic yield of CT-guided interventions and to make metabolically active lesions without morphological correlate accessible to percutaneous interventions.