Bereichsrezension: Theorie und Geschichte der Fotografie

Jens Jäger: Fotografie und GeschichtePierre Taminiaux: The Paradox of PhotographyBernd Stiegler: Montagen des Realen. Photographie als Reflexionsmedium und Kulturtechnik<br /

The hidden endoscopic burden of sleeve gastrectomy and its comparison with Roux-en-Y gastric bypass

© Published by Hellenic Society of Gastroenterology. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://www.annalsgastro.gr/index.php/annalsgastro/article/view/2284/1663BACKGROUND:This study aimed to assess the endoscopic burden of bariatric surgical procedures at our trust. This is an enhanced parallel study to "The Hidden Endoscopic burden of Roux-en-Y Gastric Bypass" published in Frontline Gastroenterology in 2013 incorporating the data for sleeve gastrectomy and comparison with Roux-en-Y gastric bypass (RYGB). METHODS:This is a retrospective study that included 211 patients undergoing sleeve gastrectomy over a 34-month period. We utilized previously collected data for the RYGB patient cohort which included 553 patients over a 29-month period. We searched our hospital endoscopic database for patients who underwent post-operative endoscopy for indications related to their surgery. RESULTS:16.6% of the sleeve gastrectomy patients required post-operative endoscopy, of whom 11.4% underwent therapeutic procedures. This compares to 20.4% of the RYGB cohort of whom 50.4% needed therapeutic procedures (P<0.001). 1.9% of sleeve gastrectomy patients encountered a post-operative staple line leak and collectively required 29 endoscopic procedures. One patient also developed stricturing (0.47%) requiring 18 pneumatic dilatations. 11.4% of the RYGB cohort developed an anastomotic stricture requiring 57 balloon dilatation procedures. To date, these procedures have accumulated an equivalent cost of €159,898 in endoscopy tariffs, or €177 per RYGB and €373 per sleeve gastrectomy performed. CONCLUSIONS:Bariatric surgery can have significant implications in terms of patient morbidity and financial cost. Having a local bariatric surgery service increases the demand for endoscopic procedures in our hospital, both in investigating for and dealing with post-operative complications. Provision of extra resources and expertise needs to be taken into account.Published versio

Evolving strategies to diagnose and manage autoimmune liver disease

Background: Primary Sclerosing Cholangitis (PSC) is a rare immune-meditated liver disease characterised by progressive destruction of bile ducts. This leads to cholestasis, biliary strictures, cirrhosis and hepatobiliary malignancy. PSC has an unpredictable prognosis, no proven treatment and overall poor long-term outcomes. While rare, the impact of PSC is high, with a large symptom burden and the need for management in specialist centres for most patients. Aims: This thesis aims to improve the understanding of PSC, from the perspective of patients, clinicians and healthcare providers. It aims to identify the barriers that PSC patients experience to their optimal medical management and explore the potential utility of two evolving technologies to improve patient experiences of their healthcare. These technologies are telemedicine and quantitative multiparametric MRI imaging. Methods: Four complementary studies were designed, using both quantitative and qualitative research methods. These studies included a 10-year retrospective cohort study into PSC at a large tertiary centre, semi-structured qualitative interviews with PSC patients recruited nationally, a questionnaire into the personal burden of medical intervention for PSC and attitudes to telemedicine, and a large observational trial of the utility of quantitative MRI techniques in PSC and related autoimmune disorders. These studies are initially discussed individually and are then combined in the final discussion chapter to provide an overall view of PSC patient and healthcare experiences. Results: All studies confirmed the large burden that PSC poses to patients and healthcare providers, along with the need for advances in new treatments and risk stratification methods. Particular challenges highlighted by patients were difficulties accessing knowledgeable medical care and how to overcome the uncertainties that PSC presented to them, both in terms of daily life but also long-term prognosis. Interest in telemedicine as one method to bypass traditional geographic barriers in accessing specialist care was high. However, hidden complexities within chronic illness behaviour, especially a particularly fragile doctor-patient relationship identified in this thesis, meant that telemedicine would not be universally accepted. Investigation into the utility of quantitative MRI technology observed correlations with existing markers of disease activity and severity, and demonstrated the ability to predict some clinically significant events. Although this was no better than existing serum biochemistry, the potential of this technology for future risk-stratification is confirmed. Conclusions: This thesis adds to the published literature of the ongoing high burden of PSC with particular added value from in-depth discussions with patients themselves. This has identified multiple areas of concern that should become priorities for further work, including the need for improved risk stratification tools to allow individualised management and prognostication, as well as improving access to specialist care. While telemedicine and new imaging technology may have future utility for patient benefit, both need further research in order to better understand their impact and utility in real-life clinical situations. PSC continues to present a challenge to patients and clinicians alike

The pathogenesis of autoimmune liver disease

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Autoimmune liver disease (AILD) encompasses 3 main distinct clinical diseases: autoimmune hepatitis, primary biliary cholangitis (formally known as cirrhosis, PBC) and primary sclerosing cholangitis (PSC). These conditions are an important, yet under-appreciated cause of patient morbidity and mortality with ongoing unmet needs for further research and clinical advances. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; There is observational evidence for genetic predisposition, with all 3 conditions being more common in first degree relatives. AILD is associated with the presence of auto-antibodies and higher risks of other non-hepatic auto-immune conditions. Genetic risk association studies have identified HLA and non-HLA risk loci for the development of disease, with some HLA loci providing prognostic information. This re-enforces the concept that genetic predisposition to autoimmunity is important, likely in the context of environmental exposures. Such environmental triggers are unclear but relevant risks include smoking, drug and xenobiotic exposure as well as the complexities of the microbiome. There is evidence for a loss of immune tolerance to self-antigens playing a part in the development of these conditions. In particular the IL-2 and IL-12 regulatory pathways have been implicated in pre-disposing to an unopposed inflammatory response within the liver. Main immunological themes revolve around loss of immune tolerance leading to T-cell mediated injury, imbalance in the regulation of immune cells and defective immune response to foreign antigens. For PBC and PSC, there is then the added complexity of the consequences of cholestasis on hepato-biliary injury, immune regulation and liver fibrosis. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Whilst specific disease causes and triggers are still lacking, AILD arises on the background of collective genetic and environmental risk, leading to chronic and abnormal hepato-biliary immune responses. Effective and more rational therapy will ultimately be developed when the multiple pathways to liver injury are better understood.</jats:p

Quantitative MRCP and metrics of bile duct disease over time in patients with primary sclerosing cholangitis:A prospective study

Background: Imaging markers of biliary disease in primary sclerosing cholangitis (PSC) have potential for use in clinical and trial disease monitoring. Herein, we evaluate how quantitative magnetic resonance cholangiopancreatography (MRCP) metrics change over time, as per the natural history of disease. Methods: Individuals with PSC were prospectively scanned using non‐contrast MRCP. Quantitative metrics were calculated using MRCP+ post‐processing software to assess duct diameters and dilated and strictured regions. Additionally, a hepatopancreatobiliary radiologist (blinded to clinical details, biochemistry and quantitative biliary metrics) reported each scan, including ductal disease assessment according to the modified Amsterdam Cholangiographic Score (MAS). Results: At baseline, 14 quantitative MRCP+ metrics were found to be significantly different in patients with PSC (N = 55) compared to those with primary biliary cholangitis (N = 55), autoimmune hepatitis (N = 57) and healthy controls (N = 18). In PSC specifically, baseline metrics quantifying the number of strictures and the number and length of bile ducts correlated with the MAS, transient elastography and serum ALP values (p &lt; 0.01 for all correlations). Over a median 371‐day follow‐up (range: 364–462), 29 patients with PSC underwent repeat MRCP, of whom 15 exhibited quantitative changes in MRCP+ metrics. Compared to baseline, quantitative MRCP+ identified an increasing number of strictures over time (p &lt; 0.05). Comparatively, no significant differences in biochemistry, elastography or the MAS were observed between timepoints. Quantitative MRCP+ metrics remained stable in non‐PSC liver disease. Conclusion: Quantitative MRCP+ identifies changes in ductal disease over time in PSC, despite stability in biochemistry, liver stiffness and radiologist‐derived cholangiographic assessment (trial registration: ISRCTN39463479)

Cardiac Safety of Modified Vaccinia Ankara for Vaccination against Smallpox in a Young, Healthy Study Population

Background Conventional smallpox vaccines based on replicating vaccinia virus (VV) strains (e.g. Lister Elstree, NYCBOH) are associated with a high incidence of myo-/pericarditis, a severe inflammatory cardiac complication. A new smallpox vaccine candidate based on a nonreplicating Modified Vaccinia Ankara (MVA) poxvirus has been assessed for cardiac safety in a large placebo-controlled clinical trial. Methods Cardiac safety of one and two doses of MVA compared to placebo was assessed in 745 healthy subjects. Vaccinia-naive subjects received either one dose of MVA and one dose of placebo, two doses of MVA, or two doses of placebo by subcutaneous injection four weeks apart;vaccinia-experienced subjects received a single dose of MVA. Solicited and unsolicited adverse events (AE) and cardiac safety parameters (recorded as Adverse Events of Special Interest, AESI) were monitored after each injection. Results A total of 5 possibly related AESI (3 cases of palpitations, 2 of tachycardia) were reported during the study. No case of myo- or pericarditis occurred. One possibly related serious AE (SAE) was reported during the 6-month follow-up period (sarcoidosis). The most frequently observed AEs were injection site reactions. Conclusions Vaccination with MVA was safe and well tolerated and did not increase the risk for development of myo-/pericarditis

A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN\u3csup\u3e®\u3c/sup\u3e) in 56-80-Year-Old Subjects

Background Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. In this Phase II trial, the safety and immunogenicity of Modified Vaccinia Ankara MVA-BN® (MVA) was assessed in a 56–80 years old population. Methods MVA with a virus titer of 1 x 108 TCID50/dose was administered via subcutaneous injection to 56–80 year old vaccinia-experienced subjects (N = 120). Subjects received either two injections of MVA (MM group) or one injection of Placebo and one injection of MVA (PM group) four weeks apart. Safety was evaluated by assessment of adverse events (AE), focused physical exams, electrocardiogram recordings and safety laboratories. Solicited AEs consisted of a set of pre-defined expected local reactions (erythema, swelling, pain, pruritus, and induration) and systemic symptoms (body temperature, headache, myalgia, nausea and fatigue) and were recorded on a memory aid for an 8-day period following each injection. The immunogenicity of the vaccine was evaluated in terms of humoral immune responses measured with a vaccinia-specific enzyme-linked immunosorbent assay (ELISA) and a plaque reduction neutralization test (PRNT) before and at different time points after vaccination. Results Vaccinations were well tolerated by all subjects. No serious adverse event related to MVA and no case of myopericarditis was reported. The overall incidence of unsolicited AEs was similar in both groups. For both groups immunogenicity responses two weeks after the final vaccination (i.e. Visit 4) were as follows: Seroconversion (SC) rates (doubling of titers from baseline) in vaccine specific antibody titers measured by ELISA were 83.3% in Group MM and 82.8% in Group PM (difference 0.6% with 95% exact CI [-13.8%, 15.0%]), and 90.0% for Group MM and 77.6% for Group PM measured by PRNT (difference 12.4% with 95% CI of [-1.1%, 27.0%]). Geometric mean titers (GMT) measured by ELISA two weeks after the final vaccination for Group MM were 804.1 and 605.8 for Group PM (with ratio of GMTs of 1.33 with 95% CI of [0.96, 1.84]). Similarly, GMTs measured by PRNT were 210.3 for Group MM and 126.7 for Group PM (with ratio 1.66 and 95% CI [0.95, 2.90]). Conclusions One or two doses of MVA were safe and immunogenic in a 56–80 years old vaccinia-experienced population. No cases of myopericarditis were observed following vaccinations with MVA. The safety, reactogenicity and immunogenicity were similar to that seen in younger (18–55 year old) healthy populations as investigated in other MVA trials. The results suggest that a single dose of MVA in a 56–80 years old population was well tolerated and sufficient to rapidly boost the long-term B cell memory response induced by a prior vaccination with a traditional smallpox vaccine. Trial Registration ClinicalTrials.gov NCT00857493