Westerly Hospital

Introduction: Autoimmune hepatitis is a well known side-effect and complication of immune checkpoint inhibitors (ICPIs) including anti-PD-1/PD-L1 inhibitors, however autoimmune cholestatic liver injury from these medications is rare. We present a case to highlight this unusual clinical course in order to better characterize the side effect profile of PD-L1 inhibitors in hepatocellular carcinoma (HCC). Case Description/Methods: A 67-year-old man with a history of unresectable HCC treated with 16 cycles of atezolizumab-bevacizumab presented to the emergency department with sudden onset, constant, non-radiating abdominal pain. Physical examination was notable for tenderness to palpation in the periumbilical region. Laboratory investigation revealed AST 74 IU/L, ALT 104 IU/L, total bilirubin 7.1 mg/dl, direct bilirubin 4.3 mg/dl. Total bilirubin prior to admission was 0.9 mg/dl. CT abdomen pelvis was notable for new ill-defined areas of liver hypoenhancement, concerning for progression of HCC. The patient developed jaundice and confusion as his total bilirubin peaked at 29.3 mg/dl. Gastroenterology was consulted for unclear etiology of cholestasis who recommended an MRCP, which was unrevealing. Liver biopsy was pursued. Pathology demonstrated portal edema and reactive bile ducts with focal lymphocytic infiltrate consisting of T-cells with an increased CD8/CD4 ratio, suspicious for autoimmune mediated injury secondary to atezolizumab. The patient ultimately developed fulminant hepatic failure despite treatment with high dose steroids, mycophenolate and antithymocyte globulin (ATG). He was discharged to home with hospice services. Discussion: We present a case of ICPI induced cholestatic liver injury due to atezolizumab, an inhibitor of PD-L1, used in combination with bevacizumab for unresectable HCC. Autoimmune hepatitis is a known side-effect of ICPIs, often treated with withdrawal of the drug and administration of high dose glucocorticoid therapy or second line treatment such as mycophenolate. ICPI mediated cholestatic injury is a rarer occurrence. While there is data to suggest efficacy of ATG, a strong immunomodulatory agent, in ICPI associated hepatitis, there is little data demonstrating efficacy in the salvage setting for ICPI associated cholestasis. Ultimately our patient failed to respond to this salvage therapy. The variance in pattern of injury and of clinical outcome in our case necessitates further characterization and guidelines for management in cases of ICPI mediated cholestatic liver injury (Figure 1).Figure 1.: A - H&E image taken at 20x magnification showing poorly differentiated carcinoma consistent with hepatocellular carcinoma in liver. B - Image taken at 20x magnification showing poorly differentiated carcinoma consistent with hepatocellular carcinoma labeled by immunohistochemical marker Glypican-3. C - H&E image taken at 20x magnification showing focal lymphocytic infiltrate. D - Image taken at 20x magnification highlighting lymphocyte infiltrate labeled by T-cell marker CD3 immunostain. E - Image taken at 20x magnification highlighting lymphocyte infiltrate labeled by immunohistochemical marker CD8. F - I mage taken at 20x magnification highlighting lymphocyte infiltrate labeled by immunohistochemical marker CD4.

This chapter contains sections titled: Introduction What Is an E-Service? Security Requirements for EServices and Applications Security for Future EServices References ]]>

Die Kernfrage dieses Buches ist: Warum sind die Menschen aberglaubisch? Oder, da Aberglaube bei vielen Menschen zu beobachten ist, wie werden sie aberglaubisch? Wie wir gesehen haben, ist die Antwort nicht einfach. Es gibt viele Faktoren, die zur Entstehung und Aufrechterhaltung von Aberglauben beitragen. Sie finden sich zwar nicht bei allen Betroffenen, doch kann jeder dieser Faktoren uns dazu bringen, das wir Uberzeugungen hegen oder Handlungen durchfuhren, die eine magische Sicht der Welt widerspiegeln. Angesichts der vielen psychologischen Einflusse, denen wir begegnet sind — und es gibt zweifellos noch weitere, die erst noch entdeckt und erforscht werden mussen -, konnen wir bei jedem Menschen damit rechnen, das er von irgendeinem magischen Glauben uberzeugt ist oder irgendein geheimes aberglaubisches Ritual praktiziert. Die reine Zahl moglicher psychologischer Einflusse gibt jedoch noch keinen Aufschlus daruber, welche Rolle diese Krafte in unserem Leben spielen. Einige gesellschaftliche und psychologische Phanomene sind bedeutsamer, auffallender und machtiger als andere. Unter entsprechenden Umstanden sind die ubrigen zwar potentiell ebenfalls einflusreich, doch treten sie zweifellos seltener und unauffalliger in Erscheinung. Nachdem wir nun die vielen Quellen aberglaubischer Vorstellungen und Verhaltensweisen aufgezahlt haben, ist der Zeitpunkt gekommen, das Thema noch einmal umfassend zu betrachten und die wichtigsten Punkte, die wir in den vorangehenden Kapiteln behandelt haben, ein weiteres Mal zu prufen.

ZusammenfassungAm 27. Oktober 1990 siegte die sechsjährige Stute Bayakoa, die dasselbe Rennen schon im Vorjahr gewonnen hatte, im Breeders’ Cup von Belmont Park mit 6 3/4 Längen Vorsprung vor dem zweitbesten Reiter. Für die, die das Schauspiel auf den Tribünen und am Fernsehen verfolgten, wurde die außergewöhnliche Leistung jedoch von einem schrecklichen Zwischenfall überschattet.

China clay or kaolin is mined extensively in east central Georgia and is the major industry in that region. The mining and processing of this mineral is known to lead to the development of a pneumoconiosis (Middleton 1936). Several limited studies have been published, but no well designed large investigation that has included most of the work force has been carried out until recently (Edenfield 1960, Kennedy et al. 1983, Oldham 1983, Altekruse et al. 1984). The present communication summarizes a recent comprehensive study that was carried out and adds some additional information to that which has been published (Morgan et al. 1988).