Disease evolution and outcomes in familial AML with germline CEBPA mutations

In-depth molecular investigation of familial leukemia has been limited by the rarity of recognized cases. This study examines the genetic events initiating leukemia and details the clinical progression of disease across multiple families harboring germ-line CEBPA mutations. Clinical data were collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course, with different mutations identified at recurrence. Deep sequencing of diagnostic and relapse paired samples confirmed that relapse-associated CEBPA mutations were absent at diagnosis, suggesting recurrence was triggered by novel, independent clones. Integrated WES and deep sequencing subsequently revealed an entirely new complement of mutations at relapse, verifying the presentation of a de novo leukemic episode. The cumulative incidence of relapse in familial AML was 56% at 10 years (n = 11), and 3 patients experienced ≥3 disease episodes over a period of 17 to 20 years. Durable responses to secondary therapies were observed, with prolonged median survival after relapse (8 years) and long-term overall survival (10-year overall survival, 67%). Our data reveal that familial CEBPA-mutated AML exhibits a unique model of disease progression, associated with favorable long-term outcomes.

Hepatocellular Carcinoma Screening With Computed Tomography Using the Arterial Enhancement Fraction With Radiologic-Pathologic Correlation.

OBJECTIVE The aim of this study was to investigate the performance of the arterial enhancement fraction (AEF) in multiphasic computed tomography (CT) acquisitions to detect hepatocellular carcinoma (HCC) in liver transplant recipients in correlation with the pathologic analysis of the corresponding liver explants. MATERIALS AND METHODS Fifty-five transplant recipients were analyzed: 35 patients with 108 histologically proven HCC lesions and 20 patients with end-stage liver disease without HCC. Six radiologists looked at the triphasic CT acquisitions with the AEF maps in a first readout. For the second readout without the AEF maps, 3 radiologists analyzed triphasic CT acquisitions (group 1), whereas the other 3 readers had 4 contrast acquisitions available (group 2). A jackknife free-response reader receiver operating characteristic analysis was used to compare the readout performance of the readers. Receiver operating characteristic analysis was used to determine the optimal cutoff value of the AEF. RESULTS The figure of merit (θ = 0.6935) for the conventional triphasic readout was significantly inferior compared with the triphasic readout with additional use of the AEF (θ = 0.7478, P < 0.0001) in group 1. There was no significant difference between the fourphasic conventional readout (θ = 0.7569) and the triphasic readout (θ = 0.7615, P = 0.7541) with the AEF in group 2. Without the AEF, HCC lesions were detected with a sensitivity of 30.7% (95% confidence interval [CI], 25.5%-36.4%) and a specificity of 97.1% (96.0%-98.0%) by group 1 looking at 3 CT acquisition phases and with a sensitivity of 42.1% (36.2%-48.1%) and a specificity of 97.5% (96.4%-98.3%) in group 2 looking at 4 CT acquisition phases. Using the AEF maps, both groups looking at the same 3 acquisition phases, the sensitivity was 47.7% (95% CI, 41.9%-53.5%) with a specificity of 97.4% (96.4%-98.3%) in group 1 and 49.8% (95% CI, 43.9%-55.8%)/97.6% (96.6%-98.4%) in group 2. The optimal cutoff for the AEF was 50%. CONCLUSION The AEF is a helpful tool to screen for HCC with CT. The use of the AEF maps may significantly improve HCC detection, which allows omitting the fourth CT acquisition phase and thus making a 25% reduction of radiation dose possible.

Monteggia lesion in an Asian small-clawed otter (Aonyx cinerea).

A 10-yr-old female Asian small-clawed otter (Aonyx cinerea) presented with a history of right forelimb lameness. Antebrachial radiographs revealed a Monteggia lesion, classified by cranial radial head luxation and distal diaphyseal ulnar fracture. Open reduction with placement of an ulnar-radial positional screw was performed. The lateral collateral ligament was reconstructed using suture anchored by a condylar screw and bone tunnel in the radius. Reduction and proper implant placement was confirmed on postoperative radiographs. The ulnar-radial positional screw was removed 6 wk postoperatively to allow proper supination and pronation. Limb function was greatly improved at this time; however, a mild lameness was still observed. At 7 mo postoperatively, the otter was ambulating lameness-free. Radiographs documented proper joint reduction and stable condylar screw. At 32 mo postoperatively, the otter continued to exhibit normal ambulation.

Gastroesophageal intussusception in a leopard (Panthera pardus).

An 8-yr-old male leopard (Panthera pardus) was presented with a 4-day history of lethargy, vomiting, and anorexia. Thoracic and abdominal radiographs revealed a soft-tissue mass cranial to the diaphragm and atypical appearance of the gastric fundus. Esophagoscopy revealed gastric mucosa in the lumen of the esophagus, which confirmed gastroesophageal intussusception. An exploratory celiotomy with manual reduction of the intussusception was performed. Reduction was verified by intraoperative esophagoscopy and gastroscopy. An incisional fundic gastropexy to the left abdominal wall was performed to reduce the chance of a recurrence of the intussusception. No postoperative complications related to the surgery were observed, and the animal resumed eating within 48 hr of surgery. A subsequent recurrence of clinical signs was not noted by the owner.

Esophageal hiatal hernia in three exotic felines--Lynx lynx, Puma concolore, Panthera leo.

Hiatal hernia was diagnosed in three exotic felines-lynx (Lynx lynx), cougar (Puma concolore), and lion (Panthera leo). All cats had a history of anorexia. Thoracic and abdominal radiographs showed evidence of a soft tissue mass within the caudal mediastinum suggestive of a hiatal hernia in all animals. A barium esophagram was performed in one case. All animals underwent thoracic or abdominal surgery for hernia reduction. Surgical procedures included: intercostal thoracotomy with herniorrhaphy and esophagopexy (lynx and cougar), and incisional gastropexy (lion). Concurrent surgical procedures performed were gastrotomy for gastric foreign body removal and jejunostomy tube placement. Clinical signs related to the hiatal hernia disappeared after surgery and recurrence of signs was not reported for the time of follow-up.

Ms. germ. fol. 59 - Leumundszeugnis und Lehrbrief für den Goldschmied Christoph Buck

Alte Signatur: 31/593; Akzessionsnummer: 1921/1638;

Na 1 Nachlass Max Horkheimer, 134 - Korrespondenzen im Zusammenhang der Sigmund-Freud-Gedächtnis-Vorlesungen 1956 u.a. mit Herbert Marcuse (p. IV 3, 1-255)

Sigmund-Freud-Gedächtnis-Vorlesungen (Sommer-Semester 1956): Korrespondenz und Aktennotizen von Max Horkheimer und Alexander Mitscherlich; Briefe u. a. von Franz Alexander, Michael Balint, Gustav Bally, Ludwig Binswanger, Helmut Coing, Erik Erikson, Heinz Hartmann, Theodor Heuss, Edoardo Krapf, Herbert Marcuse, Alexander Mitscherlich, Rene Spitz, Erwin Stengel, Robert Waelder, Frederik Wyatt, Hans Zulliger (Briefe zwischen Max Horkheimer und Alexander Mitscherlich sind nicht gesondert registriert); Norbert Altwicker: Korrespondenz im Auftrag von Max Horkheimer betrifft die Sigmund-Freud-Gedächtnis-Vorlesungen 1956; 1 Brief von Professor Helmut Coing (betrifft Sigmund-Freud-Gedächtnis-Vorlesungen 1956) an Max Horkheimer, Theodor Heuss, Georg August Zinn, das Hessische Kultusministerium, das Hessische Finanzministerium; Briefwechsel zwischen Bundespräsident Theodor Heuss und Max Horkheimer; 1 Brief von Helmut Coing an Theodor Heuss, 1956; 1 Brief von Max Horkheimer und Alexander Mitscherlich an Ernest Jones, 1956; 6 Briefe zwischen Professor Franz Alexander und Max Horkheimer, 1955-1956; 3 Briefe zwischen Professor Gustav Bally und Max Horkheimer, 1955-1956; 4 Briefe zwischen Michael Balint und Max Horkheimer, 1955-1956; 3 Briefe zwischen Ludwig Binswanger und Max Horkheimer, 1956; 4 Briefe zwischen Professor Erik H. Erikson und Max Horkheimer, 1955-1956; 3 Briefe zwischen Professor Edoardo Krapf und Max Horkheimer, 1955-1956; 6 Briefe zwischen Professor Herbert Marcuse und Max Horkheimer, 1955-1956; 14 Briefe zwischen Renè A. Spitz und Max Horkheimer, 1956; 4 Briefe zwischen Professor Erwin Stengel und Max Horkheimer, 1955-1956; 4 Briefe zwischen Professor Frederick Wyatt und Max Horkheimer, 1956; 4 Briefe zwischen Hans Zulliger und Max Horkheimer, 1955-1957; 4 Briefe zwischen Heinz Hartmann (Psychoanalytiker) und Max Horkheimer; 1 Brief von Theodor W. Adorno an Heinz Hartmann, 1955-1957; 1 Brief von Robert Waelder an Max Horkheimer, 1956;

Albertvs Et Isabella

Allegorische Darstellung: Huldigung der 17 niederländ. Provinzen gegenüber Erherzog Albrecht VII. von Österreich u. Isabella im November 1599, mit Porträtmedaillons von Ambrosius Spinola, Erzherzog Albrecht, Carolus Graf von Becquoi, Graf Moritz v. Nassau u. Graf Heinrich Friedrich v. Nassau; zur Feier des 12-jährigen Waffenstillstands zwischen Spanien und den Niederlanden

Hundert-Jähriges angedencken, das schnelle Kriegsglück des Schwedischen Heldens u. Königs Gustavi Adolphi in Eroberung aller dieser allhier beygefügter u. in Kupffer gestochnen Städte u. Plätze ... : welche sich Ao. 1630 u. 1631 alle theils durch Accord theils durch Sturm seinem siegenden Schwerde ergeben müßen

Mit 103 Stadtansichten im Miniaturformat

Auszug einer Übersicht der geographischen und historischen Verhältnisse der Grasarten Italiens

Von Prof. Schouw

Siegen oder sterben : die Helden des Burenkriegs; Bilder und Skizzen nach eigenen Erlebnissen

von Frederik Rompel. Mit einer Einl. von Albert Pfister

Uit den tweeden vrijheidsoorlog : schetsen en portretten

Frederik Rompel