Autoimmune Pancreatitis Type 2: Case Report

© 2017, © 2017 American Federation for Medical Research. A middle-aged man presents with acute pancreatitis of unknown etiology and is found to have a presentation consistent with the diagnosis of type 2 autoimmune pancreatitis (AIP). AIP is a group of rare heterogeneous diseases that are challenging to diagnose. There are 2 types of AIP. Type 1 disease is the more common worldwide than type 2 AIP. While type 1 AIP is associated with IgG4-positive antibodies, type 2 AIP is IgG4 antibody negative. Both types of AIP are responsive to corticosteroid treatment. Although type 1 AIP has more extrapancreatic manifestations and more commonly relapses, this is a case of a patient with type 2 AIP with inflammatory bowel disease and relapsing course

Kentucky Tax Law, Second Edition

A reference for Kentucky lawyers on real and personal property taxation, Kentucky sales and use taxation, Kentucky individual income taxation, corporate income taxation, and procedures before the Kentucky Board of Tax Appeals

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Multi-gene measurable residual disease assessed by digital polymerase chain reaction has clinical and biological utility in acute myeloid leukemia patients receiving venetoclax/azacitidine

Venetoclax with azacitidine (ven/aza) is a lower-intensity therapeutic regimen that has been shown to improve outcomes in elderly patients with acute myeloid leukemia (AML). Measurable residual disease (MRD) using flow cytometry is a valuable tool for the prediction of relapse in AML using conventional therapies and ven/aza; however, the prognostic value for broadscale molecular MRD after ven/aza treatment is less clear. We aimed to determine the utility of retrospective assessment using multi-gene molecular MRD by droplet digital polymerase chain reaction (ddPCR). We found this approach correlates with outcomes in a cohort of patients receiving frontline ven/aza for AML. The predictive value of ddPCR MRD persisted when NPM1 mutations were removed from analysis, as well as after adjustment for the impact of stem cell transplant on outcomes. Late achievement of MRD negativity, including after SCT, was still associated with superior outcomes compared to persistently detectable MRD. We further explored the impact of ven/aza on the burden of different classes of mutations, and identified the persistence of splicing factor mutations, commonly associated with MDS, as a consistent finding after ven/aza treatment. These data add to our understanding of the effects of ven/aza on AML disease biology and provide details on molecular depth of remission that can guide prospective trials in the future

UK-wide major trauma center tertiary trauma survey pro forma review and aggregation and consolidation into a redesigned document

ObjectivesThe trauma tertiary survey (TTS) is an essential part of the continued care for major trauma patients which is performed to ensure that all injuries have been identified and none have been overlooked during the patient’s stay. Although the Advanced Trauma Life Support Course states a need for a tertiary survey, there is currently no standard for what this survey comprises.MethodsUsing local consultant expert opinion and a literature search we identified a set of 32 TTS potential features that may be included within a TTS pro forma. Major trauma center (MTC) documents were requested from every MTC within the UK. 4 investigators sequentially interrogated each MTC TTS document looking for (1) presence of each feature and (2) how well the feature was represented on the document (0 to 4 Likert Scale). Any previously unidentified potential TTS features were noted and later reviewed for a second round of document analysis.ResultsA total of 21 out of all 26 UK MTCs had a TTS pro forma document. A total of 68 possible features were identified. Respiratory and Abdominal assessment sections were the most frequently identified features (present in 90.4% of the TTS pro formas; n=19. Neck assessment and neurological assessment were included within 85.7% of the TTS pro formas (n=18). Further aspects identified for Round 2 analysis typically included features that were thought to be important but highly specific. For example, pregnancy test and DNACPR discussions were found in 1 MTC TTS each (4%).ConclusionThis article presents a review of the existing documents at 21 MTCs in the UK, identification of features used and proposes a gold standard TTS which can be used by any doctor to perform the tertiary survey and reduce the risk of missed injuries in trauma patients.Level of Evidence3.</jats:sec

UK-wide major trauma center tertiary trauma survey pro forma review and aggregation and consolidation into a redesigned document

Objectives The trauma tertiary survey (TTS) is an essential part of the continued care for major trauma patients which is performed to ensure that all injuries have been identified and none have been overlooked during the patient’s stay. Although the Advanced Trauma Life Support Course states a need for a tertiary survey, there is currently no standard for what this survey comprises.Methods Using local consultant expert opinion and a literature search we identified a set of 32 TTS potential features that may be included within a TTS pro forma. Major trauma center (MTC) documents were requested from every MTC within the UK. 4 investigators sequentially interrogated each MTC TTS document looking for (1) presence of each feature and (2) how well the feature was represented on the document (0 to 4 Likert Scale). Any previously unidentified potential TTS features were noted and later reviewed for a second round of document analysis.Results A total of 21 out of all 26 UK MTCs had a TTS pro forma document. A total of 68 possible features were identified. Respiratory and Abdominal assessment sections were the most frequently identified features (present in 90.4% of the TTS pro formas; n=19. Neck assessment and neurological assessment were included within 85.7% of the TTS pro formas (n=18). Further aspects identified for Round 2 analysis typically included features that were thought to be important but highly specific. For example, pregnancy test and DNACPR discussions were found in 1 MTC TTS each (4%).Conclusion This article presents a review of the existing documents at 21 MTCs in the UK, identification of features used and proposes a gold standard TTS which can be used by any doctor to perform the tertiary survey and reduce the risk of missed injuries in trauma patients.Level of Evidence 3

Genomic Impact of Neoadjuvant Therapy on Breast Cancer: Incomplete Response is Associated with Altered Diagnostic Gene Signatures.

PURPOSE: Neoadjuvant therapy (NAT) has been shown to clinically downstage locally advanced breast cancers. This study aimed to determine whether a meaningful change in gene signatures occurs between pre- and post-NAT breast cancers for patients who do not achieve a pathologic complete response. METHODS: The current analysis included women from the prospective Neoadjuvant Breast Registry Symphony Trial who had breast cancer and awaited NAT. MammaPrint and BluePrint (Agendia, Inc., Irvine, CA) assays were performed on pre- and post-NAT breast tumor samples. RESULTS: At the completion of NAT, 93 patients with residual disease had their remaining tumor analyzed for MammaPrint and BluePrint. Of 93 patients, 21 switched tumor classification: 16 from high risk (HR) to low risk (LR) and 1 from LR to HR (p \u3c 0.001). Four additional patients switched molecular subtype but remained HR. Although only 17 patients switched in their MammaPrint risk classification, the underlying MPIndex was significantly altered after treatment across all patients (p \u3c 0.001). Additionally, the three BluePrint indices for luminal, human epidermal growth factor receptor 2 (HER2), and basal type also were significantly altered after treatment, in a subtype-dependent manner. CONCLUSION: This substudy showed that NAT significantly altered the genomic signature of the patient\u27s breast cancer compared with the patient\u27s pretreatment genomic profile. These alterations occurred in a subtype-dependent manner, suggesting that NAT may have either eliminated the most susceptible tumor subclone, leaving the treatment resistant clone with a different genetic signature, or altered molecular characteristics of the original cancer