Increased troponin I is associated with fatal outcome in acquired thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) has >90% mortality without therapeutic plasma exchange (TPE). Despite TPE, approximately 10% of patients still die, presumably from cardiac ischemia. We sought clinical or laboratory parameters associated with death by reviewing the records of all patients hospitalized with acquired TTP in our institution for 10 years, and collect demographics and results for hemoglobin, platelet count, creatinine, lactate dehydrogenase, transaminases, total bilirubin, creatinine kinase (CK), CK-MB, and troponin I. Sixty-eight patients were admitted 88 times, and 11 died. Survivors and non-survivors were similar in terms of sex, ethnicity, thrombocytopenia, and degree of anemia at presentation, while the latter were older, had worse renal function and higher CK, CK-MB, and troponin I (univariate analysis). However, only troponin I remained significant on multivariate analyses. We propose that patients with TTP should be monitored with troponin I to detect significant myocardial ischemia that could predict death despite TPE.

PARP1 and phospho-p65 protein expression is increased in human HER2-positive breast cancers.

Previous studies have shown that basal breast cancers, which may have an inherent "BRCAness" phenotype and sensitivity to inhibitors of poly (ADP-Ribose) polymerase (PARP), express elevated levels of PARP1. Our lab recently reported that HER2+ breast cancers also exhibit sensitivity to PARP inhibitors (PARPi) by attenuating the NF-κB pathway. In this study, we assessed PARP1 and phospho-p65, a marker of activated NF-κB levels in human breast cancer tissues. PARP1 and PARP2 copy number, mRNA, and protein expression was assessed by interrogating the PAM-50 defined breast cancer patient set from the TCGA using cBioPortal. PARP1 and phospho-p65 immunohistochemistry and correlation to clinical parameters was conducted using 307 primary breast cancer specimens (132 basal, 82 luminal, 93 HER2+) through univariate and multivariate analyses. In the PAM50 breast cancer data set, PARP1 and 2 expression was altered in 24/58 (41 %) HER2+, 32/81 (40 %) basal, and 75/324 (23 %) luminal A/B breast cancer patients. This correlated with a statistically significant increase in PARP1 protein levels in HER2+ and basal but not luminal breast cancers (p = 0.003, p = 0.027, p = 0.289, respectively). No change in PARP2 protein level was observed. Interestingly, using breast cancer specimens from 307 patients, HER2 positivity correlated with elevated PARP1 expression (p < 0.0001) and was three times more likely than HER2 negative breast cancers to exhibit high PARP1 levels. No significant differences were noted between race, ER status, or PR status for PARP1 expression. Additionally, we found a significant correlation between HER2 status and phospho-p65 expression (p < 0.0001). Lastly, a direct correlation between PARP1 and phospho-p65 (p < 0.0001) was noted. These results indicate a potential connection between HER2, PARP1, and phospho-p65. Furthermore, these data suggest that the PARPi sensitivity we previously observed in HER2+ breast cancer cells may be due to elevated PARP1 expression.

Therapy-related B-lymphoblastic leukemia associated with Philadelphia chromosome and MLL rearrangement: Single institution experience and the review of the literature.

Therapy related acute lymphoblastic leukemia (t-ALL) of B cell origin is rare and constitutes approximately 2% of all ALL. Previously compiled data on the complete cytogenetic analysis of 48 t-B-ALL cases suggested that MLL rearrangement at 11q23 gene locus is the most common abnormality. Philadelphia chromosome (Ph) and a normal karyotype were reported as the second and third most common karyotypes, respectively. We investigated cytogenetic karyotypes of six t-B-ALL cases with a pre-B cell immunophenotype. Ph + t-B-ALL was noted in four of six patients previously treated with radiation and/or chemotherapy. In addition, one case demonstrated MLL rearrangement at 11q23 locus while one case demonstrated normal cytogenetic karyotype. Five of the six t-B-ALL patients had persistent leukemia following initiation of chemotherapy for secondary leukemia with survival ranging from 10 to 21 months. To our knowledge, only fourteen patients with Ph + t-B-ALL have been described in the literature. In the current study, three of four cases with Ph + t-B-ALL were associated with treated breast carcinoma while one patient was treated for Hodgkin lymphoma. All four patients had undergone radiation therapy. The results may indicate a plausible association between Ph+t-B-ALL and prior radiation exposure.

Over-the-scope clip-assisted method for resection of full-thickness submucosal lesions of the gastrointestinal tract.

BACKGROUND AND STUDY AIMS: The over-the-scope clip (OTSC; Ovesco Endoscopy, Tübingen, Germany) is deployed after suctioning tissue into the cap. The tissue may then be resected endoscopically. The aim of this study was to evaluate the efficacy and safety of the OTSC for the endoscopic resection of gastrointestinal tumors. PATIENTS AND METHODS: This was a retrospective, observational cohort study of patients undergoing endoscopic resection of submucosal lesions. RESULTS: Eight patients underwent endoscopic resection of neuroendocrine tumors (NETs) of the duodenum (n = 4), rectum (n = 1), or stomach (n = 2), or granular cell tumor (GCT) of the esophagus (n = 1). The mean size of the lesions was 13.4 mm (range 9 - 20 mm). Application of the clip was successful in all patients. A successful endoscopic resection was accomplished in all. A complete resection (R0) was accomplished in 7/8 patients (87.5 %). A full-thickness resection was achieved in 2/8 (25.0 %), one in a patient with a gastric NET and the other in a patient with GCT of the esophagus. There were no complications. CONCLUSIONS: This case series suggests that the OTSC system may be a valuable tool for the resection of submucosal lesions, but further prospective and randomized studies are necessary to assess the indications and outcome.

Temporomandibular joint arthritis as an initial presentation of acute myeloid leukemia with myelodysplasia-related changes: a report of an unusual case.

PURPOSE: Patients with acute myeloid leukemia (AML) often present with fatigue and severe pancytopenia. We report the case of a 68-year-old woman with no significant medical history who presented with 1 year of progressively worsening bilateral temporomandibular joint (TMJ) pain. She was otherwise asymptomatic. A computed tomography scan revealed degenerative joint disease in both TMJs. Bilateral TMJ replacement was performed. MATERIALS AND METHODS: The excised TMJ tissue underwent formalin fixation and decalcification, and routine hematoxylin and eosin-stained sections were generated. RESULTS: Immunohistochemical stains showed a population of monotonous cells in the marrow space expressing CD33, CD43, and myeloperoxidase, confirming the diagnosis of myeloid neoplasm. Subsequent bone marrow biopsy with flow cytometry confirmed AML with myelodysplasia-related changes. CONCLUSIONS: Adult patients with AML can rarely present with musculoskeletal complaints alone, which could delay the diagnosis. To our knowledge, this is the first report of AML with myelodysplasia-related changes presenting in a patient with TMJ degenerative joint disease that was otherwise asymptomatic.

Identifying Errors in Forensic Autopsy Reports Using a Novel Web-Based Program.

INTRODUCTION: Autopsy reports are often complex, with ample opportunity for errors and inconsistencies. These reports are often scrutinized by both families and attorneys. Identification of errors by proofreading physicians or clerical staff can be improved by utilizing a computer program to examine reports for discrepancies. METHODS: A webpage to review demographic consistency, organ descriptions, and pertinent information regarding gunshot wounds was developed to proofread reports. Thirty completed reports were analyzed from the Jefferson County Coroner/Medical Examiner Office. Additionally, a separate individual was instructed to sabotage reports and then determine if the software could detect the alterations. RESULTS: Of the 30 completed reports analyzed, no errors/omissions were identified; however, these reports were accurate upon manual inspection. Rarely, the computer triggered a warning that an organ should be confirmed if the author used a description that differed from the software's vocabulary (e.g., the author discussed "uterine wall" instead of "uterus"). The webpage detected eight out of ten errors supplied to the five sabotaged cases. These errors ranged from inconsistent age, race, and gender, to incomplete gunshot wound descriptions. CONCLUSION: Identification of errors by a computer proofreading program can improve autopsy report quality. The webpage has been designed so that additional modules, such as strangulation proofreading, could easily be added. Furthermore, the ability of the software to detect errors will continue to improve as more words are added to its vocabulary. The webpage is freely available and can be adapted to other medical examiner offices needs from the GitHub website.