Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection.

Immune checkpoint inhibitors (ICI) are commonly used for various malignancies. A particular checkpoint inhibitor is the anti-PD-1 antibody pembrolizumab. Immune-mediated diarrhea and colitis (IMDC) is the most frequently observed immune-related adverse event (irAE) involving the gastrointestinal system. Although immune-mediated colitis precipitated by pembrolizumab is rarely life-threatening, it often necessitates a detailed diagnostic workup, including stool studies, imaging, and colonoscopy, to establish an accurate diagnosis. The coexistence of IMDC and Clostridioides difficile infection is not well understood, but patients undergoing pembrolizumab treatment have comparable risk factors to those who develop C. difficile infection. We report a case of a 76-year-old female with nonmetastatic non-small cell lung cancer who was diagnosed with IMDC responsive to steroid treatment but later developed worsening diarrhea leading to a diagnosis of checkpoint inhibitor colitis with superimposed C. difficile infection.

Headaches in a Horseback Rider.

An immunocompetent woman presented with headaches. She previouslyworked at a farm in upstate New York. Brain MRI noted pituitary enlargement and neurosurgerypursued trans-sphenoidal pituitary biopsy. Histopathology revealed ill-defined granulomaswith clusters of yeast, consistent with Histoplasma.

Pooled Testing for SARS-CoV-2 in Hospitalized Patients.

Viral testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly early in the COVID-19 pandemic, was limited by supply of reagents. We pooled nasopharyngeal samples from patients at low risk of SARS-CoV-2 infection in groups of 3 for testing. Three weeks of testing using this strategy resulted in 530 patient tests in 179 cartridges; 4 positive test groups required the use of 11 additional cartridges with an overall positive rate of 0.8% in a low-risk population. This strategy resulted in the use of 340 fewer cartridges than if each test were performed on one patient sample. Pooled testing of low-risk populations allows for continued testing even when supplies are relatively scarce.

c-Cbl mediates the degradation of tumorigenic nuclear ß-catenin contributing to the heterogeneity in Wnt activity in colorectal tumors.

Despite the loss of Adenomatous Polyposis Coli (APC) in a majority of colorectal cancers (CRC), not all CRCs bear hallmarks of Wnt activation, such as nuclear ß-catenin. This underscores the presence of other Wnt regulators that are important to define, given the pathogenic and prognostic roles of nuclear ß-catenin in human CRC. Herein, we investigated the effect of Casitas B-lineage lymphoma (c-Cbl) on nuclear ß-catenin, which is an oncoprotein upregulated in CRC due to loss-of-function APC or gain-of-function CTNNB1 mutations. Despite mechanistic rationale and recent discoveries of c-Cbl's mutations in solid tumors, little is known about its functional importance in CRC. Our study in a cohort of human CRC patients demonstrated an inverse correlation between nuclear ß-catenin and c-Cbl. Further investigation showed that the loss of c-Cbl activity significantly enhanced nuclear ß-catenin and CRC tumor growth in cell culture and a mouse xenograft model. c-Cbl interacted with and downregulated ß-catenin in a manner that was independent of CTNNB1 or APC mutation status. This study demonstrates a previously unrecognized function of c-Cbl as a negative regulator of CRC.

FDG PET metabolic tumor volume segmentation and pathologic volume of primary human solid tumors.

OBJECTIVE: The purpose of this study was to establish the correlation and reliability among the pathologic tumor volume and gradient and fixed threshold segmentations of (18)F-FDG PET metabolic tumor volume of human solid tumors. MATERIALS AND METHODS: There were 52 patients included in the study who had undergone baseline PET/CT with subsequent resection of head and neck, lung, and colorectal tumors. The pathologic volume was calculated from three dimensions of the gross tumor specimen as a reference standard. The primary tumor metabolic tumor volume was segmented using gradient and 30%, 40%, and 50% maximum standardized uptake value (SUVmax) threshold methods. Pearson correlation coefficient, intraclass correlation coefficient, and Bland-Altman analyses were performed to establish the correlation and reliability among the pathologic volume and segmented metabolic tumor volume. RESULTS: The mean pathologic volume; gradient-based metabolic tumor volume; and 30%, 40%, and 50% SUVmax threshold metabolic tumor volumes were 13.46, 13.75, 15.47, 10.63, and 7.57 mL, respectively. The intraclass correlation coefficients among the pathologic volume and the gradient-based and 30%, 40%, and 50% SUVmax threshold metabolic tumor volumes were 0.95, 0.85, 0.80, and 0.76, respectively. The Bland-Altman biases were -0.3, -2.0, 2.82, and 5.9 mL, respectively. Of the small tumors (< 10 mL), 23 of the 35 patients had PET segmented volume outside 50% of the pathologic volume, and among the large tumors (≥ 10 mL) three of the 17 patients had PET segmented volumes that were outside 50% of pathologic volume. CONCLUSION: FDG PET metabolic tumor volume estimated using gradient segmentation had superior correlation and reliability with the estimated ellipsoid pathologic volume of the tumors compared with threshold method segmentation.

Amyloid deposits in the bone marrow of patients with immunoglobulin light chain amyloidosis do not impact stem cell mobilization or engraftment.

Amyloid deposits are often found in the bone marrow in patients with Immunoglobulin light chain (AL) amyloidosis. We sought to determine whether this affects stem cell collection or engraftment after high-dose melphalan and autologous stem cell transplantation (HDM-SCT). We reviewed data on 361 patients with AL amyloidosis who had Congo red staining of pretreatment bone marrow biopsy specimens and underwent HDM-SCT between July 1994 and December 2011. We analyzed data on stem cell yield, days of stem cell collection, and days to neutrophil and platelet engraftment posttransplantation. Bone marrow amyloid deposits were found in 65% of patients (n = 233). There were no significant differences in median number of stem cells collected and days to neutrophil or platelet engraftment between patients with bone marrow amyloid deposits and those without these deposits. Thus, our data indicate that although amyloid involvement of the bone marrow is common, it does not negatively affect stem cell mobilization or neutrophil and platelet engraftment after HDM-SCT.

Gamma heavy chain disease in a patient with underlying lymphoplasmacytic lymphoma of the thyroid. Report of a case and comparison with other reported cases with thyroid involvement.

BACKGROUND: Gamma heavy chain disease with underlying thyroid pathology is rare. There are 5 reported cases in the English literature, including the present case of an elderly female with γ heavy chain disease with underlying lymphoplasmacytic lymphoma of the thyroid who initially presented with long-standing goiter and chronic thyroiditis. METHODS: The protein studies and histopathologic findings in her thyroid are described. Her case is compared with reported cases of γ heavy chain disease with thyroid involvement. RESULTS: Initial impression on most cases was chronic thyroiditis; however pathology showed 3 cases with plasmacytoma and 2 with lymphoplasmacytic infiltrate. All were diagnosed and followed up using serum and urine electrophoresis. CONCLUSION: Gamma heavy chain disease has a protean manifestation; however there appears to be a more uniform pattern of the disease when it is associated with the thyroid. The inclusion of protein studies in cases diagnosed with chronic thyroiditis by FNA may aid in establishing γ heavy chain disease with underlying thyroid involvement. In this case serum and urine electrophoresis, and immunofixation studies which are simple and affordable tests facilitated the hematologic workup and follow up.

A massive transfusion protocol incorporating a higher FFP/RBC ratio is associated with decreased use of recombinant activated factor VII in trauma patients.

We implemented a protocol incorporating a higher fresh frozen plasma (FFP)/RBC ratio for the management of trauma patients requiring massive transfusion in 2007. This study aims to identify issues that affected the effective deployment of the massive transfusion protocol (MTP) and compare outcome variables with a historic cohort. Data from 49 trauma patients who received at least 10 units of packed RBCs within 24 hours were analyzed and compared with a historic massively transfused cohort who had received recombinant activated factor VII (rFVIIa). Of the patients, 28 received an FFP/RBC ratio of 1:1 to 1:2; 12 received a lower ratio of 1:2 to 1:4; 3 received more than 1:1 and 6 had less than 1:4. Compared with the historic cohort, the 1:1-1:2 group received significantly fewer blood components and did not require rescue rFVIIa. An MTP incorporating a higher FFP/RBC ratio of 1:1 to 1:2 is associated with decreased use of blood components and may obviate the need for rFVII.