Secondary Mediastinal Bleeding Caused by Parathyroid Adenocarcinoma: A Case Report.

Introduction: The clinical picture of parathyroid tumors is mainly related to hypercalcemia such as kidney stones and bone and muscle pain. However, spontaneous cervical hemorrhage due to parathyroidoma bleeding is rare with clinical manifestations of the painful swelling and bruising of the neck accompanied by dysphagia and dyspnea. Case presentation: We report a case of a 71-year-old female patient who presented with acute cervical swelling and extensive bleeding spreading from the neck to the abdomen and 2 flanks. Investigation of patients revealed increased parathyroid hormone levels and hypercalcemia. The neck ultrasound showed the thyroid nodules in 2 lobes, and goiter plongeant on the right. Computed tomography scan images showed a hematoma spreading from the right side of the neck to the mediastinum. Result: The patient required emergency surgery due to dyspnea and hemodynamic instability. The preoperative diagnosis was cervical bleeding with the likely cause being thyroid nodule rupture. However, during the surgery, the bleeding source was determined to be the right parathyroid tumor located deeply below the superior mediastinum. The patient's histopathological result of the tumor is parathyroid adenocarcinoma. Conclusion: From our experience, the hemorrhage from parathyroid tumor should be considered as a cause of acute neck bleeding when no history of trauma or surgery is identified. Post-surgery histopathological analyses of the tumor are very important to detect parathyroid adenocarcinoma.

Persistence of Antibodies Six Months after Three COVID-19 mRNA Vaccine Doses in Patients with Inflammatory Bowel Disease.

We evaluated antibody concentrations 6 months after a third coronavirus disease 2019 messenger RNA vaccine dose in patients with inflammatory bowel diseases. Almost all patients had an antibody response, and those with a previous SARS-CoV-2 infection had higher antibody concentrations.

Humoral Immunogenicity of 3 COVID-19 Messenger RNA Vaccine Doses in Patients With Inflammatory Bowel Disease.

Herein, we evaluated the humoral immunogenicity of a third coronavirus disease 2019 messenger RNA vaccine dose in patients with inflammatory bowel diseases. All patients displayed a humoral immune response, and median antibody concentrations were higher after the third dose than after completion of the 2-dose series.

Humoral Immunogenicity of mRNA COVID-19 Vaccines Among Patients With Inflammatory Bowel Disease and Healthy Controls.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) on immune-modifying therapies may have a lower vaccine response to certain vaccines. The aim of our study was to evaluate humoral immunogenicity of mRNA coronavirus disease 2019 (COVID-19) vaccines among patients with IBD and healthy controls (HCs). METHODS: We performed a prospective study to evaluate humoral immunogenicity among patients with IBD and HCs after completion of mRNA COVID-19 vaccines. RESULTS: One hundred twenty-two patients with IBD and 60 HCs were enrolled. All HCs and 97% of patients with IBD developed antibodies. Antibody concentrations were lower in patients with IBD compared with those in HCs (median 31 vs 118 µg/mL; P < 0.001). Those who received the mRNA-1273 (Moderna) COVID-19 (median 38; interquartile range [IQR] 24-75 vs µg/mL) had higher antibody concentrations compared with those who received the Pfizer-BNT vaccine series (median 22; IQR 11-42 µg/mL; P < 0.001). Patients on immune-modifying therapy (median 26; IQR 13-50 µg/mL) had lower antibody concentrations compared with those who were on no treatment, aminosalicylates, or vedolizumab (median 59; IQR 31-75 µg/mL; P = 0.003). DISCUSSION: Almost all patients with IBD in our study mounted an antibody response. Future studies are needed in evaluating sustained humoral immunity and the impact of booster dosing in patients with IBD.

Safety of tumor necrosis factor inhibitor use in patients with concomitant malignancy.

BACKGROUND/AIMS: Safety for tumor necrosis factor inhibitors (TNFi) in cancer has been focused on risk of incident malignancies, but studies on prognostic effects have been scarce. We determined survival and recurrence rates at 1, 2, and 5 years after cancer diagnosis in patients with and without concurrent TNFi use. METHODS: Chart reviews were performed between 1996 and 2015 at the VA North Texas Healthcare System. Cases were patients with inflammatory disease, concomitant malignancy, and TNFi use while controls were patients with inflammatory disease, concomitant malignancy but no TNFi use. Cases and controls were matched for type of malignancy. Analysis was performed with log-rank tests on Kaplan-Meier curves. RESULTS: Thirty-six cases and 72 controls were identified. For cases, survival at 1, 2, and 5 years were 32 (89%), 31 (86%), and 29 (81%) compared to 63 (90%), 61 (87%), and 51 (73%) for the control group (P=0.985). For cases, recurrence rates at 1, 2, and 5 years were 3 (8%), 5 (14%), and 6 (17%) compared to 2 (3%), 5 (7%), and 7 (10%) for the control group (P=0.158). CONCLUSIONS: Our findings suggest TNFi may be safely used in select inflammatory disease patients with concurrent cancer if therapy is needed for proper disease control. However, case-by-case consideration in conjunction with an oncologist is recommended while considering the apparent safety of TNFi for patients suffering from active inflammatory diseases despite having a concomitant malignancy.

SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-ß signaling.

Cell cycle quiescence is critical for hematopoietic stem cell (HSC) maintenance. TGF-ß signaling in bone marrow niche has been identified in regulating HSC quiescence; however, the intrinsic regulatory mechanisms remain unclear. This study reports that Shp-1 knockout HSCs have attenuated quiescence and impaired long-term self-renewal. SHP-1-activated HSCs are surrounded by megakaryocytes, which regulate HSC quiescence by producing TGF-ß1. Mechanistically, SHP-1 interacts with the immunoreceptor tyrosine-based inhibition motif on TGF-ß receptor 1 and is critical for TGF-ß signaling activation in HSCs. Functionally, Shp-1 knockout HSCs do not respond to TGF-ß-enforced HSC quiescence regulation, both in vitro and in vivo. Therefore, we identify TGF-ß-SHP-1 as a novel intrinsic regulatory mechanism for HSC quiescence maintenance.

Inhibitory leukocyte immunoglobulin-like receptors: Immune checkpoint proteins and tumor sustaining factors.

Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1-5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that recruit protein tyrosine phosphatase non-receptor type 6 (PTPN6 or SHP-1), protein tyrosine phosphatase non-receptor type 11 (PTPN11 or SHP-2), or Src homology 2 domain-containing inositol phosphatase (SHIP), leading to negative regulation of immune cell activation. Certain of these receptors also play regulatory roles in neuronal activity and osteoclast development. The activation of LILRBs on immune cells by their ligands may contribute to immune evasion by tumors. Recent studies found that several members of LILRB family are expressed by tumor cells, notably hematopoietic cancer cells, and may directly regulate cancer development and relapse as well as the activity of cancer stem cells. LILRBs thus have dual concordant roles in tumor biology - as immune checkpoint molecules and as tumor-sustaining factors. Importantly, the study of knockout mice indicated that LILRBs do not affect hematopoiesis and normal development. Therefore LILRBs may represent ideal targets for tumor treatment. This review aims to summarize current knowledge on expression patterns, ligands, signaling, and functions of LILRB family members in the context of cancer development.