Citations

Abstract Trigeminal amyloidoma is a rare clinical phenomenon with scarce reports in the medical literature. This report presents a case of biopsy-proven trigeminal amyloidoma in a patient with cardiac amyloidosis. This case report sheds light on the differential diagnoses that may resemble trigeminal amyloidoma and strategies for workup and treatment.

Introduction: Tuberculosis (TB) of the spine is one of the rare secondary manifestations of the disease, while isolated TB of the sacrum is an even rarer finding of the disease. Case: The authors present the case of a male patient in their late 20s who was suffering from lower back pain radiating to the leg, on and off fever for 5 months, and stiffness of the lower back. X-ray and MRI showed a sacral mass-like lesion, which led to the suspicion of spinal TB. This diagnosis was later confirmed through adequate microbiological testing. Methods and Materials: A review of literature by a thorough search of the PubMed and Google Scholar databases was carried out, and a total of 42 patients with isolated TB of the sacrum were studied. Results and Conclusions: Sacrum in isolation is a rare location for spinal TB, often overlooked by primary physicians. A prompt diagnosis and early treatment of the disease will mitigate the risk of developing complications.

Purpose To quantify and analyze public interest trends in platelet‐rich plasma (PRP) therapy for shoulder pathology between 2011 and 2020 using Google Trends data. Methods Google Trends data were queried for online search data ranging from January 2011 to December 2020. Various combinations of terms related to PRP and shoulder pathology were queried. Terms related to corticosteroid therapy in association with shoulder pathology were also generated for comparative analysis. Analyses were performed regarding trends in online search volumes. Results Linear models were generated to evaluated trends in the volume of online searches for PRP and corticosteroid therapy for shoulder pathology. For both the PRP and steroid groups, linear models showed a statistically significant increase in search volume for the period studied ( P < .001). The PRP group showed a significantly greater growth rate than the steroid group ( P < .001). There were no statistically significant differences in online search volume when compared between different geographic and socioeconomic locations. Conclusions This study indicates consistently increasing public interest in PRP injections in the shoulder. The rate of online search volume growth of PRP is significantly greater than that of corticosteroid injections for the period studied. Clinical Relevance Awareness of patient perceptions has value in informing shared decision making, aligning patient expectations, and guiding areas of future research. Each of these has an impact on patient care. Being aware of patient interest and expectations is particularly important in areas with controversial or emerging research.

Abstract Purpose: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by systemic symptoms, cytopenias, organomegaly, and bone marrow fibrosis. JAK2 inhibitors afford symptom and spleen burden reduction but do not alter the disease course and frequently lead to thrombocytopenia. TGFβ, a pleiotropic cytokine elaborated by the MF clone, negatively regulates normal hematopoiesis, downregulates antitumor immunity, and promotes bone marrow fibrosis. Our group previously showed that AVID200, a potent and selective TGFβ 1/3 trap, reduced TGFβ1-induced proliferation of human mesenchymal stromal cells, phosphorylation of SMAD2, and collagen expression. Moreover, treatment of MF mononuclear cells with AVID200 led to increased numbers of progenitor cells (PC) with wild-type JAK2 rather than JAK2V617F. Patients and Methods: We conducted an investigator-initiated, multicenter, phase Ib trial of AVID200 monotherapy in 21 patients with advanced MF. Results: No dose-limiting toxicity was identified at the three dose levels tested, and grade 3/4 anemia and thrombocytopenia occurred in 28.6% and 19.0% of treated patients, respectively. After six cycles of therapy, two patients attained a clinical benefit by IWG-MRT criteria. Spleen and symptom benefits were observed across treatment cycles. Unlike other MF-directed therapies, increases in platelet counts were noted in 81% of treated patients with three patients achieving normalization. Treatment with AVID200 resulted in potent suppression of plasma TGFβ1 levels and pSMAD2 in MF cells. Conclusions: AVID200 is a well-tolerated, rational, therapeutic agent for the treatment of patients with MF and should be evaluated further in patients with thrombocytopenic MF in combination with agents that target aberrant MF intracellular signaling pathways.

Abstract Purpose: Microsatellite instability (MSI) is currently the only predictive biomarker of efficacy of immune checkpoint inhibitors (ICI) in metastatic colorectal cancers (mCRC). However, 10% to 40% of patients with MSI mCRC will experience a primary resistance to ICI. Experimental Design: In two cohorts of patients with MSI mCRC treated with ICI (exploratory, N = 103; validation, N = 35), 3′ RNA sequencing was performed from primary tumors. Previously described single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. Results: In the exploratory cohort, the unsupervised clustering allowed the identification of three clusters of tumors with distinct transcriptional profiles: cluster A (“stromalHIGH-proliferationLOW”), cluster B (“stromalHIGH-proliferationMED”), and cluster C (“stromalLOW-proliferationHIGH”), with an enrichment of patients progressing at first disease assessment under ICI in cluster A (30% vs. 12% in cluster B and 8.1% in cluster C; P = 0.074). Progression-free survival (PFS) was also significantly shorter in patients belonging to cluster A, compared with clusters B or C (P &lt; 0.001) with 2-year PFS rates of 33.5%, 80.5%, and 78.3%, respectively. In multivariate analysis, PFS was still significantly longer in patients belonging to cluster B [HR, 0.19; 95% confidence interval (CI), 0.08–0.45; P &lt; 0.001] and cluster C (HR, 0.25; 95% CI, 0.10–0.59; P = 0.02), compared with patients belonging to cluster A. The association of this clustering with PFS under ICI was confirmed in the validation cohort. PFS related to non–ICI-based regimens was not significantly different according to cluster. Conclusions: This unsupervised transcriptomic classification identified three groups of MSI mCRCs with different compositions of TME cells and proliferative capacities of TME/tumor cells. The “stromalHIGH-proliferationLOW” cluster is associated with a poorer prognosis with ICI treatment.

Abstract Background: Milk-alkali syndrome (MAS) resulting in hypercalcemic crisis represents a life-threatening medical emergency in the setting of excessive calcium and absorbable alkali ingestion. While an uncommon cause of altered mental status and acute renal failure in the emergency department, emergency medicine clinicians should be aware of this syndrome due to significant morbidity and mortality if left undiagnosed. Case presentation: A 63-year-old woman with history of familial hypoparathyroidism presented to our emergency department with worsening confusion, slurred speech, generalized weakness, and failure to thrive over the course of one month. Review of systems was positive for tachypnea, polydipsia, diffuse musculoskeletal pain, dehydration, poor oral intake, nausea with nonbilious nonbloody emesis, and severe fatigue. Family reported increasing difficulties with completing activities of daily living including ambulation and medication compliance. Physical examination yielded no focal neurologic deficits concerning for ischemic stroke. Laboratory investigations revealed acute renal injury, metabolic alkalosis, and severe hypercalcemia. CT imaging of the head revealed no acute intracranial abnormalities. During evaluation, the patient revealed that she had been taking 15 calcium carbonate (tums) tablets daily, along with vitamin-D and calcitriol, as a result of increased symptoms of gastroesophageal reflux disease. The patient received aggressive fluid and subcutaneous calcitonin in the emergency department. She was admitted to the hospital, where she continued to receive aggressive intravenous fluids. Calcium supplementation was withheld and chlorthalidone discontinued. After a thorough negative workup, the etiology of her hypercalcemia was deemed most likely secondary to milk-alkali syndrome. She was discharged home in stable condition on hospital day 6 without receiving hemodialysis. Conclusions: Emergency physicians should be vigilant of MAS given the potential for high morbidity if left undiagnosed. Emergency clinicians should ask about calcium supplements, as these often won't be listed on the patient's medication list and can be purchased over the counter.

Objectives:Aerodigestive disorders encompass various pathological conditions affecting the lungs, upper airway, and gastrointestinal tract in children. While advanced care has primarily occurred in specialty centers, many children first present to general pediatric gastroenterologists with aerodigestive symptoms necessitating awareness of these conditions. At the 2021 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the aerodigestive Special Interest Group held a full‐day symposium entitled, Pediatric Aerodigestive Medicine: Advancing Collaborative Care of Children with Aerodigestive Disorders. The symposium aimed to underline the significance of a multidisciplinary approach to achieve better outcomes for these complex patients.Methods:The symposium brought together leading experts to highlight the growing aerodigestive field, promote new scientific and therapeutic strategies, share the structure and benefits of a multidisciplinary approach in diagnosing common and rare aerodigestive disorders, and foster multidisciplinary discussion of complex cases while highlighting the range of therapeutic and diagnostic options. In this article, we showcase the diagnostic and therapeutic approach to oropharyngeal dysphagia (OPD), one of the most common aerodigestive conditions, emphasizing the role of a collaborative model.Conclusions:The aerodigestive field has made significant progress and continues to grow due to a unique multidisciplinary, collaborative model of care for these conditions. Despite diagnostic and therapeutic challenges, the multidisciplinary approach has enabled and greatly improved efficient, high‐quality, and evidence‐based care for patients, including those with OPD.

ABSTRACT Estrogen regulates bone mass in women and men, but the underlying cellular mechanisms of estrogen action on bone remain unclear. Although both estrogen receptor (ER)α and ERβ are expressed in bone cells, ERα is the dominant receptor for skeletal estrogen action. Previous studies using either global or cell‐specific ERα deletion provided important insights, but each of these approaches had limitations. Specifically, either high circulating sex steroid levels in global ERα knockout mice or the effects of deletion of ERα during growth and development in constitutive cell‐specific knockout mice have made it difficult to clearly define the role of ERα in specific cell types in the adult skeleton. We recently generated and characterized mice with tamoxifen‐inducible ERα deletion in osteocytes driven by the 8‐kb Dmp1 promoter (ERαΔOcy mice), revealing detrimental effects of osteocyte‐specific ERα deletion on trabecular bone volume (−20.1%) and bone formation rate (−18.9%) in female, but not male, mice. Here, we developed and characterized analogous mice with inducible ERα deletion in osteoclasts using the Cathepsin K promoter (ERαΔOcl mice). In a study design identical to that with the previously described ERαΔOcy mice, adult female, but not male, ERαΔOcl mice showed a borderline (−10.2%, p = 0.084) reduction in trabecular bone volume, no change in osteoclast numbers, but a significant increase in serum CTx levels, consistent with increased osteoclast activity. These findings in ERαΔOcl mice differ from previous studies of constitutive osteoclast‐specific ERα deletion, which led to clear deficits in trabecular bone and increased osteoclast numbers. Collectively, these data indicate that in adult mice, estrogen action in the osteocyte is likely more important than via the osteoclast and that ERα deletion in osteoclasts from conception onward has more dramatic skeletal effects than inducible osteoclastic ERα deletion in adult mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Endovascular recanalization is increasingly being utilized in symptomatic patients with chronically occluded carotid arteries. 1 In carefully selected patients, endovascular recanalization has shown to lower the risk of ischemic events when compared to medical management alone.1 However, successful endovascular revascularization is technically challenging and not without risk. 1 , 2 In this video, we demonstrate a case of a 64-year-old woman who presented with recurrent transient ischemic attacks. On imaging she was found to have a chronic total occlusion of the common carotid artery from the arch. After obtaining informed consent, the patient underwent a successful endovascular recanalization and stenting of a chronically occluded left common carotid artery with aid from an intravascular guided re-entry catheter. Post operatively the patient developed a neck hematoma which improved and she returned to her neurological baseline. She reported no further symptoms on her three month follow up.