Citations

Objective MGMT expression in brain and pituitary tumors has been correlated with temozolomide treatment. Few medical therapies are available in patients with Nelson Syndrome. The aim of the present study was to assess immunohistochemical expression of MGMT in ACTH‐secreting pituitary adenomas in patients with Nelson Syndrome. Methods Our material consisted of specimens from ACTH‐secreting pituitary adenomas from patients with Nelson Syndrome. Immunohistochemical staining for MGMT was performed using the streptavidin‐biotin‐peroxidase complex method. MGMT immunoreactivity was assessed microscopically and recorded as an estimated percentage of nuclear MGMT immunopositivity. (0=none, 1=<10%, 3=<50%, 4=>50%) Results Male:Female ratio was 3:5, with average patient age being 62 (range 57–66). Five of the eight specimens (65%) exhibited no MGMT immunoreactivity, with two out of eight cases (25%) showing slight MGMT immunopositivity and one out of eight cases (12%) demonstrating moderate MGMT immunopositivity (<25%). Conclusions Temozolomide therapy may be useful in patients with Nelson Syndrome. Absent or low MGMT staining in brain and other neoplasms has been shown to correlate with successful treatment with temozolomide, and recent reports assessing aggressive pituitary adenomas suggest similar outcome.

ABSTRACT The development of coronavirus disease 2019 (COVID-19) vaccines has proceeded at an unprecedented pace, with numerous trials conducted simultaneously across the world as a result of massive technological and financial resource expenditures. With multiple vaccines having now received regulatory approval, public health efforts to promote widespread vaccine dissemination are currently underway. There has been particular emphasis placed on vaccination of older populations, the age group in which COVID-19 infection has been most lethal. However, such widespread vaccination approaches have necessarily raised important questions related to potential interactions with underlying diseases and concomitant treatments among persons to be vaccinated. Osteoporosis is a chronic condition marked by reduced bone strength and an associated increased risk for fracture that generally requires sustained medical intervention(s). Osteoporosis is neither associated with a higher risk of COVID-19 infection nor by more pronounced disease severity following infection, such that individuals with osteoporosis need not be more highly prioritized for COVID-19 vaccination. Osteoporosis therapies do not interfere with the efficacy or side effect profiles of COVID-19 vaccines and should not be stopped or indefinitely delayed because of vaccination. Depending on the specific drug profile within an anti-osteoporosis medication category, minor adjustments to the timing of drug administration may be considered with respect to the patient's COVID-19 vaccination schedule. Herein we provide practical recommendations for the care of patients requiring treatment for osteoporosis in the setting of COVID-19 vaccination. © 2021 American Society for Bone and Mineral Research (ASBMR).

AbstractBackgroundTertiary hyperparathyroidism following kidney transplantation is most commonly characterized by 4‐gland hyperplasia, but single and double adenomatous disease has been demonstrated in this population as well. It is unknown whether preoperative imaging can assist in identifying patients who may qualify for focused surgery for adenomatous disease.Materials and methodsWe performed a retrospective review of our patient database from 1998–2018 for patients with tertiary hyperparathyroidism following renal transplant. Patient charts were reviewed for patient demographics, laboratory values, preoperative imaging, operative findings, pathology, and complications.ResultsWe identified 113 patients with tertiary hyperparathyroidism following renal transplant who underwent parathyroidectomy. There were 51 females and 62 males with a mean age of 53.4 ± 13.4 years. Median preoperative calcium and PTH were 10.9 mg/dl (IQR 10.3–11.2) and 228 pg/ml (IQR 118–305). Preoperative ultrasound was performed in 60 patients. Of these, 11 (18%) were negative, 38 (63%) showed 1–2 adenomas, and 11 (18%) showed ≥ 3 adenomas. 99mTc‐sestamibi parathyroid scintigraphy was performed in 101/113 patients. Of these, 11 (11%) were negative, 62 (61%) showed 1–2 areas of discordant sestamibi uptake, and 28 (28%) showed ≥ 3 areas of discordant uptake. Ultimately, 19 (17%) patients had a single adenoma removed, 16 (14%) had 2 adenomas removed, and (69%) had multi‐gland disease. There were 26 ectopic glands found in 21 patients, 42.3% of which were identified on preoperative imaging. 94.1% of patients were eucalcemic at last follow‐up, mean (± SD) 5.8 ± 3.6 years. Adenomas that were visualized on ultrasound were larger on pathology than those non‐visualized (997 ± 120 mg (mean ± SE) vs. 388 ± 109 mg, p = 0.0003). This was also true for parathyroid scintigraphy (647 ± 41 mg vs. 355 ± 51 mg, p = 0.0001).ConclusionIn patients with tertiary hyperparathyroidism, preoperative imaging can aid in predicting which patients will have 1–2 gland disease. In patients with 1–2 gland disease on congruent ultrasound and nuclear medicine imaging studies, the accuracy increases to 59%. Preoperative imaging can help identify ectopic glands. Larger adenomas are more likely to be identified on both imaging modalities.

Commercially available running shoes differ in terms of their relative masses. It is unclear how well consumers may be able to judge mass differences from wearing alone, though previous studies suggest that perceptual outcomes may be influenced by experimental design factors such as the length of time worn. The purpose of this study was to investigate how the number of shoes used in a testing session impacts wearers' mass perceptual accuracy. Forty-eight young adult males ran for 5 min in 4 pairs of shoes (their own running shoes plus 3 unfamiliar pairs) before being asked whether an unfamiliar running shoe was heavier or lighter than their own, and to indicate perceptions of shoe heaviness (mass), comfort, stability, and temperature using visual analogue scales (VAS). A subset (n=18) was also asked to provide global rank orderings after wearing all 4 pairs of shoes. Participants were 67% accurate in the heavier/lighter task and 64% accurate in the global rank order task. Global rank order scores and VAS heaviness marks were significantly and positively correlated. Mass accuracy scores (n=48) were then compared to a previous study (n=25) performed by the same investigators using the same methods but with 6 pairs of shoes instead of 4. No difference in accuracy scores for either the heavier/lighter comparisons or global rank order scores between the study populations was found, suggesting that the number of test shoes may not influence mass perception accuracy.

Abstract Purpose: Intratumoral immunosuppression mediated by myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) represents a potential mechanism of immune checkpoint inhibitor (ICI) resistance in solid tumors. By promoting TAM and MDSC infiltration, IL1β may drive adaptive and innate immune resistance in renal cell carcinoma (RCC) and in other tumor types. Experimental Design: Using the RENCA model of RCC, we evaluated clinically relevant combinations of anti-IL1β plus either anti-PD-1 or the multitargeted tyrosine kinase inhibitor (TKI), cabozantinib. We performed comprehensive immune profiling of established RENCA tumors via multiparameter flow cytometry, tumor cytokine profiling, and single-cell RNA sequencing (RNA-seq). Similar analyses were extended to the MC38 tumor model. Results: Analyses via multiparameter flow cytometry, tumor cytokine profiling, and single-cell RNA-seq showed that anti-IL1β reduces infiltration of polymorphonuclear MDSCs and TAMs. Combination treatment with anti-IL1β plus anti-PD-1 or cabozantinib showed increased antitumor activity that was associated with decreases in immunosuppressive MDSCs and increases in M1-like TAMs. Conclusions: Single-cell RNA-seq analyses show that IL1β blockade and ICI or TKI remodel the myeloid compartment through nonredundant, relatively T-cell–independent mechanisms. IL1β is an upstream mediator of adaptive myeloid resistance and represents a potential target for kidney cancer immunotherapy.

Abstract Context The diagnosis of osteoporosis and assessment of fracture risk prior to a sentinel fracture was transformed by the widespread clinical use of dual-energy X-ray absorptiometry (DXA) for the assessment of bone mineral density (BMD). Evidence Acquisition This review is based on a collection of primary and review literature gathered from a PubMed search of “dual energy X-ray absorptiometry,” “trabecular bone score,” and “atypical femur fracture” among other keywords. PubMed searches were supplemented by the authors’ prior knowledge of the subject. Evidence Synthesis While uncertainty exists for some aspects of osteoporosis care, patient and clinician familiarity with BMD assessment for screening and monitoring is firmly established. Beyond BMD, lateral spine images obtained with DXA can diagnose osteoporosis and refine fracture risk through the detection of unrecognized vertebral fractures. In addition, analysis of DXA lumbar spine images can reflect changes in trabecular bone microarchitecture, a component of bone “quality” that predicts risk of fracture independent of BMD. Finally, monitoring of bone health by DXA may be extended to include assessment of the femoral cortices for rare but serious adverse effects associated with antiresorptive therapies. Conclusions Increasing technologic sophistication requires additional consideration for how DXA imaging is performed, interpreted and applied to patient care. As with any test, clinicians must be familiar with DXA performance, pitfalls in analysis, and interpretation within each clinical context in which DXA is applied. With this perspective, care providers will be well positioned to contribute to continuous improvement of DXA performance and, in turn, quality of osteoporosis care.