Association between pembrolizumab-related thyroid adverse events and outcomes in early-stage triple negative breast cancer patients.

Pembrolizumab-related thyroid dysfunction has been associated with better outcomes in metastatic cancer patients. This study aims to examine the outcomes [pathological Complete Response (pCR) and event-free survival (EFS)] in early-stage triple negative breast cancer (TNBC) patients receiving preoperative therapy who developed pembrolizumab-related thyroid dysfunction. Patients were divided into four groups based on the occurrence or not of pembrolizumab-related thyroid dysfunction (group A and D, respectively) and, in case of pre-existing thyroid disorder, based on the need of levothyroxine start/adjustment or not (group B and C, respectively). pCR and EFS in groups ABC were compared to the ones in group D. Sixty-four early-stage TNBC patients were included and the median follow-up was 16.5 months (IQR 12.0-23.8). Multiple patterns of thyroid irAEs were observed (overt hypothyroidism in 56.3%, subclinical thyrotoxicosis in 28.1%, overt thyrotoxicosis and subclinical hypothyroidism in 21.9%, and 21.9% of patients). No statistical difference was found in pCR (chi-square test, p=0.611) comparing groups ABC to group D. The median EFS in groups ABC and in group D were 16.5 (IQR 12.0-24.0) and 16.0 (IQR 12.0-22.3) months, respectively (log-rank test, p=0.671). The percentage of patients obtaining pCR was 85.7% in patients developing pembrolizumab-related overt thyrotoxicosis and 42.1% in remaining patients (Chi-square test, p=0.036). The EFS was 16.0 months (IQR 12.0-25.0) in patients developing pembrolizumab-related overt thyrotoxicosis and 16.0 months (IQR 12.0-23.5) in the remaining patients (log-rank test, p=0.494). In conclusion, multiple patterns of pembrolizumab-related thyroid dysfunction occurs in early-stage TNBC. Patients developing pembrolizumab-related overt thyrotoxicosis are more likely to achieve pCR.

A multicenter study of clinical outcomes and volumetric trends in suspected microprolactinomas.

The diagnosis of pituitary microprolactinomas is often obscured by relatively low levels of elevated prolactin compared to macroprolactinomas. This may lead to varying patterns of medical therapy versus observation. We sought to correlate prolactin levels in suspected microprolactinomas with tumor volumes and clinical outcomes. This was a multicenter retrospective study of patients with pituitary microadenomas with baseline prolactin levels > 18ng/ml for males and > 30ng/ml for females. A linear-mixed model was used to depict changes in tumor volume over time. There were 65 patients with a mean tumor volume of 95.9mm3 and mean prolactin level of 59.4ng/ml. There were significantly higher prolactin levels in patients with tumors above the mean volume versus below (74.0 versus 53.4ng/ml, p = 0.027). 26 patients were observed, 31 were treated with anti-dopaminergic therapy, and 8 had surgery. There were significantly greater baseline prolactin levels for patients who were treated surgically (mean 86.4ng/ml) than those treated medically (mean 61.7 g/ml) or observed (mean 48.5ng/ml) (p = 0.02). Among the 26 patients who were surveilled, 13 patients demonstrated spontaneous tumor shrinkage, 12 remained stable, and 1 patient's tumor grew but was lost to follow-up. Linear mixed modeling demonstrated a statistically significant rate of tumor shrinkage over time of 3.67mm3/year (p = 0.03). When analyzing patients who were observed versus those requiring surgery after initially being surveilled, there were significantly greater baseline PRL/volume ratios in surgical patients versus those observed (8.1 ng/ml/mm3 versus 2.4 ng/ml/mm3, p = 0.025). Suspected microprolactinomas may demonstrate more convincingly elevated prolactin levels when measuring over 95.9mm3. Tumors with baseline prolactin levels over 50ng/ml may be more inclined to undergo medical treatment. In tumors with levels below 50ng/ml, it may be reasonable to undergo surveillance as these tumors tend to spontaneously shrink over time. In tumors that are surveilled, an elevated baseline PRL/volume ratio of > 8 ng/ml/mm3 may be indicate serial tumor growth that may necessitate medical and/or surgical intervention.

Wide-Range Excitation-Dependent Phosphorescence of Coordination Polymers Exhibiting Dynamic Anticounterfeiting, White-Light Emission, and Antibacterial Performance.

Multicolor-tunable room-temperature phosphorescence (RTP) is attracting wide attention in optoelectronic applications. Here, we propose a coordination-oriented assembly approach to achieve wide-range RTP with a benzimidazole derivative (2,7-diazabenzimidazole, DZBIM) as a luminogen. These two compounds exhibit unexpected excitation-responsive RTP emission, and the phosphorescence emission nearly covers the entire visible region with the change of the excitation wavelength from 360 to 620 nm. To the best of our knowledge, this is the first report of coordination polymers with such a full-color-tunable RTP. Compound 1 also shows white-light emission upon excitation at 280 nm. Experimental and theoretical results demonstrate that multiple intermolecular interactions and emission centers from different aggregates are responsible for the generation of multicolor emission. The white-light emission and multiple anticounterfeiting are explored. Besides, compound 1 exhibits high antibacterial activity benefiting from efficient 1O2 generation. This work provides an efficient way to prepare a color-tunable RTP.

Meeting medical emergency response criteria for hypertension is not associated with an increased likelihood of in-hospital mortality in a tertiary referral center.

Backgrounds: Rapid response team or medical emergency team (MET) calls are typically activated by significant alterations of vital signs in inpatients. However, the clinical significance of a specific criterion, blood pressure elevations, is uncertain. Objectives: The aim of this study was to evaluate the likelihood ratios associated with MET-activating vital signs, particularly in-patient hypertension, for predicting in-hospital mortality among general medicine inpatients who met MET criteria at any point during admission in a South Australian metropolitan teaching hospital. Results: Among the 15,734 admissions over a two-year period, 4282 (27.2%) met any MET criteria, with a positive likelihood ratio of 3.05 (95% CI 2.93 to 3.18) for in-hospital mortality. Individual MET criteria were significantly associated with in-hospital mortality, with the highest positive likelihood ratio for respiratory rate ≤ 7 breaths per minute (9.83, 95% CI 6.90 to 13.62), barring systolic pressure ≥ 200 mmHg (LR + 1.26, 95% CI 0.86 to 1.69). Conclusions: Our results show that meeting the MET criteria for hypertension, unlike other criteria, was not significant associated with in-hospital mortality. This observation warrants further research in other patient cohorts to determine whether blood pressure elevations should be routinely included in MET criteria.

Impact of personalized diabetes care on distress and treatment satisfaction in people with breast cancer.

AIMS: In patients with breast cancer (BCa) and diabetes (DM), diabetes distress (DD) and treatment satisfaction (DTS) can influence BCa management and outcomes. We assessed the impact of implementing a personalized diabetes care model in patients with BCa. METHODS: Patients in active treatment or surveillance for BCa with an HbA1c > 53 mmol/mol (7%) or random blood glucose >11.1 mmol/L were included. Participants were offered continuous glucose monitoring (CGM), virtual care and a dedicated diabetes provider for 6 months. Primary outcomes included DD measured by the Diabetes Distress Survey (DDS) and DTS measured by the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Questionnaires were conducted at 0, 3 and 6 months. RESULTS: Thirty-one women were enrolled (median age 61, IQR 49.0-69.0). Compared to baseline, the mean DDS score was lower at both 3 months (2.2 vs. 1.8 [n = 27], p = 0.004, SD = 0.70) and 6 months (2.3 vs. 1.8 [n = 23], p = 0.002, SD = 0.70). The mean DTSQ score was higher at 3 months (baseline: 20.5 vs. 3 months: 28.7 [n = 28], p < 0.001, SD = 9.2) and 6 months (baseline: 20.4 vs. 6 months: 30.0 [n = 26], p < 0.001, SD = 9.7). CONCLUSIONS: Personalized diabetes care models that emphasize remote management and optimize access for those with BCa may lower DD and improve DTS.

Postoperative Serum Cortisol and Cushing Disease Recurrence in Patients With Corticotroph Adenomas.

CONTEXT: In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized. OBJECTIVE: To analyze postoperative serum cortisol and recurrence rates in Cushing disease. METHODS: Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables. RESULTS: A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001). CONCLUSION: Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.

Long-Term Changes in the Size of Pituitary Microadenomas.

BACKGROUND: The estimated prevalence of pituitary lesions is 10% to 38.5% in radiologic studies. However, how frequently these incidental lesions should be monitored by serial pituitary magnetic resonance imaging (MRI) remains unclear. OBJECTIVE: To evaluate changes in pituitary microadenomas over time. DESIGN: Retrospective, longitudinal cohort study. SETTING: Mass General Brigham, Boston, Massachusetts. PATIENTS: Evidence of pituitary microadenoma from MRI. MEASUREMENTS: Dimensions of pituitary microadenomas. RESULTS: During the study period (from 2003 to 2021), 414 patients with pituitary microadenomas were identified. Of the 177 patients who had more than 1 MRI, 78 had no change in the size of the microadenoma over time, 49 had an increase in size, 34 had a decrease in size, and 16 had both an increase and decrease in size. By linear mixed model analysis, the estimated slope was 0.016 mm/y (95% CI, -0.037 to 0.069). In the subgroup analysis, pituitary adenomas with a baseline size of 4 mm or less tended to increase in size. The estimated slope was 0.09 mm/y (CI, 0.020 to 0.161). In contrast, in the subgroup with baseline tumor size greater than 4 mm, the size tended to decrease. The estimated slope was -0.063 mm/y (CI, -0.141 to 0.015). LIMITATION: Retrospective cohort, some patients were lost to follow-up for unknown reasons, and data were limited to local large institutions. CONCLUSION: During the study period, approximately two thirds of the microadenomas remained unchanged or decreased in size. The growth, if any, was slow. These findings suggest that less frequent pituitary MRI surveillance for patients with incidental pituitary microadenomas may be safe. PRIMARY FUNDING SOURCE: None.

LncRNA LINC00460 facilitates the proliferation and metastasis of renal cell carcinoma via PI3K/AKT signaling pathway.

Renal cell carcinoma (RCC) is one of the most prevalent cancers diseases in the worldwide. Long noncoding RNAs (LncRNAs) have been indicated as a mediator acted in tumorigenesis of RCC. LINC00460 has been reported to participate in many kinds of malignancies and promotes cancer progressions. However, the mechanism of LINC00460 on RCC is yet to be investigated. This study aimed to explore the potential function and regulation mechanism of LINC00460 in RCC. We analysed the LINC00460 expression and the prognosis in RCC patients using Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases. LINC00460 level in normal renal cell line and RCC cell lines were examined by qRT-PCR. We study the effects of LINC00460 on proliferation, migration, invasion, apoptosis in RCC cells lines using a series of in vivo and in vitro experiments. RNA sequencing (RNA-seq) analysis was applied to searching potential LINC00460 related signal pathway in RCC. We identified the significant up-regulated expression of LINC00460 both in RCC tissues and cell. RCC patients with elevated LINC00460 expression have shorter survival. Up-expression of LINC00460 promoted cell proliferation, invasion and migration, meanwhile down-regulation of LINC00460 exerted inhibitory effect on these activities. We crucially identified that LNC00460 promotes development of RCC by influencing the PI3K/AKT pathway. Knockdown of LNC00460 decreased the phosphorylation of AKT and mTOR. The key finding of our study showed that LINC00460 functions as an oncogene in RCC pathogenesis by mediating the PI3K/AKT.

The Effects of Diabetes and Glycemic Control on Cancer Outcomes in Individuals With Metastatic Breast Cancer.

BACKGROUND: It is unclear whether diabetes and glycemic control affects the outcomes of breast cancer, especially among those with metastatic disease. This study aims to determine the impact of diabetes and hyperglycemia on cancer progression and mortality in individuals with metastatic breast cancer (MBC). METHODS: Patients with a diagnosis of MBC between 2010 and 2021 were identified using the MBC database at 2 academic institutions. We evaluated the effects of diabetes and glycemic control on overall survival (OS) and time to next treatment (TTNT). RESULTS: We compared 244 patients with diabetes (median age 57.6 years) to 244 patients without diabetes (matched for age, sex, ethnicity, and receptor subtype). OS at 5 years [diabetes: 54% (95% CI 47-62%) vs controls: 56% (95% CI 49-63%), P = 0.65] and TTNT at 1 year [diabetes: 43% (95% CI 36-50%) vs controls: 44% (95% CI 36-51%), P = 0.33] were similar between groups. A subgroup analysis comparing those with good glycemic control and those with poor glycemic control among patients with specific receptor subtype profiles showed no differences in OS at 5 years or TTNT at 1 year. In an 8-year landmark subgroup analysis, there was worse OS among individuals with diabetes compared to controls, and OS was found to be better among those with good glycemic control compared to those with poor control. CONCLUSIONS: Diabetes was not associated with increased mortality in individuals with MBC at 5 years. However, diabetes and hyperglycemia were associated with worse OS among a cohort of longer-term survivors. These findings suggest that individualized diabetes and glycemic goals should be considered in patients with MBC.

Factors leading to alpelisib discontinuation in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative breast cancer.

PURPOSE: Alpelisib is a phosphoinositide-3-kinase inhibitor approved for hormone-receptor-positive, PIK3CA-mutated metastatic breast cancer. However, length of drug exposure, maximum-tolerated dose, and therefore clinical response can vary significantly outside of the trial setting. This study evaluates our center's "real world" experience with alpelisib and focuses on duration of therapy and factors associated with cancer progression. METHODS: Patients receiving alpelisib at our center between 2019 and 2021 were identified. We evaluated duration of alpelisib therapy and the causative reasons for drug discontinuation. The association of drug duration and dose with subsequent cancer progression were assessed, along with the association between hyperglycemia during alpelisib therapy and cancer progression. RESULTS: Sixty-two women prescribed alpelisib were included (mean age 61 years). Disease progression was the most common reason for drug discontinuation, while discontinuation within 30 days was primarily attributed to adverse events (AEs). Among those who progressed, median time to progression was longer in those on alpelisib for > 90 days compared with those on alpelisib for ≤ 90 days (187 vs. 77 days, p < 0.001). At 200 days, freedom from progression was greater for those on alpelisib for > 90 days compared to those receiving therapy for ≤ 90 days (59% vs. 19%, p = 0.001). Median blood glucose as a continuous variable was associated with disease progression (HR 1.01, 95% CI 1.00-1.02, p = 0.02). CONCLUSION: While progression of disease is the largest contributor to alpelisib discontinuation, AEs are the leading cause for early drug cessation. Shorter alpelisib exposure is associated with greater cancer progression. Further studies are needed to determine the impact of sustained hyperglycemia on cancer progression.