Interpretation of coefficients in segmented regression for interrupted time series analyses.

Background: Segmented regression, a common model for interrupted time series (ITS) analysis, primarily utilizes two equation parametrizations. Interpretations of coefficients vary between the two segmented regression parametrizations, leading to occasional user misinterpretations. Methods: To illustrate differences in coefficient interpretation between two common parametrizations of segmented regression in ITS analysis, we derived analytical results and present an illustration evaluating the impact of a smoking regulation policy in Italy using a publicly accessible dataset. Estimated coefficients and their standard errors were obtained using two commonly used parametrizations for segmented regression with continuous outcomes. We clarified coefficient interpretations and intervention effect calculations. Results: Our investigation revealed that both parametrizations represent the same model. However, due to differences in parametrization, the immediate effect of the intervention is estimated differently under the two approaches. The key difference lies in the interpretation of the coefficient related to the binary indicator for intervention implementation, impacting the calculation of the immediate effect. Conclusions: Two common parametrizations of segmented regression represent the same model but have different interpretations of a key coefficient. Researchers employing either parametrization should exercise caution when interpreting coefficients and calculating intervention effects.

A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation.

BACKGROUND: Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some of these challenges are needed. Here, we describe the characterization of KTC1101, a novel pan-PI3K inhibitor that simultaneously targets tumor cell proliferation and the tumor microenvironment. Our studies demonstrate that KTC1101 significantly increases the anti-PD-1 efficacy in multiple pre-clinical mouse models. METHODS: KTC1101 was synthesized and characterized employing chemical synthesis, molecular modeling, Nuclear Magnetic Resonance (NMR), and mass spectrometry. Its target specificity was confirmed through the kinase assay, JFCR39 COMPARE analysis, and RNA-Seq analysis. Metabolic stability was verified via liver microsome and plasma assays, pharmacokinetics determined by LC-MS/MS, and safety profile established through acute toxicity assays to determine the LD50. The antiproliferative effects of KTC1101 were evaluated in a panel of cancer cell lines and further validated in diverse BALB/c nude mouse xenograft, NSG mouse xenograft and syngeneic mouse models. The KTC1101 treatment effect on the immune response was assessed through comprehensive RNA-Seq, flow cytometry, and immunohistochemistry, with molecular pathways investigated via Western blot, ELISA, and qRT-PCR. RESULTS: KTC1101 demonstrated strong inhibition of cancer cell growth in vitro and significantly impeded tumor progression in vivo. It effectively modulated the Tumor Microenvironment (TME), characterized by increased infiltration of CD8+ T cells and innate immune cells. An intermittent dosing regimen of KTC1101 enhanced these effects. Notably, KTC1101 synergized with anti-PD-1 therapy, significantly boosting antitumor immunity and extending survival in preclinical models. CONCLUSION: KTC1101's dual mechanism of action-directly inhibiting tumor cell growth and dynamically enhancing the immune response- represents a significant advancement in cancer treatment strategies. These findings support incorporating KTC1101 into future oncologic regimens to improve the efficacy of immunotherapy combinations.

Survival rates in Hispanic/Latinx subpopulations with cervical cancer associated with disparities in guideline-concordant care.

BACKGROUND: Failure to deliver guideline-concordant treatment may contribute to disparities among Hispanic/Latinx cervical cancer patients. This study investigated the association between survival rates in Hispanic/Latinx subpopulations and the provision of guideline-concordant care. METHODS: We analyzed patients with primary cervical cancer from 2004 to 2019 (National Cancer Database). We developed nine quality metrics based on FIGO staging (2009). Clinical and demographic covariates were analyzed using Chi-squared tests. Adjusted associations between receipt of guideline-concordant care and races and ethnicities were analyzed using multivariable marginal Poisson regression models. Adjusted Cox proportional hazard models were utilized to evaluate survival probability. RESULTS: A total of 95,589 patients were included. Hispanic/Latinx and Non-Hispanic Black (NHB) populations were less likely to receive guideline-concordant care in four and five out of nine quality metrics, respectively. Nonetheless, the Hispanic/Latinx group exhibited better survival outcomes in seven of nine quality metrics. Compared to Mexican patients, Cuban patients were 1.17 times as likely to receive timely initiation of treatment in early-stage disease (RR 1.17, 95% CI 1.04-1.37, p < 0.001). Puerto Rican and Dominican patients were, respectively, 1.16 (RR 1.16, 95% CI 1.07-1.27, p < 0.001) and 1.19 (RR 1.19, 95% 1.04-1.37, p > 0.01) times as likely to undergo timely initiation of treatment in early-stage disease. Patients of South or Central American (RR 1.18, 95% CI 1.10-1.27, p < 0.001) origin were more likely to undergo timely initiation of treatment in locally advanced disease. CONCLUSION: Significant differences in survival were identified among our cohort despite the receipt of guideline concordant care, with notably higher survival among Hispanic/Latinx populations.

Region of origin and cervical cancer stage in multiethnic Hispanic/Latinx patients living in the United States.

BACKGROUND: Hispanic/Latinx people have the second highest cervical cancer incidence rates in the U.S. However, there is a lack of disaggregated data on clinical outcomes for this diverse and populous group, which is critical to direct resources and funding where they are most needed. This study assessed differences in stage at diagnosis of cervical cancer among Hispanic/Latinx subpopulations and associated factors. METHODS: We analyzed patients with primary cervical cancer from 2004 to 2019 in the National Cancer Database. Hispanic/Latinx patients were further categorized into Mexican, Puerto Rican (PR), Cuban, Dominican, and Central/South American, as per standard NCDB categories, and evaluated based on stage at diagnosis and sociodemographic characteristics. Multinomial logistic regression quantified the odds of advanced stage at presentation. Regression models were adjusted for age, education, neighborhood income, insurance status, and additional factors. RESULTS: Hispanic/Latinx cervical cancer patients were more likely to be uninsured (18.9% vs. 6.0%, p < 0.001) and more likely to live in low-income neighborhoods (28.6% vs. 16.9%, p < 0.001) when compared to non-Hispanic White populations. Uninsured Hispanic/Latinx patients had 37.0% higher odds of presenting with regional versus localized disease (OR 1.37; 95% CI, 1.19-1.58) and 47.0% higher odds of presenting with distant versus. Localized disease than insured patients (OR 1.47; 95% CI, 1.33-1.62). When adjusting for age, education, neighborhood income, and insurance status, PR patients were 48% more likely than Mexican patients to present with stage IV versus stage I disease (OR 1.48; 95% CI, 1.34-1.64). CONCLUSION: Disaggregating health data revealed differences in stage at cervical cancer presentation among Hispanic/Latinx subpopulations, with insurance status as a major predictor. Further work targeting structural factors, such as insurance status, within specific Hispanic/Latinx subpopulations is needed.

The role of ADC value and Ki-67 index in predicting the response to neoadjuvant chemotherapy in advanced stages of olfactory neuroblastoma.

OBJECTIVES: To investigate the efficacy of pretreatment ADC and Ki-67 index in the prediction of the response to neoadjuvant chemotherapy (NACT) in advanced olfactory neuroblastoma (ONB) patients. METHODS: A total of 21 advanced ONB patients (mean 43.48 years ± 14.26; range 25-69 years; 13 men and 8 women) with diffusion-weighted imaging (DWI) before NACT between June 2015 and October 2021 were retrospectively analyzed. Patients were categorized into responders and non-responders according to RECIST 1.1 after two cycles of NACT. The clinical data, ADCmean value, and Ki-67 index were analyzed. RESULTS: Kadish stage, ADCmean value, and Ki-67 index showed statistical significance between responders and non-responders. Patients with Kadish C stage were more likely to respond to platinum-based NACT (p = 0.035). Patients with the lower ADCmean value showed response to NACT (p = 0.002) and the cutoff point was 1.04 × 10-3 mm2/s. Patients with the higher Ki-67 index showed response to NACT (p = 0.003) and the cutoff point was 17.5%. Predictive performance of Ki-67 index and ADCmean value showed no significance between responders and non-responders (p = 0.865). A significant negative correlation was found between ADCmean value and Ki-67 index (r = -0.539, p = 0.038). CONCLUSIONS: The pretreatment ADCmean value, Ki-67 index and Kadish stage have the potential to predict the response to NACT in advanced ONB patients. ADVANCES IN KNOWLEDGE: This is the first study that investigated the feasibility of DWI in predicting the response to NACT in ONB patients and showed that Kadish stage, pretreatment ADCmean and Ki-67 index may play an important role in the prediction.

Value of quantitative multiparametric MRI in differentiating pleomorphic adenomas from malignant epithelial tumors in lacrimal gland.

PURPOSE: To evaluate the diagnostic performance of the quantitative parameters derived from diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI in differentiating lacrimal gland pleomorphic adenomas (LGPAs) from lacrimal gland malignant epithelial tumors (LGMETs). METHODS: Seventy-seven cases with LG epithelial tumors confirmed by histopathology (47 LGPAs and 30 LGMETs) underwent DWI and DCE-MRI. The quantitative parameters including the apparent diffusion coefficient (ADC), the volume transfer constant (Ktrans), the efflux rate constant from the extravascular extracellular space (EES) to blood plasma (Kep), and the extravascular extracellular volume fraction (Ve) were used to differentiate LGPAs from LGMETs. Independent-samples t test was conducted to compare these parameters. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Compared with LGPAs, LGMETs had significantly lower ADC value (1.090 ± 0.169mm2/s) (P < 0.001), higher Ktrans value (0.892 ± 0.517/min) (P = 0.001), and Kep value (1.300 ± 1.131/min) (P = 0.002). ADC as a diagnostic index showed a better diagnostic efficacy in predicting malignant tumors (AUC 0.914, sensitivity 90.0%, specificity 85.1%, and accuracy 87.0%) than Ktrans and Kep alone. The combination of ADC and Ktrans presented the optimal diagnostic performance for the differentiation (AUC 0.938, sensitivity 93.3%, specificity 87.2%, accuracy 89.6%). CONCLUSION: The quantitative parameters including ADC, Ktrans, and Kep derived from DWI and DCE-MRI might be potential imaging biomarkers in differentiating LGPAs from LGMETs. The combination of ADC and Ktrans is superior to other quantitative parameters in distinguishing LGPAs from LGMETs.

Diagnosis of Postlaminar Optic Nerve Invasion in Retinoblastoma With MRI Features.

BACKGROUND: Retinoblastomas (RBs) with postlaminar optic nerve invasion (PLONI) increases the risk of local recurrence or systemic metastasis. Most MRI studies on PLONI focused on optic nerve enhancement and tumor size, with reported relatively high specificity (84-98%) but low sensitivity (37-78%), which shows room for improvement, especially with regard to sensitivity. PURPOSE: To evaluate the diagnostic performance for detecting PLONI with RB using MRI features. STUDY TYPE: Retrospective. POPULATION: Fifty patients with histopathologic PLONI and 70 patients without PLONI of RB. FIELD STRENGTH/SEQUENCE: 1.5T and 3.0T, precontrast axial T1 -weighted and T2 -weighted, postcontrast axial, coronal and oblique-sagittal T1 -weighted. ASSESSMENT: The eyes were histopathologically analyzed and the preoperative MRI features of the eyes were independently evaluated by three observers. STATISTICAL TESTS: MRI features suggesting the presence of PLONI were identified by univariate and multivariable analysis. Receiver operating characteristic curve (ROC) and the area under the curve (AUC) were used to analyze diagnostic performance. RESULTS: Significant independent diagnostic factors for PLONI include: 1: Bilateral tumor (odds ratio [OR], 15.32; 95% confidence interval [CI]: 1.63-143.51); 2: Tumor with total coverage of the optic disk (OR, 6.43; 95% CI: 1.04-39.79); and 3: Optic nerve enhancement (OR, 8.43; 95% CI: 3.50-20.31). On the other hand, isointense signal of tumor on T2 WI (OR, 0.30; 95% CI: 0.12-0.75) was an independent diagnostic factor in excluding PLONI. ROC analysis showed AUC of 0.84 (95% CI: 0.77-0.91, P < 0.0001) for PLONI. Based on the cutoff of maximum Youden index, the sensitivity, specificity, and accuracy were 82%, 73%, and 77%, respectively. DATA CONCLUSION: MRI features of RB showed a strong association with PLONI. The model of MRI features demonstrated promising diagnostic performance in detecting PLONI. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1045-1052.

Determining E1 and E2 values for yttrium aluminum garnet ceramics using the Duane-Hunt limit.

A major challenge when performing scanning electron microscopy and X-ray analysis on many ceramic materials is their electrical insulation properties, which leads to buildup of the surface charge and reduced contrast in the secondary electron image. A new procedure was established to quantitatively determine the neutral state values, E1 and E2 , of yttrium aluminum garnet (YAG) ceramics using the Duane-Hunt limit (EDHL ) of Bremsstrahlung, in order to eliminate this charge effect. Thirty-eight EDHL values were linearly fitted with the last portion of X-ray spectra acquired under the incident energy, E0 , from 0.35 to 5.0 kV. According to the distribution of EDHL , two piecewise linear fitting was first employed with a breakpoint of 1.0 kV. Consequently, two intersection points of 0.54 and 2.48 kV, which correspond to E1 and E2 for YAG ceramics, were directly determined using a theoretical curve (EDHL = E0 ). As a result, the high-resolution images of the YAG ceramic grain structure were successfully obtained using the calculated E1 and E2 values.

Multiparametric MRI findings of sinonasal rhabdomyosarcoma in adults with comparison to carcinoma.

PURPOSE: To identify magnetic resonance imaging (MRI) features of sinonasal rhabdomyosarcoma in adults, including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI features as compared with carcinomas. MATERIALS AND METHODS: Sixty-four patients were included in this study, including 12 sinonasal rhabdomyosarcomas and 52 sinonasal carcinomas. MRI was completed in all 64 patients with a 3T MR scanner. Conventional MR (nonenhanced and static contrast-enhanced) imaging features, DCE-MRI parameters, and the apparent diffusion coefficients (ADCs) were analyzed by two authors independently (X.Y.W. and Y.Z.W.). RESULTS: Compared with gray matter, sinonasal rhabdomyosarcomas appeared isointense on T1 -weighted images in 11 cases (91.7%, 11 of 12), and hyperintense on T2 -weighted images in 9 patients (75%, 9 of 12). After contrast, sinonasal rhabdomyosarcomas showed inhomogeneous enhancement in 10 cases (83.3%, 10 of 12). Skull involvement was found in eight patients (66.7%) with rhabdomyosarcomas. On T2 -weighted images, sinonasal carcinomas demonstrated isointense in 31 cases (59.6%, 31/52), hyperintense in 14 (26.9%, 14/52), and hypointense in 7 (13.5%, 7/52). Skull involvement was detected in 14 cases (14/52, 26.9%). There were significant differences in T2 signal intensity (P = 0.005) and skull involvement (P = 0.016) between sinonasal rhabdomyosarcoma and carcinomas. There was a marginal difference in time to peak enhancement (P = 0.061), while no difference in time to maximum enhancement (P = 0.403), maximum contrast index (P = 0.368), and time-intensity curve types (P = 0.138) between rhabdomyosarcoma and carcinomas. The ADCs of sinonasal rhabdomyosarcoma were significantly lower than those of sinonasal carcinomas (P < 0.001). CONCLUSION: A multiparametric approach using conventional MRI with added ADCs had the potential to improve the diagnostic accuracy of sinonasal rhabdomyosarcoma in adults. Evidence level: 4 J. Magn. Reson. Imaging 2017;45:998-1004.

Magnetic Resonance Imaging Features of Schwannoma of the Sinonasal Tract.

PURPOSE: The purpose of the study was to explore the characteristic magnetic resonance imaging (MRI) findings of schwannoma of the sinonasal tract. METHODS: Eighteen patients with histopathologically confirmed sinonasal schwannoma underwent conventional MRI, and 12 had dynamic contrast-enhanced MRI studies synchronously. The morphology feature, signal intensity, enhancement degree, and time intensity curve (TIC) pattern of schwannomas were retrospectively analyzed. RESULTS: This entity appeared as a well-circumscribed, oval or fusiform soft tissue mass with a mean greatest diameter of 38 mm. Schwannomas exhibited isointense on T1-weighted image in 12 patients and hypointense in 6. On T2-weighted image, the lesions were heterogeneously isointense in 14 patients and hyperintense in 4. The lesions had heterogeneously moderate and marked contrast enhancement in 2 and 16, respectively. The mottled-, island-, and multicyst-like appearance were identified in 3, 4, and 11, respectively. Compared with inverted papilloma and lobular capillary hemangioma, the type I TIC is characteristic of schwannoma. CONCLUSIONS: A well-circumscribed mass displaying T2 intermediate signal intensity, marked enhancement, and type I TIC, with cystic changes, strongly suggests the diagnosis of sinonasal schwannoma.

Inflammatory myofibroblastic tumor: an entity of CT and MR imaging to differentiate from malignant tumors of the sinonasal cavity.

OBJECTIVE: Inflammatory myofibroblastic tumor (IMT) is chronic inflammatory lesions of unknown origins. The preoperative diagnosis for tumors in the sinonasal cavity is difficult to distinguish between IMT and aggressive malignancy in most cases. The purpose of this study was to evaluate the imaging features of IMT distinguishing the 2 types of tumors. METHODS: Computed tomography and magnetic resonance imaging were identified retrospectively with IMT in 14 cases and with aggressive malignancy in 38 cases in the sinonasal cavity proven by pathology. Imaging findings were evaluated, including the configuration, extent, margin, calcification, bone involvement, T1WI and T2WI signal intensity, and degree of enhancement. RESULTS: There was a significant difference between IMT and aggressive malignancy regarding the configuration, extension, calcification, bone change, signal intensity and homogeneous on T2-weighted imaging, and degree of enhancement (P < 0.05). CONCLUSIONS: Inflammatory myofibroblastic tumor and aggressive malignancy have some different imaging features that could be helpful in the differentiation between the lesions. Bone erosion with sclerosis, calcification when present, typically homogenous and never hyperintense of T2 appearance, and mild enhancement played an important role in differentiating sinonasal IMT from malignancies.

Sigmoid sinus diverticulum and pulsatile tinnitus: analysis of CT scans from 15 cases.

BACKGROUND: Although the imaging features of sigmoid sinus diverticulum induced pulsatile tinnitus (PT) have been presented in some extent, detailed imaging findings still have not been systematically evaluated and precise diagnostic radiographic criteria has not been established. PURPOSE: To examine the computed tomography (CT) characteristics of sigmoid sinus diverticulum accompanied with PT. MATERIAL AND METHODS: Fifteen PT patients with sigmoid sinus diverticula proven by surgery were recruited after consenting. CT images of 15 patients were obtained and analyzed, including features of diverticula, brain venous systems, integrity of the sigmoid plate, and the degree of temporal bone pneumatization. RESULTS: Sigmoid sinus diverticulum was located on the same side of PT in 15 patients. Diverticula originated at the superior curve of the sigmoid sinus in 11 patients and the descending segment of the sigmoid sinus in four patients. Sigmoid sinus diverticula focally eroded into the adjacent mastoid air cells in 12 patients and mastoid cortex in three patients. Among eight patients with unilateral dominant brain venous systems, the diverticula were seen on the dominant side in seven patients and non-dominant side in one patient. In contrast, the other seven patients showed co-dominant brain venous systems, with three presenting diverticula on the right side and four on the left. More notably, dehiscent sigmoid plate on the PT side was demonstrated in all patients. In addition, temporal bone hyper-pneumatization was found in nine patients, good and moderate pneumatization in three patients, respectively. CONCLUSION: Dehiscent sigmoid plate and extensive temporal bone pneumatization are two important imaging characteristics of the PT induced by sigmoid sinus diverticulum.