Ozanimod in Patients With Moderate to Severe Ulcerative Colitis Naive to Advanced Therapies.

BACKGROUND AND AIMS: The pivotal phase 3 True North (TN) study demonstrated the efficacy and safety of ozanimod in patients with moderately to severely active ulcerative colitis. This analysis assessed ozanimod during TN and the ongoing open-label extension (OLE) in patients with active disease who were naive to advanced therapies (ATs). METHODS: TN was a randomized, double-blind, placebo-controlled trial consisting of a 10-week induction period and 42-week maintenance period. Eligible patients could enter the OLE. Symptomatic efficacy was evaluated from induction through the OLE. Clinical, endoscopic, and mucosal outcomes were evaluated at the end of induction (Week [W] 10) and maintenance (W52), and at predefined OLE timepoints (OLE W46 and W94). Safety during TN was reported. RESULTS: This analysis included 616 AT-naive patients. Numerically greater proportions of patients receiving ozanimod than placebo achieved symptomatic response (39% vs 29%, 95% CI [-0.1, 18.8]) by W2, with significant differences (56% vs 39%, 95% CI [6.3, 26.3]) achieved by W4. Patients receiving ozanimod showed significant improvements across efficacy outcomes versus placebo at W10 and W52 (P<0.05, all endpoints). In patients on continuous ozanimod who entered the OLE in clinical response at W52, 91% maintained clinical response through OLE W94, and 74% achieved endoscopic improvement and 57% achieved mucosal healing at OLE W94. In ozanimod-treated patients without clinical response by W10 who received extended induction in the OLE, 62% achieved symptomatic response by OLE W10. Safety outcomes in AT-naive patients were consistent with the total TN population. CONCLUSION: Ozanimod is an effective, durable, and well-tolerated oral therapy for AT-naive ulcerative colitis patients.

Emulgel: A Cutting Edge Approach for Topical Drug Delivery System.

Emulgel is considered an advanced leading form of topical drug delivery system. It possesses the quality of a dual control drug mechanism for drug release as it holds the properties of both gel as well as emulsion. Emulgel is capable of overcoming the problems of the conventional route of topical drug delivery, like low spreadability and stickiness with the delivery of hydrophobic drugs, enhanced bioavailability at the local site of action, no greasy texture, and ensuring patient compliance. An emulsion is used either w/o or o/w, and the drug can be incorporated into the suitable phase of the emulsion. After that, the emulsion is incorporated into the gel phase. Several factors like oil phase, gelling agent, and emulsifier can affect the efficacy and stability. This advancement is beneficial not only for dermatology but also for cosmetology as well. Currently, emulgel-based formulations are used for the delivery of anti-inflammatory, analgesic, anti-acne, and antifungal drugs with a wide array of exploration.

The Great Imitator: Pulmonary Paraganglioma Mimicking Pulmonary Metastasis of Breast Cancer on 18 F-FDG PET/CT.

ABSTRACT: Primary pulmonary paragangliomas are rare neuroendocrine tumors and are often discovered incidentally as nonfunctioning masses. We report a case of 58-year-old woman recently diagnosed with multifocal right breast cancer and suspicious right axillary lymph nodes. 18 F-FDG PET/CT showed a well-defined marginated lesion in the lower lobe of the right lung with intense FDG uptake. Findings were suspicious for pulmonary metastases. CT-guided biopsy results were consistent with a paraganglioma. Paragangliomas can mimic metastases, especially if they are large or have a high degree of FDG uptake, and careful evaluation of imaging features and clinical findings can help differentiate these entities. Most of the time biopsy is necessary to confirm the diagnosis.

Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension.

BACKGROUNDS AND AIMS: This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis. METHODS: Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses. Adverse events were monitored from True North baseline through OLE data cutoff and expressed as exposure-adjusted incidence rates. RESULTS: This analysis included 131 patients; 54% had achieved corticosteroid-free remission at True North Week 52. In OC analyses, clinical response, clinical remission, and corticosteroid-free remission were achieved by 91.4%, 69.1%, and 67.9% of patients, respectively, at OLE Week 94 [146 weeks of total treatment]. Similarly, endoscopic improvement, histological remission, and mucosal healing were achieved by 73.3%, 67.3%, and 56.3% of patients, respectively, at OLE Week 94. Efficacy rates were lower using NRI analyses, but maintenance of efficacy was demonstrated through OLE Week 94. No new safety signals emerged from this analysis. Serious infections, malignancy, cardiovascular events, and hepatic events occurred infrequently. CONCLUSIONS: Among patients who achieved clinical response after 1 year of ozanimod treatment during True North, a high percentage sustained clinical and mucosal efficacy over 2 additional years in the OLE. No new safety signals were observed with long-term ozanimod use.

Calcaneus metastasis: a rare presentation of poorly differentiated thyroid cancer.

Summary: A 60-year-old woman presented to our clinic with an acute onset 3 months history of right ankle pain. The patient had a history of poorly differentiated thyroid cancer, which was treated with total thyroidectomy, left lateral neck dissection levels II-V and central neck dissection levels VI-VII followed by postoperative I-131 radioactive iodine (131I) ablation therapy 3.7 GBq 6 months ago. The post-131I WBS showed residual iodine-avid thyroid tissue with no other iodine-avid disease or metastasis. SPECT/CT of the neck and chest showed nonavid bilateral pulmonary nodules, discrete nodal masses in mediastinum and nonavid bone lesions. FDG-PET CT scan showed FDG-avid mediastinal lymph nodes (LN), innumerable non-FDG-avid subcentimetric pulmonary nodules and few FDG-avid lytic lesions in the skeleton. X-ray and MRI of the right ankle showed a well-marginated lytic lesion in the posterior body of calcaneus and 5 × 6 cm soft tissue mass lesion, respectively. The histopathology of the calcaneus mass confirmed a positive immunostaining for thyroid origin which includes thyroglobulin and TTF-1 with PAX-8. Endobronchial mediastinal and bronchial LN biopsy confirmed thyroid cancer metastasis. Gene mutation showed HRAS and GNA13 with a high tumor mutational burden. We describe a rare case of poorly differentiated thyroid cancer in a patient who presented with right ankle pain; we confirmed the cause to be a calcaneus metastasis from the thyroid cancer, with calcaneus being an extremely rare site for bone metastases. Gene mutations points toward treatment with immune checkpoint inhibitors. Learning points: Poorly differentiated thyroid carcinoma (PDTC) usually metastasizes to lung and bone but can rarely occur in the calcaneus. Patients with distant metastases have significantly worse long-term prognosis. Radiotherapy is effective in reducing the metastatic pains as well as reducing the size of the metastasis. PAX-8 staining can be used to differentiate thyroid carcinomas from lung adenocarcinomas. The importance of searching for gene mutations to decide the treatment of PDTC.

Cardiovascular Safety of Ozanimod in Patients With Ulcerative Colitis: True North and Open-Label Extension Analyses.

BACKGROUND & AIMS: Evaluating cardiovascular safety of sphingosine 1-phosphate (S1P) receptor modulators is warranted due to S1P receptor expression on cardiomyocytes and vascular endothelial cells. This analysis reports the cardiovascular safety of ozanimod, an S1P receptor modulator, in patients with moderately to severely active ulcerative colitis from the phase 3 True North (TN) and open-label extension (OLE). METHODS: All patients who received ozanimod in TN (n = 796) and all eligible TN patients who entered the OLE (n = 823) were included. Cardiovascular-related adverse events were evaluated in patients with up to 146 weeks of ozanimod exposure (2219 patient-years), which included 52 weeks during TN. RESULTS: On TN day 1, first-dose ozanimod resulted in a 0.2 beats per minute mean decrease in heart rate from pretreatment to hour 6; 2 patients experienced bradycardia, which resolved without treatment modification. Mean systolic and diastolic blood pressure increases of 5.1 and 2.2 mm Hg, respectively, were observed at TN week 52. No second-degree Mobitz type II atrioventricular block events were reported; 1 third-degree atrioventricular block unrelated to ozanimod occurred in the OLE. Cardiac and vascular treatment-emergent adverse events were infrequent (3.8% [31 of 823] and 8.5% [70 of 823]); no ozanimod-related cardiovascular deaths occurred. The incidences of deep-vein thrombosis (0.2%; 2 of 823), pulmonary embolism (0.2%; 2 of 823), and ischemic stroke (0.4%; 3 of 823) in the OLE were low. CONCLUSIONS: No new cardiovascular safety signals were identified, consistent with findings from previous ozanimod studies. There were few major adverse cardiovascular events or thromboembolic events, which were unrelated or unlikely related to ozanimod. Ozanimod has a well-tolerated cardiovascular safety profile when prescribed in accordance with the label. Clinical trial registry website and trial numbers: ClinicalTrials.gov numbers: NCT02435992 and NCT02531126.

Guiding Principles to Address the Impact of Algorithm Bias on Racial and Ethnic Disparities in Health and Health Care.

Importance: Health care algorithms are used for diagnosis, treatment, prognosis, risk stratification, and allocation of resources. Bias in the development and use of algorithms can lead to worse outcomes for racial and ethnic minoritized groups and other historically marginalized populations such as individuals with lower income. Objective: To provide a conceptual framework and guiding principles for mitigating and preventing bias in health care algorithms to promote health and health care equity. Evidence Review: The Agency for Healthcare Research and Quality and the National Institute for Minority Health and Health Disparities convened a diverse panel of experts to review evidence, hear from stakeholders, and receive community feedback. Findings: The panel developed a conceptual framework to apply guiding principles across an algorithm's life cycle, centering health and health care equity for patients and communities as the goal, within the wider context of structural racism and discrimination. Multiple stakeholders can mitigate and prevent bias at each phase of the algorithm life cycle, including problem formulation (phase 1); data selection, assessment, and management (phase 2); algorithm development, training, and validation (phase 3); deployment and integration of algorithms in intended settings (phase 4); and algorithm monitoring, maintenance, updating, or deimplementation (phase 5). Five principles should guide these efforts: (1) promote health and health care equity during all phases of the health care algorithm life cycle; (2) ensure health care algorithms and their use are transparent and explainable; (3) authentically engage patients and communities during all phases of the health care algorithm life cycle and earn trustworthiness; (4) explicitly identify health care algorithmic fairness issues and trade-offs; and (5) establish accountability for equity and fairness in outcomes from health care algorithms. Conclusions and Relevance: Multiple stakeholders must partner to create systems, processes, regulations, incentives, standards, and policies to mitigate and prevent algorithmic bias. Reforms should implement guiding principles that support promotion of health and health care equity in all phases of the algorithm life cycle as well as transparency and explainability, authentic community engagement and ethical partnerships, explicit identification of fairness issues and trade-offs, and accountability for equity and fairness.

Development and Validation of the Adaptive Schema Questionnaire.

Background: Schemas help with the organization and interpretation of information. Adaptive schemas indicate positive predisposing thinking patterns in an individual. This study aimed to develop a psychometrically robust tool to assess adaptive schema in a nonclinical sample. Method: This research comprises two independent studies. Study I was multiphased. In Phase I (n = 70), 36 open-ended items were generated following the Young schema therapy model and qualitatively analyzed. This facilitated the generation of 144 items in Phase II (n = 152) which were evaluated for content validity and subjected to rigorous item analysis. Exploratory factor analysis was performed in Phase III (n = 751). Confirmatory factor analysis was conducted in Study II (n = 244). Results: Exploratory factor analysis resulted in a six-factor solution comprising 25 items. These factors correspond to the six adaptive themes, namely, adequate, secured, self-reliant/autonomous, resistant, successful, and self-assured. The newly developed Adaptive Schema Questionnaire demonstrated adequate reliability (α = 0.86). Significant correlations between the obtained factors and Early Maladaptive Schemas, depression, big five personality factors, and positive and negative effects established the concurrent validity. Confirmatory factor analysis indicated acceptable goodness of fit for the obtained model. Conclusion: The developed Adaptive Schema Questionnaire is a reliable and valid instrument with promising utility in psychotherapy and research context.

18 F-FDG PET/CT Imaging of Pulmonary Hamartomas : Metabolic and Functional Characterization.

ABSTRACT: Pulmonary hamartoma is the most common benign tumor of the lung and often discovered incidentally on imaging. We report the case of a 49-year-old woman recently diagnosed with left breast cancer with suspicious left axillary lymph nodes. 18 F-FDG PET/CT showed well-circumscribed, lobulated, low-attenuation soft tissue mass in the right lower lobe lung with mild to no significant metabolic activity. CT-guided biopsy showed the lesion composed of fat, cartilage, and smooth muscle, admixed with fibroconnective tissue. The findings are consistent with pulmonary hamartoma. The presence of fat in a well-circumscribed solitary pulmonary nodule along with low metabolic activity helps in the characterization of the lesion, which can alter patient management.

The Role Of 18F-FDG PET/CT In Evaluation Of Primary CNS Lymphoma: The Path Less Travelled.

Primary central nervous system lymphoma (PCNSL) is a rare but highly aggressive lymphoma with increasing incidence in immunocompromised patients. MRI is the modality of choice in evaluating brain lesions. However, MRI is often challenging in the detection of early recurrence, assessing residual disease and response evaluation in PCNSL. 18F-FDG PET/CT has superior diagnostic performance compared with body CT in the evaluation of lymphoma. 18F-FDG PET-CT is helpful in evaluating evaluation of disease extent and differentiating primary CNS lymphoma from systemic lymphoma. Besides diagnostic and prognostic value in primary CNS lymphoma, it might also be helpful in response assessment. The role of FDG-PET in PCNSL is not fully defined. In this article we have reviewed the potential role of 18F-FDG PET/CT in initial diagnosis, baseline staging, restaging, evaluation of treatment response, prognostication, and survival analysis of PCNSL.

Variations of azygos vein: a cadaveric study with clinical relevance.

The azygos vein can be formed as a single root, two roots, and three roots, namely lateral, intermediate and the medial roots respectively. The hemiazygos vein and the accessory hemiazygos vein are the tributaries of azygos vein rather than its left side equivalents. Its variations, especially in young persons without any relevant risk factors, may result in thromboembolic illness. This study aimed to describe the morphological and morphometric variations of azygos system of veins. The present study was conducted on thirty formalin fixed adult human cadavers by dissecting azygos vein from formation to termination and variations were noted. The azygos vein was formed by a single root in 56.7%, by two roots: the lateral root and intermediate root in 36.7% cases and by the lateral root and medial root in 6.6%. The vertebral level of termination of azygos vein was seen at the level of T4 vertebrae in 70% cases, at the level of T3 vertebrae in 20% of cases and at the level of T5 vertebrae in 10% cases. The course of azygos vein was varying in 13.3%. These morphological variations can be useful while performing mediastinal surgery, mediastinoscopy, surgery of the deformations of the vertebral column, neurovascular surgeries of the retroperitoneal organs, disc herniation and fracture of thoracic vertebrae.

68Ga-DOTA-peptide PET/CT for radiotherapy planning and evaluating treatment response in the management of meningiomas.

Meningiomas overexpress somatostatin receptors (SSTR). PET imaging with SSTR ligands such as 68Ga-DOTA-peptide has recently shown high diagnostic accuracy in identification of meningiomas due to lack of normal bone and brain activity. PET-derived parameters, especially gross tumour volume (GTV) delineation improves inter-observer variability and appears to be particularly promising for RT planning. The potential strength of 68Ga-DOTA in the ongoing assessment of treatment response and disease progression in meningioma, particularly in the post-surgical and post-radiation settings is encouraging. More prospective randomized studies with large cohorts of patients are required to define the effective role of this modality.

Tumour sink effect on 68Ga-PMSA PET/CT: A case of diffuse metastatic disease of prostate cancer.

68Ga-PMSA imaging has revolutionized both diagnosis and radioligand therapy selection in patients with metastatic prostate cancer. We report a case of a 59-year-old recently diagnosed prostate cancer with high PSA level pf >2000ng/ml referred for 68Ga-PSMA PET/CT. 68Ga-PSMA PET/CT showed diffuse intense tracer uptake throughout the axial and appendicular skeleton with significantly lower uptake of 68Ga-PSMA in normal organs in a configuration of "tumour sink effect". Findings are in keeping with diffuse skeletal infiltration and suspected marrow infiltration. Given the extensive nature of bone disease and pattern, 177Lu-PSMA-targetted radioligand therapy was thought to be more appropriate in a given situation with a favourable toxicity profile.

A critical review on the role of nanotheranostics mediated approaches for targeting ß amyloid in Alzheimer's.

Alzheimer's is one of the most common neurodegenerative illnesses that affect brain cellular function. In this disease, the neurons in the brain are considered to be decaying steadily but consistently by the accumulation of amyloid mass, particularly the ß-amyloids, amyloid proteins, and Tau proteins. The most responsible amyloid-proteins are amyloid-40 and amyloid-42, which have a high probability of accumulating in excess over the brain cell, interfering with normal brain cell function and triggering brain cell death. The advancement of pharmaceutical sciences leads to the development of Nanotheranostics technology, which may be used to diagnose and treat Alzheimer's. They are the colloidal nanoparticles functionalised with the therapeutic moiety as well as a diagnostic moiety. This article discusses the prognosis of Alzheimer's, various nanotheranostics approaches (nanoparticles, quantum dots, aptamers, dendrimers, etc), and their recent advancement in managing Alzheimer's. Also, various in-vitro and in-vivo diagnostic methodologies were discussed with respect to nanotheranostics.

Describing the pathophysiology of Alzheimer's with respect to amyloid ß in the prognosis of the diseasePresenting the various nanotheranostics techniques for the detection and treatment of Alzheimer's diseaseNanoparticles, Aptamers, and Dendrimers used as diagnostic and treatment entitiesIn-vivo (MRI, OI) and In-vitro (STM, TRPS) diagnostic approaches for detecting Alzheimer's disease.

Awareness of Racial and Ethnic Bias and Potential Solutions to Address Bias With Use of Health Care Algorithms.

Importance: Algorithms are commonly incorporated into health care decision tools used by health systems and payers and thus affect quality of care, access, and health outcomes. Some algorithms include a patient's race or ethnicity among their inputs and can lead clinicians and decision-makers to make choices that vary by race and potentially affect inequities. Objective: To inform an evidence review on the use of race- and ethnicity-based algorithms in health care by gathering public and stakeholder perspectives about the repercussions of and efforts to address algorithm-related bias. Design, Setting, and Participants: Qualitative methods were used to analyze responses. Responses were initially open coded and then consolidated to create a codebook, with themes and subthemes identified and finalized by consensus. This qualitative study was conducted from May 4, 2021, through December 7, 2022. Forty-two organization representatives (eg, clinical professional societies, universities, government agencies, payers, and health technology organizations) and individuals responded to the request for information. Main Outcomes and Measures: Identification of algorithms with the potential for race- and ethnicity-based biases and qualitative themes. Results: Forty-two respondents identified 18 algorithms currently in use with the potential for bias, including, for example, the Simple Calculated Osteoporosis Risk Estimation risk prediction tool and the risk calculator for vaginal birth after cesarean section. The 7 qualitative themes, with 31 subthemes, included the following: (1) algorithms are in widespread use and have significant repercussions, (2) bias can result from algorithms whether or not they explicitly include race, (3) clinicians and patients are often unaware of the use of algorithms and potential for bias, (4) race is a social construct used as a proxy for clinical variables, (5) there is a lack of standardization in how race and social determinants of health are collected and defined, (6) bias can be introduced at all stages of algorithm development, and (7) algorithms should be discussed as part of shared decision-making between the patient and clinician. Conclusions and Relevance: This qualitative study found that participants perceived widespread and increasing use of algorithms in health care and lack of oversight, potentially exacerbating racial and ethnic inequities. Increasing awareness for clinicians and patients and standardized, transparent approaches for algorithm development and implementation may be needed to address racial and ethnic biases related to algorithms.

Accumulation of 18 F-FDG at Anomalous Systemic Arterial Supply to Normal Lung on 18 F-FDG PET/CT.

ABSTRACT: Anomalous systemic arterial supply to normal lung is an anatomical variant in which a portion of the lung is supplied by a systemic vessel without a distinct pulmonary sequestration. We report a case of mild to moderate accumulation of 18 F-FDG in the medial basal segment of left lung; corresponding CT images localize this uptake in the tortuous artery arising from the descending aorta with similar uptake to that of descending aorta. Findings are suggestive of anomalous systemic arterial supply to normal segments of the lung. Hybrid PET/CT allows precise anatomical localization and helps in differentiate benign mimics of disease, which can alter patient management.

Accumulation of 131Iodine in the nasolacrimal sac/duct after radioiodine therapy for papillary thyroid cancer.

SPECT/CT is a powerful tool for assessing unexpected concentrations of radioiodine resulting from benign uptake in organs with sodium-iodide symporter (NIS) expression. We report a case of accumulation of 131Iodine in the nasolacrimal sac/duct after radioiodine therapy for papillary thyroid cancer. A whole-body scan was taken 3 days after the administration of 5.5 GBq of 131Iodine. SPECT/CT images localized the focal tracer uptake in the nasolacrimal sac/duct likely due to nasolacrimal duct obstruction secondary to prior radioiodine or iodine therapies. Hybrid SPECT/CT allows precise anatomical localization and help differentiate benign mimics of disease, which can alter patient management.

Examining the Relationship between Academic Expectations and Suicidal Ideation among College Students in India Using the Interpersonal Theory of Suicide.

OBJECTIVE: As the second most populous country in the world, India accounts for over 20% of the global suicide deaths. Notably, young adults make up 38% of those who die by suicide in India. Yet, the literature on factors associated with suicide within this age group in India is limited. The Interpersonal Theory of Suicide (IPTS) posits thwarted belongingness and perceived burdensomeness as constructs that heighten the risk for suicide. Testing mechanisms that may mediate the relationship between common stressors for young adults in India, such as academic expectations, and suicidal ideation are important to better understand factors contributing to suicide risk within this country. METHOD: Indian college students (N = 432, Mage = 19.41, 73.1% male) completed questionnaires on academic expectations, thwarted belongingness, perceived burdensomeness, collectivism, and suicidal ideation. RESULTS: Current suicidal ideation was endorsed at a rate of 38%. Academic expectancy from the self, perceived burdensomeness, and thwarted belongingness was significantly associated with suicidal ideation. The only significantly mediated pathway was academic expectancy from others to suicidal ideation through perceived burdensomeness. Collectivism was not a significant moderator in the model. DISCUSSION: The sample endorsed high rates of suicidal ideation, highlighting the need for culturally appropriate interventions. Thwarted belongingness, perceived burdensomeness, and academic expectations from oneself may be relevant treatment targets for reducing suicidal ideation among college students in India.HIGHLIGHTSOver one-third of Indian university students endorsed suicidal ideation.Suicidal ideation related to one's own more than others' academic expectations.Results offer support for the Interpersonal Theory of Suicide within this context.