Sex-based differences in severity of chronic rhinosinusitis as reported by SNOT-22 scores.

OBJECTIVES: Chronic rhinosinusitis (CRS) is a widely prevalent condition, however its degree of severity according to sex requires further study. The literature shows that sex-based differences exist in the severity of asthma and allergic airway disease in the population. These findings point to a potential hormonal cause for this difference, but there is no study suggesting the role of sex in CRS with nasal polyps (CRSwNP). The purpose of this study was to examine the association of sex and CRSwNP severity in the United States. METHODS: This study was conducted on data gathered from 181 participants in the NAVIGATE I and NAVIGATE II randomized control trials within the OPTINOSE database. Participants were analyzed based on sex controlling for airway-related comorbidities, including history of asthma, race, and ethnicity. SNOT-22 scores were assessed as a quality-of-life outcome measure for CRS. The association between sex and SNOT-22 scores was determined using multiple linear regression. RESULTS: There were 81 female and 100 male participants. SNOT-22 scores were significantly higher in females. The average reported SNOT-22 score was 53.8 ± 16.5 in females and 46.8 ± 18.8 in males. On adjusted regression, the association of sex and SNOT-22 scores approached but didn't reach significance (ß: -4.97; 95 % CI: -10.68-0.73; p = 0.09). CONCLUSIONS: On average, females had more severe manifestations of CRSwNP in comparison to males, with the adjusted association approaching statistical significance. Further studies, potentially looking at hormones as a cause of pathogenesis, are needed to better elucidate the role of sex in CRSwNP.

Recurrent adamantinomatous craniopharyngiomas show MAPK pathway activation, clonal evolution and rare TP53-loss-mediated malignant progression.

The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children and adults. Although the biology of primary craniopharyngioma is starting to be unravelled, little is known about the biology of recurrence. To fill this gap in knowledge, we have analysed through methylation array, RNA sequencing and pERK1/2 immunohistochemistry a cohort of paired primary and recurrent samples (32 samples from 14 cases of ACP and 4 cases of PCP). We show the presence of copy number alterations and clonal evolution across recurrence in 6 cases of ACP, and analysis of additional whole genome sequencing data from the Children's Brain Tumour Network confirms chromosomal arm copy number changes in at least 7/67 ACP cases. The activation of the MAPK/ERK pathway, a feature previously shown in primary ACP, is observed in all but one recurrent cases of ACP. The only ACP without MAPK activation is an aggressive case of recurrent malignant human craniopharyngioma harbouring a CTNNB1 mutation and loss of TP53. Providing support for a functional role of this TP53 mutation, we show that Trp53 loss in a murine model of ACP results in aggressive tumours and reduced mouse survival. Finally, we characterise the tumour immune infiltrate showing differences in the cellular composition and spatial distribution between ACP and PCP. Together, these analyses have revealed novel insights into recurrent craniopharyngioma and provided preclinical evidence supporting the evaluation of MAPK pathway inhibitors and immunomodulatory approaches in clinical trials in against recurrent ACP.

Mixed Gonadal Dysgenesis: A Narrative Literature Review and Clinical Primer for the Urologist.

PURPOSE: Mixed gonadal dysgenesis is a difference of sex development that is often confused with other conditions. Individuals have a 45,X/46,XY karyotype. Gonads are characterized by a streak gonad and a dysgenetic testis at varying levels of descent. Persistent Müllerian structures are typical (eg, hemi-uterus). There is significant phenotypic heterogeneity of the internal and external genitalia that, together with different interpretations of the definition, have contributed to a poor understanding of the condition among pediatric urologists. Mixed gonadal dysgenesis is one manifestation of the 45,X/46,XY karyotype. 45,X/46,XY mosaicism can also be associated with typical female or male external genitalia. This review aims to clarify the mixed gonadal dysgenesis definition and to provide urologists with diagnostic and management considerations for affected individuals. MATERIALS AND METHODS: We searched 3 medical databases for articles related to mixed gonadal dysgenesis. Two hundred eighty-seven full-text abstracts and manuscripts were reviewed for content pertinent to: (1) clarifying the definition of mixed gonadal dysgenesis, and (2) describing the following related to the care of affected individuals: prenatal and neonatal evaluation and management, genital surgery, gonadal malignancy risk and management, fertility, gender dysphoria/incongruence, puberty and long-term outcomes, systemic comorbidities, and transitional care. RESULTS: Fifty articles were included. Key points and implications for each of the above topics were summarized. CONCLUSIONS: Mixed gonadal dysgenesis exists on a wide phenotypic spectrum and management considerations reflect this heterogeneity. Care for individuals with mixed gonadal dysgenesis is complex, and decisions should be made in a multidisciplinary setting with psychological support.

Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC (Pdx1-Cre, LSL-KrasG12D/+, LSL-Trp53R172H/+) and poorly metastatic KPflC (Pdx1-Cre, LSL-KrasG12D/+, Trp53fl/+) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KPflC, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs). Using biomechanical assessments, second harmonic generation imaging, and birefringence analysis, we show that NID2 reduction by CRISPR interference (CRISPRi) in CAFs reduces stiffness and matrix remodeling in three-dimensional models, leading to impaired cancer cell invasion. Intravital imaging revealed improved vascular patency in live NID2-depleted tumors, with enhanced response to gemcitabine/Abraxane. In orthotopic models, NID2 CRISPRi tumors had less liver metastasis and increased survival, highlighting NID2 as a potential PDAC cotarget.

Application of intraoperative structured light scanning to enable post-operative evaluation of digital and 3D-printed penile models.

BACKGROUND: Penile phenotype in hypospadias is currently assessed visually or manually (e.g., ruler, goniometer) for clinical, education, and research applications. However, these methods lack precision and accuracy across raters and cannot be reevaluated retrospectively following a surgical repair. The project aim was to evaluate the precision and reliability of penile dimensions obtained from digital and three dimensional (3D) printed models created from intraoperative (OR) structured light scans (SLS) during primary pediatric penile procedures. METHODS: Boys ages 1 month to 6 years underwent first- or single-stage penile surgery at a single institution were enrolled in this prospective study (IRB #20-000143). For each patient, immediately following placement of a stay suture under consistent manual tension, intra-operative dimension measurements with a ruler were obtained. A digital 3D model was created prior to penile repositioning using an Artec Space Spider scanner and Artec Studio 13 software. Following the case, two different raters completed 10 digital measurements of each generated model in Autodesk Fusion 360. These digital models were subsequently 3D printed and two different raters completed 10 manual dimension measurements of each 3D printed model using a ruler. A one-way random effects intraclass correlation coefficient (ICC) evaluated measures of agreement between and within raters, respectively. Analyses were conducted in R version 4.2. RESULTS: Six scans were obtained (hypospadias: 4, circumcision: 2). Intra-rater assessments showed excellent precision across repeated digital measurements; manual measurements of 3D printed models had excellent reliability for glans width and penile length but poor to good reliability for glans height. Inter-rater reliability was good to excellent for glans width (0.77-0.95) and good for penile length (0.71-0.88). However, there was poor inter-rater reliability for glans height (0-0.14). Following training regarding glans height location, there was an improvement in precision and repeatability of manual and digital measurements. CONCLUSION: Digital measurement of OR-derived 3D models resulted in excellent repeatability for each rater and improved between-rater reliability over manual measurement of 3D printed models alone, ensuring that images can be compared by various surgeons both now and in the future. SLS is promising as a novel modality to digitally generate 3D models, thereby informing phenotypic analysis for research and education. Further development of digital measurement methods to ensure consistency between raters for quantitative assessment of additional parameters and assessment of the technology within the pre-operative environment for surgical planning is planned.

Paediatric cerebellar glioblastoma - long-term survival following surgery and adjuvant chemoradiotherapy: A case report and literature review.

Introduction: Paediatric cerebellar glioblastoma is an exceptionally rare clinical entity, with very few cases described in the literature. In the majority of reported cases, prognosis is extremely poor, despite surgical and oncological management. The paucity of data results in lack of consensus as to the optimal management of these patients, with the objective of prolonging survival. Research question: Do patient or tumour characteristics suggest more favourable rates of progression-free survival in paediatric cerebellar glioblastoma? Material and methods: Tumour histopathology plus retrospective molecular analysis of archived samples, as well treatment strategy and patient characteristics of a six-year-old child with cerebellar glioblastoma and prolonged progression-free survival were assessed. Characteristics in the published literature that inferred prolonged survival were identified and compared. Results: Paediatric cerebellar glioblastoma is extremely rare, with only a handful of cases reported over several decades, during which time diagnostic and therapeutic techniques have evolved markedly. Consequently, the scarcity of data with sufficient granularity means that limited conclusions can be drawn. Specific clinical and histopathological factors (i.e. female sex, young age, EGFR negativity and surgical resection plus adjuvant chemoradiotherapy) may indicate a more favourable progression-free survival. Discussion and conclusion: Rates of progression-free survival in this rare condition are generally poor, however, several patient and tumour characteristics may infer more favourable prognosis. As increasingly refined means of diagnosis and characterisation are developed, particularly as a result of advances in molecular analyses, more adjuvant treatment options are likely to come on stream in future.

Genomic Landscape of Circulating Tumor DNA in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Treated With Abemaciclib: Data From the SCRUM-Japan Cancer Genome Screening Project.

PURPOSE: To understand the mutational landscape of circulating tumor DNA (ctDNA) and tumor tissue of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) treated with abemaciclib + endocrine therapy (ET). METHODS: Blood samples for ctDNA and/or tissue samples were collected from abemaciclib-treated patients with HR+/HER2- MBC enrolled in the SCRUM-Japan MONSTAR-SCREEN project. Blood samples were collected before abemaciclib initiation (baseline) and at disease progression/abemaciclib discontinuation (post abemaciclib treatment). Clinical and genomic characteristics including neoplastic burden (measured by shedding rate and maximum variant allele frequency [VAF]) were assessed at baseline. Genomic alterations in ctDNA were compared in paired baseline and post abemaciclib treatment samples. RESULTS: All patients (N = 97) were female (median age, 57 years [IQR, 50-67]). In baseline ctDNA (n = 77), PIK3CA (37%), TP53 (28%), ESR1 (16%), and GATA3 (11%) were the most frequently mutated genes. Baseline tissue samples (n = 79) showed similar alteration frequencies. Among patients with baseline ctDNA data, 30% had received previous ET. ESR1 alteration frequency (35% v 8%; P < .01), median shedding rate (3 v 2), and maximum somatic VAF (4 v 0.8; both P < .05) were significantly higher in ctDNA from patients with previous ET than those without previous ET. In paired ctDNA samples (n = 33), PIK3CA and ESR1 alteration frequencies were higher after abemaciclib treatment than at baseline, though not statistically significant. Among the post-treatment alterations, those newly acquired were detected most frequently in FGF3/4/19 (18%); PIK3CA, TP53, CCND1, and RB1 (all 15%); and ESR1 (12%). CONCLUSION: We summarized the ctDNA and cancer tissue mutational landscape, including overall neoplastic burden and PIK3CA and ESR1 hotspot mutations in abemaciclib-treated patients with HR+/HER2- MBC. The data provide insights that could help optimize treatment strategies in this population.

Incidence of Sinusitis Postoperatively in Orthognathic Surgery: A Systematic Review and Meta-Analysis.

Maxillary osteotomies as a component of orthognathic surgery disrupt the normal anatomy and function of the sinus. The osteotomy with advancement of the inferior component of the sinus leaves a bony and mucosal opening in the sinus. Immediately after surgery, nasal drainage is impeded because of intranasal swelling. Acute and chronic maxillary sinusitis would be expected; however, its incidence as an expected complication is not well documented. A systematic review and meta-analysis was completed using PubMed to determine the incidence of sinusitis after maxillary orthognathic surgery. Studies were reviewed by two authors, and incidence data were extracted. Two hundred six articles were identified with 24 meeting the criteria for analysis. The incidence of sinusitis was based on 4213 participants who had undergone orthognathic surgery. Twenty-three studies reported a total number of sinusitis cases, and the results demonstrated a pooled incidence of 3.3% (95% confidence interval: 1.77, 6.06). One study did not report a total number of cases but reported chronic sinusitis survey-duration-based and Lund-Mackay scores. These scores, respectively, worsened from 7.6 to 14.8 and from 1.58 to 2.90 postoperatively. Despite the variability of maxillary surgery, the surgical technique, and the postoperative management, the incidence is low but sinusitis does occur. Prospective studies with validated questionnaires within the context of a specific protocol may further elucidate the causality of sinusitis. Further, patients with sinonasal symptoms postsurgery should be encouraged to consult with an otolaryngologist to ensure prompt treatment.

Effect of insulin insufficiency on ultrastructure and function in skeletal muscle.

BACKGROUND: Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with ß-cell dysfunction and normal insulin sensitivity have decreased skeletal muscle mass. This project asks how insulin deficiency impacts on the structure and function of the remaining skeletal muscle in these animals. METHODS: Skeletal muscle function was determined by measuring exercise capacity and specific muscle strength prior to and after insulin supplementation for 28 days in 12-week-old mice with conditional ß-cell deletion of the ATP binding cassette transporters ABCA1 and ABCG1 (ß-DKO mice). Abca1 and Abcg1 floxed (fl/fl) mice were used as controls. RNAseq was used to quantify changes in transcripts in soleus and extensor digitorum longus muscles. Skeletal muscle and mitochondrial morphology were assessed by transmission electron microscopy. Myofibrillar Ca2+ sensitivity and maximum isometric single muscle fibre force were assessed using MyoRobot biomechatronics technology. RESULTS: RNA transcripts were significantly altered in ß-DKO mice compared with fl/fl controls (32 in extensor digitorum longus and 412 in soleus). Exercise capacity and muscle strength were significantly decreased in ß-DKO mice compared with fl/fl controls (P = 0.012), and a loss of structural integrity was also observed in skeletal muscle from the ß-DKO mice. Supplementation of ß-DKO mice with insulin restored muscle integrity, strength and expression of 13 and 16 of the dysregulated transcripts in and extensor digitorum longus and soleus muscles, respectively. CONCLUSIONS: Insulin insufficiency due to ß-cell dysfunction perturbs the structure and function of skeletal muscle. These adverse effects are rectified by insulin supplementation.

Cost-Effectiveness and Budget Impact of a Novel Antithrombotic Drug Removal System to Reduce Bleeding Risk in Patients on Preoperative Ticagrelor Undergoing Cardiac Surgery.

BACKGROUND: Antithrombotic drugs, including the P2Y12 inhibitor ticagrelor, increase the risk of perioperative bleeding in patients requiring urgent cardiac surgery. Perioperative bleeding can lead to increased mortality and prolong intensive care unit and hospital stays. A novel sorbent-filled hemoperfusion cartridge that intraoperatively removes ticagrelor via hemoadsorption can reduce the risk of perioperative bleeding. We estimated the cost-effectiveness and budget impact of using this device versus standard practices to reduce the risk of perioperative bleeding during and after coronary artery bypass grafting from the US healthcare sector perspective. METHODS: We used a Markov model to analyze the cost-effectiveness and budget impact of the hemoadsorption device in three cohorts: (1) surgery within 1 day from last ticagrelor dose; (2) surgery between 1 and 2 days from last ticagrelor dose; and (3) a combined cohort. The model analyzed costs and quality-adjusted life years (QALYs). Results were interpreted as both incremental cost-effectiveness ratios and net monetary benefits (NMBs) at a cost-effectiveness threshold of $100,000/QALY. We analyzed parameter uncertainty using deterministic and probabilistic sensitivity analyses. RESULTS: The hemoadsorption device was dominant for each cohort. Patients with less than 1 day of washout in the device arm gained 0.017 QALYs at a savings of $1748 (USD), for an NMB of $3434. In patients with 1-2 days of washout, the device arm yielded 0.014 QALYs and a cost savings of $151, for an NMB of $1575. In the combined cohort, device gained 0.016 QALYs and a savings of $950 for an NMB of $2505. Per-member-per-month cost savings associated with device was estimated to be $0.02 for a one-million-member health plan. CONCLUSION: This model found the hemoadsorption device to provide better clinical and economic outcomes compared with the standard of care in patients who required surgery within 2 days of ticagrelor discontinuation. Given the increasing use of ticagrelor in patients with acute coronary syndrome, incorporating this novel device may represent an important part of any bundle to save costs and reduce harm.

Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse.

Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT activation can be monitored in real time in diverse tissues, including in individual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications.

Reversal and removal of oral antithrombotic drugs in patients with active or perceived imminent bleeding.

Remarkable progress has been made in the pharmacological management of patients with cardiovascular disease, including the frequent use of antithrombotic agents. Nonetheless, bleeding complications remain frequent and potentially life-threatening. Therapeutic interventions relying on prompt antithrombotic drug reversal or removal have been developed to assist clinicians in treating patients with active bleeding or an imminent threat of major bleeding due to urgent surgery or invasive procedures. Early phase studies on these novel strategies have shown promising results using surrogate pharmacodynamic endpoints. However, the benefit of reversing/removing antiplatelet or anticoagulant drugs should always be weighed against the possible prothrombotic effects associated with withdrawal of antithrombotic protection, bleeding, and surgical trauma. Understanding the ischemic-bleeding risk tradeoff of antithrombotic drug reversal and removal strategies in the context of urgent high-risk settings requires dedicated clinical investigations, but challenges in trial design remain, with relevant practical, financial, and ethical implications.

Associations of community-level particulate matter with high-acuity visit presentation for sinusitis.

BACKGROUND: Exposure to particulate matter <2.5 µm in diameter (PM2.5) has been linked to increased sinusitis prevalence and morbidity. However, studies analyzing environmental exposures and sinusitis have not explored the effect of PM2.5 on healthcare presentation patterns. OBJECTIVE: This study aims to characterize the relationship of community-level PM2.5 with high-acuity visits in sinusitis patients. METHODS: A retrospective analysis based on medical records of 2092 adults presenting with chronic rhinosinusitis, acute rhinosinusitis, or sinus/nasal polyps to an urban academic medical center from 2010 to 2019 was conducted. We linked medical records (individual-level) with data on PM2.5 exposure at the community level, using residential zip-code data from the Chicago Health Atlas covering the years 2015-2019. Multivariable binary logistic regression with Generalized Estimating Equations examined adjusted associations between PM2.5 and high-acuity visits - including emergency department and inpatient settings. RESULTS: Our sample was 69 % female, with a mean age of 46.9 years. From 2015 to 2019, the average PM2.5 exposure in zip-codes examined was 11.66 µg/m3 with a range of 11.14-11.79 µg/m3. In adjusted models, odds of a high-acuity visit were significantly higher in patients residing in zip-codes in the top tertile of PM2.5 exposure compared to the bottom tertile (OR: 1.74; CI: 1.20-2.51). CONCLUSION: Community-level PM2.5 exposure was associated with high-acuity visits among sinusitis patients. These associations need to be studied through more rigorous, prospective investigations, as they may have potential public health implications and underscore a need to mitigate PM2.5 exposures at a community-level.

Systemic Steroids for Otolaryngology-Head and Neck Surgery Disorders: An Evidence-Based Primer for Clinicians.

OBJECTIVE: To offer pragmatic, evidence-informed guidance on the use of systemic corticosteroids (SCS) for common otolaryngologic disorders. DATA SOURCES: PubMed, Cochrane Library, and American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guidelines. REVIEW METHODS: A comprehensive search of published literature through November 2021 was conducted on the efficacy of SCS, alone or in combination with other treatments, for managing disorders in otolaryngology and the subdisciplines. Clinical practice guidelines, systematic reviews, and randomized controlled trials, when available, were preferentially retrieved. Interventions and outcomes of SCS use were compiled to generate summary tables and narrative synthesis of findings. CONCLUSIONS: Evidence on the effectiveness of SCS varies widely across otolaryngology disorders. High-level evidence supports SCS use for Bell's palsy, sinonasal polyposis, and lower airway disease. Conversely, evidence is weak or absent for upper respiratory tract infection, eustachian tube dysfunction, benign paroxysmal positional vertigo, adenotonsillar hypertrophy, or nonallergic rhinitis. Evidence is indeterminate for acute laryngitis, acute pharyngitis, acute sinusitis, angioedema, chronic rhinosinusitis without polyps, Ménière's disease, postviral olfactory loss, postoperative nerve paresis/paralysis, facial pain, and sudden sensorineural hearing loss. IMPLICATIONS FOR PRACTICE: Clinicians should bring an evidence-informed lens to SCS prescribing to best counsel patients regarding the risks, anticipated benefits, and limited data on long-term effects. Alternate routes of corticosteroid administration-such as sprays, drops, inhalers, and intralesional injections-may be preferable for many disorders, particularly those that are self-limited or require a prolonged duration of therapy. Prudent use of SCS reduces the risk of medication-related adverse effects. Clinicians who are conversant with high-level evidence can achieve optimal outcomes and stewardship when prescribing SCS.

Demographic Factors and Comorbid Conditions Related to Health Care Presentation Among Patients With Sinusitis.

BACKGROUND: Social determinants of health (SDOH) and comorbid conditions (CMCs) influence the setting of presentation for care; however, few studies have explored this relationship in the context of sinus disease. OBJECTIVE: This study aims to characterize the relationship of SDOH and CMCs with acuity of health care presentation setting in adults with sinusitis. METHODS: A retrospective analysis based on medical records (demographics, visit types, and ICD-10 codes) of 1842 adult patients presenting with sinusitis to an urban academic medical center was conducted. Chi-square analysis was used to assess bivariate associations of SDOH (age, race/ethnicity, sex, insurance type, and employment status) and CMCs (depression, body mass index [BMI], allergy, and gastroesophageal reflux disease [GERD]) with high-acuity visit types-including emergency department (ED) and inpatient visits. Multivariable binary logistic regression was performed to examine the adjusted associations between SDOH and high-acuity visits. RESULTS: The sample's mean age was 46.8 years, with 68.5% females and 31.5% males. In adjusted models, the odds of high-acuity visit presentation was higher for males than females (odds ratio [OR]: 1.57; confidence interval [CI]: 1.22-2.01); non-Hispanic Blacks (OR: 2.21; CI: 1.58-3.09) as well as Hispanics/Latinos (OR: 2.10; CI:1.43-3.08) than Whites; unemployed (OR: 1.90; CI: 1.47-2.46.) than employed. Age was positively associated with high-acuity presentation. While GERD was associated with increased odds of high-acuity presentation (OR: 2.80; CI: 1.64-4.78), BMI, allergy, and depression did not have a statistically significant association with these visit types. These associations were independent of insurance coverage, which was not statistically associated with high-acuity visits. CONCLUSION: SDOH and CMCs were associated with high-acuity healthcare presentation in adults with sinusitis. While this study highlights how SDOH affect healthcare usage patterns among people with sinusitis, further investigation is needed to identify and address the causes of these patterns.

Indications for absorbable steroid-eluting sinus implants: Viewpoint via the Delphi method.

Absorbable steroid-eluting sinus implants provide targeted corticosteroid release over a sustained period and are designed to prevent both undesirable adhesion formation and sinus ostia restenosis. Here, we highlight the key evidence of these implants to date and query a group of experts via a Delphi process on the indications and optimal timing for intraoperative or in-office placement of these implants. Six of a total of 12 statements reached consensus and were accepted. Overall, experts largely agree that intraoperative or in-office use of steroid-eluting stents could be considered for patients: (1) who are diabetic or intolerant of oral steroids, (2) undergoing extended frontal sinus surgery, and (3) with recurrent stenosis. Given the lack of expert consensus on other key statements, clinicians should carefully consider these treatment options on a case-by-case basis after shared decision-making.

Antithrombotic drug removal from whole blood using Haemoadsorption with a porous polymer bead sorbent.

AIM: To evaluate the ability of the DrugSorb™-AntiThrombotic Removal (ATR) haemoadsorption device utilizing porous polymer bead sorbent technology to remove three commonly used antithrombotic drugs from whole blood. METHODS AND RESULTS: We evaluated the removal of apixaban, rivaroxaban, and ticagrelor by the DrugSorb-ATR haemoadsorption device in a benchtop clinical scale model using bovine whole blood. Blood spiked at clinically relevant concentrations of an antithrombotic agent was continuously circulated through a 300-mL DrugSorb-ATR haemoadsorption device at a flow rate of 300 mL/min. Drug concentration was monitored over 6 h to evaluate drug removal. Results were compared with a control circuit without the haemoadsorption device. Removal rates at 30, 60, 120, and 360 minutes were: apixaban: 81.5%, 96.3%, 99.3% >99.8%; rivaroxaban: 80.7%, 95.1%, 98.9%, >99.5%; ticagrelor: 62.5%; 75%, 86.6%, >95% (all P <0.0001 vs. control). Blood pH and haematological parameters were not significantly affected by the DrugSorb-ATR haemoadsorption device when compared with the control circuit. CONCLUSION: DrugSorb-ATR efficiently removes apixaban, rivaroxaban, and ticagrelor in a clinical-scale benchtop recirculation circuit with the bulk of removal occurring in the first 60 minutes. The clinical implications of these findings are currently investigated in patients undergoing on-pump cardiothoracic surgery in two US pivotal trials (ClinicalTrials.gov Identifiers: NCT04976530 and NCT05093504).

A State-of-the-Art Roadmap for Biomarker-Driven Drug Development in the Era of Personalized Therapies.

Advances in biotechnology have enabled us to assay human tissue and cells to a depth and resolution that was never possible before, redefining what we know as the "biomarker", and how we define a "disease". This comes along with the shift of focus from a "one-drug-fits-all" to a "personalized approach", placing the drug development industry in a highly dynamic landscape, having to navigate such disruptive trends. In response to this, innovative clinical trial designs have been key in realizing biomarker-driven drug development. Regulatory approvals of cancer genome sequencing panels and associated targeted therapies has brought personalized medicines to the clinic. Increasing availability of sophisticated biotechnologies such as next-generation sequencing (NGS) has also led to a massive outflux of real-world genomic data. This review summarizes the current state of biomarker-driven drug development and highlights examples showing the utility and importance of the application of real-world data in the process. We also propose that all stakeholders in drug development should (1) be conscious of and efficiently utilize real-world evidence and (2) re-vamp the way the industry approaches drug development in this era of personalized medicines.

Long term survival after multiple microwave ablations for colorectal cancer lung metastases: A case report.

Colorectal cancer is one of the leading causes of cancer-associated morbidity and mortality in the world, with lower survival rates when metastases are present. We present a case of a 69-year-old man, diagnosed with metastatic rectal cancer to the lungs in 2015. Over the course of 5 years, he was treated with 4 microwave ablation procedures to both his lungs. Despite this, he does not have any local recurrence or any symptoms since he was first diagnosed 7 years ago. This case highlights the potential for microwave ablation to be used for curative intent in pulmonary metastases in colorectal cancer as an alternative to more invasive and complex procedures such as metastasectomies or lung resection, as well as the benefit of using microwave ablation for disease control to improve patients' quality of life.