Citations

Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term “malignant” is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.

Abstract Background Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology‐based topics spanning the field. Methods In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence‐Based Review with Recommendations, Evidence‐Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses format, and completed sections underwent a thorough and iterative consensus‐building process. The final document underwent rigorous synthesis and review prior to publication. Results The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology‐based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. Conclusion As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

AbstractBackgroundCoronary calcification is a strong indicator of coronary artery disease, and patients with a “zero” coronary calcification score have a much lower risk of future cardiac events than those with even small amounts of calcium. However, false‐negative (incorrect zero scores) may occur if small calcifications are missed at CT due to limited spatial resolution.PurposeTo demonstrate lower limits of detection for coronary calcification using an ultra‐high‐resolution (UHR) mode on a clinical photon‐counting‐detector CT (PCD‐CT), compared to a conventional energy‐integrating‐detector CT (EID‐CT).MethodsChicken eggshell fragments (0.4–0.8 mm) mimicking coronary calcifications were scanned on a clinical PCD‐CT (NAEOTOM Alpha) in UHR mode and a conventional EID‐CT (SOMATOM Force) with matched tube potential and radiation dose levels to the PCD‐CT. PCD‐CT images were reconstructed with a sharp kernel (Qr68) and a quantum iterative algorithm (QIR‐3). Two sets of EID‐CT images were reconstructed: routine clinical kernel (Qr36, ADMIRE‐3) and a sharper kernel (Qr54) with similar noise to PCD‐CT images. With institutional review board approval, in vivo exams performed with the PCD‐CT in UHR mode were compared against patients’ clinical EID‐CT exams. The visibility of calcifications on PCD‐CT and EID‐CT images was assessed and compared qualitatively.ResultsPCD‐CT images visualized all calcified fragments, while EID‐CT failed to detect those below 0.6 mm using a routine protocol. EID‐CT with Qr54 improved visibility but distorted boundaries. Calcifications were less visible on EID‐CT than PCD‐CT as phantom sizes increased. 0.6‐ and 0.7‐mm calcified fragments were barely visible on 35‐ and 40‐cm phantom EID‐CT images. Patient cases showed small calcifications missed on EID‐CT but detected on PCD‐CT.ConclusionAt matched radiation dose, PCD‐CT in UHR mode provided higher spatial resolution and improved the detectability of small calcified fragments for different phantom/patient sizes in comparison to EID‐CT.

AbstractBackgroundOne in three patients with stage III colon cancer will experience tumor recurrence. It is uncertain whether physical activity during and after postoperative chemotherapy for stage III colon cancer improves overall survival after tumor recurrence.MethodsA prospective cohort study nested within a randomized multicenter trial of patients initially diagnosed with stage III colon cancer who experienced tumor recurrence (N = 399) was conducted. Postoperative physical activity before tumor recurrence was measured. Physical activity energy expenditure was quantified via metabolic equivalent task hours per week (MET‐h/week). The primary end point was overall survival after tumor recurrence. Multivariable flexible parametric survival models estimated relative and absolute effects with two‐sided hypothesis tests.ResultsCompared with patients expending <3.0 MET‐h/week of physical activity (comparable to <1.0 h/week of brisk walking), patients with ≥18.0 MET‐h/week of physical activity (comparable to 6 h/week of brisk walking) had a 33% relative improvement in overall survival time after tumor recurrence (hazard ratio, 0.67; 95% CI, 0.42–0.96). The overall survival rate at 3 years after tumor recurrence was 61.3% (95% CI, 51.8%–69.2%) with <3.0 MET‐h/week of physical activity and 72.2% (95% CI, 63.1%–79.6%) with ≥18 MET‐h/week of physical activity (risk difference, 10.9 percentage points; 95% CI, 1.2–20.8 percentage points).ConclusionsHigher postoperative physical activity is associated with improved overall survival after tumor recurrence in patients initially diagnosed with stage III colon cancer. These data may be relevant to patients who, despite optimal postoperative medical therapy, have a high risk of tumor recurrence.

AbstractBackgroundThe impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT‐22) and University of Washington Quality of Life (UWQOL) are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling.MethodsPatients with previously untreated SNMs were prospectively enrolled (2015–2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT‐22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL.ResultsAmong 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT‐22 QOL in patients with skull base erosion (p = 0.02). SNOT‐rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005).ConclusionsOur findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex‐specific and symptom‐related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T‐staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL.

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.

Alzheimer’s disease (AD) is one representative dementia characterized by the accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain, resulting in cognitive decline and memory loss. AD is associated with neuropsychiatric symptoms, including major depressive disorder (MDD). Recent studies showed a reduction in mGluR5 expression in the brains of stress-induced mice models and individuals with MDD compared to controls. In our study, we identified depressive-like behavior and memory impairment in a mouse model of AD, specifically in the 6xTg model with tau and Aβ pathologies. In addition, we investigated the expression of mGluR5 in the brains of 6xTg mice using micro-positron emission tomography (micro-PET) imaging, histological analysis, and Western blot analysis, and we observed a decrease in mGluR5 levels in the brains of 6xTg mice compared to wild-type (WT) mice. Additionally, we identified alterations in the ERK/AKT/GSK-3β signaling pathway in the brains of 6xTg mice. Notably, we identified a significant negative correlation between depressive-like behavior and the protein level of mGluR5 in 6xTg mice. Additionally, we also found a significant positive correlation between depressive-like behavior and AD pathologies, including phosphorylated tau and Aβ. These findings suggested that abnormal mGluR5 expression and AD-related pathologies were involved in depressive-like behavior in the 6xTg mouse model. Further research is warranted to elucidate the underlying mechanisms and explore potential therapeutic targets in the intersection of AD and depressive-like symptoms.

Background: Recent literature has found rapid uptake of short-acting filgrastim biosimilars but slower uptake of other biosimilars, such as infliximab, in both Medicare and privately insured enrollees. Objectives: To describe patient, provider, and health plan characteristics associated with a switch to biosimilar among existing infliximab patients. Research Design: We constructed a retrospective panel dataset of patients undergoing active infliximab treatments and the choice of infliximab drug for each infusion. We used mixed logit regression controlling for patient, provider, and health plan characteristics as well as time-fixed effects. Subjects: Medicare Advantage and privately insured enrollees with evidence of active infliximab treatments between 2016 and 2020 (n=357,430). Measures: Our primary outcome of interest was to switch from infliximab originator to one of the infliximab biosimilars. Exposure variables of interest variables such as out-of-pocket, site of care, and in-network deductible. Results: Our study found nominally low switching among existing infliximab originator users (3.4%). We found that patients who previously received 1 infliximab originator infusion were 63.7% more likely to switch to biosimilar compared with patients who previously received administration of 20 infliximab originators. We found that biosimilar’s placement as health’s plan preferred drug was attributed to higher likelihood of biosimilar use (odds ratio: 1.666; P -value=0.001). We did not observe any statistically significant effect among out-of-pocket amount or deductible with respect to switch to infliximab biosimilar. Conclusions: To encourage uptake and switch to biosimilar, policymakers should consider targeted policies that include leveraging health plan tools such as placement of biosimilar as preferred drug and aim to educate patients on the clinical equivalence between infliximab biosimilar and originator.

IMPORTANCEPatients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not been well established.OBJECTIVETo evaluate the associations of pain, opioid consumption, and adverse events with different dosages of pregabalin and gabapentin in patients undergoing spine surgery.DATA SOURCESPubMed/MEDLINE, Embase, Web of Science, Cochrane library, and Scopus databases were searched for articles until August 7, 2021.STUDY SELECTIONRandomized clinical trials conducted among patients who received pregabalin or gabapentin while undergoing spine surgery were included.DATA EXTRACTION AND SYNTHESISTwo investigators independently performed data extraction following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) reporting guideline. The network meta-analysis was conducted from August 2022 to February 2023 using a random-effects model.MAIN OUTCOMES AND MEASURESThe primary outcome was pain intensity measured using the Visual Analog Scale (VAS), and secondary outcomes included opioid consumption and adverse events.RESULTSTwenty-seven randomized clinical trials with 1861 patients (median age, 45.99 years [range, 20.00-70.00 years]; 759 women [40.8%]) were included in the systematic review and network meta-analysis. Compared with placebo, the VAS pain score was lowest with gabapentin 900 mg per day, followed by gabapentin 1200 mg per day, gabapentin 600 mg per day, gabapentin 300 mg per day, pregabalin 300 mg per day, pregabalin 150 mg per day, and pregabalin 75 mg per day. Additionally, gabapentin 900 mg per day was found to be associated with the lowest opioid consumption among all dosages of gabapentin and pregabalin, with a mean difference of −22.07% (95% CI, −33.22% to −10.92%) for the surface under the cumulative ranking curve compared with placebo. There was no statistically significant difference in adverse events (nausea, vomiting, and dizziness) among all treatments. No substantial inconsistency between direct and indirect evidence was detected for all outcomes.CONCLUSIONS AND RELEVANCEThese findings suggest that gabapentin 900 mg per day before spine surgery is associated with the lowest VAS pain score among all dosages. In addition, no differences in adverse events were noted among all treatments.