Citations

The SAR Colorectal and Anal Cancer Disease-focused Panel rectal cancer MRI restaging report template can be used to clarify common areas of confusion and deliver essential insights to ensure that clinically relevant information is effectively communicated to the treatment team.

Objective Cognitive impairment is prevalent in rheumatoid arthritis (RA), yet risk factors are not well understood. We explored associations between clinical characteristics and cognitive impairment in an RA cohort. Methods Data were from a longitudinal RA cohort at Veterans Affairs Puget Sound Health Care System. Cognition was evaluated using the Saint Louis University Mental Status (SLUMS) examination. Demographics and health factors, objectively measured physical function, participant‐reported symptoms, RA disease characteristics, and comorbidities were evaluated. Univariable linear regressions explored the association between clinical factors and SLUMS scores. Those with P < 0.1 in the univariable models were evaluated in separate multivariable linear regressions controlling for age, sex, and years of education. Results A total of 145 participants with RA were included, with a mean age of 64.5 (SD 11.6) years, and were predominantly male (74%). Using SLUMS, 42 participants (29%) had normal cognition, 83 (57%) had mild cognitive impairment, and 20 (14%) had dementia. Physical performance (aβ: 0.35, confidence interval [CI] 0.11 to 0.59), self‐reported exhaustion (aβ: −2.22, CI −3.44 to −0.99), pain (aβ: −0.25, CI −0.50 to −0.00), disability (aβ: −1.79, CI −3.16 to −0.42), and trouble falling asleep (aβ: −2.57, CI −4.00 to −1.14) were all independently associated with a lower SLUMS score (all P < 0.05). Conclusion Cognitive impairment was prevalent in our cohort of veterans with RA and was associated with several modifiable clinical factors. Future longitudinal studies are needed to determine the directionality of these associations and evaluate interventions for modifiable risk factors that may mitigate cognitive dysfunction. image

Background Immune-related adverse events (irAEs) remain largely unpredictable, potentially affecting multiple organ systems and occurring at almost any point during and even occasionally after immune checkpoint inhibitor (ICI) treatment. To identify populations at risk for these immune-mediated toxicities, we analyzed genetic characteristics and immune markers associated with clinically significant irAEs. Methods We carried out a genome-wide association study on 373 white patients receiving ICI treatment. We identified single nucleotide polymorphisms associated with irAEs. Blood cytokine profiling and peripheral blood mononuclear cell RNA sequencing were performed at pretreatment baseline and 6–8 weeks after ICI initiation. Findings were validated in two external cohorts. Results We identified genetic haplotypes in VWA8 (Von Willebrand Factor A Domain Containing 8) , OSBPL6 (Oxysterol Binding Protein Like 6), and ADAMTS9-AS2 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif 9 Antisense RNA 2) associated with grade ≥2 irAEs. Patients carrying risk haplotypes for one or more genes exhibited significantly greater rates of grade ≥2 (OR 3.02; 95% CI 1.83 to 5.02; p<0.001), grade ≥3 (OR 3.59; 95% CI 1.93 to 6.64; p<0.001), and multiple type irAE (OR 2.60; 95% CI 1.53 to 4.39; p<0.001). Serum CCL3 levels were significantly elevated in individuals carrying risk haplotypes (p=0.03). Gene expression analysis demonstrated activated autoimmune and inflammatory pathways in the genetic risk group. Conclusions Novel polymorphisms in VWA8, OSBPL6, and ADAMTS9-AS2 may impact immune pathways, promote inflammation, potentiate autoimmune phenotypes, and convey risk of irAE in ICI-treated patients.

ABSTRACT The World Health Organization (WHO) 5th Edition and International Consensus Classification (ICC) have continued to delineate more genetically defined acute leukemias. Both recognize genetic aberrations associated with myelodysplastic syndromes/neoplasms (MDS) as defining MDS‐related AML (AML‐MR). Mutations in RUNX1 are included in this category in the ICC, but not WHO. The current classifications are unclear on how acute leukemias with ambiguous lineage (ALAL), including those of mixed lineage (MPAL) and those without a defined lineage (AUL), should be categorized in the presence of such mutations. Our multi‐institutional study aims to determine the significance of RUNX1 mutation in ALAL compared to de novo AML. Newly diagnosed MPAL, AUL, and AML with RUNX1 mutations were collected. ALAL with MDS‐related cytogenetics, BCR::ABL1 , KMT2A rearrangements, or ZNF384 or BCL11b abnormalities were excluded. We analyzed 17 cases of ALAL and 71 cases of AML that met inclusion criteria. ALAL‐ RUNX1 and AML‐ RUNX1 showed overlapping mutational landscapes with frequent comutations in MDS‐associated genes. No ALAL‐ RUNX1 or AML‐ RUNX1 cases showed concomitant TP53 mutation. ALAL‐ RUNX1 had more bone marrow blasts and more karyotypic abnormalities; however, neither impacted survival, nor did RUNX1 variant allele frequency (VAF). Survival analysis revealed similarly poor outcomes between them. AML‐directed therapies and allogeneic hematopoietic stem cell transplant trended toward improved survival in ALAL‐ RUNX1; however, it did not reach significance. Our results suggest ALAL‐ RUNX1 is associated with younger age, higher blasts, and more karyotypic abnormalities, but has similar clinical and genetic features and outcomes to AML‐ RUNX1 . Our findings suggest, like other MR mutations, RUNX1 ‐mutated ALALs should be included within AML‐MR.

Abstract Objectives/Background This study was undertaken to review the published literature and provide a position statement from the American Headache Society regarding the safety, efficacy, and impact on access to care of telemedicine for the clinical management of patients with headache disorders. Access to specialized care in headache medicine is severely limited in the United States and worldwide. Telemedicine has been used as an approach to care delivery in headache medicine for more than a decade, with accelerated adoption during the COVID‐19 pandemic. There is now uncertainty regarding the extent to which telemedicine will be accepted by health systems and reimbursed by payers moving forward. The purpose of this position statement is to summarize evidence and clinical experience supporting the utility of telemedicine in headache medicine. Methods Evidence regarding the safety and efficacy of telemedicine, and patient and clinician satisfaction with the use of telemedicine for headache specialty care, was gathered from a variety of sources, including PubMed, Google Scholar, and ClinicalTrials.gov . The results and conclusions based upon these results were reviewed and discussed by the authors and the Board of Directors of the American Headache Society to confirm consistency with clinical experience and to achieve consensus. Results Several randomized clinical trials and observational studies have been performed to compare telemedicine with in‐person visits in the management of patients with headache disorders. These studies showed consistently that telemedicine is noninferior to in‐person care based upon multiple outcome measures, including disability measures, patient satisfaction, and clinician satisfaction. In addition, these studies found that telemedicine rarely leads to a missed diagnosis of secondary headache or mismanagement of primary headache. Telemedicine has substantial advantages for patients, including improved access to care and reduced costs associated with obtaining care. Studies evaluating health care utilization indicate no significant differences between patients evaluated and treated virtually versus in person. Obvious limitations of telemedicine include the inability to perform an in‐person physical exam or to perform injections. For a substantial number of patients, however, these limitations are outweighed by its advantages. The experience with telemedicine reported in the literature is consistent with the experience of the Board of Directors of the American Headache Society, who endorse its use for patients when feasible and appropriate. Conclusion Telemedicine has significantly advanced the care of patients with headache disorders. Its further development and deployment should be supported and reimbursed.

Abstract Our inability to obtain nerve samples from the vast majority of neuropathic pain patients impedes our ability to understand the disease, creates challenges in understanding mechanisms in specific patient populations, and limits our ability to make treatment decisions based on quantifiable molecular data. Fields like oncology have overcome these problems to take advantage of the insight that sequencing offers for understanding mechanisms of disease and have leveraged these molecular insights to dramatically change the treatment landscape in the past decade. Here we tested the hypothesis that skin biopsies could be used to gain insight into neuronal transcriptomic changes in patients with paclitaxel-induced peripheral neuropathy (PIPN). Our analysis reveals that hundreds of differentially expressed genes (DEGs) found through bulk RNA sequencing in these skin biopsies are likely contributed by dorsal root ganglion (DRG) neuronal axons and/or terminals. Up-regulated genes were representative of broad class of nociceptors whereas down-regulated genes were associated with putative injured DRG neurons expressing the PDIA2 gene. DEGs that could be confidently associated with specific subsets of skin cells were mostly expressed by keratinocytes supporting a growing literature tying keratinocyte-neuron communication abnormalities to pain in PIPN. We validated these findings by analyzing additional previously published datasets and through prospectively conducted spatial transcriptomics experiments on human skin biopsies. Our findings warrant further assessment of skin biopsies in additional neuropathic pain populations to gain insight into DRG neuron changes that have previously been thought to be inaccessible in routine clinical or scientific assessments in most patients.

Abstract Objective The objective of this study was to summarize the available evidence regarding the clinical value and trend over time of lumbar cerebrospinal fluid (CSF) opening pressure utilization to diagnose spontaneous intracranial hypotension (SIH). Background CSF opening pressure obtained via lumbar puncture is one of the diagnostic criteria for SIH based on the International Criteria for Headache Disorders, 3rd Edition (ICHD‐3), but it has questionable utility as an initial investigation for diagnosing SIH. Methods The authors performed a systematic literature review and meta‐analysis. PubMed/MEDLINE, Scopus, and Cochrane Library were searched from inception to October 2022. Original studies and case series in English reporting three or more patients with suspected or known SIH and CSF pressure measurement were included. Meta‐analyses and meta‐regression were used to calculate pooled estimates and examine the impact of age, sex, and publication year on outcomes, including CSF pressure < 60 mm CSF, orthostatic headache, and positive findings on brain magnetic resonance imaging (MRI), spinal imaging, and radionuclide studies. Results For every 1‐year increase in the year of publication, the odds of reporting low CSF pressure decreased by 6.20% (adjusted odds ratio [aOR] = 0.94, aOR 95% confidence interval [CI] = [0.90, 0.97], p = 0.001), the odds of reporting a positive brain MRI increased by 4.67% (aOR = 1.05, aOR 95% CI = [1.01, 1.09], p = 0.026), and the odds of reporting orthostatic headache increased by 9.13% (aOR = 1.09, aOR 95% CI = [1.03, 1.15], p = 0.002). Each 1% increase in the percentage of patients with orthostatic headache was associated with a 3.13% increase in the odds of low CSF pressure (aOR = 1.03, aOR 95% CI = [1.01, 1.05], p = 0.003). Similarly, as the percentage of patients with low CSF pressure increased by 1%, there was a 2.53% increase in the odds of orthostatic headache (aOR = 1.03, aOR 95% CI = [1.01, 1.04], p = 0.005). It was estimated that 31.9% of patients with SIH had normal opening pressure (95% CI = [24.0%, 40.8%], prediction interval = [5.0%, 80.5%]). Every 1% increase in the percentage of patients with positive brain MRI was associated with a 5.25% increase in the odds of positive spinal imaging (aOR = 1.05, aOR 95% CI = [1.00, 1.11], p = 0.047). Age and positive radionuclide study did not significantly impact the outcomes measured. The corresponding I 2 for each outcome was reduced by controlling for study‐wide covariates believed to impact the prevalence of each outcome. Sensitivity analyses did not reveal discrepancies in results when studies requiring outcomes of interest were removed. Conclusion Our analysis found that recent studies indicate a reduced reliance on opening pressure for diagnosing SIH. Rather, results suggest an increasing reliance on contrast‐enhanced brain MRI, spine imaging, and clinical features for SIH diagnosis.

The TransMet trial and Norwegian studies have shown excellent outcomes in highly selected patients undergoing liver transplant (LT) for unresectable colorectal liver metastases (uCRLM). Our aim is to provide an updated analysis of the current state of LT for uCRLM in the United States. Adult patients with a diagnosis of uCRLM listed for LT between December 2017 and March 2025 were identified from the United Network for Organ Sharing database and analyzed. An analysis of living donor LT (LDLT) and deceased donor LT (DDLT) was performed. During this period, 222 patients were listed, and 158 received an LT across 33 centers. Of these, 76 (48.1%) underwent LDLT, and 82 patients (51.9%) underwent DDLT. Of the 82 deceased donors, 56 (68.2%) were out-of-sequence offers. Overall, the 3-year survival and disease-free survival rates were 66.7% and 44.0%, respectively. The 3-year survival for LDLT and DDLT was 74.1% and 57.3% ( p =0.04), respectively. While these results have not yet reached the acceptable threshold established for other LT indications, they have improved and are expected to continue improving after the implementation of prioritization points. Given the potential variability of oncologic selection criteria and graft quality, we call for the standardization of nationally accepted selection criteria for listing patients for LT with uCRLM and for providing early access to high-quality organs. To achieve this, it is imperative to create, update, and maintain national databases that allow for the collection of more granular oncological variables.

Abstract The tumor landscape of pancreatic ductal adenocarcinoma (PDAC) is refractory to conventional photon radiotherapy (RT) because of a fibrotic tumor microenvironment (TME) that promotes chronic hypoxia and reduced immune surveillance. The radiobiological factors unique to carbon ion RT (CIRT), such as high linear energy transfer and less dependence on oxygen, make it well-suited to overcome the PDAC TME. In this study, we utilized clonal syngeneic KPC pancreatic tumor cell lines and tumors to examine this postulate and to identify underlying factors that affect the response of PDAC to CIRT. Although KPC cell lines exhibited radiobiological effectiveness greater than 3, subcutaneous tumors in the mouse hind leg showed lower radiobiological effectiveness—1.3 based on quintupling time—at a linear energy transfer between 70 and 80 keV/μm. Four days after CIRT, we observed widespread transcriptomic changes in the tumor immune microenvironment, suggesting increased infiltration of antitumor immune cells and elevated expression of antitumor T-cell cytokines, MHC class I molecules, and co-stimulatory signals. Fewer immunologic changes were observed following photon irradiation. By 7 days after CIRT, tumor-supportive transcriptomic programs characterized by protumor cytokines, M2 macrophages, and cancer-associated fibroblasts emerged, promoting resistance and limiting the durability of tumor growth delay. These findings suggest that CIRT may offer a favorable platform compared with conventional photon RT for combining with immunotherapies. Furthermore, these data highlight the risk of using in vitro survival data alone in treatment planning and indicate that underlying TME factors affect the response of PDAC in vivo.