Citations

This study investigated the first multiomics data for association with tolerance to central hypovolemia in humans. Analyzing gene expression, proteins, and genetic variants in individuals with high and low tolerance to simulated hemorrhage, the findings show that severe blood loss causes widespread transcriptional changes, including the activation of innate immune system pathways and inhibition of gas transport processes. This research can help identify molecular factors that influence individuals’ tolerance levels for progressive blood loss.

Airway hyperreactivity and hASM cell proliferation (hyperplasia) are hallmark characteristics of asthma. The results of the present study showed that short-term exposure of nonasthmatic hASM to TNFα (a proinflammatory cytokine) can also induce hASM cell proliferation via activation of an ER stress pathway. Identification of the ER stress signaling pathway as important in mediating hASM hyperplasia may provide an important therapeutic target for treating asthma or acute inflammation.

Abstract The purpose of this study was to evaluate the incidence and outcomes of traumatic lunate fractures in a Level I trauma center over a 20-year period. Traumatic lunate fractures are rare, making it difficult to determine their frequency, outcomes, and patterns in clinical practice. A retrospective evaluation of 57 patients was conducted at a single institution from 2000 to 2022. Imaging studies, including radiographs, computed tomography, and magnetic resonance imaging, were reviewed to confirm traumatic etiology and fracture pattern. Fifty-seven lunate fractures met inclusion criteria: 11 were isolated and 46 had associated carpal fractures. Treatment included immobilization in 31 patients and surgery in 26. At a mean follow-up of 20.5 months (range, 2–186), average wrist flexion–extension range of motion was 90 degrees (range, 45–160), and grip strength averaged 26 kg (range, 6–48). Patient-reported outcomes were collected at a mean of 105 months (range, 12–226), with mean scores of 27 for the Disabilities of the Arm, Shoulder, and Hand, 19 for the Patient-Rated Wrist Evaluation, and 77 for the Mayo Wrist Score. Complications included 25 cases of posttraumatic arthritis, 2 cases each of avascular necrosis (AVN), nonunion, and complex regional pain syndrome, and 1 hardware infection. Posttraumatic arthritis was more frequently observed in patients with dorsal intercalated segment instability (DISI), age over 50 years, and displaced fractures. Lunate fractures occur in conjunction with greater arc injuries. Volar pole fractures were the most common fracture type observed. Predictors of long-term osteoarthritis included age over 50 years, DISI deformity, and displaced fractures at the time of diagnosis. Surgical fixation methods resulted in comparable outcomes. Two lunates progressed to AVN, both of which occurred following open operative fixation. Prognostic, Level IV

Abstract Column-type wrists, which exhibit increased scaphoid flexion during radial deviation, often experience greater loss of motion after periscaphoid arthrodesis compared with row-type wrists. Dynamic radiographic series are typically used to differentiate these kinematic patterns. In this study, we evaluate capitate morphology as a means of predicting column- or row-type carpal kinematics. This study investigated whether wrist kinematic patterns could be predicted using simple anteroposterior (AP) radiographs. We hypothesized that capitate morphology, given its close articulation with the scaphoid, influences these patterns. We analyzed 75 wrist motion radiographic series from 45 patients. Capitates were classified as either Type I (rectangular) or Type II (pentagonal) based on their shape. Wrist kinematic patterns were categorized as row- or column-type based on the degree of scaphoid length shortening during radial deviation. Our analysis revealed that a Type II capitate was a significant predictor of column-type wrists, with an odds ratio of 6.01 compared with Type I (p = 0.014). Furthermore, Type II capitates were associated with increased scaphoid flexion and reduced translation. Capitate morphology, as assessed from a plain AP radiograph, can serve as an easily accessible marker and reliable predictor of wrist motion patterns. This could potentially aid in surgical planning and patient counseling, particularly when dynamic radiographic series are not feasible. Diagnostic, Level III.

This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 (online only) for more . PURPOSE To provide updated guidance regarding the therapy for multiple myeloma. METHODS ASCO and Ontario Health (Cancer Care Ontario) convened a joint Expert Panel and conducted an updated systematic review of the literature. RESULTS The updated review identified a total of 161 relevant randomized trials. UPDATED RECOMMENDATIONS Daratumumab therapy may be offered to patients with high-risk smoldering myeloma. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as initial therapy for transplant eligible patients. They should also be offered at least lenalidomide maintenance, with or without daratumumab, carfilzomib, and/or dexamethasone. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as therapy for suitable transplant-ineligible patients. Patients with relapsed or refractory multiple myeloma should be offered triplet therapy or T-cell redirecting therapies according to a set of recommended principles. Additional information is available at www.asco.org/hematologic-malignancies-guidelines .

Background: There is no consensus scoring system for staging and prognosis in hepatocellular carcinoma (HCC), which is the fourth leading cause of cancer-related mortality worldwide. Commonly used systems include the albumin–bilirubin (ALBI) score, the Barcelona staging classification (Barcelona Clinic Liver Cancer, BCLC), the Model for End-Stage Liver Disease (MELD), and the model to estimate survival in ambulatory HCC patients (MESIAH). Liver secretion of pseudocholinesterase (PCHE) has been linked to liver function but is poorly studied in the natural history of HCC. We evaluated whether serum PCHE level predicts HCC mortality and whether it enhances existing scoring systems. Methods: We conducted a retrospective cohort study of individuals diagnosed with HCC. We collected variables including PCHE level, clinical data used in scoring systems, and time to mortality or liver transplant. We then analyzed the association between these variables and survival using Kaplan–Meier curves, Cox proportional hazards regression models, receiver operating characteristic (ROC) curves, and area under the curve (AUC) calculations. Results: We identified 420 individuals with HCC who were tested for PCHE levels, with a follow-up time of more than 20 years. There was a strong inverse relationship between PCHE level and overall survival, with the lowest quartile having high mortality and poor outcomes. Low PCHE level was associated with hepatitis C virus (HCV) infection, vascular invasion, poor liver function, and a high likelihood of liver transplant. In contrast, the highest quartile was associated with metabolic dysfunction–associated steatotic liver disease (MASLD) as the underlying cause. Compared with validated scoring systems, ALBI, BCLC, MELD 3.0, and MESIAH, the PCHE level was an independent predictor of mortality. PCHE levels could predict 3-month survival as well as or better than the other scoring systems, with an AUC of 0.74. PCHE level could also predict mortality related to hepatectomy. The addition of PCHE level to MESIAH and ALBI scoring systems could further improve the ability to predict overall mortality in HCC. Conclusions: PCHE is a reliable stand-alone biomarker of HCC prognosis. It is an independent predictor of mortality and can improve the accuracy of existing scoring systems. Improved risk stratification could improve outcomes by informing treatment decisions regarding hepatectomy or other interventions.

Key Points This study reveals the temporal development and progression of senescence in an arteriovenous fistula of uremic mice. Senescent genes including p21 increased 7 days after arteriovenous fistula placement, and p16 and phosphorylated p53 cells accumulate between days 14 and 28. Transcriptomic analyses confirm established genes in arteriovenous fistula failure and suggest a collection of novel genes of interest. Background Hemodialysis therapy for ESKD requires suitable vascular access, most commonly the arteriovenous fistula (AVF). Forty percent of AVFs fail within 1 year, leading to morbidity and care costs. Failure mechanisms remain unclear, and current therapies are inadequate. Cellular senescence may be critical in AVF failure, and ESKD itself may accelerate senescence and subsequent vascular dysfunction. Senescence follows AVF placement in rodents with normal kidney function, but the temporal and spatial features in uremic conditions are unknown. This study aimed to characterize AVF changes in uremic mice over time and versus control vessels. Methods Six- to eight-week-old male C57BL6/J mice underwent five/six nephrectomy. Twenty-eight days later, an AVF was created by cuff anastomosis (right carotid artery to the right jugular vein). Transcriptomic analysis was performed 7 days post-AVF, and further samples were collected at 14 and 28 days post-AVF creation for histologic assessment. Results AVF outflow vein morphometry showed reduced neointimal cell density. Whole transcriptomic analysis of outflow versus control veins at 7 days post-AVF placement revealed 1187 upregulated and 3256 downregulated genes. Differentially expressed genes were significantly enriched in two established senescence-related gene sets, SenMayo (a curated panel of approximately 125 genes validated across species to capture senescence and associated proteins) and SenSig (a broader panel assessed to represent fibrotic and stress-induced cell response). Histologically, senescence markers p16, p21, and phospho53 increased between days 14 and 28. Genes common to our dataset, SenMayo, and SenSig were validated with quantitative reverse transcription PCR. Conclusions These data support established markers of AVF failure, such as matrix-metalloproteinases and monocyte chemokines, and identify potential novel modulators of AVF survival that may inform senolytic strategies to improve patency. In summary, this study reveals for the first time the chronologic progression of vascular senescence in the AVF of uremic mice.

Abstract Viral infections are estimated to contribute to 12% to 20% of all cancers worldwide, with virus-driven malignancies disproportionately affecting low- and middle-income countries, whereas metabolic and nonviral factors predominate in high-income regions. Key oncogenic viruses that cause solid tumors include high-risk human papillomaviruses, Epstein–Barr virus, hepatitis B virus, hepatitis C virus, Kaposi sarcoma–associated herpesvirus, and Merkel cell polyomavirus. Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy by boosting immune responses against tumors. Although viral infection–associated tumors often exhibit “hot” immune profiles, clinical outcomes with ICIs remain inconsistent. Some studies report improved survival in virus-associated cancers, whereas others indicate no clear benefit, which might reflect high variability in tumor microenvironments and immune responses. In this review, we aim to explore the direct and indirect contribution of different viruses to carcinogenesis in solid tumors, with a particular focus on immunotherapy effectiveness based on infection status.