Citations

AbstractINTRODUCTIONIncreasing evidence indicates that α‐synuclein (αSYN) oligomers are toxic. We sought to determine whether αSYN oligomers were associated with faster cognitive decline in prospectively‐followed patients with dementia with Lewy bodies (DLB).METHODSEight autopsy‐confirmed patients with DLB were selected based on rapid or slow cognitive decline determined by the rate of change of Mini‐Mental State Examination (MMSE) scores. Quantitative neuropathologic analysis of αSYN oligomers, Lewy‐related pathology, phosphorylated tau, and amyloid‐β was conducted in hippocampal subfields (CA1‐4 and subiculum) and the entorhinal cortex.RESULTSDLB with rapid cognitive decline showed greater CA1 αSYN oligomer burden (p = 0.029) and tau burden (p = 0.029) than DLB with slow decline. The groups showed comparable burden of Lewy‐related pathology and amyloid‐β pathology in the hippocampal formation and entorhinal cortex.DISCUSSIONHippocampal accumulation of αSYN oligomers and phosphorylated tau is associated with rapid cognitive decline in DLB. Therapeutic strategies targeting αSYN oligomers warrant further investigation.Highlights Proximity ligation assay (PLA) and digital pathology for oligomer quantification. Abundant α‐synuclein (αSYN) oligomers in CA1 of patients with dementia with Lewy bodies (DLB) with rapid decline. First human brain study linking αSYN oligomers to cognitive trajectory. Potential therapeutic implications of targeting αSYN oligomers in DLB.

The NCCN Guidelines for Thyroid Carcinoma address the management of different types of thyroid carcinoma, including papillary, follicular, oncocytic, medullary, and anaplastic carcinoma. The NCCN Thyroid Carcinoma Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on the panel’s most recent recommendations regarding systemic therapies for thyroid carcinoma as well as the supporting clinical data.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adult Cancer Pain provide recommendations for the comprehensive management of pain in patients with cancer. This article will focus on methods for screening for pain, safe and appropriate prescription of opioid and miscellaneous analgesics, and the optimization of nonpharmacologic interventions including integrative and interventional strategies for treatment of cancer-related pain. Additionally, the NCCN Guidelines discuss methods for the safe reduction of opioids when appropriate, as well as techniques for encouraging the judicious use of opioids. The complete version of the NCCN Guidelines for Adult Cancer Pain addresses additional issues that are not covered here, including management of pain during a pain crisis, management of procedure-related pain and anxiety, pain management for cancer survivors, and the use of nonopioid and adjuvant analgesics for cancer-related pain.

Abstract The Centiloid scale is the standard for Amyloid (Aβ) PET quantification, widely used in research, clinical settings, and trial stratification. However, variability between tracers and scanners remains a challenge. This study introduces DeepSUVR, a deep learning method to correct Centiloid quantification, by penalising implausible longitudinal trajectories during training. The model was trained using data from 2,098 participants (6,762 Aβ PET scans) in AIBL/ADNI and validated using 15,806 Aβ PET scans from 10,543 participants across 10 external datasets. DeepSUVR increased correlation between tracers, and reduced variability in the Aβ-negatives. It showed the strongest association with cognition, highest AUC against visual reads and best longitudinal consistency between studies. DeepSUVR also increased the effect size for detecting lower Centiloid increase per year in the A4 study. DeepSUVR advances Aβ PET quantification, outperforming standard approaches, which is particularly important for consistent decision making and to detect subtle and early changes in clinical interventions.

Fundamento: A angiotomografia computadorizada (ATC) com descarte triplo (TRO; do inglês, triple rule-out) é um protocolo sincronizado ao eletrocardiograma (ECG) que permite a avaliação simultânea das artérias coronárias, da aorta torácica e das artérias pulmonares em um único exame. É especialmente útil para pacientes com risco baixo a moderado de síndrome coronariana aguda no pronto atendimento, particularmente quando dissecção aórtica e embolia pulmonar também são consideradas no diagnóstico diferencial. Objetivo: O presente estudo visou comparar, em termos de dose de radiação e qualidade da imagem, dois protocolos de TRO: totalmente sincronizado ao ECG (protocolo A) e parcialmente sincronizado ao ECG (protocolo B), ambos incluindo cobertura da aorta abdominal. Tal comparação de protocolos pode ser útil quando algoritmos de reconstrução iterativa não estiverem disponíveis e a transição manual entre em protocolos parcialmente sincronizados ao ECG for necessária. Métodos: A dose de radiação foi avaliada usando o produto dose-comprimento, a dose efetiva e a dose virtual. Os valores de atenuação foram medidos nas artérias coronárias e pulmonares, bem como na aorta descendente e abdominal. A qualidade da imagem e a conspicuidade dos vasos foram avaliadas por meio de uma escala Likert de 5 pontos. Resultados: Um total de 56 pacientes foi incluído. O protocolo B demonstrou exposição à radiação significativamente menor em comparação ao protocolo A em todas as métricas: mediana do produto dose-comprimento (1,1 mSv [intervalo interquartil: 0,9 a 1,1] versus 2,2 mSv [intervalo interquartil: 1,6 a 2,8]), dose efetiva (17,0 mSv [intervalo interquartil: 14,3 a 18,1] versus 32,6 mSv [intervalo interquartil: 24,4 a 42,7]) e dose virtual (16,2 [intervalo interquartil: 9,3 a 20,4] versus 34,7 [intervalo interquartil: 19,9 a 43,5]). Todas as diferenças foram estatisticamente significativas (p < 0,001). Não houve diferenças significativas nas medidas de atenuação ou na avaliação qualitativa das imagens entre os dois protocolos. Conclusão: A ATC com TRO parcialmente sincronizada ao ECG proporciona qualidade de imagem comparável à técnica totalmente sincronizada ao ECG, reduzindo significativamente a exposição à radiação, tornando-se uma alternativa mais eficiente em termos de dose de radiação, quando algoritmos de reconstrução iterativa não estiverem disponíveis e a transição manual for necessária.

Importance SARS-CoV-2 infection has been linked to neurotoxic effects and cognitive deficits. Objective To determine whether decreases in cognitive function were accelerated after SARS-CoV-2 infection compared with individuals not infected. Design, Setting, and Participants Multicenter, prospective cohort study from 2016 to 2022 among 3525 participants alive on March 1, 2020, and enrolled in The Atherosclerosis Risk in Communities (ARIC) study and the Collaborative Cohort of Cohorts for COVID-19 Research study who completed a prepandemic cognitive assessment and a pandemic-era assessment of SARS-CoV-2 infection. Final analyses performed in November 2024. Exposure SARS-CoV-2 infection determined via self-report of a positive SARS-CoV-2 test or health care professional diagnosis of COVID-19, a positive SARS-CoV-2 antinucleocapsid antibody response, or presence of an administrative code for COVID-19 on medical records. Main outcomes and measures A neuropsychological battery assessed multiple cognitive domains, and a cocalibrated confirmatory factor analysis generated factor scores for global cognitive function. The primary outcome was the rate of excess change in cognitive function. Results The 3525 eligible participants had a mean (SD) age of 80.8 (4.7) years, 2085 (59.1%) were female, 752 (21.4%) were Black, and 2773 (78.6%) were White. SARS-CoV-2 infection was detected among 307 participants (8.7%), 103 of whom (33.6%) were hospitalized. Among uninfected participants, the mean annualized change in cognitive function was −0.09 (95% CI, −0.13 to −0.04). Compared with this rate, change was faster (β = −0.06; 95% CI, −0.09 to −0.02) among participants hospitalized for infection, but not different from participants who were infected but not hospitalized (β = 0.00; 95% CI, −0.02 to 0.03). The association among participants hospitalized for infection was evident in the cognitive domains of memory and executive function, but not language. Conclusions and relevance This cohort study of older participants found accelerated decreases in cognition among individuals hospitalized for SARS-CoV-2 infection, but not nonhospitalized infection, in comparison with individuals not yet infected.

PURPOSE Despite international medical graduates (IMGs) accounting for up to one third of all practicing oncologists in the United States, and nearly half of fellowship trainees, little is known about their contributions to presentations at international oncology meetings. Therefore, we investigated the representation of IMGs in invited faculty roles at the ASCO Annual Meeting as a representative example. METHODS Presentation data from ASCO 2022 and 2023 Annual Meetings were obtained from program guides. We collected presentation-level and speaker-level variables of invited faculty roles and original research. Speakers were categorized as American medical graduate (AMG), IMG, non–US-based, or non-MD (Doctor of Medicine). Univariable and multivariable analyses assessed factors influencing selection for invited faculty roles. RESULTS A total of 2,590 presentations by 2,109 unique speakers were reviewed, including primary research presenters and invited faculty. Among the 1,352 presentations by AMGs, 30% were primary research and 70% were invited faculty roles. For the 374 presentations by IMGs, 41% were primary research and 59% were invited faculty roles. Notably, first-author IMGs were significantly less likely to receive invited faculty roles relative to their primary research output compared with first-author AMGs (adjusted odds ratio, 0.69 [95% CI, 0.53 to 0.90]; P = .006), even when accounting for academic rank, presumed sex, and year. CONCLUSION Relative to IMGs' original research output, IMGs appear to receive fewer invitations for ASCO Annual Meeting invited faculty roles compared with AMGs. Our findings suggest potential underrepresentation and under-recognition of IMGs in these roles, despite their contributions to the oncology workforce in the United States.

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well- annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied environments and providing the tools for future development of personalized volumetric reports to patients undergoing BM treatment.

AbstractBackgroundGastric cancer with synchronous peritoneal metastases is a debilitating disease with limited treatment options. This article describes an update of the 2018 Chicago Consensus guidelines addressing the management of gastric cancer with synchronous peritoneal metastases in line with the most recent evidence.MethodsA clinical management pathway was updated through two rounds of a Delphi consensus to assess agreement levels with pathway blocks. Supporting evidence underwent evaluation using a rapid literature review. Meta‐analyses were performed as appropriate.ResultsOverall, the level of evidence in this disease subset was low to moderate. Of 124 participants in the first round, 109 (88%) responded in the second round. Strong consensus (>90%) was achieved in six of eight blocks (75%) in rounds 1 and 2. A multidisciplinary preoperative assessment and diagnostic laparoscopy should be offered to all patients, whereas patients with a high burden of disease or progression should undergo nonsurgical management. Patients with stable/responsive disease and a low peritoneal carcinomatosis index should subsequently be offered treatment with regional therapeutic interventions and cytoreductive surgery. In patients who are cytology‐positive, systemic therapy can be used to convert them to cytology‐negative, with subsequent surgery offered according to the patient's goals of care. Meta‐analysis of observational and randomized control trials revealed a survival benefit with the addition of intraperitoneal chemotherapy to cytoreductive surgery (hazard ratio, 0.52).ConclusionsThe consensus‐driven clinical pathway for gastric cancer with synchronous peritoneal metastases offers vital clinical guidance for practitioners. There is a growing body of high‐quality evidence to support management strategies, and future clinical trials are eagerly awaited.

AbstractNeuroendocrine neoplasms (NENs) with peritoneal metastases (PM) represent a complex clinical challenge because of low incidence and heterogeneous phenotypes. This commentary describes the results of a national consensus aimed at addressing clinical management of patients with NENs and PM. An update of the 2018 Chicago consensus guidelines was conducted with a modified Delphi technique, which encompassed two rounds of voting. The levels of agreement for various pathway blocks were assessed, and key systemic therapy concepts were summarized by content experts. Supporting evidence was evaluated via a rapid literature review. Overall, the level of evidence for the management of PM in this disease was universally low. In total, 107 participants responded in the first round, with 88 of 107 (82%) participating in the second round. Strong consensus (>90%) was achieved in five of seven (71%) and seven of seven (100%) blocks in rounds 1 and 2, respectively. A multidisciplinary approach including psychosocial and wellness assessments received a strong positive recommendation. Management of NENs with PM was organized according to disease grade and symptom profiles. In grade 1 and 2 well‐differentiated NENs, cytoreductive surgery received strong support (>95%) after the management of functional syndromes (if present). For grade 3 well‐differentiated NENs, systemic therapy is the primary recommendation, with surgical resection considered in select cases. Given the limited evidence, the consensus‐driven clinical pathway offers vital clinical guidance for the management of NENs with PM. The need for high‐quality evidence remains critical to the field.