Citations

The clinical courses of 51 patients with postherpetic pain who were referred to the Pain Clinic were reviewed. Twenty-three patients were treated on a trial basis with an intensive series of sensory and sympathetic blocks, whereas 28 control patients, who were seen before the initiation of this study, were treated with other modalities. Fifteen control patients (54%) were disabled by postherpetic neuralgia, as compared with four patients (17%) in the trial group.

ABSTRACT Glioblastoma (GBM), the most aggressive primary brain tumour in adults, presents significant challenges due to its universal recurrence and limited survival rates. A key driver of GBM progression is the subpopulation of brain tumour‐initiating cells (BTICs), which contribute to therapy resistance and interact with the tumour microenvironment, particularly the cellular components in the subventricular zone (SVZ). Extracellular vesicles (EVs) are critical mediators of intercellular communication, carrying bioactive molecules, such as proteins and RNAs, that can modulate the behaviour of recipient cells. This study investigates the role of EVs in GBM's communication with non‐cancer cells. We utilised the proximity‐labelling system TurboID to achieve global and unbiased labelling of proteins within GBM‐derived EVs. By inducing TurboID expression in primary‐cultured human BTICs from GBM patients, we achieved efficient biotinylation of EV proteins without compromising vesicle integrity, and performed proteomic analysis of biotinylated proteins, which revealed a diverse cargo within BTIC‐EVs. Our method marks the first implementation of TurboID for unbiased global labelling of EV protein cargo in primary cells. This approach facilitates the investigation of EV‐mediated communication and potential therapeutic targets, contributing to the understanding of GBM's complex interactions with the brain's microenvironment and identification of biomarkers for improved diagnosis and treatment response.

Morphine sulfate, a narcotic analgesic, possesses the undesirable side effects of central depression, tolerance, and dependency. Opiate receptors have been found in the brain and the spinal cord. Intrathecally applied opiates produce potent analgesia that can be antagonized by naloxone. The time-response study with tail-flick response after intrathecal injections of a small dosage of morphine (25 μg) demonstrated a long-lasting analgesia. Intrathecal injections of morphine or opiate-like peptides may become a predictable modality of pain relief without attendant loss of other neurologic function.

Background Percutaneous left atrial appendage occlusion (LAAO) is an alternative to long‐term anticoagulation for preventing ischemic stroke in patients with atrial fibrillation. There are limited long‐term outcomes data for “real‐world” patients undergoing LAAO. Methods We performed a retrospective cohort study using the National Cardiovascular Data Registry LAAO registry from January 1, 2016, through December 31, 2019. We linked LAAO data to inpatient Medicare fee‐for‐service claims data using probabilistic matching to establish a cohort of patients 65 years and older undergoing LAAO with a WATCHMAN device. The primary outcomes were any stroke and all‐cause mortality. Results A total of 34 975 patients with a mean±SD CHA 2 DS 2 ‐VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or transient ischemic attack, vascular disease, age 65 to 74 years, and sex category) score of 4.7±1.4 were included. The median follow‐up was 2.8 years (interquartile range, 2.2–3.7 years). The cumulative incidence of any stroke was 1.57 per 100 person‐years (95% CI, 1.45–1.70), with a 1‐year and 5‐year any stroke estimate of 1.70% (95% CI, 1.57–1.84%) and 5.70% (95% CI, 5.37–6.05%), respectively. The cumulative incidence of ischemic stroke was 1.36 per 100 person‐years (95% CI, 1.25–1.48), with a 1‐year and 5‐year ischemic stroke estimate of 1.42% (95% CI, 1.30–1.54%) and 5.03% (95% CI, 4.71–5.36%), respectively. The cumulative incidence of death was 10.82 per 100 person‐years (95% CI, 10.49–11.13), with a 5‐year mortality estimate of 44.34% (95% CI, 43.35–45.23%). Conclusions Long‐term stroke rates in a large nationally representative cohort of Medicare patients following LAAO were low and durably consistent during long‐term follow‐up despite a high thromboembolic risk. High mortality rates in this elderly population underscore the importance of incorporating patient values and preferences when considering LAAO.

Purpose: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) improves prostate cancer (PCa) localization, particularly in biochemical recurrence (BCR). The primary objective was to assess management patterns after PSMA-PET for BCR at 2 academic centers. Methods: This study evaluated clinical management within 6 months after first PSMA-PET for patients with BCR after local therapy. Management categories included no treatment, local therapy, systemic therapy, and metastasis-directed therapy (MDT). We also evaluated clinical management decision variation across strata of PSMA-PET results PSA levels (<2.0, 2.0-4.99, and ≥5.0 ng/mL) at time of imaging. Results: We identified 581 patients who received PSMA-PET from February 2021 to June 2023. PSMA-PET findings were negative in 142 (24%) and demonstrated localized recurrence in 86 (15%), regional nodal disease in 60 (10%), and distant metastasis in 293 (50%). Distant metastasis was identified in 105 (35%) patients with PSA < 2.0, 67 (60%) with PSA 2.0 to 4.99, and 115 (71%) with PSA ≥ 5.0. In patients with negative PSMA-PET, 63 (44%) received treatment. Conversely, 92% with detected metastases were treated (systemic therapy in 189 [64%], MDT in 75 [26%], and local therapy in 7 [2%]). Treatments differed by the PSA level within strata of PSMA-PET findings. Among 293 patients with metastases, MDT was used more commonly in patients with PSA < 2.0 (37%) than PSA 2.0 to 4.99 (30%) or PSA ≥ 5.0 (13%). Conclusions: Most patients undergoing PSMA-PET for BCR had identifiable disease and initiated therapy within 6 months. Identification of distant metastases and treatment choices differed by the PSA level at imaging. Prospective research is needed to determine whether earlier detection and treatment initiation improve clinical outcomes.

ABSTRACT Iron deficiency (ID) is a top five leading cause of disability‐adjusted life‐years in women of reproductive age around the world. Despite its enormous health burden, no screening guidelines exist for the detection and treatment of ID in women of reproductive age. We sought to determine the cost‐effectiveness of screening versus no screening for ID in women of reproductive age in the United States. A lifetime simulation of women of reproductive age was conducted using a Markov cohort model under three strategies: (1) no screening, (2) screening at a ferritin threshold of 15 μg/L, and (3) screening at a ferritin threshold of 25 μg/L, from the US health system perspective, and at a willingness‐to‐pay threshold of $100 000/quality‐adjusted life year (QALY). Epidemiologically informed ID prevalence estimates sourced from the National Health and Nutrition Examination Survey were employed for model parameterization. The primary outcome was the incremental cost‐effectiveness ratio (ICER, in $/QALY). Base‐case results for the three strategies accrued $209 700, $210 200, and $210 200 discounted lifetime costs and 23.6, 24.0, and 24.4 discounted lifetime QALYs, respectively. Screening at a ferritin threshold of 25 μg/L was the cost‐effective intervention with an ICER of $680/QALY (95% credible interval $350–$750/QALY). In dual base‐case analyses examining intravenous rather than oral iron repletion for treatment, screening at a ferritin threshold of 25 μg/L remained the cost‐effective intervention with an ICER of $2300/QALY (95% CI $1800–$3800/QALY). In probabilistic sensitivity analyses, screening at a ferritin threshold of 25 μg/L was the cost‐effective intervention in 100% of 10 000 second order Monte Carlo iterations.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses, as well as occult primary cancer, salivary gland cancer, and mucosal melanoma (MM). The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers 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 summarize the panel’s most recent recommendations regarding management of nasopharynx cancer and ongoing research in this area.

Background/Objectives: Stereotactic body radiation therapy (SBRT) for skull base reirradiation is particularly challenging, as patients have already received substantial radiation doses to the region, and nearby normal organs may have approached their tolerance limit from prior treatments. In this study, we reviewed the characteristics and capabilities of four advanced external beam radiation delivery systems and four modern treatment planning systems and evaluated the treatment plan quality of each technique using skull base reirradiation patient cases. Methods: SBRT plans were generated for sixteen skull base reirradiation patients using four modalities: the GK plan for the Elekta Leksell Gamma Knife Perfexion/ICON, the CyberKnife (CK) plan for the Accuray CyberKnife, the intensity-modulated proton therapy (IMPT) plan for the Hitachi ProBeat-FR proton therapy machine, and the volumetric-modulated arc therapy (VMAT) plan for the Varian TrueBeam STx. These plans were evaluated and compared using two novel gradient indices in addition to traditional dosimetry metrics for targets and organs at risk (OARs). The steepest border gradient quantified the percent prescription dose fall-off per millimeter at the boundary between the target and adjacent critical structures. This gradient index highlighted the system’s ability to spare nearby critical OARs. The volume gradient assessed the extent of dose spread outside the target toward the patient’s body. Results: All plans achieved comparable target coverage and conformity, while IMPT and VMAT demonstrated significantly better uniformity. The GK plans exhibited the highest border gradient, up to 20.9%/mm, followed by small-spot-size IMPT plans and CK plans. Additionally, IMPT plans showed the benefit of reduced dose spread in low-dose regions and the lowest maximum and mean doses to the brainstem and carotid artery. Conclusions: The advanced external beam radiotherapy modalities evaluated in this study are well-suited for SBRT in skull base reirradiation, which demands precise targeting of tumors with highly conformal doses and steep dose gradients to protect nearby normal structures.

ImportanceAlthough prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown improved sensitivity and specificity compared with conventional imaging for the detection of biochemical recurrent (BCR) prostate cancer, the long-term outcomes of a widespread shift in imaging are unknown.ObjectiveTo estimate long-term outcomes of integrating PSMA-PET into the staging pathway for recurrent prostate cancer.Design, Setting, and ParticipantsThis decision analytic modeling study simulated outcomes for patients with BCR following initial definitive local therapy. Inputs used were from the literature and a retrospective cohort study conducted at 2 institutions. The base case analysis assumed modest benefits of earlier detection and treatment, and scenario analyses considered prostate-specific antigen (PSA) level at imaging and different outcomes of earlier vs delayed treatment. The analysis was performed between April 1, 2023, and May 1, 2024.Exposures(1) Immediate PSMA-PET imaging, (2) conventional imaging (computed tomography and bone scan [CTBS]) followed by PSMA-PET if CTBS findings were negative or equivocal, and (3) CTBS alone.Main Outcomes and MeasuresThe main outcomes were detection of metastases, deaths from prostate cancer, and life-years and quality-adjusted life-years (QALYs) gained.ResultsThe model estimated that per 1000 simulated patients with BCR (assumed median age, 66 years), PSMA-PET is expected to diagnose 611 (95% uncertainty interval [UI], 565-656) patients with metastasis compared with 630 (95% UI, 586-675) patients diagnosed using CTBS followed by PSMA-PET and 297 (95% UI, 202-410) patients diagnosed using CTBS alone. Moreover, the estimated number of prostate cancer deaths was 512 (95% UI, 472-552 deaths) with PSMA-PET, 520 (95% UI, 480-559 deaths) with CTBS followed by PSMA-PET, and 587 (95% UI, 538-632 deaths) with CTBS alone. Imaging with PSMA-PET yielded the highest number of QALYs, which were 824 (95% UI, 698-885) higher than CTBS. These results differed by PSA level at the time of testing, with the highest incremental life-years and QALYs and lowest number of deaths from prostate cancer among patients with PSA levels of at least 5.0 ng/mL. Finally, the estimates were sensitive to the expected benefit of initiating therapy for recurrent prostate cancer earlier in the disease course.Conclusions and RelevanceThe results of this decision-analytic model suggest that upfront PSMA-PET imaging for the evaluation of BCR is expected to be associated with reduced cancer mortality and gains in life-years and QALYs compared with the conventional imaging strategy, assuming modest benefits of earlier detection and treatment.