Publications by authors named "J Paul Murphy"

6,958 Publications

Blocking ActRIIB and restoring appetite reverses cachexia and improves survival in mice with lung cancer.

Nat Commun 2022 Aug 8;13(1):4633. Epub 2022 Aug 8.

Division of Endocrinology, Department of Medicine, Weill Cornell Medicine, New York, NY, 10065, USA.

Cancer cachexia is a common, debilitating condition with limited therapeutic options. Using an established mouse model of lung cancer, we find that cachexia is characterized by reduced food intake, spontaneous activity, and energy expenditure accompanied by muscle metabolic dysfunction and atrophy. We identify Activin A as a purported driver of cachexia and treat with ActRIIB-Fc, a decoy ligand for TGF-β/activin family members, together with anamorelin (Ana), a ghrelin receptor agonist, to reverse muscle dysfunction and anorexia, respectively. Ana effectively increases food intake but only the combination of drugs increases lean mass, restores spontaneous activity, and improves overall survival. These beneficial effects are limited to female mice and are dependent on ovarian function. In agreement, high expression of Activin A in human lung adenocarcinoma correlates with unfavorable prognosis only in female patients, despite similar expression levels in both sexes. This study suggests that multimodal, sex-specific, therapies are needed to reverse cachexia.
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http://dx.doi.org/10.1038/s41467-022-32135-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360437PMC
August 2022

Multimodality treatment of pediatric Ewing sarcoma: A single-center 10-year analysis of outcomes.

Surgery 2022 Aug 4. Epub 2022 Aug 4.

Department of Pediatric Surgery, University of Texas Southwestern Medical Center and Children's Health, Dallas, TX. Electronic address:

Background: Ewing sarcoma, a malignancy originating from the bone or soft tissues most commonly diagnosed in adolescents, requires multimodality therapy. Although both surgical resection and radiation therapy are effective local control modalities, there are limited data comparing outcomes in patients treated with surgery versus radiation. We sought to determine whether there were differences in 5-year local failure-free survival, event-free survival, and overall survival based on the modality used for local control.

Methods: Patients treated for Ewing sarcoma at a single tertiary pediatric hospital between 2010 and 2020 were included for retrospective analysis. Patient and tumor demographics, treatment information, and patient response to therapies were collected from the medical record. Outcome measures were local failure-free survival, event-free survival, and overall survival at 5 years from diagnosis.

Results: Sixty-one patients met inclusion criteria. All patients received chemotherapy, and 68.9% of patients presented with localized disease. Of these, 23.8% were treated with radiation alone; the remaining 76.2% underwent resection ± radiation. A total of 52.4% of patients with localized disease achieved R0 resection. Only 3 patients experienced local progression; there was no difference between treatment groups. There was no significant association between local control modality and event-free survival or overall survival in patients with localized disease, regardless of margin status.

Conclusion: There was no significant difference in 5-year local failure-free survival, event-free survival, or overall survival in Ewing sarcoma patients treated with radiation versus surgery ± radiation, regardless of whether or not R0 resection was achieved. Future directions include a multi-institutional study to allow for further subgroup analysis and increased sample size.
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http://dx.doi.org/10.1016/j.surg.2022.05.036DOI Listing
August 2022

Gender differences in interoceptive accuracy and emotional ability: An explanation for incompatible findings.

Neurosci Biobehav Rev 2022 Aug 3:104808. Epub 2022 Aug 3.

Department of Psychology, Royal Holloway, University of London.

Most theories of emotion describe a crucial role for interoceptive accuracy, the perception of the body's internal physiological signals, in emotional experience. Despite support for interoceptive accuracy's role in emotion, findings of gender differences in emotional and interoceptive processing are incompatible with theory; women typically show poorer interoceptive accuracy, but women often outperform men on measures of emotional processing and recognition. This suggests a need to re-evaluate the relationship between interoceptive accuracy and emotion considering sex and gender. Here we extend Pennebaker and Roberts' (1992) theory of gender differences in the use of interoceptive signals for emotional experience, proposing that language socialisation may result in gender differences in the propensity to label internal state changes as physiological or emotional, respectively. Despite outstanding questions concerning the fractionation of interoceptive and emotional domains, this theory provides a plausible explanation for seemingly incompatible findings of gender differences in interoceptive and emotional abilities.
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http://dx.doi.org/10.1016/j.neubiorev.2022.104808DOI Listing
August 2022

Short- and Long-Term Risk of Lead Dislodgement Events: Real-World Experience From Product Surveillance Registry.

Circ Arrhythm Electrophysiol 2022 Aug 4:101161CIRCEP122011029. Epub 2022 Aug 4.

Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, MA (T.M.).

Background: Lead dislodgement (LD) has been one of the most common early complications after cardiovascular implantable electronic device implant. However, limited data are available on the clinical characteristics and long-term outcomes of LD events. The aim of this study was to examine the risk factors, clinical significance, and management strategies of LD events after cardiovascular implantable electronic device implant.

Methods: This study was a retrospective cohort analysis of 20 683 patients who underwent cardiovascular implantable electronic device implant between January 1, 2010 and January 31, 2020 in Medtronic's Product Surveillance Registry, with a mean follow-up time of 3.3±2.5 SD years. The study population was divided into 2 groups: group A with LD events (N=350) and group B without LD events (N=20 333).

Results: During this period, 350 patients (1.69%) had LD events involving 371 leads (0.95%), among a total of 39 060 leads implanted. Passive fixation type (right atrium pacing lead, =0.041), lower sensing amplitude (right ventricle defibrillating lead, =0.020), and lower lead impedance at implant (right atrium pacing lead, =0.009) were associated with increased LD risk. Multivariate analysis showed female sex (hazard ratio, 1.520, =0.008) and higher body mass index (hazard ratio, 1.012, =0.001) were independently associated with increased risk of LD events. LD events were not associated with significant changes in the long-term risks of cardiac and overall mortality. In group A, repositioning the dislodged leads increased the risk of a second LD event compared with implanting new leads (=0.012).

Conclusions: Female sex and higher body mass index were associated with higher risk of LD events in the Product Surveillance Registry. Among patients with dislodged leads, implanting new leads was associated with lower risk of future LD events. Further studies on how to reduce LD risk and to improve management of these events are needed.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT01524276.
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http://dx.doi.org/10.1161/CIRCEP.122.011029DOI Listing
August 2022

Contextual decision-making and alcohol use disorder criteria: Delayed reward, delayed loss, and probabilistic reward discounting.

Psychol Addict Behav 2022 Aug 4. Epub 2022 Aug 4.

Department of Psychological Science.

Objective: Alcohol use disorder (AUD) is an etiologically heterogeneous psychiatric disorder defined by a collection of commonly observed co-occurring symptoms. It is useful to contextualize AUD within theoretical frameworks to identify potential prevention, intervention, and treatment approaches that target personalized mechanisms of behavior change. One theoretical framework, behavioral economics, suggests that AUD is a temporally extended pattern of cost/benefit analyses favoring drinking decisions. The distribution of costs and benefits across choice outcomes is often unequally distributed over time and has different probabilities of receipt, such that delay and probability become critical variables. The present study examines the relations between different forms of economic discounting (delayed reward, delayed cost, and probabilistic reward) and individual symptoms of AUD to inform etiological models.

Method: Participants ( = 732; 41% female, 4.2% Black, 88.1% White, 8% Hispanic) completed an online survey with measures of AUD symptoms and economic discounting. We examined relations between economic discounting and AUD symptoms with zero-order correlations, in separate models (factor models), and in models controlling for an AUD factor (factor-controlled models).

Results: Delayed reward discounting was positively associated with the give up AUD criteria across all three levels of analysis. Probability discounting was associated with social/interpersonal problems across two out of three sets of analyses. Consistent with the broad discounting literature, effect sizes were small (range = -.15 to .13).

Conclusions: These results support the idea that AUD criteria are etiologically distinct, resulting in varying AUD profiles between persons that are differentially associated with behavioral economic discounting. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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http://dx.doi.org/10.1037/adb0000867DOI Listing
August 2022
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