Plasma Cytokines/Chemokines as Predictive Biomarkers For Lymphedema in Breast Cancer Patients

Breast cancer-related lymphedema (BCRL) occurs in ~ 40% of patients after axillary lymph node dissection (ALND), radiation therapy (RT), or chemotherapy. First-line palliative treatment utilizes compression garments and specialized massage. Reparative microsurgeries have emerged as a second-line treatment, yet both compression and surgical therapy are most effective at early stages of LE development. Identifying patients at the highest risk for BCRL would allow earlier, more effective treatment. Perometric arm volume measurements, near-infrared fluorescent lymphatic imaging (NIRF-LI) data, and blood were collected between 2016 and 2021 for 40 study subjects undergoing treatment for breast cancer. Plasma samples were evaluated using MILLIPLEX human cytokine/chemokine panels at pre-ALND and at 12 months post-RT. A Mann-Whitne

Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes

BACKGROUND: Fabry disease is a rare, multisystemic disorder caused by GLA gene variants that lead to alpha galactosidase A deficiency, resulting in accumulation of glycosphingolipids and cellular dysfunction. Fabry-associated clinical events (FACEs) cause significant morbidity and mortality, yet the long-term effect of Fabry therapies on FACE incidence remains unclear. METHODS: This posthoc analysis evaluated incidence of FACEs (as a composite outcome and separately for renal, cardiac and cerebrovascular events) in 97 enzyme replacement therapy (ERT)-naïve and ERT-experienced adults with Fabry disease and amenable GLA variants who were treated with migalastat for up to 8.6 years (median: 5 years) in Phase III clinical trials of migalastat. Associations between baseline characteristics and incidence of FACEs were also evaluated. RESULTS: During long-term migalastat treatment, 17 patients (17.5%) experienced 22 FACEs and there were no deaths. The incidence rate of FACEs was 48.3 events per 1000 patient-years overall. Numerically higher incidence rates were observed in men versus women, patients aged >40 years versus younger patients, ERT-naïve versus ERT-experienced patients and men with the classic phenotype versus men and women with all other phenotypes. There was no statistically significant difference in time to first FACE when analysed by patient sex, phenotype, prior treatment status or age. Lower baseline estimated glomerular filtration rate (eGFR) was associated with an increased risk of FACEs across patient populations. CONCLUSIONS: The overall incidence of FACEs for patients during long-term treatment with migalastat compared favourably with historic reports involving ERT. Lower baseline eGFR was a significant predictor of FACEs

Classification of pig calls produced from birth to slaughter according to their emotional valence and context of production

Vocal expression of emotions has been observed across species and could provide a non-invasive and reliable means to assess animal emotions. We investigated if pig vocal indicators of emotions revealed in previous studies are valid across call types and contexts, and could potentially be used to develop an automated emotion monitoring tool. We performed an analysis of an extensive and unique dataset of low (LF) and high frequency (HF) calls emitted by pigs across numerous commercial contexts from birth to slaughter (7414 calls from 411 pigs). Our results revealed that the valence attributed to the contexts of production (positive versus negative) affected all investigated parameters in both LF and HF. Similarly, the context category affected all parameters. We then tested two different automated methods for call classification; a neural network revealed much higher classification accuracy compared to a permuted discriminant function analysis (pDFA), both for the valence (neural network: 91.5%; pDFA analysis weighted average across LF and HF (cross-classified): 61.7% with a chance level at 50.5%) and context (neural network: 81.5%; pDFA analysis weighted average across LF and HF (cross-classified): 19.4% with a chance level at 14.3%). These results suggest that an automated recognition system can be developed to monitor pig welfare on-farm.publishedVersio

Kinks in the discrete sine-Gordon model with Kac-Baker long-range interactions

We study effects of Kac-Baker long-range dispersive interaction (LRI) between particles on kink properties in the discrete sine-Gordon model. We show that the kink width increases indefinitely as the range of LRI grows only in the case of strong interparticle coupling. On the contrary, the kink becomes intrinsically localized if the coupling is under some critical value. Correspondingly, the Peierls-Nabarro barrier vanishes as the range of LRI increases for supercritical values of the coupling but remains finite for subcritical values. We demonstrate that LRI essentially transforms the internal dynamics of the kinks, specifically creating their internal localized and quasilocalized modes. We also show that moving kinks radiate plane waves due to break of the Lorentz invariance by LRI.Comment: 11 pages (LaTeX) and 14 figures (Postscript); submitted to Phys. Rev.

Association of comorbidity burden with abnormal cardiac mechanics: Findings from the HyperGEN study

BACKGROUND: Comorbidities are common in heart failure (HF), and the number of comorbidities has been associated with poor outcomes in HF patients. However, little is known about the effect of multiple comorbidities on cardiac mechanics, which could impact the pathogenesis of HF. We sought to determine the relationship between comorbidity burden and adverse cardiac mechanics. METHODS AND RESULTS: We performed speckle‐tracking analysis on echocardiograms from the HyperGEN study (n=2150). Global longitudinal, circumferential, and radial strain, and early diastolic (e') tissue velocities were measured. We evaluated the association between comorbidity number and cardiac mechanics using linear mixed effects models to account for relatedness among subjects. The mean age was 51±14 years, 58% were female, and 47% were African American. Dyslipidemia and hypertension were the most common comorbidities (61% and 58%, respectively). After adjusting for left ventricular (LV) mass index, ejection fraction, and several potential confounders, the number of comorbidities remained associated with all indices of cardiac mechanics except global circumferential strain (eg, β=−0.32 [95% CI −0.44, −0.20] per 1‐unit increase in number of comorbidities for global longitudinal strain; β=−0.16 [95% CI −0.20, −0.11] for e' velocity; P≤0.0001 for both comparisons). Results were similar after excluding participants with abnormal LV geometry (P<0.05 for all comparisons). CONCLUSIONS: Higher comorbidity burden is associated with worse cardiac mechanics, even in the presence of normal LV geometry. The deleterious effect of multiple comorbidities on cardiac mechanics may explain both the high comorbidity burden and adverse outcomes in patients who ultimately develop HF

Clinical outcomes among young patients with Fabry disease who initiated agalsidase beta treatment before 30 years of age: An analysis from the Fabry registry

Background Clinical manifestations of classic Fabry disease (α-galactosidase A deficiency) usually occur in childhood, while complications involving major organs typically develop in adulthood. Outcomes of Fabry-specific treatment among young patients have not been extensively reported. Our aim was to analyze clinical outcomes among patients aged 5–30 years at initiation of treatment with agalsidase beta using data from the Fabry Registry (NCT00196742, sponsor: Sanofi). Methods Reported GLA variants were predicted to be associated with the classic phenotype or not classified in fabry-database.org. Linear mixed models were conducted to assess changes over ≥2-year follow-up in the estimated glomerular filtration rate (eGFR) stratified by low (LRI) and high (HRI) renal involvement (defined by proteinuria/albuminuria levels), and changes in interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) Z-scores stratified by median age at first treatment. Self-reports (‘yes’/‘no’) of abdominal pain, diarrhea, chronic peripheral pain (denoting neuropathic pain), and acute pain crises at baseline were compared with reports after ≥0.5-year and ≥2.5-year follow-up using McNemar's test. Results Male (n = 117) and female patients (n = 59) with LRI initiated treatment at a median age of 19.9 and 23.6 years, respectively, and were followed for a median of 6.3 and 5.0 years, respectively. The eGFR slopes were −1.18 (Pfrom 0 5.5 years and ≥4.5 years, respectively). Older females (treatment initiation at median age 27.5 years) had a slope of LVPWT Z-scores of 0.18/year (n = 12, Pfrom 0 = 0.028), whereas IVST Z-scores remained stable (n = 13, 0.10/year, Pfrom 0 = 0.304) during a median follow-up of ≥3.7 years. These slopes did not significantly differ from slopes of younger females. Reports of chronic peripheral pain and acute pain crises by males, and of diarrhea and acute pain crises by females, significantly reduced after a median follow-up of ≥4.0 years. After a median follow-up of ≥5.4 years, reports of all four symptoms significantly decreased among males, whereas among females only reports of abdominal pain significantly decreased. Conclusions During sustained treatment with agalsidase beta in young Fabry patients with a predicted classic phenotype or with unclassified GLA variants with similar characteristics, the decline in eGFR was modest among male and female patients with LRI. The greater decline in eGFR among older, proteinuric (i.e., HRI) males may suggest a benefit of earlier treatment. Overall, echocardiographic variables remained stable, particularly among males and younger females. Significant reductions in symptom reports occurred primarily among males after longer follow-up and were less noticeable among females. These observed trends are suggestive of an overall improvement after treatment in young patients, but warrant larger longitudinal studies.publishedVersio