Long-Term Pooled Safety Analysis of Palbociclib in Combination with Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Updated Analysis with up to 5 Years of Follow-Up

BackgroundPrevious studies demonstrated the tolerability of palbociclib plus endocrine therapy (ET). This analysis evaluated safety based on more recent cutoff dates and a longer palbociclib treatment exposure.Patients and MethodsData were pooled from three randomized studies of patients with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative (HR+/HER2−) advanced breast cancer (ABC), including postmenopausal women who had not received prior systemic treatment for advanced disease (PALOMA‐1/‐2) and pre‐ and postmenopausal women who had progressed on prior ET (PALOMA‐3).ResultsUpdated cutoff dates were December 21, 2017 (PALOMA‐1), May 31, 2017 (PALOMA‐2), and April 13, 2018 (PALOMA‐3). Total person‐years of treatment exposure were 1,421.6 with palbociclib plus ET (n = 872) and 528.4 with ET (n = 471). Any‐grade neutropenia and infections were more frequent with palbociclib plus ET (82.1% and 59.2%, respectively) than with ET (5.1% and 39.5%). The hazard ratios were 1.6 (p = .0995) for grade 3/4 infections, 1.8 (p = .4358) for grade 3/4 viral infections, 1.4 (p = .0001) for infections, and 30.8 (p < .0001) for neutropenia. Febrile neutropenia was reported in 1.4% of patients receiving palbociclib plus ET. Cumulative incidence of all‐grade hematologic adverse events in both arms peaked during the first year of treatment and plateaued over the 5 subsequent years. Interstitial lung disease was reported in 13 patients receiving palbociclib plus ET and 3 receiving ET.ConclusionThis 5‐year, long‐term analysis demonstrated that palbociclib plus ET has a consistent and stable safety profile and is a safe treatment for patients with HR+/HER2− ABC.Implications for PracticeSeveral treatments for patients with breast cancer are associated with long‐term or latent adverse events. This long‐term, 5‐year analysis demonstrated that palbociclib plus endocrine therapy has a consistent and stable safety profile without cumulative or delayed toxicities. These results further support palbociclib plus endocrine therapy as a safe and manageable treatment in clinical practice for patients with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer.     

Early integration of bilateral touch in the primary somatosensory cortex

Animal, as well as behavioural and neuroimaging studies in humans have documented integration of bilateral tactile information at the level of primary somatosensory cortex (SI). However, it is still debated whether integration in SI occurs early or late during tactile processing, and whether it is somatotopically organized. To address both the spatial and temporal aspects of bilateral tactile processing we used magnetoencephalography in a tactile repetition‐suppression paradigm. We examined somatosensory evoked‐responses produced by probe stimuli preceded by an adaptor, as a function of the relative position of adaptor and probe (probe always at the left index finger; adaptor at the index or middle finger of the left or right hand) and as a function of the delay between adaptor and probe (0, 25, or 125 ms). Percentage of response‐amplitude suppression was computed by comparing paired (adaptor + probe) with single stimulations of adaptor and probe. Results show that response suppression varies differentially in SI and SII as a function of both spatial and temporal features of the stimuli. Remarkably, repetition suppression of SI activity emerged early in time, regardless of whether the adaptor stimulus was presented on the same and the opposite body side with respect to the probe. These novel findings support the notion of an early and somatotopically organized inter‐hemispheric integration of tactile information in SI. Hum Brain Mapp 36:1506–1523, 2015. © 2014 Wiley Periodicals, Inc.     

Intraluminal Intestinal Administration of Oxygenated Perfluorocarbon Improves Acid–Base and Cardiopulmonary Parameters After Acute Mesenteric Ischemia. An Experimental Study in Rabbits

Purpose The aim of this study was to evaluate the effects of the intraluminal intestinal administration of oxygenated perfluorocarbon, during experimental acute intestinal ischemia, on the acid–base blood status and the cardiopulmonary parameters. Methods Thirty-six rabbits were separated into three groups: (a) Control group (ischemia alone), (b) PFC-O₂ group (ischemia plus infusion of oxygenated F-Decalin in intraluminal intestinal administration), and (c) PFC group (ischemia plus infusion of nonoxygenated F-Decalin in intraluminal intestinal administration). An equal number of the animals was then subjected to 8 h of intestinal ischemia by ligation of the superior mesenteric artery (subgroups 1), the mesenteric vein (subgroups 2) or both vessels (subgroups 3). At 0, 2, 4, 6, and 8 h arterial blood samples were taken for acid–base status tests and the vital signs (heart and respiratory rate, pressure of inferior vena cava, and systolic arterial pressure) were noted. The statistical analysis was performed by the nonparametric Kruskal–Wallis test. Results There were no significant differences in any of the studied parameters (pH, base excess, respiratory gases, pressure of inferior vena cava, systolic arterial pressure, heart and respiratory rate) between animals of the same group and subgroup. In addition, the differences among Control and PFC groups and their equal subgroups were not significant. On the other hand, the measurements of the PFC-O₂ animals showed significant differences at 4, 6, and 8 h of ischemia (P < 0.05) in comparison with those from the Control and PFC groups. Conclusion We conclude that the intraluminal intestinal administration of oxygenated perfluorocarbons may thus be a useful adjunctive therapy in the treatment of patients with acute mesenteric ischemia.     

The long-term clinical relevance of calcar atrophy caused by stress shielding in total hip arthroplasty: a 10-year, prospective, randomized study

Eighty osteoarthritic female patients were randomly allocated to 4 equal groups; the Zwey-Muller, the Corail, the Optifix, or Autophor 900S cementless total hip arthroplasties (THAs) were implanted; and bone density changes, at different sites, were prospectively studied. In zone 7, the greatest reduction of bone density values was observed at 2 years (group A: 24%, group B: 8%, group C: 14.8%, and group D: 18.5%). In all groups, a similar pattern of slow but progressive recovery of bone mineral density changes after the third year was observed, approaching baseline values at 10 years, during which all patients showed satisfactory clinical results. We suggest that the clinical and theoretical relevance of the stress-shielding phenomenon in THA has been overestimated in the literature.     

Salvage of the Foot for Recurrent Malignant Peripheral Nerve Sheath Tumor

Malignant peripheral nerve sheath tumors are rare soft tissue tumors accounting for 3% to 10% of all soft tissue tumors. They are strongly related to neurofibromatosis type 1, an autosomal dominant disease, and are characterized by aggressive biologic behavior, high local recurrence rates, and frequent metastases. Although the major nerves of the lower extremities are a common location of these tumors, scarce cases have been reported of malignant peripheral nerve sheath tumors involving the interdigital nerves of the foot. We report the case of a patient with non-neurofibromatosis type 1 and a recurrent malignant peripheral nerve sheath tumor of the first interdigital nerve of the foot treated successfully with limb salvage surgery with wide resection margins and reconstruction with an autogenous fibula graft.     

Perfluorocarbon liquids in vitreoretinal surgery: a review of applications and toxicity

Since their introduction by Chang et al. in 1987, perfluorocarbon liquids (PFCLs) have become a useful tool in vitreoretinal surgery. They are synthetic compounds with carbon-fluorine chemical chains that have specific physico-chemical properties, which make them valuable for the intraoperative management of the retina by simplifying vitreoretinal surgical maneuvers in a variety of settings. These maneuvers include retinal detachments associated with proliferative vitreous retinopathy, following penetrating trauma, giant retinal tears, dislocated lenses or lens implants and complications from proliferative diabetic vitreoretinopathy. Purified PFCLs are generally considered to be biologically inert. Despite the stability of PFCLs during vitreoretinal surgery, several studies have indicated that these compounds may be associated with toxicity in ocular tissues. The purpose of this review is to report the use and toxicity of PFCLs in vitreoretinal surgery and to present the latest perspectives on modified PFCLs (hydrofluorocarbon liquids (HFCLs) and HFCL-oligomers).