Citations

PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430 ). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m 2 ) + gemcitabine (1,000 mg/m 2 ) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 ( nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent ( nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.

Abstract Multiple myeloma (MM) develops from well-defined precursor stages; however, invasive bone marrow (BM) biopsy limits screening and monitoring strategies for patients. We enumerated circulating tumor cells (CTC) from 261 patients (84 monoclonal gammopathy of undetermined significance, 155 smoldering multiple myeloma, and 22 MM), with neoplastic cells detected in 84%. We developed a novel approach, MinimuMM-seq, which enables the detection of translocations and copy-number abnormalities through whole-genome sequencing of highly pure CTCs. Application to CTCs in a cohort of 51 patients, 24 with paired BM, was able to detect 100% of clinically reported BM biopsy events and could replace molecular cytogenetics for diagnostic yield and risk classification. Longitudinal sampling of CTCs in 8 patients revealed major clones could be tracked in the blood, with clonal evolution and shifting dynamics of subclones over time. Our findings provide proof of concept that CTC detection and genomic profiling could be used clinically for monitoring and managing disease in MM. Significance: In this study, we established an approach enabling the enumeration and sequencing of CTCs to replace standard molecular cytogenetics. CTCs harbored the same pathognomonic MM abnormalities as BM plasma cells. Longitudinal sampling of serial CTCs was able to track clonal dynamics over time and detect the emergence of high-risk genetic subclones. This article is highlighted in the In This Issue feature, p. 247

Abstract Background Transient swelling is common after lip injections with hyaluronic acid (HA) based fillers. Swelling and other injection‐site reactions may relate to the injection procedure itself, or to gel properties, which differ between fillers due to differences in manufacturing methods. Objectives To evaluate safety and effectiveness of lip injections with two HA fillers manufactured using different gel technologies. Methods In a study sample of 40 subjects, treatment with two soft tissue filler product (HA RK or HA JUS ) was randomly assigned. Subjects were injected with 0.5 cc per upper and lower lip using a standardized injection procedure. Early‐onset adverse events (AEs) were assessed by evaluation up to Day 14. Aesthetic improvement, subject satisfaction, and AEs post‐Day 14 were assessed up to 24 weeks. Results In subjects treated with HA RK , the intensity of early onset swelling, erythema, and pain/tenderness was lower than in subjects treated with HA JUS . Aesthetic improvement was achieved in both groups, and most subjects were satisfied with the appearance of their lips. Treatment‐related AEs post‐Day 14 mostly related to the implant site; most were mild‐to‐moderate, and none were serious. Conclusions The intensity of early‐onset swelling, and other injection‐site reactions was lower in subjects treated with HA RK than in subjects treated with HA JUS . Since both the injection volume and injection procedure were standardized, the difference in local tolerability between the two HA fillers may relate to differences in gel properties. Aesthetic improvement, subject satisfaction, and AE profiles post‐Day 14, however, were similar between filler groups.

Post-stroke depression (PSD) is a biopsychosocial disorder that affects individuals who have suffered a stroke at any point. PSD has a 20 to 60 percent reported prevalence among stroke survivors. Its effects are usually adverse, can lead to disability, and may increase mortality if not managed or treated early. PSD is linked to several other medical conditions, including anxiety, hyper-locomotor activity, and poor functional recovery. Despite significant awareness of its adverse impacts, understanding the pathogenesis of PSD has proved challenging. The exact pathophysiology of PSD is unknown, yet its complexity has been definitively shown, involving mechanisms such as dysfunction of monoamine, the glutamatergic systems, the gut-brain axis, and neuroinflammation. The current effectiveness of PSD treatment is about 30–40 percent of all cases. In this review, we examined different pathophysiological mechanisms and current pharmacological and non-pharmacological approaches for the treatment of PSD.

AbstractPurposePatients with Ebstein anomaly (EA) have a variety of clinical manifestation. The assessment of structural and geometric characteristics of the heart is important for optimal management.MethodsWe retrospectively analyzed echocardiography database from 2009 to 2020. We evaluate patients in two groups: patients with EA were in Group 1 and children without cardiovascular pathology were in Group 2. All children in both groups underwent echocardiography according to American Society of Echocardiography recommendations. The shape of the heart chambers and their function were studied in both groups.ResultsThere were 153 in Group 1 and 2000 children without cardiovascular disease in Group 2. It was shown that in children with EA, the shape of the ventricle became less spherical, which was accompanied by a decrease in myocardial mass, and the ejection fraction was reduced 34% of patients. The functional volume (non‐atrialized part) of the right ventricle in patients with EA was reduced, and its contractility was preserved in 62% of cases. Preservation of the contractile properties of the right ventricle in most cases was associated with higher systolic pressure in its cavity.ConclusionTAPSE, TESV, and the velocity of the annulus fibrous ring movement according to tissue dopplerography in patients with EA do not allow us to assess the contractility of the right ventricle. The myocardial performance index (MPI) characterizes a decrease in the functional volume of the right ventricle.