Prognostic and predictive implications of sterile alpha motif and HD domain-containing protein 1 (SAMHD1) expression in breast cancer.

Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a dNTP hydrolase important for intracellular dNTP homeostasis and serves as tumor suppressor and modulator of antimetabolite efficacy in cancer, though largely unexplored in breast cancer (BC). A cohort of patients with early BC (n = 564) with available gene expression data (GEP) was used. SAMHD1 protein expression was assessed by immunohistochemistry performed on tissue microarrays.

Performance of rapid antigen tests to detect SARS-CoV-2 variant diversity and correlation with viral culture positivity: implication for diagnostic development and future public health strategies.

Unlabelled: Antigen-based rapid diagnostic tests (Ag-RDTs) provide timely results, are simple to use, and are less expensive than molecular assays. Recent studies suggest that antigen-based testing aligns with virus culture-based results (a proxy of contagiousness at the peak viral phase of illness); however, the performance of Ag-RDTs for newer SARS-CoV-2 variants is unclear. In this study, we (i) assessed the performance of Ag-RDTs and diagnostic antibodies to detect a range of SARS-CoV-2 variants and (ii) determined whether Ag-RDT results correlated with culture positivity.

Functional Outcome and Hemorrhage Rates After Bridging Therapy With Tenecteplase or Alteplase in Patients With Large Ischemic Core.

Background And Objectives: IV tenecteplase is an alternative to alteplase before mechanical thrombectomy (MT) in patients with large-vessel occlusion (LVO) ischemic stroke. Little data are available on its use in patients with large ischemic core. We aimed to compare the efficacy and safety of both thrombolytics in this population.

Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size.

Background: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied.

Methods: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group).

Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups.

Multiple myeloma (MM) is twice as common in Black individuals compared with in White individuals, and diabetes mellitus (DM) disproportionately affects Black patients. Although numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms. We conducted a retrospective clinical study of 5383 patients with MM of which 15% had DM (White, 12% and Black, 25%).

Evaluation of mechanical thrombectomy in acute ischemic stroke related to a distal arterial occlusion: A randomized controlled trial.

Rationale: Mechanical thrombectomy (MT) associated with the best medical treatment (BMT) has recently shown efficacy for the management of acute ischemic stroke (AIS) secondary to a large vessel occlusion. However, evidence is lacking regarding the benefit of MT for more distal occlusions.

Aim: To evaluate the efficacy in terms of good clinical outcome at 3 months of MT associated with the BMT over the BMT alone in AIS related to a distal occlusion.

Impact of Time to Fixation on Outcomes of Operative Treatment of Intra-articular Distal Radius Fractures.

Background: The incidence of operative treatment of distal radius fractures (DRFs) has increased recently, but the optimal timing for surgical fixation remains unclear. We hypothesized that: (1) an increase in time to fixation of intra-articular DRFs would increase the likelihood of postoperative complications; and (2) increased time from injury to fixation would lead to longer surgical time and worse range of motion (ROM) outcomes.

Methods: We retrospectively reviewed 299 fractures in 284 adult patients who underwent open reduction and internal fixation (ORIF) of a closed, intra-articular DRF at our institution over a 10.

Sequencing T-cell redirection therapies leads to deep and durable responses in patients with relapsed/refractory myeloma.

T-cell redirection therapy using chimeric antigen receptor (CAR) T cells and bispecific antibodies (BiAbs) has shown promising efficacy in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), leading to the approval of 2 CAR T-cell products and numerous BiAb trials. Data on the outcomes after relapse following BiAbs are urgently required to develop strategies for sequencing salvage therapies. We identified 58 patients progressing after a BiAb trial at Mount Sinai Hospital.

The association between adiposity and anti-proliferative response to neoadjuvant endocrine therapy with letrozole in post-menopausal patients with estrogen receptor positive breast cancer.

The impact of adiposity on the efficacy of endocrine treatment in patients with estrogen receptor positive breast cancer is poorly investigated. Here, we retrospectively investigated in a cohort of 56 patients whether body mass index and/or mammary adiposity are associated with anti-proliferative response in the neoadjuvant setting. Anti-proliferative response was defined as high Ki67 at baseline (Ki67) and low Ki67 at surgery (Ki67), using the 14% cut-off.

Safety and Efficacy of Cangrelor in Acute Stroke Treated with Mechanical Thrombectomy: Endovascular Treatment of Ischemic Stroke Registry and Meta-analysis.

Background And Purpose: Rescue therapies are increasingly used in the setting of endovascular therapy for large-vessel occlusion strokes. Among these, cangrelor, a new P2Y12 inhibitor, offers promising pharmacologic properties to join the reperfusion strategies in acute stroke. We assessed the safety and efficacy profiles of cangrelor combined with endovascular therapy in patients with large-vessel-occlusion stroke.

Thrombectomy Complications in Large Vessel Occlusions: Incidence, Predictors, and Clinical Impact in the ETIS Registry.

Background And Purpose: Procedural complications in thrombectomy for large vessel occlusions of the anterior circulation are not well described. We investigated the incidence, risk factors, and clinical implications of thrombectomy complications in daily clinical practice.

Methods: We used data from the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France.

Impact of Prior Antiplatelet Therapy on Outcomes After Endovascular Therapy for Acute Stroke: Endovascular Treatment in Ischemic Stroke Registry Results.

Background And Purpose: The influence of prior antiplatelet therapy (APT) uses on the outcomes of patients with acute ischemic stroke treated with endovascular therapy is unclear. We compared procedural and clinical outcomes of endovascular therapy in patients on APT or not before stroke onset.

Methods: We analyzed 2 groups from the ongoing prospective multicenter Endovascular Treatment in Ischemic Stroke registry in France: patients on prior APT (APT+) and patients without prior APT (APT-) treated by endovascular therapy, with and without intravenous thrombolysis.

Continuous positive airway pressure for respiratory support during COVID-19 pandemic: a frugal approach from bench to bedside.

Background: We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter ("Filter Frugal CPAP", FF-CPAP) in and out the ICU.

Methods: (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course.

Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect.

The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits.

Digital analysis of distant and cancer-associated mammary adipocytes.

Adipocytes and cancer-associated adipocytes (CAAs) are poorly investigated cells in the tumor microenvironment. Different image analysis software exist for identifying and measuring these cells using scanned hematoxylin and eosin (H&E)-stained slides. It is however unclear which one is the most appropriate for breast cancer (BC) samples.

The clinical, histologic, and genotypic spectrum of -related myopathy: A case series.

Objective: To clarify the prevalence, long-term natural history, and severity determinants of -related myopathy (SEPN1-RM), we analyzed a large international case series.

Methods: Retrospective clinical, histologic, and genetic analysis of 132 pediatric and adult patients (2-58 years) followed up for several decades.

Results: The clinical phenotype was marked by severe axial muscle weakness, spinal rigidity, and scoliosis (86.

Identification, Heritability, and Relation With Gene Expression of Novel DNA Methylation Loci for Blood Pressure.

We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with <1×10.

Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.

Objective: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.

Better Collaterals Are Independently Associated With Post-Thrombolysis Recanalization Before Thrombectomy.

Background and Purpose- In acute stroke patients with large vessel occlusion, the goal of intravenous thrombolysis (IVT) is to achieve early recanalization (ER). Apart from occlusion site and thrombus length, predictors of early post-IVT recanalization are poorly known. Better collaterals might also facilitate ER, for instance, by improving delivery of the thrombolytic agent to both ends of the thrombus.

Thrombus Length Predicts Lack of Post-Thrombolysis Early Recanalization in Minor Stroke With Large Vessel Occlusion.

Background and Purpose- Whether bridging therapy, that is, intravenous thrombolysis [IVT] followed by mechanical thrombectomy, is beneficial as compared with IVT alone in minor stroke (National Institutes of Health Stroke Scale ≤5) with large vessel occlusion is unknown and should be tested in randomized trials. To help select the most appropriate candidates for such trials, we aimed to identify strong predictors of lack of post-IVT early recanalization (ER)-a surrogate marker of poor outcome. Methods- From a large multicenter French registry of patients with large vessel occlusion referred for thrombectomy immediately after IVT start between 2015 and 2017, we extracted 97 minor strokes with ER evaluated on first angiographic run or noninvasive imaging ≤3 hours from IVT start.

Post-Thrombolysis Recanalization in Stroke Referrals for Thrombectomy: Incidence, Predictors, and Prediction Scores.

Background and Purpose—Whether all acute stroke patients with large vessel occlusion need to undergo intravenous thrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis early recanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely, (3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence and predictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design. Methods—Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership) or in a non MT-capable center (drip-and-ship) after magnetic resonance– or computed tomography–based imaging between 2015 and 2017.

Perfluorocarbon Labeling of Human Glial-Restricted Progenitors for F Magnetic Resonance Imaging.

One of the fundamental limitations in assessing potential efficacy in Central Nervous System (CNS) transplantation of stem cells is the capacity for monitoring cell survival and migration noninvasively and longitudinally. Human glial-restricted progenitor (hGRP) cells (Q-Cells) have been investigated for their utility in providing neuroprotection following transplantation into models of amyotrophic lateral sclerosis (ALS) and have been granted a Food and Drug Administration (FDA) Investigational New Drug (IND) for intraspinal transplantation in ALS patients. Furthermore, clinical development of these cells for therapeutic use will rely on the ability to track the cells using noninvasive imaging methodologies as well as the verification that the transplanted GRPs have disease-relevant activity.

National randomized controlled trial of virtual house calls for Parkinson disease.

Objective: To determine whether providing remote neurologic care into the homes of people with Parkinson disease (PD) is feasible, beneficial, and valuable.

Methods: In a 1-year randomized controlled trial, we compared usual care to usual care supplemented by 4 virtual visits via video conferencing from a remote specialist into patients' homes. Primary outcome measures were feasibility, as measured by the proportion who completed at least one virtual visit and the proportion of virtual visits completed on time; and efficacy, as measured by the change in the Parkinson's Disease Questionnaire-39, a quality of life scale.