Citations

The purpose of this study was to determine whether maternal urinary phthalate metabolite concentrations are associated with the development of higher blood pressure or pregnancy-induced hypertension (PIH). Participants were women without chronic hypertension who enrolled in The Infant Development and the Environment Study, a prospective pregnancy cohort conducted at four U.S. academic medical centers from 2010–2012. Prenatal records were reviewed to obtain blood pressure measurements and diagnoses of PIH (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome, defined as hemolysis, elevated liver enzymes, and low platelet count). Complete-case analyses used multivariable linear and logistic regression for analysis of blood pressure measurements and PIH diagnoses, respectively. In the final dataset (N = 668), higher concentrations of first-trimester monoethyl phthalate (MEP) and mono-3-carboxypropyl phthalate (MCPP) and third-trimester mono-isobutyl phthalate (MiBP) were significantly associated with a medical chart diagnosis of PIH. First-trimester mono-n-butyl phthalate (MBP) and MEP along with the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) were each associated with increased systolic blood pressure across pregnancy. In conclusion, several phthalate metabolite concentrations were significantly associated with PIH and greater increases in systolic blood pressure across pregnancy.

SummaryIntroductionPost‐colonoscopy colorectal cancers (PCCRCs) have been proposed as a performance metric for colonoscopy quality assurance programs. Previously, there was no standardised terminology or reporting methods. In 2018, the World Endoscopy Organization (WEO) advised standardised definitions and prevalence calculation methodology.AimsTo assess PCCRC burden using WEO standardised methods, to explore causes of heterogeneity, and to review changes in prevalence over timeMethodsWe updated a prior systematic review by searching Ovid MEDLINE and EMBASE databases from 1 January 2013 to 31 January 2021 to identify population‐based studies (or multicentre studies representative of the local population) reporting PCCRC prevalence (PROSPERO [CRD42020183796]). Two authors independently determined study eligibility, assessed quality, and extracted data. We estimated the PCCRC 3‐year prevalence using WEO‐recommended methodologies and investigated between‐study sources of heterogeneity. We examined changes in prevalence over time.ResultsFifteen studies reporting on 25 872 PCCRC cases met eligibility criteria. Pooled PCCRC 3 year prevalence was 8.2% (95% CI = 6.9%‐9.4%, I2 = 98.2%) across four European studies using WEO precise methodology. Proximal PCCRC prevalence was greater than distal (9.7% [95% CI = 7.0%‐12.4%] vs 5.4% [95% CI = 2.9%‐7.8%], I2 = 99.2%). Seven studies reporting PCCRC rates over time showed no consistent trend: four showed a decrease, one an increase and two were unchanged. Between‐study heterogeneity was high.ConclusionsPooled 3‐year PCCRC prevalence was 8.2% (95% CI = 6.9%‐9.4%). Despite WEO standardised methodology to define and calculate PCCRC rates, there was significant heterogeneity among studies. Comparing rates between populations remains challenging and additional studies are needed to better understand the global PCCRC burden to inform quality assurance programs.

Abstract Myelofibrosis (MF) is a clonal stem cell neoplasm characterized by abnormal JAK-STAT signaling, chronic inflammation, cytopenias, and risk of transformation to acute leukemia. Despite improvements in the therapeutic options for patients with MF, allogeneic hematopoietic stem cell transplantation remains the only curative treatment. We previously demonstrated multiple immunosuppressive mechanisms in patients with MF, including increased expression of programmed cell death protein 1 (PD-1) on T cells compared with healthy controls. Therefore, we conducted a multicenter, open-label, phase 2, single-arm study of pembrolizumab in patients with Dynamic International Prognostic Scoring System category of intermediate-2 or greater primary, post-essential thrombocythemia or post-polycythemia vera myelofibrosis that were ineligible for or were previously treated with ruxolitinib. The study followed a Simon 2-stage design and enrolled a total of 10 patients, 5 of whom had JAK2V617mutation, 2 had CALR mutation, and 6 had additional mutations. Most patients were previously treated with ruxolitinib. Pembrolizumab treatment was well tolerated, but there were no objective clinical responses, so the study closed after the first stage was completed. However, immune profiling by flow cytometry, T-cell receptor sequencing, and plasma proteomics demonstrated changes in the immune milieu of patients, which suggested improved T-cell responses that can potentially favor antitumor immunity. The fact that these changes were not reflected in a clinical response strongly suggests that combination immunotherapeutic approaches rather than monotherapy may be necessary to reverse the multifactorial mechanisms of immune suppression in myeloproliferative neoplasms. This trial was registered at www.clinicaltrials.gov as #NCT03065400.

Case: A 41-year-old woman sustained a distal radius fracture with concomitant median nerve transection. The wound was consistent with an inside-to-outside mechanism with noted metaphyseal bone loss at the level of the median nerve injury. The median nerve was not amenable to primary repair, and given concern for inability to define the zone of the injury, the patient underwent delayed reconstruction of the nerve. Conclusion: A review of the literature highlights the rare incidence of this combined injury that can be undetected or misdiagnosed as an acute carpal tunnel syndrome or stretch injury to the median nerve.

Abstract Background The objective was to systematically evaluate the sensitivity of diffusion‐weighted magnetic resonance imaging (DW‐MRI) for transient global amnesia (TGA) across various time frames compared to the reference‐standard clinical criteria. Methods All indexed publications related to TGA and MRI through June 2020 were retrieved by a medical librarian. Two independent reviewers identified original research studies of adults with a clinical diagnosis of TGA using Caplan and Hodges and Warlow criteria (reference standard) who were evaluated with DW‐MRI. Pooled estimates and its 95% confidence intervals (CI) for the proportion of acute TGA patients with positive DW‐MRI (i.e., sensitivity) were obtained using random‐effects meta‐analysis for various time frames. Quality assessment was performed using the revised Quality of Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool. Results After screening 665 reports, we identified 81 potentially relevant studies. Twenty‐three studies representing 1688 patients met eligibility criteria, but not all studies had data available for meta‐analysis. The pooled sensitivity (also described as positivity rate) of DW‐MRI was 15.6% (95% CI = 2.6%–35.0%) between 0 and 12 h from symptom onset, 23.1% (95% CI = 6.1%–45.7%) at 0–24 h, 72.8% (95% CI = 40.8%–96.3) at 12–24 h, 68.8% (95% CI = 44.8%–88.8%) at 24–36 h, 72.4% (95% CI = 59.8%–83.5%) at 36–48 h, 82.8% (95% CI = 54.7%–99.6%) at 48–60 h, 66.9% (95% CI = 47.5%–83.9%) at 60–72 h, and 72.0% (95% CI = 30.1%–100.0%) at 72–96 h. There was significant concern for risk of bias in the QUADAS‐2 domains of patient selection and index test, yielding a low level of certainty in the pooled estimates. Conclusion DW‐MRI lesions are uncommon in patients with TGA early after symptom onset, but the sensitivity (i.e., positivity rate) of DW‐MRI increases with time. Despite the limited quality of existing evidence, obtaining an early DW‐MRI in patients with clinical diagnosis of TGA in the acute setting is likely a low‐yield test.

AbstractSince vaccination for SARS‐CoV‐2 coronavirus started, the trajectory of patient numbers infected with the virus has improved once; however, variants of SARS‐CoV‐2 have emerged and more people have been infected; therefore, pandemic status is still far from resolution. Government and social efforts to prevent coronavirus infection continue in most states in the US and globally even after the Centers for Disease Control and Prevention declared some restriction relief for fully vaccinated people in March 2021. Healthcare institutions and various professional organizations have developed guidelines or policies to prevent the spread of these coronaviruses in the setting of apheresis. In this report, the issues that apheresis services may encounter under the current COVID‐19 (SARS‐CoV‐2 coronavirus disease) pandemic will be discussed with potential strategies that can be adapted for efficient and optimum use of apheresis resources.

Abstract Architectural proteins alter the shape of DNA. Some distort the double helix by introducing sharp kinks. This can serve to relieve strain in tightly-bent DNA structures. Here, we design and test artificial architectural proteins based on a sequence-specific Transcription Activator-like Effector (TALE) protein, either alone or fused to a eukaryotic high mobility group B (HMGB) DNA-bending domain. We hypothesized that TALE protein binding would stiffen DNA to bending and twisting, acting as an architectural protein that antagonizes the formation of small DNA loops. In contrast, fusion to an HMGB domain was hypothesized to generate a targeted DNA-bending architectural protein that facilitates DNA looping. We provide evidence from Escherichia coli Lac repressor gene regulatory loops supporting these hypotheses in living bacteria. Both data fitting to a thermodynamic DNA looping model and sophisticated molecular modeling support the interpretation of these results. We find that TALE protein binding inhibits looping by stiffening DNA to bending and twisting, while the Nhp6A domain enhances looping by bending DNA without introducing twisting flexibility. Our work illustrates artificial approaches to sculpt DNA geometry with functional consequences. Similar approaches may be applicable to tune the stability of small DNA loops in eukaryotes.