A phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects.

BACKGROUND: Cognitive difficulties have been described after chemotherapy for breast cancer, but there is no standard of care to improve cognitive outcomes in these patients. This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during chemotherapy for breast cancer. METHODS: Patients with stage I-III breast cancer, scheduled for neo/adjuvant chemotherapy, completed a cognitive battery prior to and 4 weeks after completing chemotherapy. Memantine (10 mg BID) was administered concurrent with chemotherapy. Our primary cognitive outcome was visual working memory assessed by the Delayed Matching to Sample test. We used the Brief Medication Questionnaire to assess acceptability. RESULTS: Of 126 patients approached, 56 (44%) enrolled. Forty-five (80%) received ≥1 dose of memantine and completed pre-post assessments. Seventy-six percent reported taking ≥90% of scheduled doses. Participants were mean age of 56, 77% White, and 57% had stage I disease. Sixty-four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%-91% across objective cognitive domain composite measures. Sixty-six percent self-reported stable or improved cognitive symptoms. There were seven greater than or equal to grade 3 adverse events; two were possibly related to memantine. Only 5% reported that taking memantine was a disruption to their lives. CONCLUSIONS: Memantine was well-tolerated and consistently taken by a large majority of patients receiving breast cancer chemotherapy. The majority demonstrated stable or improved cognition from pre- to post-assessment. Randomized trials are needed to determine memantine's efficacy to ameliorate cognitive loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT04033419.

Breaking the binary: Gender versus sex analysis in human brain imaging.

Despite decades of pursuit, human brain imaging has yet to uncover clear neural correlates of male-female behavioral differences. Given that such behavior does not always align with sex categories, we argue that neuroimaging research may find more success by partitioning subjects along nonbinary gender attributes in addition to sex. We review the handful of studies that have done this, several of which find as good or better association between brain measures and "gender" as they do with "sex." Recent advances in operationalizing "gender" as a multidimensional variable should facilitate such studies, along with discovery-based approaches that mine brain imaging data for gender-associated attributes, independent of sex.

COVID-19 Vaccine-Associated Lymphadenopathy in Breast Imaging Recipients: A Review of Literature.

The unpredictability of the coronavirus disease 2019 (COVID-19) pandemic has created an ongoing global healthcare crisis. Implementation of a mass vaccination program to accelerate disease control remains in progress. Although injection site soreness, fatigue, and fever are the most common adverse reactions reported after a COVID-19 vaccination, ipsilateral lymph node enlargement has increasingly been observed. In patients undergoing routine screening and surveillance for breast cancer, interpreting lymphadenopathy (LAP) is challenging in the setting of a recent COVID-19 vaccination. With a growing proportion of the population receiving the vaccine, a multifaceted approach is necessary to avoid unnecessary and costly workup. In this comprehensive review, we summarize the existing literature on COVID-19 vaccine-associated LAP in breast imaging patients.

Current Practice of Stress Ulcer Prophylaxis in Surgical Departments in Mecklenburg Western Pomerania, Germany.

BACKGROUND: Despite the growing concern over its potentially severe side effects and considerable economic burden, stress ulcer prophylaxis (SUP) is still frequently prescribed to patients in medical non-intensive care units. Recent data indicate that the situation is similar in surgical departments. Currently, data on the concepts within and regulation of routine SUP practice in surgical departments are sparse. The present study was designed to examine the current practice of SUP in Mecklenburg West Pomerania, Germany, and to identify possible reasons for the dissociation of medical literature and clinical practice. METHODS: A questionnaire-based survey was conducted to elucidate current SUP practices in surgical departments of acute care hospitals in Mecklenburg Western Pomerania, Germany. RESULTS: In most surgical departments (68%), a standard operating procedure (SOP) for SUP had not been developed. In departments with an existing SOP, 47.6% of responding medical staff members (MSM) with prescribing authority did not know of its existence. Of the MSMs aware of the existence of an SUP-SOP, only 42.9% indicated that they were familiar with its content. Critical re-evaluation of SUP indications upon transfer from the intensive care unit (ICU) to the general hospital ward (GHW) and before hospital discharge was performed frequently or systematically by only about half of the responding MSMs. DISCUSSION: In the face of continued massive over-prescription of SUP in the perioperative routine, the development of easy-to-use local guidelines and their strict implementation in the clinical routine, as well as intensified medial education on this subject, may be effective tools to reduce acid-suppressive medication (ASM) associated side effects and economic burden.

Current practice of stress ulcer prophylaxis in a surgical patient cohort in a German university hospital.

INTRODUCTION: Stress ulcer prophylaxis (SUP) has been a widespread practice both in intensive care units (ICU) and internal wards at the beginning of the twenty-first century. Clinical data suggests an important overuse of acid suppressive therapy (AST) for this indication. Data on current clinical practice of SUP in surgical patients in a non-ICU setting are spares. In the light of a growing number of reports on serious side effects of AST, this study evaluates the use of AST for SUP in a normal surgical ward in a German university hospital. METHODS: Between January 2016 and June 2016, SUP was analysed retrospectively in 1132 consecutive patients of the Department of Surgery of the Universitätsmedizin Greifswald. RESULTS: The patients managed with and without SUP were similar with respect to demographic data and treatment with anticoagulants, SSRI and glucocorticoids. Patients with SUP were treated more frequently by cyclooxygenase inhibiting drugs (NSAID, COX2-inhibitors), were more frequently treated in the intermediated care unit and had a longer hospital stay. Risk factors for the development of stress ulcers were similarly present in patient groups managed with and without SUP. About 85.7-99.6% of patients were given SUP without an adequate risk for stress ulcer development, depending on the method used for risk assessment. DISCUSSION: Still today, SUP is widely overused in non-ICU surgical patients. Information campaigns on risk factors for stress ulcer development and standard operating procedures for SUP are required to limit potential side effects and increased treatment costs.

Differences in infection control and diagnostic measures for multidrug-resistant organisms in the tristate area of France, Germany and Switzerland in 2019 - survey results from the RH(E)IN-CARE network.

BACKGROUND: Multidrug-resistant organisms (MDROs) are a public health threat. Single-centre interventions, however, are likely to fail in the long term, as patients are commonly transferred between institutions given the economic integration across borders. A transnational approach targeting larger regions is needed to plan overarching sets of interventions. Here, we aim to describe differences in diagnostic and infection prevention and control (IPC) measures in the fight against MDROs. METHODS: In 2019, we systematically assessed diagnostic algorithms and IPC measures implemented for detection and control of MDROs at three tertiary academic care centres (Freiburg; Strasbourg; Basel). Data were collected using a standardised data collection sheet to be filled in by every centre. Uncertainties were clarified by direct contact via telephone or email with the data supplier. Internal validity was checked by at least two researchers independently filling in the survey. RESULTS: All centres have established a primarily culture-based, rather than a nucleic acid amplification-based approach for detection of MDROs (i.e., vancomycin-resistant Enterococci [VRE], methicillin-resistant Staphylococcus aureus [MRSA], extended-spectrum beta-lactamase-producing Enterobacteriaceae [ESBL], carbapenemase-producing and carbapenem-resistant Gram-negatives [CPGN/CRGN]). IPC measures differed greatly across all centres. High-risk patients are screened for most MDROs on intensive care unit (ICU) admission in all centres; only the French centre is screening all patients admitted to the ICU for VRE, MRSA and ESBL. Patients colonised/infected by MRSA, quinolone-resistant ESBL Klebsiella spp. and CPGN/CRGN are isolated everywhere, whereas patients colonised/infected by VRE and ESBL are usually not isolated in the German centre. CONCLUSIONS: In contrast to the French and Swiss centres, the German centre no longer uses isolation measures to control VRE and quinolone-susceptible ESBL. Overall, the French centre is more focused on intercepting MDRO transmission from outside, whereas the German and Swiss centres are more focused on intercepting endemic MDRO transmission. These findings point to important challenges regarding future attempts to standardise IPC measures across borders.    .

RhoGEF17, a Rho-specific guanine nucleotide exchange factor activated by phosphorylation via cyclic GMP-dependent kinase Iα.

RhoGEF17, the product of the ARHGEF17 gene, is a Rho-specific guanine nucleotide exchange factor (GEF) with an unusual structure and so far unknown function. In order to get insights in its regulation, we studied a variety of signaling pathways for activation of recombinantly expressed RhoGEF17. We found that in the presence of stable cGMP analogs RhoGEF17 associates with and is phosphorylated by co-expressed cGKIα at distinct phosphorylation sites leading to a cooperative activation of RhoA, the Rho dependent kinases (ROCK) and serum response factor-induced gene transcription. Activation of protein kinase A did not induce phosphorylation of RhoGEF17 nor altered its activity. Furthermore, we obtained evidence for a ROCK-driven positive feedback mechanism involving serine/threonine protein phosphatases, which further enhanced cGMP/cGKIα-induced RhoGEF17 activation. By using mutants of RhoA which are phosphorylation resistant to cGK or mimic phosphorylation at serine 188, we could show that RhoGEF17 is able to activate RhoA independently of its phosphorylation state. Together with the ROCK-enforced activation of RhoGEF17 by cGMP/cGKIα, this might explain why expression of RhoGEF17 switches the inhibitory effect of cGMP/cGKIα on serum-induced RhoA activation into a stimulatory one. We conclude that RhoGEF17, depending on its expression profile and level, might drastically alter the effect of cGMP/cGK involving signaling pathways on RhoA-activated downstream effectors.