Citations

SummaryMultiagent chemoimmunotherapy remains the standard of care treatment for Burkitt lymphoma leading to a cure in the majority of cases. However, frontline treatment regimens are associated with a significant risk of treatment related toxicity especially in elderly and immunocompromised patients. Additionally, prognosis remains dismal in refractory/relapsed Burkitt lymphoma. Thus, novel therapies are required to not only improve outcomes in relapsed/refractory Burkitt lymphoma but also minimize frontline treatment related toxicities. Recurrent genomic changes and signalling pathway alterations that have been implicated in the Burkitt lymphomagenesis include cell cycle dysregulation, cell proliferation, inhibition of apoptosis, epigenetic dysregulation and tonic B‐cell receptor‐phosphatidylinositol 3‐kinase (BCR‐PI3K) signalling. Here, we will discuss novel targeted therapy approaches using small molecule inhibitors that could pave the way to the future treatment landscape based on the understanding of recurrent genomic changes and signalling pathway alterations in the lymphomagenesis of adult Burkitt lymphoma.

Abstract Background Intensive care unit (ICU) clinicians encounter frequent challenges with managing vast amounts of fragmented data while caring for multiple critically ill patients simultaneously. This may lead to increased provider cognitive load that may jeopardize patient safety. Objectives This systematic review assesses the impact of centralized multipatient dashboards on ICU clinician performance, perceptions regarding the use of these tools, and patient outcomes. Methods A literature search was conducted on February 9, 2023, using the EBSCO CINAHL, Cochrane Central Register of Controlled Trials, Embase, IEEE Xplore, MEDLINE, Scopus, and Web of Science Core Collection databases. Eligible studies that included ICU clinicians as participants and tested the effect of dashboards designed for use by multiple users to manage multiple patients on user performance and/or satisfaction compared with the standard practice. We narratively synthesized eligible studies following the SWiM (Synthesis Without Meta-analysis) guidelines. Studies were grouped based on dashboard type and outcomes assessed. Results The search yielded a total of 2,407 studies. Five studies met inclusion criteria and were included. Among these, three studies evaluated interactive displays in the ICU, one study assessed two dashboards in the pediatric ICU (PICU), and one study examined centralized monitor in the PICU. Most studies reported several positive outcomes, including reductions in data gathering time before rounds, a decrease in misrepresentations during multidisciplinary rounds, improved daily documentation compliance, faster decision-making, and user satisfaction. One study did not report any significant association. Conclusion The multipatient dashboards were associated with improved ICU clinician performance and were positively perceived in most of the included studies. The risk of bias was high, and the certainty of evidence was very low, due to inconsistencies, imprecision, indirectness in the outcome measure, and methodological limitations. Designing and evaluating multipatient tools using robust research methodologies is an important focus for future research.

OBJECTIVE: Certifications in psychiatric-mental health nursing promote safe practice by psychiatric-mental health nurse practitioners (PMHNPs) and nurses (PMHNs) and help protect the public from harm. This protection begins with the development of an examination that meets rigorous national education, practice, and accreditation standards and reflects PMHNPs’ or PMHNs’ clinical practice. Achievement and maintenance of a certification is a journey that involves a commitment to lifelong learning and the improvement of the field of psychiatric-mental health nursing through involvement in the examination process. METHODS: This discussion paper outlines the role nurses can play in the development of certification examinations. It describes the process of developing an effective certification examination, including the role of standards, accrediting bodies, and content experts; determining necessary tasks, knowledge, and skills; surveying practitioners to validate information; writing test questions; and ongoing analysis of examination content. The Psychiatric-Mental Health Nurse Practitioner (across the lifespan) Certification (PMHNP-BC) is presented as an example of the process. RESULTS: This discussion paper raises awareness of how certification exams are developed, PMHNPs participate in certification development, and volunteering promotes career development. CONCLUSION: The PMHNP-BC examination is based on education, practice, and certification accreditation standards and reflects current clinical practice. PMHNPs can (a) point to the rigor of certification as an indication of the quality of care they deliver, (b) volunteer to participate in the examination process to ensure examination rigor, and (c) advance their careers through the development and application of a valuable skill set.

Excessive alcohol consumption represents an important burden for health systems worldwide and is a major cause of liver- and cancer-related deaths. Alcohol consumption is mostly assessed by self-report that often underestimates the amount of drinking. While alcohol use disorders identification test - version C is the most widely used test for alcohol use screening, in patients with liver disease the use of alcohol biomarker could help an objective assessment. The amount of alcohol that leads to significant liver disease depends on gender, genetic background, and coexistence of comorbidities (i.e., metabolic syndrome factors). All patients with alcohol-associated liver disease are recommended to follow complete abstinence and they should be treated within multidisciplinary teams. Abstinence slows down and even reverses the progression of liver fibrosis and can help recompensate patients with complicated cirrhosis. Whether there is a safe amount of alcohol in the general population is a matter of intense debate. Large epidemiological studies showed that the safe amount of alcohol to avoid overall health-related risks is lower than expected even in the general population. Even one drink per day can increase cancer-related death. In patients with any kind of chronic liver disease, especially in those with metabolic-associated steatotic liver disease, no alcohol intake is recommended. This review article discusses the current evidence supporting the deleterious effects of small-to-moderate amounts of alcohol in the general population and in patients with underlying chronic liver disease.

PURPOSE To assess efficacy and toxicity of cisplatin (C) and gemcitabine (G) with intensity-modulated radiation therapy (IMRT) in patients with locally advanced vulvar cancer not amenable to surgery. METHODS Patients enrolled in a single-arm phase II study. Pretreatment inguinal-femoral nodal assessment was performed. Sixty-four Gy IMRT was prescribed to the vulva, with 50-64 Gy delivered to the groins/low pelvis. Radiation therapy (RT) plans were quality-reviewed pretreatment. C 40 mg/m2 and G 50 mg/m2 were administered once per week throughout IMRT. Complete pathologic response (CPR) was the primary end point. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adverse events were assessed with Common Terminology Criteria for Adverse Events v 4.0. RESULTS Fifty-seven patients enrolled, of which 52 were evaluable. The median age was 58 years (range, 25-58), and 94% were White. Forty (77%) had stage II or III disease, and all had squamous histology. A median of six chemotherapy cycles (range, 1-8) were received. Eighty-five percent of RT plans were quality-reviewed with 100% compliance to protocol. Seven patients came off trial because of toxicity or patient withdrawal. Of 52 patients available for pathologic assessment, 38 (73% [90% CI, 61 to 83]) achieved CPR. No pelvic exenterations were performed. With a median follow-up of 51 months, the 12-month PFS was 74% (90% CI, 62.2 to 82.7) and the 24-month OS was 70% (90% CI, 57 to 79). The most common grade 3 or 4 adverse events were hematologic toxicity and radiation dermatitis. There was one grade 5 event unlikely related to treatment. CONCLUSION Weekly C and G concurrent with IMRT sufficiently improved CPR in women with locally advanced vulvar squamous cell carcinoma not amenable to surgical resection.

Background: Pancreas transplantation is a crucial surgical intervention for managing diabetes, but it faces challenges such as its invasive nature, stringent patient selection criteria, organ scarcity, and centralized expertise. Despite the steadily increasing number of pancreas transplants in the United States, there is a need to understand global trends in interest to increase awareness of and participation in pancreas and islet cell transplantation. Methods: We analyzed Google Search trends for “Pancreas Transplantation” and “Islet Cell Transplantation” from 2004 to 14 November 2023, assessing variations in search interest over time and across geographical locations. The Augmented Dickey–Fuller (ADF) test was used to determine the stationarity of the trends (p < 0.05). Results: Search interest for “Pancreas Transplantation” varied from its 2004 baseline, with a general decline in peak interest over time. The lowest interest was in December 2010, with a slight increase by November 2023. Ecuador, Kuwait, and Saudi Arabia showed the highest search interest. “Islet Cell Transplantation” had its lowest interest in December 2016 and a more pronounced decline over time, with Poland, China, and South Korea having the highest search volumes. In the U.S., “Pancreas Transplantation” ranked 4th in interest, while “Islet Cell Transplantation” ranked 11th. The ADF test confirmed the stationarity of the search trends for both procedures. Conclusions: “Pancreas Transplantation” and “Islet Cell Transplantation” showed initial peaks in search interest followed by a general downtrend. The stationary search trends suggest a lack of significant fluctuations or cyclical variations. These findings highlight the need for enhanced educational initiatives to increase the understanding and awareness of these critical transplant procedures among the public and professionals.

Endometrial cancer (EC) is the most diagnosed gynecologic malignancy, and its incidence and mortality are increasing. The prognosis is highly dependent on the disease spread. Surgical staging includes retroperitoneal evaluation to detect potential lymph node metastases. In recent years, systematic lymphadenectomy has been replaced by sentinel lymph node (SLN) biopsy and ultrastaging, allowing for the detection of macrometastases, micrometastases, and isolated tumor cells (ITCs). Micrometastases and ITCs have been grouped as low-volume metastases (LVM). The reported prevalence of LVM in studies enrolling more than one thousand patients with apparent early-stage EC ranges from 1.9% to 10.2%. Different rates of LVM are observed when patients are stratified according to disease characteristics and their risk of recurrence. Patients with EC at low risk for recurrence have low rates of LVM, while intermediate- and high-risk patients have a higher likelihood of being diagnosed with nodal metastases, including LVM. Macro- and micrometastases increase the risk of recurrence and cause upstaging, while the clinical significance of ITCs is still uncertain. A recent meta-analysis found that patients with LVM have a higher relative risk of recurrence [1.34 (95% CI: 1.07–1.67)], regardless of adjuvant treatment. In a retrospective study on patients with low-risk EC and no adjuvant treatment, those with ITCs had worse recurrence-free survival compared to node-negative patients (85.1%; CI 95% 73.8–98.2 versus 90.2%; CI 95% 84.9–95.8). However, a difference was no longer observed after the exclusion of cases with lymphovascular space invasion. There is no consensus on adjuvant treatment in ITC patients at otherwise low risk, and their recurrence rate is low. Multi-institutional, prospective studies are warranted to evaluate the clinical significance of ITCs in low-risk patients. Further stratification of patients, considering histopathological and molecular features of the disease, may clarify the role of LVM and especially ITCs in specific contexts.

Background Extended sedentary behavior is a risk factor for chronic disease and mortality, even among those who exercise regularly. Given the time constraints of incorporating physical activity into daily schedules, and the high likelihood of sitting during office work, this environment may serve as a potentially feasible setting for interventions to reduce sedentary behavior. Methods and Results A randomized cross‐over clinical trial was conducted at an employee wellness center. Four office settings were evaluated on 4 consecutive days: stationary or sitting station on day 1 (referent), and 3 subsequent active workstations (standing, walking, or stepper) in randomized order. Neurocognitive function (Selective Attention, Grammatical Reasoning, Odd One Out, Object Reasoning, Visuospatial Intelligence, Limited‐Hold Memory, Paired Associates Learning, and Digit Span) and fine motor skills (typing speed and accuracy) were tested using validated tools. Average scores were compared among stations using linear regression with generalized estimating equations to adjust standard errors. Bonferroni method adjusted for multiple comparisons. Healthy subjects were enrolled (n=44), 28 (64%) women, mean±SD age 35±11 years, weight 75.5±17.1 kg, height 168.5±10.0 cm, and body mass index 26.5±5.2 kg/m 2 . When comparing active stations to sitting, neurocognitive test either improved or remained unchanged, while typing speed decreased without affecting typing errors. Overall results improved after day 1, suggesting habituation. We observed no major differences across active stations, except decrease in average typing speed 42.5 versus 39.7 words per minute with standing versus stepping ( P =0.003). Conclusions Active workstations improved cognitive performance, suggesting that these workstations can help decrease sedentary time without work performance impairment. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06240286.

Abstract Purpose To assess intra‐ (repeatability) and inter‐observer (reproducibility) variability of laser speckle flowgraphy (LSFG) for retinal blood flow (RBF) measurement in 20 eyes of wild type (C57BL/6J) mice and effect of intravitreal Aflibercept on RBF in optic nerve head (ONH) region of 10 eyes of Ins2 (Akita) diabetic mice. Methods ‘Mean blur rate (MBR)’ was measured for all quadrants of tissue area (MT), vessel (MV) and total area (MA) of ONH region. Changes in MT were analysed at each timepoint. Repeatability was evaluated by measuring MBR variability without changing mouse head position, and reproducibility after resetting mouse head position by another operator. Coefficient of repeatability (CR) through Bland–Altman plot method coefficient of variation (COV) and Intraclass correlation coefficient (ICC) was calculated. Intravitreal Aflibercept (1 μg) was administered to Akita eyes and intraocular pressure (IOP) was measured using a tonometer at baseline, day 7, 14, 21 and 28 post‐injection. Hurvich and Tsai's criterion was used. Results Coefficient of repeatability values of repeatability and reproducibility for all quadrants were within limits of agreement. Reliability was excellent (ICC 0.98–0.99) and reproducibility was moderate to excellent (ICC 0.64–0.96). There was a non‐significant IOP increase in all Akita eyes at Day 28 ( p > 0.05), and significant increase in MT in all quadrants at Day 21 and superior, inferior and temporal quadrants at Day 28 ( p < 0.05). Conclusion Laser speckle flowgraphy demonstrates excellent repeatability and moderate to excellent reproducibility in measuring RBF. Intravitreal Aflibercept injection results in a significant increase in MT up to 28 days post‐injection without significant increase in IOP.