bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two free light chain assays: performance of the free light chain ratio as risk factor for MGUS progression
Authors: Andress Benjamin , Wang Qian , Pazdernik Vanessa , Kalass Stephanie , Dispenzieri Angela , Murray David , Willrich Maria
Published: November 2023

Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell dyscrasia, present in ~3% of the population over 50yo. MGUS carries a 1% per year risk of malignant transformation for the rest of the affected individual’s life; long-term followup is recommended for all patients with MGUS. Different risk stratification models exist to evaluate potential for progression to malignancy. The Mayo risk model, published in 2005, uses the presence of 3 risk factors (abnormal free light chain (FLC) kappa/lambda ratio (KLr), M-spike ≥1.5 g/dL, non-IgG isotype) to confer a 3% per year risk of progression instead of the average 1%. For many years, the only FDA-approved measurement of FLC was the FreeLite assay (Binding Site), which uses polyclonal sheep antibodies. Recently, other FLC assays have become available in the US, including the Sebia FLC ELISA, which employs rabbit polyclonal antibodies. The assays have similar reference intervals (RI), however differences in analytical performance between the FreeLite and Sebia were previously reported. The objective of this study was to determine the performance of the Sebia FLC assay in the Mayo risk stratification model of MGUS patients for progression in comparison to FreeLite. Cryopreserved serum samples from a cohort of 923 MGUS patients with available long-term clinical followup (median follow-up time: 7.7years, range: 0.0 to 46.9) was used to measure FLC using Sebia ELISA on a DS2 automated platform (Dynex) and FreeLite on a Siemens BNII nephelometer. Passing-Bablok (P-B) regression and Spearman correlation were used to compare the KLr between assays. Cox proportional hazards models for progression to multiple myeloma or a related plasma cell malignancy were used to estimate the prognostic effect and ability to discriminate low and high risk of abnormal KLr for each assay. Analyses were carried out in R software. Correlation between Sebia and FreeLite KLr had a Spearman r = 0.796; P-B fit: Sebia KLr = 0.825*(FreeLite KLr) – 0.048, 95% CI of slope: 0.810-0.839). With FreeLite, 32.9% of patients had a KLr outside RI for the method. For Sebia, 48.0% of patients had a KLr outside the method specific RI. Despite the individual samples analytical disagreement, both assays showed similar clinical performance for risk stratification: Sebia abnormal KLr was associated with a hazard ratio (HR) of 2.77 (95%CI: 1.79-4.28 c-statistic=0.6505) for progression, while FreeLite abnormal KLr was associated with a HR of 3.31 (95%CI: 2.20-5.00, c-statistic=0.6529), and the difference in c-statistics was not statistically significant (p=0.93). The risk assessment is performed only once per patient, at the initial diagnosis of MGUS. The similarity in clinical performance between FreeLite and Sebia assays support the use of either method as a predictor for risk of progression for MGUS patients.
Analysis of daratumumab reporting in type and screen orders to identify opportunities for information system improvement
Authors: Morse Patrick , Thibodeaux Suzanne , Jackups Ronald
Published: November 2023

The rapid growth of monoclonal antibody therapies has resulted in a wide variety of targeted treatments towards malignancies. The presence of these antibodies in patient plasma can interfere with blood bank testing, which in turn can create a delay in the process of pretransfusion testing and provision of blood products to patients. Availability of information regarding particular medications can help guide blood bank processes and testing algorithms. Reporting of patient medications that can interfere with blood bank testing, including targeted therapeutic antibodies (e.g. anti-CD38 therapies such as daratumumab), often relies on the ordering provider to provide that information. At our institution, the type and screen (T&S) order contains a prompt that requests the history of daratumumab administration. Available responses are “yes”, “no”, or “unknown”, with the default answer of “unknown”. The goal of this study was to evaluate the reporting practice of daratumumab history in the T&S order and identify potential areas for process improvement. We retrospectively reviewed T&S orders for patients receiving daratumumab therapy during 2022 at a single institution. Of 370 patients who were receiving daratumumab therapy, 214 (57.8%) had T&S orders. Forty of the 214 patients (18.7%) with T&S orders had at least one order with a “yes” answer indicating daratumumab administration. Of the 40 patients with an answer of “yes”, 16 (40%) were associated with the initial T&S after starting therapy. Of the other answer options, 23 of 40 (57.5%) indicated “unknown” and 1 (2.5%) indicated “no”. The remaining T&S orders ordered after the initial order were evaluated for consistency in response. Of 352 total T&S orders placed after the initial T&S orders, 62 (17.6%) were “yes” answers, 4 (1.1%) were “no” answers, and 286 (81.3%) were “unknown”. These results suggest that manual reporting of daratumumab therapy is not optimized at time of initial T&S orders placed after daratumumab treatment is started and is further misaligned with treatment status with subsequent T&S orders. Development of automated methods may help improve the process of reporting medications to the blood bank to guide testing. Future directions include development of an informatics-based approach to link the patient’s medical administration record (MAR) to the laboratory information system (LIS) to provide history of daratumumab therapy to the blood bank. This approach will prioritize: (1) compatibility with the blood bank’s current workflow for testing, (2) clinical needs for ordering laboratory testing, and (3) adaptability for reporting of other relevant interfering therapies to the blood bank as well as to other clinical laboratories.
Banking Law in Italian Legal Consulting between the Fourteenth and the Fifteenth Centuries
Authors: Conetti Mario
Published: November 2023

Banking operations in northern and central Italy between late fourteenth and early fifteenth century were very sophisticated and often gave rise to disputes involving the expertise only law professors could provide. To provide solutions which were at the same time viable and grounded in legal culture, lawyers went beyond merely practical considerations to work out legal institutions as a framework to banking activities. In doing so, they developed a proper banking law, a peculiar legal system.
Upper Extremity Functional Outcomes After Breast Cancer Treatment: An Analysis of DASH Score in Breast Reconstruction Patients
Authors: Humar Pooja , Moroni Elizabeth , Raghuram Anjali , Balogun Zainab , Nguyen Xuan-Mai , Zhang Casey , De La Cruz Carolyn
Published: November 2023

Background

Patients undergoing postoncologic breast reconstruction can experience upper extremity (UE) functional deficits.

Objectives

In this study, we utilized the disabilities of the arm, shoulder, and hand (DASH) questionnaire to identify patient factors that impacted UE functional recovery.

Methods

Patients who underwent oncologic followed by reconstructive surgery by a single surgeon from 2014 to 2019 and completed the DASH survey were included. A DASH score was calculated for each patient, with values ranging from 0 (no impairment) to 100 (severe impairment). Regression analysis was conducted to identify significant predictors for DASH score with a significance level for entry and stay set at P = .15.

Results

Among 289 patients who underwent breast reconstruction, 157 completed the questionnaire. The average patient age was 52.6yrs ± 8.6 at the time of reconstruction. A total of 111 had implant-based reconstruction, 15 had autologous reconstruction, and 24 had a combination of both. Average DASH score was 7.7 (range 0.0-52.5), with 74.1% of patients having a score greater than 0. Regression analysis showed 5 variables associated with significantly higher DASH scores: age between 50 and 60 years (P = .13), history of radiation (P = .01), placement of a subpectoral implant (P = .06), postoperative complications (P = .10), and lymphedema (P < .01). Autologous breast reconstruction (P = .04) was associated with a significantly lower DASH score.

Conclusions

Implant-based reconstruction, radiation history, postoperative complications, and age at reconstruction were associated with increased UE functional impairment in patients who underwent breast reconstructive surgery. Identification of these factors can inform areas for potential practice changes and improve patient counseling regarding postoperative expectations.

Level of Evidence: 3
Identifying the potential miRNA biomarkers based on multi-view networks and reinforcement learning for diseases
Authors: Su Benzhe , Wang Weiwei , Lin Xiaohui , Liu Shenglan , Huang Xin
Published: November 2023

MicroRNAs (miRNAs) play important roles in the occurrence and development of diseases. However, it is still challenging to identify the effective miRNA biomarkers for improving the disease diagnosis and prognosis. In this study, we proposed the miRNA data analysis method based on multi-view miRNA networks and reinforcement learning, miRMarker, to define the potential miRNA disease biomarkers. miRMarker constructs the cooperative regulation network and functional similarity network based on the expression data and known miRNA–disease relations, respectively. The cooperative regulation of miRNAs was evaluated by measuring the changes of relative expression. Natural language processing was introduced for calculating the miRNA functional similarity. Then, miRMarker integrates the multi-view miRNA networks and defines the informative miRNA modules through a reinforcement learning strategy. We compared miRMarker with eight efficient data analysis methods on nine transcriptomics datasets to show its superiority in disease sample discrimination. The comparison results suggested that miRMarker outperformed other data analysis methods in receiver operating characteristic analysis. Furthermore, the defined miRNA modules of miRMarker on colorectal cancer data not only show the excellent performance of cancer sample discrimination but also play significant roles in the cancer-related pathway disturbances. The experimental results indicate that miRMarker can build the robust miRNA interaction network by integrating the multi-view networks. Besides, exploring the miRNA interaction network using reinforcement learning favors defining the important miRNA modules. In summary, miRMarker can be a hopeful tool in biomarker identification for human diseases.
The Home Office’s Racism Studies Before the Macpherson Inquiry: Revisiting Administrative Criminology’s Corpus
Authors: Molina Julian
Published: November 2023

This article examines the history of Home Office research on racism between 1976 and 1997. By analysing archival materials, the article focusses on the methodological orientations and bureaucratic negotiations associated with this corpus of administrative criminological studies. The article describes how Home Office criminologists adopted a stance that privileged quantification, restudies and aligning its research with pre-existing policy paradigms of Situational Crime Prevention and multi-agency coordination. In response to campaigners’ calls for racial justice, Home Office policy officials used this research to demonstrate governmental concern, manage media coverage and coordinate community stakeholders. The article argues that British criminology should move beyond dismissing administrative criminology as ‘theoretical empiricism’ to enable a more critical appraisal of the entangled histories of racism, criminology and crime policy.
Taking Prison to Court: Exploring the Judicial Review of Prison Decision-Making Through Supreme Court Judges in Israel
Authors: Dagan Netanel , Baron Shmuel
Published: November 2023

Scholars have criticized the gap between judicial work and the realities of prison life. In this article, drawn from qualitative findings from Supreme Court Judges in Israel, we analysed how such Judges negotiate their administrative judicial review over prison officials’ decisions. We found that through their judicial review, the Judges either bureaucratise, re-sentence the prisoner or reform prison life. Each theme imagines differently both the purpose of judicial review, as well as the values, emotions, legal ‘tool-kit’, and players (prison service, the claiming prisoners) involved in the review process. The findings move the scholarly focus of judicial decision-making from the quantity to the quality of punishment and expand the understanding of judicial consciousness regarding prison life.
The Victimization of Rohingyas in Myanmar and Bangladesh: Breaking the Silence - Postcolonial Criminology, Ethnography and Genocide
Authors: Soundararajan Manikandan , Jaishankar Karuppannan , Bushell Mark , Telford Luke , Treadwell James
Published: November 2023

This paper gives voice to the victims of ethnic cleansing in Myanmar. Using criminological ethnographic research in refugee camps in Bangladesh, we examine the qualitative accounts of violence and persecution and ‘break the silence’ by giving voice to Rohingya people who had fled military violence. We place the Rohingya’s testimonies within a wider theoretical and historical discussion that also addresses the condition of criminology when it comes to understanding and analysing the crime of all crimes—genocide. In recent years, the potential for postcolonial criminology in explaining global inequalities and injustices has been much discussed. However, we critique parts of this debate and instead emphasize the importance of foregrounding the realities of extreme victimization of powerless individuals such as the Rohingya.
Global prevalence of cardiovascular risk factors based on the Life's Essential 8 score: an overview of systematic reviews and meta-analysis
Authors: López-Bueno Rubén , Núñez-Cortés Rodrigo , Calatayud Joaquín , Salazar-Méndez Joaquín , Petermann-Rocha Fanny , López-Gil José Francisco , del Pozo Cruz Borja
Published: November 2023

Cardiovascular health (CVH) is a critical issue for global health. However, no previous study has determined the prevalence of cardiovascular risk factors based on the American Heart Association’s (AHA) Life’s Essential 8 (LE8). Therefore, we aimed to estimate the global prevalence of the eight cardiovascular risk factors identified in the LE8. A systematic search of systematic reviews with meta-analysis on cardiovascular risk factors covering data reported between 2000 and 2019 was conducted on PubMed, Epistemonikos, and the Cochrane Library until 1 May 2023. After applying exclusion criteria, 79 studies remained in the final selection for the narrative synthesis in the systematic review, of which 33 of them were used in the meta-analysis which included 2 555 639 participants from 104 countries. The overall pooled prevalence of cardiovascular risk factors was as follows: insufficient physical activity, 26.3% (95% CI 2.3%–63.4%), no adherence to a healthy diet, 34.1% (95% CI 5.8%–71.2%), nicotine exposure, 15.4% (95% CI 10.4%–21.2%), insufficient sleep quality, 38.5% (95% CI 14.0%–66.7%), obesity, 17.3% (95% CI 6.1%–32.6%), dyslipidemia, 34.1% (95% CI 33.8%–34.4%), diabetes, 12.0% (95% CI 7.0%–18.2%), and hypertension, 29.4% (95% CI 23.3%–35.8%). These results warrant prevention strategies aimed at reducing insufficient sleep quality, and no adherence to a healthy diet as leading cardiovascular risk factors worldwide. The high prevalence of hypertension among children and adults is concerning and should also be adequately addressed through global policies.
The workload and satisfaction of pharmacists and pharmacy assistants after installation of an automated tablet dispensing and packaging system in a tertiary university hospital in Malaysia
Authors: Ramachandram Dinesh Sangarran , Tan Ching Hooi , Selvaraj Amutha , Appalasamy Jamuna Rani , Kow Chia Siang
Published: November 2023

Objective

The aim of this study was to examine the impact of pharmacy automation on the workload and satisfaction of pharmacists and pharmacy assistants in an inpatient setting.

Methods

This was an observational, cross-sectional survey using a convenience sampling method conducted at the University Malaya Medical Centre (UMMC) In-Patient Pharmacy. A validated online questionnaire assessed user satisfaction and task duration.

Results

A total of 21 pharmacists and 18 pharmacy assistants participated in the survey. Most pharmacists (n = 17/21) were confident in the system, and both pharmacists and pharmacy assistants perceived it to be beneficial for patients (n = 33/39) and for reducing medication errors (n = 32/39). Pharmacy assistants spent approximately 5.34 hours on traditional work including filling medication orders (1.44 hours) after automated tablet dispensing and packaging system (ATDPS) implementation. Pharmacists spent 1.19 hours filling medication orders and 1.71 hours checking/verifying them, in contrast.

Conclusion

Pharmacists focused mainly on clinical duties with healthcare colleagues, while pharmacy assistants handled various medication orders. Nevertheless, ATDPS reduced pharmacy staff workload in medication handling, achieving user satisfaction.
Phase 1 Open-Label Dose Escalation Trial for the Development of a Human Bacillus Calmette-Guérin Challenge Model for Assessment of Tuberculosis Immunity In Vivo
Authors: Blazevic Azra , Edwards Rachel L , Xia Mei , Eickhoff Christopher S , Hamzabegovic Fahreta , Meza Krystal A , Ning Huan , Tennant Janice , Mosby Karla J , Ritchie James C , Girmay Tigisty , Lai Lilin , McCullough Michele , Beck Allison , Kelley Colleen , Edupuganti Srilatha , Kabbani Sarah , Buchanan Wendy , Makhene Mamodikoe K , Voronca Delia , Cherikh Sami , Goll Johannes B , Rouphael Nadine G , Mulligan Mark J , Hoft Daniel F
Published: November 2023

Background

A controlled human infection model for assessing tuberculosis (TB) immunity can accelerate new vaccine development.

Methods

In this phase 1 dose escalation trial, 92 healthy adults received a single intradermal injection of 2 × 106 to 16 × 106 colony-forming units of Bacillus Calmette-Guérin (BCG). The primary endpoints were safety and BCG shedding as measured by quantitative polymerase chain reaction, colony-forming unit plating, and MGIT BACTEC culture.

Results

Doses up to 8 × 106 were safe, and there was evidence for increased BCG shedding with dose escalation. The MGIT time-to-positivity assay was the most consistent and precise measure of shedding. Power analyses indicated that 10% differences in MGIT time to positivity (area under the curve) could be detected in small cohorts (n = 30). Potential biomarkers of mycobacterial immunity were identified that correlated with shedding. Transcriptomic analysis uncovered dose- and time-dependent effects of BCG challenge and identified a putative transcriptional TB protective signature. Furthermore, we identified immunologic and transcriptomal differences that could represent an immune component underlying the observed higher rate of TB disease incidence in males.

Conclusions

The safety, reactogenicity, and immunogenicity profiles indicate that this BCG human challenge model is feasible for assessing in vivo TB immunity and could facilitate the vaccine development process.

Clinical Trials Registration

NCT01868464 (ClinicalTrials.gov).
Multisite Mpox Infection and Viral Dynamics Among Persons With HIV in Metro Atlanta
Authors: Damhorst Gregory L , Fujita A Wendy , Fitts Eric , Szabo Brittany , Bowers Heather B , Sabino Courtney , Ahmed Alaa , Wang Ethan , Piantadosi Anne , McLendon Kaleb , Sullivan Julie , Greenleaf Morgan , McCaslin Divine , Palmore Melody , Anderson Albert M , Aldred Bruce , Gunthel Clifford , Martin Greg S , Colasanti Jonathan A , Lam Wilbur A , Bassit Leda , Rao Anuradha , Sheth Anandi N , Titanji Boghuma K
Published: November 2023

The 2022 mpox outbreak primarily involved sexual transmission among men who have sex with men and disproportionately affected persons with human immunodeficiency virus (HIV). We examined viral dynamics and clinical features in a cohort evaluated for mpox infection at a comprehensive HIV clinic in Atlanta, Georgia. Viral DNA was found in 8 oropharyngeal and 5 anorectal specimens among 10 mpox cases confirmed by lesion swab polymerase chain reaction. Within-participant anatomic site of lowest cycle threshold (Ct) value varied, and lower Ct values were found in oropharyngeal and anorectal swabs when corresponding symptoms were present. This provides insight into mpox infection across multiple anatomic sites among people with HIV.
Effectiveness of Influenza Vaccination During Pregnancy Against Laboratory-Confirmed Seasonal Influenza Among Infants Under 6 Months of Age in Ontario, Canada
Authors: Fell Deshayne B , Russell Margaret , Fung Stephen G , Swayze Sarah , Chung Hannah , Buchan Sarah A , Roda Weston , Smolarchuk Christa , Wilson Kumanan , Crowcroft Natasha S , Schwartz Kevin L , Gubbay Jonathan B , McGeer Allison J , Smieja Marek , Richardson David C , Katz Kevin , Zahariadis George , Campigotto Aaron , Mubareka Samira , McNally J Dayre , Karnauchow Timothy , Zelyas Nathan , Svenson Lawrence W , Kwong Jeffrey C
Published: November 2023

Background

Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited.

Methods

We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010 to 2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders.

Results

Among 23 806 infants tested for influenza, 1783 (7.5%) were positive and 1708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI], 50%–74%). VE was similar by trimester of vaccination (first/second, 66% [95% CI, 40%–80%]; third, 63% [95% CI, 46%–74%]), infant age at testing (0 to <2 months, 63% [95% CI, 46%–75%]; 2 to <6 months, 64% [95% CI, 36%–79%]), and gestational age at birth (≥37 weeks, 64% [95% CI, 50%–75%]; < 37 weeks, 61% [95% CI, 4%–86%]). VE against influenza hospitalization was 67% (95% CI, 50%–78%).

Conclusions

Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available.
Mechanisms of mitochondrial reorganization
Authors: Maruyama Tatsuro , Hama Yutaro , Noda Nobuo N
Published: November 2023

The cytoplasm of eukaryotes is dynamically zoned by membrane-bound and membraneless organelles. Cytoplasmic zoning allows various biochemical reactions to take place at the right time and place. Mitochondrion is a membrane-bound organelle that provides a zone for intracellular energy production and metabolism of lipids and iron. A key feature of mitochondria is their high dynamics: mitochondria constantly undergo fusion and fission, and excess or damaged mitochondria are selectively eliminated by mitophagy. Therefore, mitochondria are appropriate model systems to understand dynamic cytoplasmic zoning by membrane organelles. In this review, we summarize the molecular mechanisms of mitochondrial fusion and fission as well as mitophagy unveiled through studies using yeast and mammalian models.
Hydrogen in Argentina and South America: a national and regional strategy for development
Authors: Romano Francisco J , Giralt Cecilia
Published: November 2023

Strategies and roadmaps are programmatic policy tools where each country establishes a vision, sets objectives, and projects measures to achieve them in different time horizons, based on the analysis of the national context, opportunities, and barriers. The comparative analysis of these strategies offers a perspective of the elements taken into account and the trends in the tools projected for the development of the new hydrogen sector worldwide.
Safety and effectiveness of denosumab in Japanese patients with rheumatoid arthritis: A 2-year post-marketing surveillance study
Authors: Tanaka Yoshiya , Mizutani Hideki , Fujii Kunimitsu , Okubo Naoki
Published: November 2023

Objectives

To investigate the 2 year safety and effectiveness of denosumab 60 mg in patients with rheumatoid arthritis (RA) in clinical practice in Japan.

Methods

This 2 year, prospective, observational cohort study included patients who initiated treatment with denosumab 60 mg for the progression of bone erosion associated with RA. Key endpoints were adverse drug reactions (ADRs), progression of bone erosion, and 28-joint Disease Activity Score based on C-reactive protein or erythrocyte sedimentation rate. Univariate and multivariate analyses were conducted to determine the risk factors for ADRs and the progression of bone erosion.

Results

In the safety analysis set (n = 1239), the incidence of ADRs was 3.0%; the most common ADRs were hypocalcaemia (1.2%) and osteonecrosis of jaw-related events (0.6%). A history of any drug allergy was a statistically significant risk factor associated with the occurrence of ADRs. In the effectiveness analysis set (n = 815), the incidence of progression of bone erosion was 8.7%. Steinbrocker stage and initial steroid dose were statistically significant risk factors associated with the progression of bone erosion.

Conclusion

Denosumab demonstrated safety and effectiveness over a 2 year period in RA patients without any new safety concerns.
Endogenous Uncertainty and Credit Crunches
Authors: Straub Ludwig , Ulbricht Robert
Published: November 2023

We develop a theory of endogenous uncertainty in which the ability of investors to learn about firm-level fundamentals is impaired during financial crises. At the same time, higher uncertainty reinforces financial distress. Through this two-way feedback loop, a temporary financial shock can cause a persistent reduction in risky lending, output, and employment that coincides with increased uncertainty, default rates, credit spreads, and disagreement among forecasters. We embed our mechanism into standard real business cycle and New-Keynesian models and show how it generates endogenous and internally persistent processes for the efficiency and labour wedges.
High hydrostatic pressure participates in atrial fibrosis through the p300/p53/Smad3 pathway
Authors: Yu Shenghuan , Zeng Long , Rao Fang , Deng Chunyu , Zhang Mengzhen , Xiao Haiyin , Xiao Feifei , Xue Yumei , Wu Shulin , Du Zhimin , Wei Wei
Published: November 2023

As an independent risk factor of atrial fibrillation (AF), hypertension (HTN) can induce atrial fibrosis through cyclic stretch and hydrostatic pressure. The mechanism by which high hydrostatic pressure promotes atrial fibrosis is unclear yet. p300 and p53/Smad3 play important roles in the process of atrial fibrosis. This study investigated whether high hydrostatic pressure promotes atrial fibrosis by activating the p300/p53/Smad3 pathway. Biochemical experiments were used to study the expression of p300/p53/Smad3 pathway in left atrial appendage (LAA) tissues of patients with sinus rhythm (SR), AF, AF + HTN, and C57/BL6 mice, hypertensive C57/BL6 mice and atrial fibroblasts of mice. To investigate the roles of p300 and p53 in the process of atrial fibrosis, p300 and p53 in mice atrial fibroblasts were knocked in or knocked down, respectively. The expression of p300/p53/Smad3 and fibrotic factors was higher in patients with AF and AF + HTN than those with SR only. The expressions of p300/p53/Smad3 and fibrotic factors increased in hypertensive mice. Curcumin (Cur) and knocking down of p300 reversed the expressions of these factors. 40 mmHg hydrostatic pressure/overexpression of p300 upregulated the expressions of p300/p53/Smad3 and fibrotic factors in mice LAA fibroblasts. While Cur or knocking down p300 reversed these changes. Knocking down/overexpression of p53, the expressions of p53/Smad3 and fibrotic factors also decreased/increased, correspondingly. High hydrostatic pressure promotes atrial fibrosis by activating the p300/p53/Smad3 pathway, which further increases the susceptibility to AF.
Chronic rhinosinusitis with nasal polyps: eosinophils versus B lymphocytes in disease pathogenesis
Authors: Kariyawasam Harsha H. , James Louisa K.
Published: November 2023

Purpose of review

To highlight the current evidence that supports the view that eosinophils may not drive disease in chronic rhinosinusitis with nasal polyps (CRSwNP) and the emerging evidence for B cells as an important player in this disease.

Recent findings

Eosinophil depletion studies in CRSwNP do not fully support a critical role for eosinophils in CRSwNP. Almost complete eosinophil depletion with dexpramipexole had no impact on polyp size reduction or clinical improvement. Anti-interleukin (IL)-5 and IL-5Rα inhibition were more effective though with less clinical impact when compared to anti-immunoglobulin E (IgE) or IL-4Rα inhibition strategies. As IL-5Rα is also expressed on CRSwNP derived IgE+ and IgG4+ plasma cells to the same extent as eosinophils, improvements in CRSwNP with IL-5 inhibition may suggest a role for B cells over eosinophils in CRSwNP. We review both eosinophils and B cells in the context of CRSwNP and highlight the current evidence that supports an emerging role for B cells.

Despite many aspects of immunopathology in CRSwNP explainable by B cell dysfunction, B cells have so far been ignored in CRSwNP. Further work is needed, as targeting B cells may offer an exciting new therapeutic option in the future.
PCSK9 Inhibitors—A New Hope for Dyslipidemia in HIV
Authors: Datla Sanjana , Kumar Sundeep
Published: November 2023

Cardiovascular disease has become increasingly prevalent in the HIV population. Antiretroviral therapy and HIV itself independently increase the risk of dyslipidemia. While statins are currently the predominant therapy to treat dyslipidemia in HIV patients, drug–drug interactions and adverse drug events can limit their use. Proprotein convertase subtilisin/kexin type 9 inhibitors have shown promising results in preliminary trials by significantly reducing low density lipoprotein and other atherogenic lipid levels. They should be considered as an early intervention alongside statins in HIV patients with dyslipidemia.
Effect of Metformin on Plasma Exposure of Rifampicin, Isoniazid, and Pyrazinamide in Patients on Treatment for Pulmonary Tuberculosis
Authors: Kumar Agibothu Kupparam Hemanth , Kadam Abhijit , Karunaianantham Ramesh , Tamizhselvan Manoharan , Padmapriyadarsini Chandrasekaran , Mohan Anant , Jeyadeepa B. , Radhakrishnan Ammayappan , Singh Urvashi B. , Bapat Shraddha , Mane Aarti , Kumar Pradeep , Mamulwar Megha , Bhavani Perumal Kannabiran , Haribabu Hemalatha , Rath Nibedita , Guleria Randeep , Khan Abdul Mabood , Menon Jaykumar ,   METRIF Team
Published: November 2023

Background:

To evaluate the effect of metformin on the plasma levels of rifampicin, isoniazid, and pyrazinamide in patients with drug-sensitive pulmonary tuberculosis being treated with first-line antituberculosis treatment (ATT) and to assess the influence of gene polymorphisms on the metabolic pathway of metformin and plasma levels of antitubercular drugs.

Methods:

Nondiabetic adults aged 18–60 years with pulmonary tuberculosis were randomized to either the standard ATT (ATT group) or ATT plus metformin (METRIF group) groups in a phase IIB clinical trial. An intensive pharmacokinetic study with blood collection at 0 hour (predosing), followed by 1, 2, 4, 6, 8, and 12 hours after dosing was conducted during the first month of treatment in a subset of 60 study participants after a minimum of 14 doses. Plasma concentrations of rifampicin, isoniazid, pyrazinamide, and metformin were measured by high-performance liquid chromatography using validated methods, and pharmacokinetic parameters and OCT1 and MATE1 gene polymorphisms were compared between the groups.

Results:

Significant increases in the clearance of rifampicin, isoniazid, and pyrazinamide were observed in patients in the METRIF group (n = 29) compared with those in the ATT group (n = 31). The AA genotypes of the single-nucleotide polymorphism of rs2289669 (MATE1) in the METRIF group showed a significantly decreased area under the concentration–time curve to the last observation point and increased clearance of rifampicin.

Conclusions:

Metformin altered rifampicin and isoniazid plasma concentrations in patients receiving antituberculosis treatment for pulmonary tuberculosis with little effect on sputum conversion at the end of treatment. Studies with larger sample sizes are needed to understand host drug–drug interactions.
Efficiency and Safety of Internal Limiting Membrane Peeling with Different Forceps for Macular Disease
Authors: Chang Hsin-Ho , Chen Shih-Jen , Hsu Chia-An , Chou Yu-Bai
Published: November 2023

Purpose

To compare the efficiency and safety of internal limiting membrane (ILM) peeling between the Sharkskin forceps and End-grasping forceps in various macular diseases.

Methods

It is a prospective cohort block-randomized study conducted in a tertiary medical center. Seventy subjects with macular hole, epiretinal membrane, vitreomacular traction syndrome or myopic foveoschisis, receiving pars plana vitrectomy and ILM peeling surgery were equally divided into Sharkskin forceps group and End-grasping forceps group. The duration of ILM peeling, the number of attempts to initiate peeling and peeling-related retinal damage were evaluated by recorded video and optical coherence tomography.

Results

In the Sharkskin group, we demonstrated significantly fewer attempts to initiate ILM peeling compared with End-grasping group, with an average of 1.9 and 3.1 attempts (p=0.0001); and a lower incidence of retinal microstructural damage (20% versus 45%, p<0.0001). Moreover, the mean depth of inner retinal injury at the initiating site exhibited distinct difference post-operatively at 3 months between the Sharkskin group then the End-grasping group (4.3um versus 30.0um, p=0.001).

Conclusions

Sharkskin forceps provide better efficiency and outcome in ILM peeling in patients with various vitreomacular interface diseases, including reduced risk of retinal injury and fewer attempts to initiate ILM flap.
Cataract surgery in setting of ocular surface disease
Authors: Sarnicola Enrica , Sarnicola Caterina , De Bernardo Maddalena , Rosa Nicola , Sarnicola Vincenzo
Published: November 2023

Purpose of review

The purpose of this article is to review the available strategies to successfully identify and manage ocular surface disease (OSD) pre, intra and post-cataract surgery.

Recent findings

Cataract surgery and OSD have an intricate relationship: the surgical procedure can induce or exaggerate OSD symptoms, while OSD can negatively impact surgical refractive outcomes and increase the rate of postoperative complications.

Improving the health and stability ocular surface is the key to enhance post cataract surgery refractive outcomes and avoid complications. This is pivotal for patients affected by severe OSD, but is also important for patients with minimal signs or symptoms. A correct diagnosis and a stepwise approach are the keys to improve the quality of life of such patients.
Noninvasive Computed Tomography–Based Deep Learning Model Predicts In Vitro Chemosensitivity Assay Results in Pancreatic Cancer
Authors: Kanda Taishu , Wakiya Taiichi , Ishido Keinosuke , Kimura Norihisa , Nagase Hayato , Yoshida Eri , Nakagawa Junichi , Matsuzaka Masashi , Niioka Takenori , Sasaki Yoshihiro , Hakamada Kenichi
Published: November 2023

Objectives

We aimed to predict in vitro chemosensitivity assay results from computed tomography (CT) images by applying deep learning (DL) to optimize chemotherapy for pancreatic ductal adenocarcinoma (PDAC).

Materials and Methods

Preoperative enhanced abdominal CT images and the histoculture drug response assay (HDRA) results were collected from 33 PDAC patients undergoing surgery. Deep learning was performed using CT images of both the HDRA-positive and HDRA-negative groups. We trimmed small patches from the entire tumor area. We established various prediction labels for HDRA results with 5-fluorouracil (FU), gemcitabine (GEM), and paclitaxel (PTX). We built a predictive model using a residual convolutional neural network and used 3-fold cross-validation.

Results

Of the 33 patients, effective response to FU, GEM, and PTX by HDRA was observed in 19 (57.6%), 11 (33.3%), and 23 (88.5%) patients, respectively. The average accuracy and the area under the receiver operating characteristic curve (AUC) of the model for predicting the effective response to FU were 93.4% and 0.979, respectively. In the prediction of GEM, the models demonstrated high accuracy (92.8%) and AUC (0.969). Likewise, the model for predicting response to PTX had a high performance (accuracy, 95.9%; AUC, 0.979).

Conclusions

Our CT patch–based DL model exhibited high predictive performance in projecting HDRA results. Our study suggests that the DL approach could possibly provide a noninvasive means for the optimization of chemotherapy.
“Splainin” Health and Nutrition Science to a Doubtful Public
Authors: Rowe Sylvia , Alexander Nick
Published: November 2023

It is hardly a secret that the health, nutrition, and other science communication environment has over the past few years become ever-more problematic. The authors of the present article have repeatedly documented the challenges posed to public understanding of science by the rise of social media and other internet communication “tools” and the diminishing influence of such media as journals, legacy news organizations, and other traditional conduits of scientific information.

Various remedies have been proposed for facilitating greater public appreciation and comprehension of science. In the current article, the authors offer a bold, if not surprising, new proposal: initiate or broaden public exposure to the true nature of the scientific method/process. They suggest that health and science communicators not hold back in extolling the noisy and highly contentious process by which hypotheses are explored and eventually accepted or rejected. If communicators, they argue, convince audiences of the messy, even argumentative, way in which science actually evolves, it may be easier to encourage a greater open-mindedness toward previously unpopular, even uncomprehended, dreaded, or despised, scientific ideas. The issue is of paramount importance, especially now, as keeping the public focus on science, not individual scientists, is critical.
MELD score predicts short-term outcomes after surgical management of proximal humerus fractures: a matched analysis
Authors: Shi Brendan Y. , Upfill-Brown Alexander , Li Alan , Wu Shannon Y. , Ahlquist Seth , Hart Christopher M. , Kremen Thomas J. , Lee Christopher , Stavrakis Alexandra I.
Published: November 2023

Objective:

We aimed to evaluate the difference in 30-day outcomes after surgical management of proximal humerus fractures (PHFs) between patients with and without chronic liver disease as defined by a MELD score greater than 10.

Design:

This was a retrospective database review.

Setting:

All centers participating in the American College of Surgeons National Surgical Quality Improvement Program database were included.

Patients/Participants:

Patients with proximal humerus fractures who (1) underwent ORIF, HA, or SA and (2) had calculable MELD scores were included.

Intervention:

Open reduction and internal fixation, hemiarthroplasty, or shoulder arthroplasty was used for treatment.

Main outcome measurements:

Thirty-day complications, mortality, readmission, and reoperation rates were measured.

Results:

Of the total 1732 PHF patients identified, 300 had a MELD score higher than 10. After propensity matching by significant covariates, MELD score higher than 10 was found to be significantly associated with higher rates of 30-day mortality, 30-day readmission, transfusion within 72 hours, and systemic complications. Among patients with a MELD score higher than 10, treatment with SA or HA instead of ORIF was associated with a higher rate of transfusion and longer operative time. There were no significant differences between treatment cohorts regarding mortality, reoperation, readmission, or complications.

Conclusions:

A MELD score higher than 10 is associated with higher risk of surgical complications, transfusion, and death in patients undergoing surgery for proximal humerus fractures. Among patients with a MELD score higher than 10, ORIF was associated with a lower transfusion rate and shorter operative time than arthroplasty or hemiarthroplasty.

Level of Evidence:

Prognostic Level III.
Management of Children With Uncomplicated Cellulitis in Emergency and Hospital Settings
Authors: St. Cyr Grace , Jaffe Jana , McMahon Maxwell , Florin Todd A. , Verre Michael C. , Chua Wee-Jhong
Published: November 2023

Objective

The aim of the study is to establish consensus recommendations on features used to determine the route of antibiotic administration and disposition for children with uncomplicated cellulitis.

Methods

Modified Delphi methodology was performed with 2 rounds of confidential surveys of Emergency medicine and hospital medicine (HM) providers at Lurie Children's Hospital to assess cellulitis management in children (ages 6 months–18 years) without signs of sepsis or abscess formation. Using a 9-point Likert scale, emergency medicine providers ranked features by perceived level of importance when deciding initial antibiotic route and HM providers ranked features on importance when transitioning to oral antibiotics. Responses were grouped as not important (1–3), neutral (4–6), and important (7–9) and re-evaluated in the second round to reach consensus, defined as ≥70% agreement.

Results

Emergency medicine providers (n = 17) reached consensus on 15 of 16 features (93.8%), 10 deemed important. Participants reached greatest consensus (100%) on fevers/chills, lymphangitis, and functional impairment as considerations for initiating intravenous antibiotics. HM providers (n = 15) reached consensus on 9 of 11 factors (81.8%), with 7 considered important when deciding on readiness for oral antibiotics. Providers indicated that stability, rather than reduction, of erythematous margins is sufficient to consider transition and de-escalation of therapy at less than 24 hours if all other clinical improvement criteria are met.

Conclusions

This study achieved consensus on important features for treatment and disposition of children with uncomplicated cellulitis in both emergency and inpatient contexts. These features have the potential to aid in decision making and improve standardization of clinical practice.
Health Care Provider Bias in Estimating the Health Literacy of Caregivers in a Pediatric Emergency Department
Authors: Dorsey Bridget F. , Cook Lawrence J. , Katz Adam D. , Sapiro Heather K. , Kadish Howard A. , Holsti Maija
Published: November 2023

Background

Health literacy is a growing concern because of its effects on communication and health outcomes. One aspect of this communication is the ability of the health care provider to estimate the health literacy of a patient or their caregiver. The objectives of this study are to quantify misestimation of caregiver health literacy by providers and identify potential descriptive or demographic factors that might be related to those misestimations.

Methods

Providers were asked to perceive descriptive factors and estimate the health literacy of caregivers in a pediatric Emergency Department. Then, the health literacy of the caregiver was tested using the Short Assessment of Health Literacy, and cross-tabulated with provider estimates.

Results

Providers correctly estimated the health literacy of the caregivers 60% of the time, and misestimates were often underestimates (27.7%) rather than overestimates (12.3%). Providers overestimated the health literacy of 24.1% of fathers and only 9.8% of mothers (P= 0.012). They correctly estimated the health literacy of 63.9% of English-speaking caregivers compared with 30.6% of Spanish-speaking caregivers, and underestimated the health literacy of 50% of Spanish-speaking caregivers and 24.8% of English-speaking caregivers (P< 0.001). Providers correctly estimated the health literacy of 34.4% of racially and ethnically diverse caregivers compared with 71.5% of White/non-Hispanic caregivers. They underestimated the health literacy of 52.1% of these racially and ethnically diverse caregivers and 16.8% of White/non-Hispanic caregivers (P< 0.001).

Conclusions

Providers often overestimate and underestimate the health literacy of parents in the pediatric emergency department. Misestimates are related to race, caregiver role, and language spoken by the caregiver. When providers misestimate health literacy, they may use words or phrases that are above or below the health literacy level of the caregiver. These results suggest a need for further health literacy research and interventions in provider education and clinical practice.
Optimizing Outcomes in Lymphedema Reconstruction
Authors: Garza Rebecca M. , Wong Daniel , Chang David W.
Published: November 2023

Learning Objectives:

After studying this article, the participant should be able to: 1. Describe current surgical techniques for treating primary and secondary lymphedema. 2. Optimize the surgical care of patients with lymphedema.

Over the past decade, significant advances have been made in the surgical treatment of lymphedema. The most notable changes have been the reintroduction and evolution of physiologic techniques, including lymphovenous bypass—sometimes referred to as lymphovenous anastomosis in the literature—and vascularized lymph node transplant. These surgical modalities are now often used as first-line surgical options or may be combined with nonphysiologic approaches, including direct excision and suction-assisted lipectomy. Surgeons continue to debate the most appropriate sequence and combination of surgical treatment, particularly for patients at both extremes of the severity spectrum. Furthermore, debate remains around the need to apply different treatment approaches for patients with upper versus lower extremity involvement and primary versus secondary cause. In this article, we provide a summary of the surgical techniques currently used for both primary and secondary lymphedema and provide our recommendations for optimizing the surgical care of patients with lymphedema.