bluuebunny/crossref_metadata_2025 huggingface dataset:
Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings
Authors: Boyett Brent , Nadipelli Vijay R. , Solem Caitlyn T. , Chilcoat Howard , Bickel Warren K. , Ling Walter
Published: September 2022

Background

This analysis describes participants’ opioid use disorder (OUD) outcomes for 18 months after discontinuing extended-release buprenorphine injection (BUP-XR, SUBLOCADE).

Methods

The RECOVER (Remission From Chronic Opioid Use: Studying Environmental and Socioeconomic Factors on Recovery) study recruited participants from BUP-XR clinical trials (NCT02357901, NCT025100142, and NCT02896296) to assess whether there were sustained benefits after leaving the trial. Abstinence from opioids and from all illicit substances (excluding medical cannabis), health-related quality of life, depression, and employment were measured after BUP-XR discontinuation and change in outcomes assessed at 6, 12, and 18 months. Results were analyzed within the full cohort and by duration of BUP-XR treatment (0–2 months, 3–5 months, 6–11 months, 12 months, or 13–18 months) with and without inverse probability weights adjusting for differences in baseline characteristics.

Results

Of 533 participants, 529 were assessed over the 18-month study period. Further posttrial pharmacotherapy was reported by 33% of participants. At RECOVER baseline, longer BUP-XR was associated with higher abstinence (0–2 months BUP-XR [n = 116]: 38.8%; 3–5 months BUP-XR [n = 61]: 41.0%; 6–11 months BUP-XR [n = 86]: 68.6%; 12 months BUP-XR [n = 135]: 71.9%; 18 months BUP-XR [n = 131]: 88.2%) and greater 12-Item Short Form Health Survey mental component scores. Over 60% of participants had stable or improved outcomes at 6, 12, and 18 months assessments. Overall 47% of participants self-reported sustained opioid abstinence for the full 18-month follow-up, with greater sustained abstinence associated with longer BUP-XR treatment duration. A sensitivity analysis, removing patients receiving medications for OUD, yielded similar results.

Conclusions

Participants from BUP-XR clinical trials who continued into RECOVER maintained or improved on numerous outcomes over 18 months, demonstrating the long-term positive impact of OUD pharmacotherapy.
Autonomic Nervous System Function and Central Pain Processing in People With Frozen Shoulder
Authors: Mertens Michel G. , Struyf Filip , Lluch Girbes Enrique , Dueñas Lirios , Verborgt Olivier , Meeus Mira
Published: September 2022

Objectives:

The pathophysiology of a frozen shoulder (FS) is thought to be related to chronic inflammation. Chronic inflammation may disturb the immune system and consequently the nervous system as part of an overarching system. The aim of this study was to determine the presence of disturbed autonomic nervous system function and altered central pain processing (CPP) in patients with FS. Secondarily, the presence of psychological variables (catastrophizing and hypervigilance) and self-reported associated symptoms of altered CPP in patients with FS were investigated.

Methods:

Patients with FS and healthy controls completed the Composite Autonomic Symptom Score (autonomic function) and underwent quantitative sensory testing to assess tactile sensitivity (ie, allodynia), pressure pain thresholds (PPTs, ie, hyperalgesia), temporal summation of pain, and Conditioned Pain Modulation (CPM). Psychological issues were explored with the Pain Catastrophizing Scale and the Pain Vigilance and Awareness Questionnaire, and self-reported symptoms associated with altered CPP were determined with the Central Sensitization Inventory.

Results:

Thirty-two patients with FS and 35 healthy controls were analyzed in the study. Patients with FS showed more self-reported autonomic symptoms and symptoms of altered CPP, higher levels of pain catastrophizing and hypervigilance, and are more sensitive to tactile touches and mechanical pressure compared with controls.

Discussion:

On the basis of the effect sizes, between-group differences in allodynia, hyperalgesia, catastrophizing, and hypervigilance were clinically relevant, but only local allodynia, hyperalgesia, catastrophizing, and hypervigilance were statistically different. Therefore, obvious altered CPP was not present at the group level in patients with FS compared with controls.
A National Survey of Neonatal Nurses' Knowledge, Beliefs, and Practices of Antibiotic Stewardship
Authors: Hamidi Maryam , Blatz Mary Ann
Published: September 2022

Background:

In the neonatal intensive care unit, implementation of antibiotic stewardship programs has been challenging, especially for staff nurses.

Purpose:

To identify neonatal nurses' knowledge and attitudes toward antibiotic stewardship programs in neonatal intensive care units.

Methods:

This was a descriptive survey study to assess knowledge, attitudes, and beliefs of neonatal nurses related to antibiotic stewardship. The survey consisted of 23 questions, 6 of which were open-ended. The questions evaluated perceptions of general understanding of antibiotic stewardship, administration of antibiotics, information and perspective about antibiotic use, antibiotic resistance, and availability and usage of resources and education related to antibiotics. The survey was posted online for about 3 months on the Web site of a professional organization of neonatal nurses.

Results:

Of the 78 neonatal nurses who responded to the survey, 39% were very familiar with the term antibiotic stewardship. The majority of participants did not question the treating provider about the choice, route, or dose of antibiotics. The majority also agreed that more education is needed to achieve the goal of incorporating principles of antibiotic stewardship more fully into practice in the neonatal intensive care unit.

Implications for Practice:

Results suggest that although most nurses are familiar with the term antibiotic stewardship, they would like to have more education on the appropriate use of antibiotics.

Implications for Research:

Further studies are needed to identify nurse involvement in applying the principles of antibiotic stewardship programs while working with the vulnerable population of preterm infants.
Regional Variation in Access to Oncologic Care and Racial Disparities Among Cervical Cancer Patients
Authors: Alimena Stephanie , Davis Michelle , Pelletier Andrea , Terry Kathryn , King Martin , Feldman Sarah
Published: September 2022

Objectives:

The goal of this study was to determine whether access to gynecologic oncologists is correlated with disparate outcomes among cervical cancer patients, especially among Black women.

Materials and Methods:

An ecological study was performed using the National Cancer Database among stage I-IVA cervical cancer patients from 2004 to 2014. Data from the National Cancer Institute, the Society of Gynecologic Oncology, and the United States Census were compiled to describe access to care by region. Factors associated with receipt of optimal treatment (defined as surgery and/or radiation for stage IA-IB1 and IIA1; radiation and chemotherapy for stage IB2, IIA2, IIB-IVA or node positive disease) were identified using multivariate logistic regressions stratified by region, controlling for confounding factors including the number of gynecologic oncologists per states in each subregion. Cox multivariate survival analyses stratified by region were also performed.

Results:

Of 42,213 women, 17.0% were Black. On multivariate analysis controlling for confounders, all Southern women were less likely to receive optimal treatment (adjusted odds ratio [aOR]: 0.80, 95% confidence interval [95% CI]: 0.75–0.85, P<0.001) compared with Northeastern women. Black women in the South (aOR: 0.76, 95% CI: 0.70–0.83, P<0.001) and Midwest (aOR: 0.78, 95% CI: 0.68–0.90, P<0.001) were less likely to receive optimal treatment compared with non-Black women in those regions. Black women in the South (adjusted hazard ratio [aHR]: 1.11, 95% CI: 1.04-1.18, P<0.001) and West (aHR: 1.34, 95% CI: 1.11–1.62, P=0.002) had worse mortality compared with non-Black women in those regions, despite controlling for access to gynecologic oncologists. The South, Midwest, and West had proportionally fewer cancer centers and gynecologic oncologists compared with the Northeast.

Conclusions:

Southern women are at risk of inadequate treatment for cervical cancer, and Black Southern women are at even higher risk of inadequate treatment and worse overall survival despite controlling for access to gynecologic oncologists. Social determinants of health and other barriers besides access to oncologists likely contribute to observed regional and racial disparities among cervical cancer patients.
Percutaneous nephrolithotomy and laparoscopic surgery efficacy and renal function outcomes for large and complex renal calculi
Authors: Pak Yuriy , Kalyagina Nina , Yagudaev Daniel
Published: September 2022

Background

There is limited published evidence regarding the incidence of intraoperative and postoperative events and the effect of percutaneous nephrolithotomy (PCNL) in supine and prone positions and laparoscopic pyelolithotomy on kidney function in patients with large and complex calculi.

Materials and methods

We evaluated the surgical outcomes of 97 patients with large and complex kidney stones. The patients were divided into 3 groups: those who underwent PCNL in the prone position, PCNL in the supine position, and pyelolithotomy by laparoscopy and retroperitoneoscopy. General surgical outcomes, size of residual stones, stone-free rate, glomerular filtration rate (GFR), and split GFR obtained from Tc-99m renal dynamic scintigrams were analyzed.

Results

Percutaneous nephrolithotomy in the prone position was correlated with improved function of the affected kidney. In the supine PCNL group, none of the analyzed indicators demonstrated a significant difference. Dynamic nephroscintigrams revealed negative changes in terms of accumulation and secretion of the affected kidney. A slight decrease in creatinine clearance was noted. However, positive dynamics in split GFR and secretory index were seen in this group. The laparoscopic group showed positive results in all analyzed parameters. However, full assessment of the function of the affected kidney in this group was limited due to restricted use of laparoscopic pyelolithotomy for complex stones.

Conclusions

Percutaneous nephrolithotomy in the prone position resulted in the most favorable renal functional outcomes for patients with high-grade renal calculi, whereas a laparoscopic approach may be preferred for patients with stones of lower grades. The most significant factors that adversely affected renal function were intraoperative bleeding volume, kidney stone size and density, and body mass index.
Cerebral venous thrombosis in a young asymptomatic COVID-19 patient
Authors: Dias Rafael , dos Reis Ricardo Soares , de Sousa Sara Pereira , Rocha Ana Filipa , Ribeiro Ana Margarida , Almeida Jorge
Published: September 2022

We report an unusual case of cerebral venous thrombosis (CVT temporally associated with an otherwise asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While coronavirus disease 2019 (COVID-19) has been associated with thrombotic events at different sites, most published cases report on symptomatic SARS-CoV-2 infection. We are confident this was an otherwise asymptomatic infection as the patient reported no symptoms and molecular and serological testing was consistent with infection more than 3weeks in the past.

We believe this is an important report as it adds to the existing literature on thrombotic events in patients with COVID. It may even inform discussion of COVID vaccines and CVT since our patient, as those reported in association with vaccines, also had thrombocytopenia on admission.
The value of surgeon’s perception during transurethral resection of bladder tumors: can we trust in our eyes and experience to predict grade and staging?
Authors: Vale Luís , Sousa José , Abreu-Mendes Pedro , Vale Pedro , Dias Nuno , Dinis Paulo , Antunes-Lopes Tiago , Silva João
Published: September 2022

Background:

Transurethral resection of newly diagnosed bladder tumors (TURBT) is a hallmark ¡n the treatment of bladder cancer. We evaluated the surgeon capacity to predict bladder tumor stage (T), grade, and presence of muscular layer based upon cystoscopic characteristics during primary TURBT.

Methods:

Prospective study enrolling 100 consecutive patients undergoing primary TURBT for newly diagnosed bladder cancers. Cystoscop¡c tumor characteristics at the time of TURBT was evaluated by an urology senior and a resident regarding histological grade, invasion (T stage), and presence of muscular layer in the specimen. We analyzed the surgeon’s accuracy in predicting these parameters using the final histology as gold standard. In addition, the predictive capacity between seniors and residents was compared.

Results:

The resident’s arm correctly predicted tumor invasiveness in 76% of cases, while seniors correctly predicted 87% of cases. Regarding tumor grade, high grade cancer was reported in 78% of the specimens and 75% and 77% of them were correctly predicted by residents and seniors, respectively. Finally, 80% of the TURBT specimens had muscle representativeness. In nearly 75% of the cases, both resident and senior correctly predicted the TURBT resection depth (presence of detrusor muscle in the specimen). The positive predictive value for this parameter was 79% for the resident, and 81% for the senior, and the negative predictive value was 25% and 40%, respectively.

Conclusion:

The surgeon’s naked eye analysis showed a good, but limited predictive ability to detect non-muscle invasive and high-grade bladder tumors in TURBT specimens. Positive predictive value for muscle representativeness is around 80%, which reinforces the need of carrying out a careful and extensive TURBT, irrespective of the surgeon experience.
Machine Learning for Automated Calculation of Vestibular Schwannoma Volumes
Authors: Cass Nathan D. , Lindquist Nathan R. , Zhu Qibang , Li Hao , Oguz Ipek , Tawfik Kareem O.
Published: September 2022

Hypothesis

Machine learning-derived algorithms are capable of automated calculation of vestibular schwannoma tumor volumes without operator input.

Background

Volumetric measurements are most sensitive for detection of vestibular schwannoma growth and important for patient counseling and management decisions. Yet, manually measuring volume is logistically challenging and time-consuming.

Methods

We developed a deep learning framework fusing transformers and convolutional neural networks to calculate vestibular schwannoma volumes without operator input. The algorithm was trained, validated, and tested on an external, publicly available data set consisting of magnetic resonance imaging images of medium and large tumors (178–9,598 mm3) with uniform acquisition protocols. The algorithm was then trained, validated, and tested on an internal data set of variable size tumors (5–6,126 mm3) with variable acquisition protocols.

Results

The externally trained algorithm yielded 87% voxel overlap (Dice score) with manually segmented tumors on the external data set. The same algorithm failed to translate to accurate tumor detection when tested on the internal data set, with Dice score of 36%. Retraining on the internal data set yielded Dice score of 82% when compared with manually segmented images, and 85% when only considering tumors of similar size as the external data set (>178 mm3). Manual segmentation by two experts demonstrated high intraclass correlation coefficient (0.999).

Conclusion

Sophisticated machine learning algorithms delineate vestibular schwannomas with an accuracy exceeding established norms of up to 20% error for repeated manual volumetric measurements—87% accuracy on a homogeneous data set, and 82% to 85% accuracy on a more varied data set mirroring real world neurotology practice. This technology has promise for clinical applicability and time savings.
A Retrospective Assessment of Midline Catheter Failures Focusing on Catheter Composition
Authors: Bunch Joseph
Published: September 2022

Vascular access specialists are responsible for assessing the patient in their unique situation and determining the correct vascular access device to complete the therapeutic goal without complication or failure. This retrospective cohort study compared the failure rates of a variety of polyurethane (PU) midline catheters and a midline catheter constructed of an emerging hydrophilic biomaterial (HBM). A total of 205 patients received a midline catheter and were situationally randomized by the facility where they received it. Patients who had received a midline catheter between March 2021 and May 2021 were assessed for catheter-related failures leading to increased staff time, delays in treatment, or replacement with a new vascular access device to complete the therapy. There were 101 patients in the PU cohort and 104 patients in the HBM cohort. Comparing overall failure rates between the groups revealed a 23.8% failure rate in the PU control group and only a 3.8% failure rate in the HBM group. This suggests that a midline catheter constructed of HBM biomaterial is associated with significantly lower rates of failure, thereby improving patient experience and health care economics.
Safety Competency
Authors: Dillon-Bleich Kimberly , Dolansky Mary A. , Burant Christopher J. , Madigan Elizabeth A. , Singh Mamta K.
Published: September 2022

Background:

Patient safety is a priority in health care systems. Nurses' safety competence along with environmental and personal factors plays a role in patient safety.

Purpose:

The purpose of this study was to explore the relationships among safety competency, structural empowerment, systems thinking, level of education, and certification.

Methods:

A cross-sectional exploratory design was used to collect data from nurses (n = 163) practicing in a large Midwestern hospital system.

Results:

There were significant positive correlations between safety competency and (a) structural empowerment, (b) systems thinking, and (c) certification. Systems thinking explained 12.9% of the variance in the knowledge component of safety competency and 6.8% of the variance in the skill component of safety competency. Certification explained 2.4% of the variance in the skill component of safety competency.

Conclusions:

Understanding factors that affect safety competency supports the development of effective interventions that may improve safety.
Data for Equity: Creating an Antiracist, Intersectional Approach to Data in a Local Health Department
Authors: Gould L. Hannah , Farquhar Stephanie E. , Greer Sophia , Travers Madeline , Ramadhar Lisa , Tantay L. , Gurr Danielle , Baquero María , Vasquez Ayanna
Published: September 2022

Objective:

To develop recommendations to embed equity into data work at a local health department and a framework for antiracist data praxis.

Design:

A working group comprised staff from across the agency whose positions involved data collection, analysis, interpretation, or communication met during April-July 2018 to identify and discuss successes and challenges experienced by staff and to generate recommendations for achieving equitable data practices.

Setting:

Local health department in New York City.

Results:

The recommendations encompassed 6 themes: strengthening analytic skills, communication and interpretation, data collection and aggregation, community engagement, infrastructure and capacity building, and leadership and innovation. Specific projects are underway or have been completed.

Conclusions:

Improving equity in data requires changes to data processes and commitment to racial and intersectional justice and process change at all levels of the organization and across job functions. We developed a collaborative model for how a local health department can reform data work to embed an equity lens. This framework serves as a model for jurisdictions to build upon in their own efforts to promote equitable health outcomes and become antiracist organizations.
Pausing TPN to Decrease Abnormal Newborn Screens: A NICU Quality Initiative
Authors: Wiggins Jaclyn B. , Khan Marium , Vergales Brooke D.
Published: September 2022

Introduction:

Detection of metabolic and genetic disorders via the newborn screen (NBS) remains a great diagnostic achievement in medicine. Unfortunately, many false positives for neonates due to acute illness lead to repeat testing. For example, the rate of abnormal NBS in very low birth weight (VLBW) neonates at the University of Virginia was 66%, with 23% due to total parenteral nutrition (TPN) on the amino acid profile.

Methods:

This study describes a quality improvement (QI) initiative completed in the NICU at a quaternary care center. The primary and secondary outcomes were the percentage of abnormal NBSs in VLBWs and all admissions. The intervention required a pause in TPN, and a dextrose-containing fluid ran for 4 hours before collecting the NBS. During PDSA cycle 1, the TPN pause occurred at 1400, and the collection of the NBS occurred at 1800. During PDSA cycle 2, we aimed to decrease the number of blood draws per neonate and, thus, paused the TPN at 0000 to enable NBS collection at 0400 with routine morning laboratory work.

Results:

The rate of abnormal screens in VLBWs decreased from 66% to 49%; P < 0.006; 95% CI, 0.04–0.27, and the rate of abnormal screens in all admissions dropped from 45.2% to 28.8%; P < 0.0001; 95% CI, 0.06–0.51. Hospital costs decreased from $244.79 to $170.86 per patient in the cost of the NBS cards alone.

Conclusion:

By pausing TPN for 4 hours before drawing the NBS, we decreased the number of abnormal NBS in all admissions while also decreasing hospital costs.
The Objective Buttocks Assessment Scale (OBAS): a new and complete method to assess the gluteal region.
Authors: Roccaro Giovanni , Hersant Barbara , Pensato Rosita , Pizza Chiara , Rega Umberto , D’Andrea Francesco , Meningaud Jean Paul , La Padula Simone
Published: September 2022

Introduction:

New treatment methods to improve and enhance buttocks appearance require globally accepted scales for aesthetic research and patient evaluation. The purpose of our study was to develop a set of grading scales for objective assessment of the gluteal region and assess their reliability and validity.

Materials and methods:

Twelve photonumeric grading scales were created. Eleven aesthetic experts rated photographs of 650 women in 2 validation sessions. Responses were analyzed to assess inter-rater and intra-rater reliability. The Rasch model was used as part of the validation process.

Results:

All the scales exceeded criteria for acceptability, reliability and validity. Overall inter-rater reliability and intra-rater reliability were both “almost perfect” (p=0.15 and p=0.16 respectively).

Conclusion:

Consistent outcomes between raters and by individual raters at 2 time points confirm the reliability of the Objective Buttocks Assessment Scale in female patients and suggest it will be a valuable tool for use in research and clinical practice.
Short-term Administration of the HIV Protease Inhibitor Saquinavir Improves Skull Bone Healing with Enhanced Osteoclastogenesis
Authors: Liu Haixia , Shen Yun , Zhao Bingkun , Poon Enoch H. , Qi Shengcai , Ker Dai Fei Elmer , Billiar Timothy R. , Cooper Gregory M. , Xu Yuanzhi , Wang Dan
Published: September 2022

Background:

Utilizing immunomodulatory methods to address the challenging issue of craniofacial bone repair may be a potentially effective approach. The protease inhibitor Saquinavir (SQV) has shown to inhibit the inflammatory response by targeting the TLR4/MyD88. Independently, inhibition of TLR4 or MyD88 led to enhanced skull bone repair. Therefore, we aimed to investigate the effects of SQV on skull bone healing.

Methods:

The effects of SQV on skull bone healing was assessed via gene expression, histology, immunohistochemistry and tomography in a mouse calvarial defect model. Subsequently, the role of SQV in cell viability, migration, osteogenic and osteoclastogenic differentiation was also evaluatedin vitro.

Results:

1-week SQV administration improved skull bone healing based on µCT and histomorphometric analyses. Compared to the vehicle control, 1-week SQV treatment (1) enhanced osteoclast infiltration (TRAP staining) at day 7, but not at days 14 and 28; (2) induced more CD206+M2 macrophage infiltration, but not F4/80+M0 macrophages at days 7, 14 and 28; and (3) elevated osteoclastogenic geneRANKL(qPCR) expression and other osteogenic and cytokine expression. Furthermore,in vitrodata showed that SQV administration did not influence MC3T3-E1 cell migration or mineralization, while higher concentrations of SQV inhibited cell viability. SQV treatment also enhanced the osteoclastic differentiation of bone marrow-derived precursors, and partially reversed HMGB1-driven osteoclastogenesis inhibition and elevated pro-inflammatory cytokine expression.

Conclusions:

The improved skull bone repair following short-term SQV treatment may involve enhanced osteoclastogenesis and modulated inflammatory response post-skull injury.
Transtibial prosthetic socket fitting: Australian prosthetist perspectives on primary challenges, management strategies, and opportunities for workflow and technological innovation
Authors: Armitage Lucy , McDonald Kirsty A. , Kark Lauren , Buller Angela , Ford Belinda
Published: September 2022

Background:

Following transtibial amputation, a custom-built socket is the most common interface between the prosthesis and residual limb. Desire from both prosthetists and prosthesis users for improved socket fitting processes have been well documented. However, there is currently limited information available about prosthetists’ experiences of how prosthetic manufacturing workflow can contribute to socket fit problems.

Objectives:

This study aims to determine how socket fit problems are currently detected and managed by prosthetists and to identify challenges, management strategies, and opportunities for workflow and technological innovation during prosthesis manufacture and socket fitting.

Study design:

Mixed-method (quantitative and qualitative) survey.

Methods:

An online survey was developed and piloted in consultation with members of the Australian Orthotic Prosthetic Association. The final 25-question survey was distributed through their membership database. Mixed methods were used to analyze survey items. Qualitative items were grouped and coded under themes relating to challenges, management strategies, and opportunities. Quantitative data were analyzed using nonparametric descriptive methods.

Results:

Twenty-three respondents with a range of experience completed the survey. Seven of eight major Australian states/territories were represented. Primary workflow stages presenting challenges with limited strategies/solutions available to the prosthetists were roll-on liner selection, mold or cast modifications, communication with the client, and check socket fitting. Suggested solutions included improved socket–limb interface monitoring technology.

Conclusions:

This study provides the first insights into prosthetist-identified challenges and limitations at different stages of the socket workflow and presents a starting point for more targeted research into innovation that may assist in these processes.
A mAb for the detection of the antiretroviral drug emtricitabine
Authors: Youngpairoj Ae S. , Vanderford Thomas H. , Reed Matthew S. , Granade Timothy C. , Pau Chou-Pong , Pohl Jan , Switzer William M. , Heneine Walid
Published: September 2022

Antibody-based testing for emtricitabine (FTC), a critical component of pre-exposure prophylaxis and antiretroviral therapy, would provide low-cost detection for clinical monitoring to improve adherence. We developed a mAb (5D2) to FTC and demonstrated its high specificity and physiologically relevant linear range of detection in a competitive enzyme immunoassay. Thus, this mAb is a key reagent that will enable simple and low-cost lateral flow assays and enzyme immunoassays for adherence monitoring.
The association between comorbidities and coronavirus disease 2019 hospitalization among people with HIV differs by age
Authors: Moran Caitlin A. , Oliver Nora T. , Szabo Brittany , Collins Lauren F. , Nguyen Minh Ly T. , Shah N. Sarita , Moanna Abeer , Colasanti Jonathan A. , Cantos Valeria D. , Armstrong Wendy S. , Sheth Anandi N. , Ofotokun Ighovwerha , Kelley Colleen F. , Marconi Vincent C. , Lahiri Cecile D.
Published: September 2022

Objectives:

To determine whether factors associated with coronavirus disease 2019 (COVID-19) hospitalization among people with HIV (PWH) differ by age stratum.

Design:

Retrospective cohort study.

Methods:

All adult PWH with a positive SARS-CoV-2 PCR in a public safety-net health system between 1 March 2020 and 28 February 2021 and a Veterans Affairs Medical Center between 1 1 March 2020 and 15 November 2020 in Atlanta, Georgia were included. We performed multivariable logistic regression to determine demographic and clinical factors associated with COVID-19 hospitalization overall and stratified by age less than 50 and at least 50 years.

Results:

Three hundred and sixty-five PWH (mean age 49 years, 74% cisgender male, 82% black) were included. Ninety-six percent were on antiretroviral therapy (ART), 87% had CD4+ T-cell count at least 200 cells/μl, and 89% had HIV-1 RNA less than 200 copies/ml. Overall, age [adjusted odds ratio (aOR) 95% confidence interval (CI) 1.07 (1.04–1.10)], later date of SARS-CoV-2 infection [aOR 0.997 (0.995–1.00)], heart disease [aOR 2.27 (1.06–4.85)], and history of hepatitis C virus (HCV) [aOR 2.59 (1.13–5.89)] were associated with COVID-19 hospitalization. Age-adjusted comorbidity burden was associated with 30% increased risk of hospitalization [aOR 1.30 (1.11–1.54)]. Among 168 PWH less than 50 years old, older age [aOR 1.09 (1.01–1.18)] and no ART use [aOR 40.26 (4.12–393.62)] were associated with hospitalization; age-adjusted comorbidity burden was not (P = 0.25). Among 197 PWH at least 50, older age [aOR 1.10 (1.04–1.16)], heart disease [aOR 2.45 (1.04–5.77)], history of HCV [aOR 3.52 (1.29–9.60)], and age-adjusted comorbidity burden [aOR 1.36 (1.12–1.66)] were associated with hospitalization.

Conclusion:

Comorbidity burden is more strongly associated with COVID-19 hospitalization among older, rather than younger, PWH. These findings may have important implications for risk-stratifying COVID-19 therapies and booster recommendations in PWH.
Macrophage-mediated PDGF Activation Correlates With Regenerative Outcomes Following Musculoskeletal Trauma
Authors: Chowdary Ashish R. , Maerz Tristan , Henn Dominic , Hankenson Kurt D. , Pagani Chase A. , Marini Simone , Gallagher Katherine , Aguilar Carlos A. , Tower Robert J. , Levi Benjamin
Published: September 2022

Objective:

Our objective was to identify macrophage subpopulations and gene signatures associated with regenerative or fibrotic healing across different musculoskeletal injury types.

Background:

Subpopulations of macrophages are hypothesized to fine tune the immune response after damage, promoting either normal regenerative, or aberrant fibrotic healing.

Methods:

Mouse single-cell RNA sequencing data before and after injury were assembled from models of musculoskeletal injury, including regenerative and fibrotic mouse volumetric muscle loss (VML), regenerative digit tip amputation, and fibrotic heterotopic ossification. R packages Harmony, MacSpectrum, and Seurat were used for data integration, analysis, and visualizations.

Results:

There was a substantial overlap between macrophages from the regenerative VML (2 mm injury) and regenerative bone models, as well as a separate overlap between the fibrotic VML (3 mm injury) and fibrotic bone (heterotopic ossification) models. We identified 2 fibrotic-like (FL 1 and FL 2) along with 3 regenerative-like (RL 1, RL 2, and RL 3) subpopulations of macrophages, each of which was transcriptionally distinct. We found that regenerative and fibrotic conditions had similar compositions of proinflammatory and anti-inflammatory macrophages, suggesting that macrophage polarization state did not correlate with healing outcomes. Receptor/ligand analysis of macrophage-to-mesenchymal progenitor cell crosstalk showed enhanced transforming growth factor β in fibrotic conditions and enhanced platelet-derived growth factor signaling in regenerative conditions.

Conclusion:

Characterization of macrophage subtypes could be used to predict fibrotic responses following injury and provide a therapeutic target to tune the healing microenvironment towards more regenerative conditions.
A Delay in Adjuvant Therapy Is Associated With Worse Prognosis Only in Patients With Transitional Circulating Tumor Cells After Resection of Pancreatic Ductal Adenocarcinoma
Authors: Javed Ammar A. , Floortje van Oosten Anne , Habib Joseph R. , Hasanain Alina , Kinny-Köster Benedict , Gemenetzis Georgios , Groot Vincent P. , Ding Ding , Cameron John L. , Lafaro Kelly J. , Burns William R. , Burkhart Richard A. , Yu Jun , He Jin , Wolfgang Christopher L.
Published: September 2022

Objectives:

The aim of the study was to assess the association of circulating tumor cells (CTCs) with survival as a biomarker in pancreatic ductal adenocarcinoma (PDAC) within the context of a delay in the initiation of adjuvant therapy.

Background:

Outcomes in patients with PDAC remain poor and are driven by aggressive systemic disease. Although systemic therapies improve survival in resected patients, factors such as a delay in the initiation of adjuvant therapy are associated with worse outcomes. CTCs have previously been shown to be predictive of survival.

Methods:

A retrospective study was performed on PDAC patients enrolled in the prospective CircuLating tUmor cellS in pancreaTic cancER trial (NCT02974764) on CTC-dynamics at the Johns Hopkins Hospital. CTCs were isolated based on size (isolation by size of epithelial tumor cells; Rarecells) and counted and characterized by subtype using immunofluorescence. The preoperative and postoperative blood samples were used to identify 2 CTC types: epithelial CTCs (eCTCs), expressing pancytokeratin, and transitional CTCs (trCTCs), expressing both pancytokeratin and vimentin. Patients who received adjuvant therapy were compared with those who did not. A delay in the receipt of adjuvant therapy was defined as the initiation of therapy ≥8 weeks after surgical resection. Clinicopathologic features, CTCs characteristics, and outcomes were analyzed.

Results:

Of 101 patients included in the study, 43 (42.5%) experienced a delay in initiation and 20 (19.8%) did not receive adjuvant therapy. On multivariable analysis, the presence of trCTCs (P=0.002) and the absence of adjuvant therapy (P=0.032) were associated with worse recurrence-free survival (RFS). Postoperative trCTC were associated with poorer RFS, both in patients with a delay in initiation (12.4 vs 17.9 mo, P=0.004) or no administration of adjuvant chemotherapy (3.4 vs NR, P=0.016). However, it was not associated with RFS in patients with timely initiation of adjuvant chemotherapy (P=0.293).

Conclusions:

Postoperative trCTCs positivity is associated with poorer RFS only in patients who either experience a delay in initiation or no receipt of adjuvant therapy. This study suggests that a delay in the initiation of adjuvant therapy could potentially provide residual systemic disease (trCTCs) a window of opportunity to recover from the surgical insult. Future studies are required to validate these findings and explore the underlying mechanisms involved.
Reconstructing electron transfer components from an Fe(II) oxidizing bacterium
Authors: Jain Abhiney , Kalb Madison J. , Gralnick Jeffrey A.
Published: September 2022

Neutrophilic Fe(II) oxidizing bacteria play an important role in biogeochemical processes and have also received attention for multiple technological applications. These micro-organisms are thought to couple their metabolism with extracellular electron transfer (EET) while oxidizing Fe(II) as electron donor outside the cell. Sideroxydans lithotrophicus ES-1 is a freshwater chemolithoautotrophic Fe(II) oxidizing bacterium that is challenging to culture and not yet genetically tractable. Analysis of the S. lithotrophicus ES-1 genome predicts multiple EET pathways, which are proposed to be involved in Fe(II) oxidation, but not yet validated. Here we expressed components of two of the proposed EET pathways, including the Mto and Slit_0867–0870 PCC3 pathways, from S. lithotrophicus ES-1 into

Aeromonas hydrophila

, an established model EET organism. We demonstrate that combinations of putative inner membrane and periplasmic components from the Mto and Slit_0867–0870 PCC3 pathways partially complemented EET activity in

Aeromonas

mutants lacking native components. Our results provide evidence for electron transfer functionality and interactions of inner membrane and periplasmic components from the Mto and Slit_0867–0870 PCC3 pathways. Based on these findings, we suggest that EET in S. lithotrophicus ES-1 could be more complicated than previously considered and raises questions regarding directionality of these electron transfer pathways.
The Role of Titanium Particles and Ions in the Pathogenesis of Peri-Implantitis
Authors: Asa’ad Farah , Thomsen Peter , Kunrath Marcel F.
Published: September 2022

Titanium (Ti) particles and ions have been investigated in recent years as important factors in the pathogenesis of peri-implantitis. However, their role in the pathogenesis is yet to be fully understood. A review of pertinent literature was performed in various databases to determine the current position of Ti particles and ions role in the pathogenesis of peri-implantitis. There are several in vitro, preclinical and clinical published studies that have addressed the role of Ti particles and ions in the pathogenesis of peri-implantitis. These studies explored the effect of Ti particles and ions in the pathogenesis of peri-implantitis with respect to foreign body reaction, cellular response, epigenetic mechanisms, namely DNA methylation, and the oral microbiome. Studies have shown that the release of Ti particles/ions during implant insertion, early healing stages, late healing stages, and treatments during peri-implantitis might contribute to peri-implantitis through different mechanisms, such as foreign body reaction, cellular response, DNA methylation, and shaping the oral microbiome by increasing dysbiosis. However, further studies are needed to elucidate the complex interactions between all these mechanisms and Ti particles/ions in the pathogenesis and progression of peri-implantitis.
Oxidative Stress is Intrinsic to Staphylococcal Adaptation to Fatty Acid Synthesis Antibiotics
Authors: Wongdontree Paprapach , Millan-Oropeza Aaron , Upfold Jennifer , Lavergne Jean-Pierre , Halpern David , Lambert Clara , Page Adeline , Kénanian Gérald , Grangeasse Christophe , Henry Céline , Fouet Agnès , Gloux Karine , Anba-Mondoloni Jamila , Gruss Alexandra
Published: September 2022

Antibiotics inhibiting the fatty acid synthesis (FASII) pathway of the major pathogenStaphylococcus aureusreach their enzyme targets, but bacteria continue growth by using environmental fatty acids (eFAs) to produce phospholipids. We assessed how extreme changes in membrane phospholipids provoked by FASII-antibiotics affect globalS. aureusphysiology. Anti-FASII provoked massive lasting expression changes without genomic rearrangements. Several regulators, rather than one master switch, contributed to the timing of anti-FASII adaptation. Numerous virulence and adhesion factors showed decreased levels and/or activity. Conversely, stress response protein levels increased, and correlated with greater tolerance to peroxides. Notably, peroxide priming stimulated eFA incorporation efficiency and facilitated adaptation to FASII inhibition. These findings establish a link between oxidative stress and FA incorporation. Consistent with major shift in protein expression, anti-FASII-adaptedS. aureuskilled an insect host more slowly but continued multiplying. Thus, while anti-FASII-adapted populations are less equipped to damage the host, they may be better fit for long term survival, and could constitute a reservoir for re-infection.
Design and approval of the nutritional warnings’ policy in Peru: Milestones, key stakeholders, and policy drivers for its approval
Authors: Francisco Diez-Canseco , Cavero Victoria , Álvarez-Cano Juan , Saavedra-Garcia Lorena , Taillie Lindsey Smith , Dillman Carpentier Francesca , Miranda J. Jaime
Published: September 2022

Background

Nutritional warnings are used as a public health strategy to prevent increases in obesity prevalence. Peru approved in 2013 and implemented in 2019 a Law requiring nutritional warnings on the marketing and packaging of processed foods high in sugar, sodium, saturated fat, and containing transfat. The complexity behind the implementation of this set of policies over six years provide unique learnings, essential to inform the obesity prevention context, especially when facing strong opposition from powerful stakeholders such as the food industry.

Aims

Describe milestones and key stakeholders’ roles and stances during the nutritional warnings policy design in Peru; and identify and analyze the main drivers of policy change that explain its approval.

Methodology

In 2021, interviews were conducted with 25 key informants, advocates and opponents of the policy, closely involved in its design. Interviews were analyzed using the Kaleidoscope Model as a theoretical framework. Relevant policy documents and news were also analyzed.

Results

Milestones for this policy were the approval of the Law, Regulation, and Manual. Policy supporters were mainly from the Congress, civil society organizations, and Health Ministers; whereas opponents came from other parties in the Congress, ministries linked to the economic sector, the food industry, and media. Across the years, warning’s evolved from a single text, to traffic lights, to the approved black octagons. Main challenges included the strong opposition of powerful stakeholders; the lack of agreement for defining the appropriate evidence for nutritional warning parameters and design; and the political instability of the country. Based on the Kaleidoscope Model, the policy successfully targeted a relevant problem (unhealthy eating decisions) and had powerful advocates who effectively used focusing events to reposition the warnings in the policy agenda across the years. Negotiations weakened the policy but led to its approval. Importantly, government veto players were mostly in favor of the policy, which enabled its final approval despite the strong opposition.

Conclusions

Despite the strong opposition faced and technical and political difficulties to define the best parameters and warnings’ design, Peru’s nutritional warnings policy was approved. Lessons learned are essential to inform similar and related prevention policies in Peru and elsewhere.
Heparin Does Not Regulate Circulating Human PCSK9
Authors: Xia Vivian Q. , Ong Chui Mei , Zier Lucas S. , MacGregor John S. , Wu Alan H. B. , Chorba John S.
Published: September 2022

Background

PCSK9 chaperones the hepatic low-density lipoprotein receptor (LDLR) for lysosomal degradation, elevating serum LDL cholesterol and increasing the risk of atherosclerotic heart disease. Though the major effect on the hepatic LDLR comes from secreted PCSK9, the details of PCSK9 reuptake into the hepatocyte remain unclear. In both tissue culture and animal models, heparan sulfate proteoglycans (HSPGs) on hepatocytes act as co-receptors to promote PCSK9 reuptake. We hypothesized that if this PCSK9:HSPG interaction is important in humans, disrupting the interaction with unfractionated heparin (UFH) would acutely displace PCSK9 from the liver and increase plasma PCSK9.

Methods

We obtained remnant plasma samples from 160 subjects undergoing cardiac catheterization before and after administration of intravenous UFH. PCSK9 levels were determined using a commercial ELISA.

Results

Median plasma PCSK9 concentrations were 113 ng/ml prior to UFH and 119 ng/ml afterwards. This difference was not significantly different (p = 0.83, 95% CI of difference: −6.23 to 6.31 ng/ml). Tests for equivalence provided 95% confidence that UFH administration would not raise PCSK9 levels by more than 4.7% of the baseline value. No predefined subgroups exhibited an effect of UFH on circulating PCSK9.

Conclusion

Administration of UFH does not result in a clinically meaningful effect on circulating PCSK9 in humans. These results suggest that disruption of the PCSK9:HSPG interaction does not affect PCSK9 reuptake into the liver. Further, they cast doubt on the clinical utility of disrupting the PCSK9:HSPG interaction as a therapeutic strategy for PCSK9 inhibition.

Graphical Abstract

Clinical Perspective

What is new?

Prior tissue culture and animal data suggest that PCSK9 interacts with hepatic heparan sulfate proteoglycans to enter the liver and raise cholesterol levels

We found no evidence that heparin, a competitive inhibitor of heparan sulfate proteoglycans, acutely affects PCSK9 in humans

What are the clinical implications?

Heparin is unlikely to be successfully repurposed as a PCSK9 inhibitor
Appetitive mapping of the human nucleus accumbens
Authors: Parker Jonathon J. , Rolle Cammie E. , Shivacharan Rajat S. , Barbosa Daniel A. N. , Feng Austin , Huang Yuhao , Kakusa Bina W. , Prieto Tom , Jaffe Richard A. , Williams Nolan R. , Halpern Casey H.
Published: September 2022

There is strong evidence for the putative role of the nucleus accumbens (NAc) in appetitive motivation. A first-in-human feasibility trial of responsive deep brain stimulation (rDBS) for loss of control eating provided a rare opportunity to examine the physiologic and structural underpinnings of NAc function in a human participant with dysregulated appetition. Patient-specific probabilistic tractography was supplemented by intraoperative microelectrode recordings and stimulation testing to confirm appetitive circuit engagement. Personalized visual stimuli we used to provoke and map appetitive units within the NAc, prior to the surgical implantation of a rDBS system, which was safe, feasible, and well-tolerated. Ambulatory patient-triggered recordings provide ongoing electrophysiologic surveillance of NAc activity time-locked to eating behavior in the real-world. This technique described provides a proof-of-concept for utilizing simultaneous intracranial activity and real-time appetitive responses to guide implantation of a rDBS system to treat loss of control eating.
The impact of access to financial services on mitigating COVID-19 mortality globally
Authors: Watkins Todd A. , Nguyen Khue , Ali Hamza , Gummakonda Rishikesh , Pelman Jacques , Taracena Brianna
Published: September 2022

The COVID-19 pandemic has disproportionately affected different social and demographic groups, deepening the negative health implications of social and economic inequalities and highlighting the importance of social determinants of health. Despite a deep literature on pandemic-related disparities, specifically regarding social determinants and health outcomes, the influence of the accessibility of financial services on health outcomes during COVID-19 remains largely unexplored. Modeling (pre-omicron) COVID-19 mortality across 142 nations, we assess the impact of national-level usage and access to formal financial services. Two financial access indexes constructed through principal component analysis capture (1) usage of and access to formal financial tools and (2) reliance on alternative and informal financial tools. On average, nations with higher pre-pandemic use of and access to formal financial services had substantially lower population mortality risk from COVID-19, controlling for key population health, demographic, and socioeconomic covariates. The scale of effect is similar in magnitude—but opposite in direction—to major risk factors identified in previous literature, such as lung cancer, hypertension, and income inequality. Findings suggest that financial services deserve greater attention both in the public health literature related to COVID-19 and more broadly in policy discussions about fostering better public health overall.