bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-Reported Outcomes on Subjective Nipple Sensation After Double-Incision and Periareolar Mastectomy for Chest Masculinization
Authors: Chen Amy , Garvey Shannon R. , Nanda Asha D. , Friedman Rosie , Jia Emmeline , Morgenstern Monica , Barron Sivana , Tobias Adam , Cauley Ryan P.
Published: March 2024

We evaluated patient-reported outcomes to assess for patient and procedural factors associated with postchest masculinization subjective nipple sensation. Patients who underwent double-incision or periareolar mastectomies for chest masculinization by a single senior surgeon (2015–2019) were surveyed at 2 time points regarding postoperative nipple sensation and satisfaction, including patient-reported outcomes using BODY-Q modules (Q-Portfolio.org). Demographic, operative, and postoperative variables were obtained from medical records. Patients were stratified according to survey responses. Univariate and multivariate analyses were performed.

Response rate was 42% for survey 1 and 22% for survey 2. Of the 151 survey 1 responders, 138 (91.4%) received double-incision mastectomies and 13 (8.6%) received periareolar mastectomies. Among Survey 1 responders, 84.6% periareolar patients and 69.6% double-incision patients reported “completely” or “a little” nipple sensation preservation, and the difference trended toward significance (P = 0.0719). There was a stepwise increase in proportion of patients reporting sensation with greater recovery time until response to survey 1. Obesity (P = 0.0080) and greater tissue removed (P = 0.0247) were significantly associated with decreased nipple sensation. Nipple satisfaction scores were significantly higher for patients reporting improved nipple sensation (P = 0.0235). Responders to survey 2 who reported greater satisfaction with nipple sensation were significantly more likely to report preserved sensitivity to light touch (P = 0.0277), pressure (P = 0.0046), and temperature (P = 0.0031). Preserved erogenous sensation was also significantly associated with greater satisfaction (P = 0.0018).

In conclusion, we found that nipple sensation may be associated with postoperative nipple satisfaction. Operative techniques to optimize nipple sensation preservation may improve this population's postoperative satisfaction.
Reversal in Centers for Medicare & Medicaid Services Reimbursement for Deep Inferior Epigastric Perforator Flap Reconstruction—Empowering Plastic Surgeons in Sustaining Microsurgical Accessibility
Authors: Das Rishub K. , Villanueva Karie G. , Slack Ginger C. , Festekjian Jaco H.
Published: March 2024

This Editorial discusses the recent overturning of a proposed Centers for Medicare & Medicaid Services policy that reduced reimbursement for deep inferior epigastric perforator flap breast reconstruction. The authors highlight the importance of advocacy efforts in sustaining access to complex microsurgical procedures, even those under investigation such as breast reinnervation and lymphatic reconstruction.
Analysis of Operation Duration in Thoracodorsal Artery Perforator Free-Flap Surgery of the Lower Extremities
Authors: Ha Yooseok , Park Seong Oh , Park Ji Ah , Kim Si Yeon , Shim Hyung-Sup , Kim Youn Hwan
Published: March 2024

Purpose

This retrospective study aimed to identify the factors that affect the duration of thoracodorsal artery perforator (TDAP) free-flap surgery and to offer strategies for optimizing the surgical procedure.

Methods

We analyzed 80 TDAP flap surgeries performed by a single surgeon between January 2020 and December 2022, specifically focusing on free flaps used for lower-extremity defects with single-artery and single-vein anastomosis. The operation duration was defined as the time between the surgeon's initial incision and completion of reconstruction. Linear regression analyses were conducted to identify the factors affecting operation duration.

Results

The average operative duration was 149 minutes (range, 80–245 minutes). All flaps survived, although 8 patients experienced partial flap loss. The operative duration decreased with increasing patient age and when end-to-end arterial anastomosis was performed. However, the risk increased with larger flap sizes and in patients with end-stage renal disease.

Conclusions

Our study identified several factors and methods that could accelerate TDAP free-flap procedures. These findings offer valuable insights for optimizing surgical processes and improving overall surgical outcomes. Although further research is needed to confirm and expand upon these findings, our study provides important guidance for surgeons in developing effective strategies for TDAP flap surgery.
Diversity, Equity, and Inclusion in Plastic Surgery
Authors: Swanson Eric
Published: March 2024

Background

The number of publications on the subject of diversity, equity, and inclusion has surged in the last 5 years. However, a systematic review of this topic has not been published.

Method

Six top plastic surgery journals were queried from 2018 to 2023 using the search term “diversity.” Methods, conclusions, and recommendations were tabulated.

Results

A total of 138 publications were identified; 68 studies presented data suitable for analysis. All studies were retrospective. Currently, over 40% of plastic surgery residency applicants are women. The proportion of women in integrated plastic surgery residents is now 43%. In 2021 and 2022, the percentage of female first-year residents exceeded men. The percentage of female presenters at meetings (34%) is double the number in the workforce (17%). Twenty-five percent of academic faculty positions and 22% of program director positions are now held by women. Underrepresented minorities account for fewer than 10% of applicants to integrated plastic surgery residencies.

Discussion

The proportion of Black and Hispanic applicants to integrated plastic surgery residencies (6% and 8%, respectively) mirrors the proportion of Black and Hispanic medical students (7% and 6%, respectively). Numerous recommendations have been made to increase the proportion of underrepresented minorities in plastic surgery programs.

Conclusions

The representation of women in plastic surgery has increased dramatically. A lack of Hispanics and Blacks reflects a small pool of applicants, as opposed to a “leaky pipeline.”
Thoracic cavity irrigation prevents retained hemothorax and decreases surgical intervention in trauma patients
Authors: Al Tannir Abdul Hafiz , Biesboer Elise A. , Golestani Simin , Tentis Morgan , Maring Morgan , Gellings Jaclyn , Peschman Jacob R. , Murphy Patrick B. , Morris Rachel S. , Elegbede Anuoluwapo , de Moya Marc A. , Carver Thomas W.
Published: March 2024

INTRODUCTION

Retained hemothorax (HTX) is a common complication following thoracic trauma. Small studies demonstrate the benefit of thoracic cavity irrigation at the time of tube thoracostomy (TT) for the prevention of retained HTX. We sought to assess the effectiveness of chest irrigation in preventing retained HTX leading to a secondary surgical intervention.

METHODS

We performed a single-center retrospective study from 2017 to 2021 at a Level I trauma center, comparing bedside thoracic cavity irrigation via TT versus no irrigation. Using the trauma registry, patients with traumatic HTX were identified. Exclusion criteria were TT placement at an outside hospital, no TT within 24 hours of admission, thoracotomy or video-assisted thoracoscopic surgery (VATS) prior to or within 6 hours after TT placement, VATS as part of rib fixation or diaphragmatic repair, and death within 96 hours of admission. Bivariate and multivariable analyses were conducted.

RESULTS

A total of 370 patients met the inclusion criteria, of whom 225 (61%) were irrigated. Patients who were irrigated were more likely to suffer a penetrating injury (41% vs. 30%, p = 0.03) and less likely to have a flail chest (10% vs. 21%, p = 0.01). On bivariate analysis, irrigation was associated with lower rates of VATS (6% vs. 19%, p < 0.001) and retained HTX (10% vs. 21%, p < 0.001). The irrigated cohort had a shorter TT duration (4 vs. 6 days, p < 0.001) and hospital length of stay (7 vs. 9 days, p = 0.04). On multivariable analysis, thoracic cavity irrigation had lower odds of VATS (adjusted odds ratio, 0.37; 95% confidence interval [CI], 0.30–0.54), retained HTX (adjusted odds ratio, 0.42; 95% CI, 0.25–0.74), and a shorter TT duration (β = −1.58; 95% CI, −2.52 to −0.75).

CONCLUSION

Our 5-year experience with thoracic irrigation confirms findings from smaller studies that irrigation prevents retained HTX and decreases the need for surgical intervention.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Assessment of Wound-Related Pain Experiences of Patients With Chronic Wounds
Authors: Wei Min , Zheng Huiling , Xu Xinyue , Ji Yihong , Yu Xiujuan , Lu Lin , Sun Ying , Zhao Zhiying , Liu Xiaojun , Jiang Wei , Zhang Xiya , Qiu Yansen , Weng Yajuan
Published: March 2024

PURPOSE:

The primary aims of this study were to evaluate the prevalence of wound-related pain (WRP) in patients with chronic wounds and assess the use of pain relief measures.

DESIGN:

A cross-sectional study.

SUBJECTS AND SETTING:

A convenience sample of patients with chronic wounds was recruited from outpatient clinics of 12 hospitals covering 7 of 13 cities in the Jiangsu province located in eastern China from July 10 to August 25, 2020. The sample comprised 451 respondents, and their mean age was 54.85 (SD 19.16) years; 56.1% (253/451) patients were male.

METHODS:

An investigator-designed questionnaire was used to collect pain-related information from patients. The questionnaire consisted of 4 parts: (1) basic demographic and clinical information (patient and wound characteristics); (2) wound baseline pain; (3) wound-related procedural pain and pain relief method; and (4) the effect of WRP on the patient. Pain was assessed using the Numerical Rating Scale (NRS) scored from 0 (no pain) to 10 (worst pain). Severity of pain was based on NRS scores' classification as mild (1-3), moderate (4-6), and severe (7-10). The survey was conducted from July 10 to August 25, 2020. Participants were instructed on use of the NRS and then completed the questionnaire following dressing change independently.

RESULTS:

The 3 most common types of chronic wounds were traumatic ulcers, surgical wounds, and venous leg ulcers. The 3 most prevalent locations were lower limbs, feet, and thorax/abdomen. Of all patients, 62.5% (282/451) and 93.8% (423/451) patients experienced wound baseline pain and wound-related procedural pain, respectively. The mean score of wound baseline pain was 3.76 (SD 1.60) indicating moderate pain. During wound management, the highest pain score was 6.45 (SD 2.75) indicating severe pain; the most severe pain scores were associated with debridement. The use of drugs to relieve wound pain was low, while the use of nondrug-based analgesia was relatively high. Because of WRP, patients with chronic wounds feared dressing changes, hesitated to move, and showed a decline in sleep quality.

CONCLUSIONS:

Wound baseline pain and wound-related procedural pain were very common in patients with chronic wounds. In the future, targeted intervention plans should be developed by combining drug-based and nondrug-based analgesia according to pain severity.
Unveiling the Hidden Consequences: Initial Impact of COVID-19 on Colorectal Cancer Operation
Authors: Ferrari Davide , Violante Tommaso , Day Courtney N , McKenna Nicholas P , Mathis Kellie L , Dozois Eric J , Larson David W
Published: March 2024

BACKGROUND:

The COVID-19 pandemic has severely affected healthcare systems globally, resulting in significant delays and challenges in various medical treatments, particularly in cancer care. This study aims to investigate the repercussions of the pandemic on surgical interventions for colorectal cancer (CRC) in the US, using data from the National Cancer Database.

STUDY DESIGN:

We conducted a retrospective analysis of the National Cancer Database, encompassing adult patients who underwent surgical procedures for colon and rectal cancer in 2019 (pre-COVID) and 2020 (COVID). We examined various demographic and clinical variables, including patient characteristics, tumor staging, surgical approaches, and socioeconomic factors.

RESULTS:

The analysis included 105,517 patients, revealing a 17.3% reduction in surgical cases during the initial year of the pandemic. Patients who underwent surgery in 2020 displayed more advanced clinical and pathological tumor stages compared to those treated in 2019. After diagnosis, no delay was reported in the treatment. Patients operated during the pandemic, Black patients, uninsured, and Medicaid beneficiaries had worse stage colon and rectal cancer, and individuals with lower incomes bore the burden of advanced colon cancer.

CONCLUSIONS:

The impact of the COVID-19 pandemic on CRC surgery transcends a mere decline in case numbers, resulting in a higher prevalence of patients with advanced disease. This study underscores the exacerbated disparities in cancer care, particularly affecting vulnerable populations. The COVID-19 pandemic has left a significant and enduring imprint on CRC surgery, intensifying the challenges faced by patients and healthcare systems. Comprehensive studies are imperative to comprehend the long-term consequences of delayed screenings, diagnoses, and treatments as healthcare planning for the future must consider the unintended repercussions of pandemic-related disruptions.
Hybrid Illumina-Nanopore assembly improves identification of multilocus sequence types and antimicrobial resistance genes of Staphylococcus aureus isolated from Vermont dairy farms: comparison to Illumina-only and R9.4.1 nanopore-only assemblies
Authors: Chakrawarti Ashma , Eckstrom Korin , Laaguiby Pheobe , Barlow John W.
Published: March 2024

Antimicrobial resistance (AMR) in Staphylococcus aureus is a pressing public health challenge with significant implications for the dairy industry, encompassing bovine mastitis concerns and potential zoonotic threats. To delve deeper into the resistance mechanisms of S. aureus, this study employed a hybrid whole genome assembly approach that synergized the precision of Illumina with the continuity of Oxford Nanopore. A total of 62 isolates, collected from multiple sources from Vermont dairy farms, were sequenced using the GridION Oxford Nanopore R9.4.1 platform and the Illumina platform, and subsequently processed through our long-read first bioinformatics pipeline.

Our analyses showcased the hybrid-assembled genome’s superior completeness compared to Oxford Nanopore (R9.4.1)-only or Illumina-only assembled genomes. Furthermore, the hybrid assembly accurately determined multilocus sequence typing (MLST) strain types across all isolates. The comprehensive probe for antibiotic resistance genes (ARGs) using databases like CARD, Resfinder, and MEGARES 2.0 characterized AMR in S. aureus isolates from Vermont dairy farms, and revealed the presence of notable resistance genes, including beta-lactam genes blaZ, blaI, and blaR. In conclusion, the hybrid assembly approach emerged as a tool for uncovering the genomic nuances of S. aureus isolates collected from multiple sources on dairy farms. Our findings offer a pathway for detecting AMR gene prevalence and shaping AMR management strategies crucial for safeguarding human and animal health.
Clostridioides difficile detection and infection in children: are they just small adults?
Authors: Watkin Sam , Yongblah Francis , Burton James , Hartley John C. , Cloutman-Green Elaine
Published: March 2024

Clostridioides difficile is a well-recognized healthcare-associated pathogen, with its significance widely recognized in adult populations. Despite this, there is limited data on the significance of detection within paediatric populations, both for individual patient management and wider transmission risk-based considerations. High rates of colonization are understood to occur in infants, with increasing levels up to 11 months, and colonization rates similar to adults by 8 years old. Sources of C. difficile are ubiquitous, with detection in companion animals and food sources, as well as within the clinical and wider environment. Due to the close interactions that occur between children and the environment, it is understandable that increasing recognition is afforded to the community acquisition of C. difficile in children. Other risk factors for the detection of C. difficile in children are similar to those observed in adults, including prior hospitalization and underlying conditions affecting gut health and motility. Recent studies have shown rising awareness of the role of asymptomatic carriage of C. difficile in healthcare transmission. Prior to this, paediatric patient populations were less likely to be screened due to uncertainty regarding the significance of detection; however, this increased awareness has led to a review of possible carriage testing pathways. Despite this increased attention, C. difficile infection remains poorly defined in paediatric populations, with limited dedicated paediatric data sets making comparison challenging. This is further complicated by the fact that infection in children frequently self resolves without additional therapies. Due to this, C. difficile remains a management challenge in paediatric settings.
COMPARING EFFICACY AND SAFETY OF LEFT ATRIAL APPENDAGE CLOSURE DEVICES: A NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Davis John W , Mai Steven L , Harmouch Wissam , Reisler Jenna , MacKay Micaela , Davis Elizabeth , Rich Mike
Published: March 2024

Introduction

Atrial fibrillation-related stroke is a leading cause of morbidity and mortality. Options for prevention include left atrial appendage closure devices or oral anticoagulation. However, it remains unclear which option may be superior overall.

Methods

We conducted a systematic review and network meta-analysis of all clinical trials comparing the WATCHMAN, Amplatzer Amulet (Amulet), and/or OACs. The primary outcomes of interest were any stroke and all-cause death. Safety outcomes included any thromboembolism, device embolization, and pericardial effusion. We calculated risk ratios and heterogeneity statistics for each comparison, and calculated the probability of intervention superiority where at least one comparison was significant.

Results

There were 441 articles identified from the search, from which 5 eligible RCTs were identified (n=1,811). Compared to OACs (all warfarin), risk of stroke was non-significantly decreased with WATCHMAN (RR=0.90, 95% CI: 0.48, 1.72, I2=13.4%), but risk with Amulet was non-significantly lower than WATCHMAN (RR=0.95, 95% CI: 0.50, 1.81). However, observed risk of all-cause death was significantly lower with Amulet than OAC (RR=0.53, 95% CI: 0.33, 0.85, I2=0%) and trended towards significance versus WATCHMAN (RR=0.74, 95% CI: 0.55, 1.02, p=0.06). The P-score was 0.982, signifying a >98% probability Amulet was superior to all alternatives. Risk of thromboembolism was non-significantly increased with WATCHMAN (RR=2.04, 95% CI: 0.23, 18.4) and Amulet (RR=1.54, 95% CI: 0.11, 22.1), with head-to-head comparison favoring Amulet (RR=0.76, 95% CI: 0.17, 3.38, I2=0%). Versus WATCHMAN, device embolization risk was non-significantly elevated with Amulet (RR= 2.38, 95% CI: 0.67, 8.43, I2=0%). Finally, risk of pericardial effusion was significantly elevated with Amulet versus OACs (RR=27.0, 95% CI: 3.48, 210) and versus WATCHMAN (RR=2.11, 95% CI: 1.41, 3.17, I2=0%). The inverse P-score for Amulet (0.9995) indicated a very high probability Amulet was inferior to alternatives.

Conclusion

While risk of some adverse events was greater with Amulet, we estimated >98% probability Amulet is superior to alternatives in risk of death. Pooled patient-level analyses are warranted.
A genetic and clinical risk factor algorithm to aid in identifying new cases of chronic kidney disease from the general population
Authors: Rodwell Graham , Ioannidis John P. A. , Kim Stuart K.
Published: March 2024

One of the biggest challenges in treating chronic kidney disease (CKD) is that 80 – 90% of people with this disease are undiagnosed, and thus do not access healthcare promptly. The problem arises because early stage CKD has no overt symptoms and the current policy is to perform diagnostic tests (e.g. glomerular filtration rate and urinary albumin to creatinine ratio) only when accompanied by risk factors such as old age, hypertension and diabetes. Genetic testing may be useful to identify those most likely to have CKD and who therefore may benefit from screening. This work describes the development of an algorithm termed RICK (for RIsk for Chronic Kidney disease) that employs a polygenic risk score for CKD plus clinical risk factors to identify people at risk. In data from the UK biobank, those in the top decile of RICK have a 4.4-fold increased risk of CKD, and about 34% of all those with CKD are included in this decile. Using RICK to selectively test those in the general population with highest risk may help in early identification of CKD and thereby facilitate early access to renal healthcare.

Lay Summary

One of the biggest challenges in renal health is that 80 – 90% of people with Chronic Kidney Disease (CKD) are undiagnosed, and thus do not access healthcare promptly. The problem arises because early stage CKD has no overt symptoms and the current policy is to perform diagnostic tests (e.g. glomerular filtration rate and urinary albumin to creatinine ratio) only when accompanied by risk factors such as old age, hypertension and diabetes.

This work describes the development of an algorithm termed RICK (for RIsk for Chronic Kidney disease) that employs a genetic test for CKD plus clinical risk factors to identify people at risk and who therefore may benefit from screening. Those in the top ten percentile of RICK have a 15-fold increased risk of stage 3 CKD. Diagnostic testing of the top decile would capture about 43% of the undiagnosed stage 3 CKD cases. Thus, using RICK to selectively test those with highest risk could have an immense impact on renal health by facilitating early identification of CKD and thereby enabling access to healthcare.
A Novel Coach-Approach to Clinical Faculty Mentoring and the UW Department of Medicine Clinical Faculty Development Program
Authors: Alstott James D , Gent Chariti , Bell Christine Fabian , Marlin Daniel R , Hernandez Anthony , Schulman Esther , Gehl Sharon , Schnapp Lynn M , Stein James H
Published: March 2024

Background

Clinical faculty at academic health centers may benefit from specific mentorship and proficiencies that are distinct from those on research tracks. We describe the creation, activities, and one-year impact of a faculty development program that included novel professional coaching training (the Clinical Faculty Mentoring Program, CFMP) which was supplemented by skills- and knowledge-building activities (the Clinical Faculty Development Series, CFDS).

Methods

The goals and components of the CFMP and CFDS are described in detail. A mixed methods evaluation plan guided collection of confidential survey and interview data before and after the first year of these activities. We used paired t-tests to identify statistically significant changes.

Results

The 43 clinical mentors reported significant gains in job satisfaction, teaching attitudes, knowledge of mentorship competencies, and confidence with coaching skills for mentorship (all p<0.05). Of mentor respondents, 88% found the coach approach to mentoring program to be “very” or “somewhat” helpful. Coaching behavioral domains with the greatest evidence of improvement were supporting the mentee to integrate new awareness, insight, learning into their worldview and behaviors (p=0.0503) and managing time and focus of mentoring sessions (p=0.022). All 37 mentees had at least one meeting with a mentor (100%). Over 9 months, 39 virtual CFDS sessions had an average participation of 38 participants (range 22-59). A majority of surveyed faculty (>55%) agreed or strongly agreed the CFDS sessions provided valuable opportunities for skills development with teaching, leadership, wellness, diversity, equity, inclusion, and promotion.

Conclusions

Among clinical mentors, our novel coach approach to clinical faculty mentoring and skill-building had favorable effects on job satisfaction, knowledge of mentorship competencies, and confidence in coaching skills. Outcomes from the clinical faculty development series supported the mentoring program outcomes. Longitudinal follow-up is needed to determine how this program will impact mentees.
Cortical Visual Processing Differences in Myopia and Blur
Authors: Steinfeld Katia , Murray Micah M.
Published: March 2024

Myopia is projected to impact over 50% of the global population by 2050. Despite links to long-lasting anatomical changes in visual cortices, little is known of potential consequences of myopia on visual brain functions, such as visual completion. We hypothesized that adults suffering from moderate myopia process attentionally demanding visual stimuli under optical blur differently than emmetropic adults. Non myopes (N=12) and low-to-mild myopes(N=13) were tested under −3 diopters of lens-induced blur. Participants performed an illusory contour discrimination task while 128-channel EEG was recorded. Each trial also included an intervening, task-irrelevant dartboard stimulus. Visual evoked potentials (VEPs) to the illusory contour (IC), no contour (NC), and dartboard stimuli were analyzed using an electrical neuroimaging framework. We provide evidence for cortical processing differences between non myopes and mild myopes at 218-2800ms post-stimulus during visual completion, but not during viewing of dartboards. These differences stemmed from topographic modulations, indicative of the engagement of distinct networks of brain regions that were localized to medial portions of the occipital pole. Moreover, the predominant VEP topography during this time period both correlated with extent of refractive error and also was an excellent classifier of myopia vs. emmetropia. By contrast, our analyses provided no evidence for differences in visual completion processes between groups. To our knowledge, this is the first study of myopia pairing high-density EEG and a behavioral task. Collectively, this pattern of findings supports a model of myopia wherein low-level visual cortices are impacted at relatively late post-stimulus processing stages.
Illicit Fentanyl Use Independently Predicts HCV Seroconversion Among a Cohort of People Who Inject Drugs in Tijuana and San Diego
Authors: Friedman Joseph R , Abramovitz Daniela , Skaathun Britt , Rangel Gudelia , Harvey-Vera Alicia , Vera Carlos F , Artamonova Irina , Muñoz Sheryl , Martin Natasha K , Eger William H , Bailey Katie , Go Bo-Shan , Bourgois Philippe , Strathdee Steffanie A
Published: March 2024

Background

Illicitly manufactured fentanyl (IMF) increases overdose mortality, but its role in infectious disease transmission is unknown. We examined whether IMF use predicts HCV and HIV incidence among a cohort of people who inject drugs (PWID) in San Diego, CA and Tijuana, Mexico.

Methods

PWID were recruited into a prospective cohort in two waves during 2020-2022, undergoing semi-annual interviewer-administered surveys, HIV and HCV serology through February 2024. Cox regression was conducted to examine predictors of seroconversion considering self-reported IMF use as a fixed or lagged, time-dependent covariate.

Results

Of 398 PWID at baseline, 67% resided in San Diego, 70% were male, median age was 43, 42% reported receptive needle sharing and 25% reported using IMF. Participants contributed a median of 6 semi-annual study visits (IQR:4-6). HCV incidence was 14.26 per 100 person-years (95% CI: 11.49-17.02), and HIV incidence was 1.29 (1.00-2.28). IMF was associated with HCV seroconversion, with a univariable hazard ratio (HR) of 1.68 (95%CI: 1.12-2.53) which remained significant in multivariable models (adjHR1.54; 95%CI:1.01-2.34). The direction of the relationship with HIV was similar, albeit not significant, with an HR of 2.53 (0.7-9.15).

Conclusion

We document a novel association between IMF and HCV seroconversion among PWID in Tijuana-San Diego. There was insufficient power to detect if a similar relationship held for HIV. IMF’s short half-life may destabilize PWID— increasing the need for repeat dosing and sharing smoking materials and syringes. Tailoring medication dosing for opioid use disorder and new preventative care approaches may reduce HCV transmission in the fentanyl era.

In this cohort study of people who inject drugs in Tijuana, Mexico, and San Diego, California, fentanyl use was independently associated with HCV seroconversion. Tailored treatment and prevention efforts are needed for patients using fentanyl to minimize blood-borne infections.
A Wearable In-pad Diagnostic for the Detection of Disease Biomarkers in Menstruation Blood
Authors: Dosnon Lucas , Rduch Thomas , Meyer Charlotte , Herrmann Inge K.
Published: March 2024

The pain-free regular monitoring of blood-based biomarkers is a highly appealing yet difficult-to-realize approach for the early detection of pathological changes, including cancers, infections, or metabolic diseases, such as diabetes. While a major focus of the research community lies on the investigation of pain-free blood sampling and devices for venous blood analysis, menstruation blood remains a largely ignored sampling source. Growing evidence shows excellent correlation between biomarker levels in menstruation blood and venous blood for an entire clinical panel of analytes. Here, we introduce a wearable, microfluidic diagnostic platform integrated into standard hygiene pads for the electronic-free naked eye-readable direct detection of disease biomarkers in menstruation blood (MenstruAI). We demonstrate semi-quantitative biomarker detection from menstruation using infection and inflammation biomarker C-reactive protein (CRP), gynecological cancer biomarkers (CEA and CA-125), and endometriosis biomarker CA-125 as representative examples of relevant proteinaceous biomarkers. The color-changes induced by the presence of these biomarkers can be read-out by the naked eye as well as by a machine-learning algorithm implemented into a smartphone-app, enabling semi-quantitative analysis. The presented MenstruAI platform has the potential to revolutionize women’s health by providing a non-invasive, affordable, and accessible approach to health monitoring, potentially democratizing healthcare by making health services more available and equitable.
The iCARE feasibility non-experimental design study: An integrated collection of education modules for fall and fracture prevention for healthcare providers in long term care
Authors: Rodrigues Isabel B. , Ioannidis George , Kane Lauren , Hillier Loretta M. , McArthur Caitlin , Adachi Jonathan , Thabane Lehana , Heckman George , Holroyd-Leduc Jayna , Jaglal Susan , Kaasalainen Sharon , Straus Sharon , Abbas Momina , Tarride Jean-Eric , Marr Sharon , Hirdes John , Lau Arthur N. , Costa Andrew , Papaioannou Alexandra
Published: March 2024

Falls and hip fractures are a major health concern among older adults in long term care (LTC) with almost 50% of residents experiencing a fall annually. Hip fractures are one of the most important and frequent fall-related injuries in LTC. The purpose of this study was to determine the feasibility (recruitment rate and adaptations) of implementing the PREVENT (Person-centred Routine Fracture PreEVENTion) model in practice, with a subobjective to understand facilitators and barriers. The model includes a multifactorial intervention on diet, exercise, environmental adaptations, hip protectors, medications (including calcium and vitamin D), and medication reviews to treat residents at high risk of fracture. Our secondary outcomes aimed to assess change in knowledge uptake of the guidelines among healthcare providers and in the proportion of fracture prevention prescriptions post-intervention. We conducted a mixed-methods non-experimental design study in three LTC homes across southern Ontario. A local champion was selected to guide the implementation. We reported recruitment rates using descriptive statistics and adaptations using content analysis. We reported changes in knowledge uptake using the paired sample t-test and the percentage of osteoporosis medications prescriptions using absolute change. Within five months, we recruited three LTC homes. We required two months to identify and train the local champion over three 1.5-hour train-the-trainer sessions, and the champion required three months to deliver the intervention to the healthcare team. We identified several facilitators, barriers, and adaptations. Benefits of the model include easy access to the Fracture Risk Scale, clear and succinct educational material catered to each healthcare professional, and an accredited educational module for physicians and nurses. Challenges included misperceptions between the differences in fall and fracture prevention strategies, fear of perceived side effects associated with fracture prevention medications, and time barriers with completing the audit report. Our study did not increase knowledge uptake of the guidelines, but there was an increase in the proportion of osteoporosis medication post-intervention.
Detection of early-onset severe preeclampsia by cell-free DNA fragmentome
Authors: Zhang Haiqiang , Qiao Longwei , Hu Xintao , Zhang Chunhua , Lin Yu , Zhao Jingyu , Wu Xiaojuan , Song Xiaoyan , Tang Hui , Xue Ying , Sun Yang , Ou Rijing , Wang Xinxin , Zhang Yan , Jin Xin , Wang Ting
Published: March 2024

Early-onset severe preeclampsia (EO-PE) is a distinct and highly consequential form of preeclampsia (PE), presenting significant challenges for early detection. Here, we investigated the fragmentation pattern of plasma cell-free DNA (cfDNA) in EO-PE patients. We uncovered that the nucleotide composition at the 5’ end (i.e. ends motif) of plasma cfDNA showed a unique pathological preference in EO-PE pregnancies and gestational-psychology preference in healthy pregnancies. By integrating 91 EO-PE specific motifs into a machine-learning model, we achieved accurate prediction of EO-PE development in early pregnancies. Remarkably, our model demonstrated robust performance in an independent cohort of 74 early pregnancies and 1,241 non-invasive prenatal testing (NIPT) samples with ultra-low sequencing depth. Additionally, we revealed that these PE-specific motif signatures lacked tissue specificity, originating extracellularly, and were associated with the abnormal concentration of DNA fragmentation factor subunit beta (DFFB) in EO-PE patients’ plasma. These findings establish the plasma DNA fragmentome as a non-invasive and cost-effective biomarker that can be simultaneously captured during NIPT for early EO-PE detection and provide valuable insights into cfDNA production mechanisms in preeclampsia patients.
Zero-Shot Prompting is the Most Accurate and Scalable Strategy for Abstracting the Mayo Endoscopic Subscore from Colonoscopy Reports Using GPT-4
Authors: Yim Richard P. , Rudrapatna Vivek A.
Published: March 2024

Structured Abstract

Introduction

Large-language models can help extract information from clinical notes, making them potentially useful for research in ulcerative colitis. However, it remains unclear if these models will scale well in practice.

Methods

We analyzed the performance and cost of programmatically using GPT-4 to abstract Mayo endoscopic subscores (MES) from 499 colonoscopy reports using different prompting strategies.

Results

Zero-shot prompting, where GPT-4 is instructed without examples, was most accurate (83.55%)andcost-effective ($0.097/note).

Discussion

Using GPT-4 to automatically curate the MES and other variables is a practical strategy for quantifying UC activity and measuring improvements to clinical care.
Primary progressive aphasia in Italian and English: a cross-linguistic cohort study
Authors: Mazzeo Salvatore , Hardy Chris JD , Jiang Jessica , Morinelli Carmen , Moschini Valentina , Brooks Ella , Johnson Jeremy CS , Chokesuwattanaskul Anthipa , Volkmer Anna , Rohrer Jonathan D , Ingannato Assunta , Bagnoli Silvia , Padiglioni Sonia , Nacmias Benedetta , Sorbi Sandro , Bessi Valentina , Warren Jason D
Published: March 2024

Background and objectives

Primary progressive aphasia (PPA) signifies a diverse group of neurodegenerative disorders principally affecting language functions. The major syndromic variants of PPA present with distinct profiles of linguistic deficits. However, current concepts and diagnosis of PPA are largely based on English-speaking patients, while few studies have explored how PPA syndromes might vary between languages. Here we undertook a comprehensive neuropsychological comparison of all major PPA syndromes in two languages with contrasting characteristics: Italian and English.

Methods

We retrospectively compared the PPA cohorts attending our specialist referral centres on neuropsychological tests sampling a range of linguistic and general cognitive domains. The cohorts comprised 106 native Italian-speakers with PPA (14 nonfluent/agrammatic variant [nfvPPA], 20 semantic variant [svPPA], 41 logopenic variant [lvPPA], 31 mixed PPA [mPPA]) and 166 native English-speakers with PPA (70 nfvPPA, 45 svPPA, 42 lvPPA, 9 mPPA). Neuropsychological scores were normalised to healthy older native speakers (adjusted for age and years of education) and dichotomised (impaired/unimpaired) to identify the proportion of each cohort showing impairment on each test. Cohorts were compared in logistic regression models, covarying for symptom duration and overall cognitive severity.

Results

The English PPA cohort was significantly younger (mean 62.7 years) than the Italian cohort (mean 65.9 years; p=0.003), with longer symptom duration (mean 4.6 vs 3.1 years; p=0.048), a higher proportion of nfvPPA cases (42% vs. 13%, p<0.001) and lower proportions of lvPPA (25% vs. 38%, p=0.019) and mPPA (5% vs. 29%, p<0.001). Compared with Italian-speaking patients, English-speaking nfvPPA patients had less frequent expressive agrammatism (p=0.015) and more frequently impaired single-word comprehension (p=0.013) and nonverbal working memory (p=0.041). English svPPA patients had more frequent surface dyslexia (p=0.046) and dysgraphia (p=0.021), while English lvPPA patients had more frequently impaired single-word comprehension (p<0.001), word repetition (p=0.02), nonverbal working memory (p=0.005) and visuospatial perception (p<0.001).

Discussion

Language-specific characteristics importantly influence PPA phenotypes: degeneration of language networks may predispose to expressive agrammatism in Italian (reflecting its morphological complexity) and to impaired spoken word processing and regularisation errors in English (reflecting its articulatory, acoustic and orthographic complexity). These findings have implications for diagnosis, management and cross-linguistic collaborative initiatives in PPA.
Circulating Levels of Angiotensinogen, Sex, and Hormone Therapy - The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Lidani Karita C. F. , Trainor Patrick J. , Buscaglia Robert , Foster Kristoff , Jaramillo Sophia , Michael Kirolos , Landry Alexander Pete , Michos Erin D. , Ouyang Pamela , Morgan Erin S. , Tsimikas Sotirios , DeFilippis Andrew P.
Published: March 2024

Background

Angiotensinogen, the unique precursor of all angiotensin hormones of the Renin-Angiotensin-Aldosterone System (RAAS), is now a potential target in a novel pharmacological approach to hypertension. Investigating the factors that influence angiotensinogen levels, including sex hormones, may have important therapeutic implications.

Methods

Plasma angiotensinogen and sex hormones levels were measured in 5,171 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Linear models were employed to determine the associations of angiotensinogen with sex hormones, and mediation analysis was performed to evaluate the effect of HT on blood pressure (BP) and hypertension through angiotensinogen.

Results

Angiotensinogen levels were significantly higher in postmenopausal women receiving HT (n=760) compared to women not receiving HRT (n=1,675) and in men (n=2,736). A positive association was present between angiotensinogen and estrogen levels that differed in magnitude between sexes and by HT status among postmenopausal women (women on HT: r=0.44, p< 0.0001; women not on HT: r=0.09, p=0.0002; and men: r= 0.07, p=0.0003). The type of HT formulation (estrogen or estrogen/progesterone) and its duration of use did not significantly affect angiotensinogen levels. HT indirectly increased systolic BP (β=1.24) and the odds of hypertension (OR=1.065) through its effect of increasing angiotensinogen.

Conclusions

A positive association was present between angiotensinogen and estrogen levels that differed by HT status. HT impacts systolic BP and hypertension indirectly by increasing angiotensinogen. This study underscores the role of angiotensinogen in hypertension, and the complex relationship between HT and hypertension.
Cardiac Stasis Imaging, Stroke and Silent Brain Infarcts in Patients with Non-Ischemic Dilated Cardiomyopathy
Authors: Rodríguez-González Elena , Martínez-Legazpi Pablo , González-Mansilla Ana , Espinosa M. Ángeles , Mombiela Teresa , Guzmán-De-Villoria Juan A. , Borja Maria Guadalupe , Díaz-Otero Fernando , Gómez de Antonio Rubén , Fernández-García Pilar , Fernández-Ávila Ana I , Pascual-Izquierdo Cristina , del Álamo Juan C , Bermejo Javier
Published: March 2024

Background

Cardioembolic stroke is one of the most devastating complications of non-ischemic dilated cardiomyopathy (NIDCM). However, in clinical trials of primary prevention, the benefits of anticoagulation were hampered by the risk of bleeding. If indices of cardiac blood stasis account for the risk of stroke, they may be useful to individualize primary prevention treatments.

Methods

We performed a cross-sectional study in patients with NIDCM and no history of atrial fibrillation (AF) from two sources: 1) a prospective enrollment of unselected patients with left ventricular (LV) ejection fraction <45% and 2) a retrospective identification of patients with a history of previous cardioembolic neurological event. The primary endpoint integrated a history of ischemic stroke, transient ischemic attack (TIA), or the presence intraventricular thrombus, or a silent brain infarction (SBI) by imaging. From echocardiography, we calculated blood flow inside the LV and its residence time (RT). The study was registered inClinicalTrials.gov(NCT03415789).

Results

Of the 89 recruited patients, 18 showed a positive primary endpoint: 9 patients had a history stroke or TIA and another 9 were diagnosed with SBIs in the brain imaging.RTperformed good to identify the primary endpoint (AUC (95% CI)= 0.75 (0.61-0.89), p= 0.001). ART> 2.21 cycles showed a sensitivity of 0.88 (0.77-1.00) and specificity of 0.70 (0.10-0.81). When accounting only for identifying a history of stroke or TIA, AUC forRTwas 0.92 (0.85-1.00) with and odds ratio= 7.2 (2.3 – 22.3) per cycle, p< 0.001.

Conclusions

In patients with NIDCM in sinus rhythm, stasis imaging derived from echocardiographyis is closely related to the burden of stroke. Stasis imaging may be useful to address stroke risk in patients with systolic dysfunction.
A human commons cell atlas reveals cell type specificity for OAS1 isoforms
Authors: Galvez-Merchán Ángel , Booeshaghi A. Sina , Pachter Lior
Published: March 2024

We describe an open source Human Commons Cell Atlas comprising 2.9 million cells across 27 tissues that can be easily updated and that is structured to facilitate custom analyses. To showcase the flexibility of the atlas, we demonstrate that it can be used to study isoforms of genes at cell resolution. In particular, we study cell type specificity of isoforms of OAS1, which has been shown to offer SARS-CoV-2 protection in certain individuals that display higher expression of the p46 isoform. Using our commons cell atlas we localize the OAS1 p44b isoform to the testis, and find that it is specific to round and elongating spermatids. By virtue of enabling customized analyses via a modular and dynamic atlas structure, the commons cell atlas should be useful for exploratory analyses that are intractable within the rigid framework of current gene-centric cell atlases.
Translocation of YopJ family effector proteins through the VirB/VirD4 T4SS ofBartonella
Authors: Fromm Katja , Ortelli Monica , Boegli Alexandra , Dehio Christoph
Published: March 2024

The evolutionary conserved YopJ family comprises numerous type-III-secretion system (T3SS) effectors of diverse mammalian and plant pathogens that acetylate host proteins to dampen immune responses. Acetylation is mediated by a central acetyltransferase domain that is flanked by conserved regulatory sequences, while a non-conserved N-terminal extension encodes the T3SS-specific translocation signal.Bartonellaspp. are facultative-intracellular pathogens causing intra-erythrocytic bacteremia in their mammalian reservoirs and diverse disease manifestations in incidentally infected humans. Bartonellae do not encode a T3SS, but most species possess a type-IV-secretion system (T4SS) to translocateBartonellaeffector proteins (Beps) into host cells. Here we report that the YopJ homologs present in Bartonellae species represent genuine T4SS effectors. Like YopJ family T3SS effectors of mammalian pathogens, the ‘BartonellaYopJ-like effector A’ (ByeA) ofBartonella tayloriialso targets MAP kinase signaling to dampen pro-inflammatory responses, however, translocation depends on a functional T4SS. A split-NanoLuc luciferase-based translocation assay identified sequences required for T4SS-dependent translocation in conserved regulatory regions at the C-terminus and proximal to the N-terminus of ByeA. The T3SS effectors YopP fromYersinia enterocoliticaand AvrA fromSalmonellaTyphimurium were also translocated via theBartonellaT4SS, while ByeA was not translocated via theYersiniaT3SS. Our data suggest that YopJ family T3SS effectors may have evolved from an ancestral T4SS effector, such as ByeA ofBartonella. In this evolutionary scenario, the signal for T4SS-dependent translocation encoded by N- and C-terminal sequences remained functional in the derived T3SS effectors due to the essential role these sequences coincidentally play in regulating acetyltransferase activity.

Significance Statement

Bacterial pathogens use diverse secretion systems to translocate effector proteins into eukaryotic host cells. Evolutionary successful translocation systems and effector proteins have been acquired by many plant and animal pathogens via horizontal gene transfer. The YopJ family comprises numerous T3SS effectors that share a unique acetyltransferase activity that interferes with various host cell functions. Our study revealed that YopJ homologs in the pathogenBartonellaare genuine T4SS effectors and implies an evolutionary scenario in which T3SS-dependent YopJ family effectors may have evolved from such an ancestral T4SS effector by fusion of an N-terminal type-III-secretion signal. Such switches in secretion system specificity of host-targeted effectors may represent an underappreciated phenomenon in effector evolution.