bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Treatment Intensity at the End of Life in Patients With Cancer: A Systematic Review
Authors: Lawday Samuel , Zucker Benjamin E. , Gardner Shona , Robb James , Leandro Lorna , Hollingworth William , Blazeby Jane , McNair Angus G.K. , Chamberlain Charlotte
Published: November 2024

Objective:

To synthesize evidence of surgical treatment intensity, defined as a measure of the quantity of invasive procedures, received by patients in patients with cancer within a defined time period around the ‘end of life’ (EoL).

Background:

Concern regarding overly ‘aggressive’ care or high health care utilization at the EoL, particularly in cancer, is growing. The contribution surgery makes to the quality and cost of EoL care in cancer has not yet been quantified.

Methods:

This PROSPERO registered systematic review used PRIMSA guidelines to search electronic databases for observational studies detailing surgical intensity at the EoL in adult cancer patients. Intensity was compared by disease, individual characteristics, geographical region, and palliative care involvement. A risk of bias tool assessed quality and a narrative synthesis of findings was completed.

Results:

In total, 39 papers were identified in this search. Up to 79% of patients underwent invasive procedures in the last month of life. Heterogeneity in patient groups, inclusion criteria, and EoL time periods lead to huge variation in results, with treatment intention often not identified. Patient, geographical, and pathological factors, alongside involvement of palliative/hospice care, were all identified as contributors to treatment intensity variation.

Conclusions:

A significant proportion of patients with cancer undergo invasive and costly invasive procedures at the EoL. There is significant reporting heterogeneity, with variation in patient inclusion criteria and EoL timeframes, demonstrating uncertainty within the literature. Identification of the context where surgical treatment intensity at the EoL is potentially inappropriate is not currently possible.
The Effects of a Stepped-Care Mental Health Program on Trauma Recidivism at a Level 1 Trauma Center
Authors: Rivas Gabriella A. , Gammel Juliette , George Kola , Ruggiero Kenneth J. , Davidson Tatiana , Espeleta Hannah C. , Hartsock Langdon , Reid Kristoff
Published: November 2024

OBJECTIVES:

This study aimed to analyze the effects of a stepped-care mental health program (TRRP) on trauma recidivism at a single institution.

METHODS:

Designs:

Retrospective review.

Setting:

Single level 1 trauma center.

Patient Selection Criteria:

Trauma activation patients presenting at a single level 1 trauma center between 2017 and 2021 were selected. Data on demographics, mechanism of injury, readmissions, and TRRP participation were recorded.

Outcome Measures and Comparisons:

Main outcomes included recidivism rates, risk factors for representation, and determining whether a change in readmission risk existed after participation in TRRP.

RESULTS:

Intotal, 4484 patients were included, with a mean age of 44.8 years. 65.9% were men and 34.1% were women. Overall, 14.2% (637/4484) patients presenting to the same institution have experienced an unrelated traumatic incident after their index injury. Overall, 75.6% patients identified by TRRP participated in at least 1 TRRP service. Patients who did not participate in TRRP were statistically significantly more likely to be recidivists (15.6%) than those who did (10.9%, P < 0.001). Multivariable binary logistic regression analysis demonstrated statistically significant associations between increased trauma recidivism and being unmarried, Black/African American race, no use of seatbelts, alcohol intoxication at index injury, history of depression, alcohol use disorder, smoking, and government insurance (P ≤ 0.024). The multivariable regression model predicted a decrease in trauma recidivism by 33% in privately insured patients (P = 0.002), by 33% after participation in TRRP (P < 0.001), and by 18% after participation in each additional step of the TRRP program (P < 0.001).

CONCLUSIONS:

Results demonstrate reduced rates of trauma recidivism with involvement of the Trauma Resilience and Recovery Program. Although programs focused solely on psychosocial interventions may be sufficient to reduce the risk of subsequent traumatic events, further development of trauma rehabilitation programs should address both the psychosocial consequences of traumatic injuries and reinjury and readmission prevention.

LEVEL OF EVIDENCE:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Efferocytosis: A new therapeutic target for stroke
Authors: Gao Li , Manaenko Anatol , Zeng Feng , Li Jingchen , Liu Lele , Xie Ruichuan , Zhang Xiaohua , Zhang John H. , Mei Qiyong , Tang Jiping , Hu Qin
Published: November 2024

Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.
Outcomes of Concomitant Mitral Intervention in Hypertrophic Obstructive Cardiomyopathy Surgery?: A Systematic Review and Meta-Analysis of Contemporary Evidence
Authors: Domondon Ileana Anika A. , de Guzman Ronacyn M. , Bruno Clint Jomar P. , Jaffar-Karballai Mona , Alroobi Ahmad , Siddique Mushfiqur , Bitar Mohannad , Enaya Halah H. , Al-Tawil Mohammed , Haneya Assad
Published: November 2024

The 2020 American Heart Association Guidelines advise not to perform mitral valve replacement (MVR) during septal myectomy (SM) to alleviate outflow obstruction. This study aims to review outcomes after concomitant mitral valve (MV) intervention versus SM alone. We conducted a comprehensive literature search across Embase, PubMed, and Scopus. Studies published up to June 15, 2024 were considered. We included studies that compared SM alone to concomitant MV repair or replacement. Subgroup analyses based on MV intervention were performed. Seven studies met our criteria, including 1 randomized and 6 observational studies. The total sample size was 17,565 patients with hypertrophic cardiomyopathy (11,849 SM, 2303 SM + MVR, and 3390 SM + MV repair). Patients who underwent SM + MV intervention had more pronounced preoperative MV regurgitation. SM + MVR was associated with significantly higher early mortality [risk ratio (RR): 2.85, 95% confidence interval (CI): 2.37–3.43, P < 0.00001, I² = 0%]. However, there was no difference in early mortality in patients who underwent SM + MV repair compared with SM alone (RR: 1.14, 95% CI: 0.88–1.49, P = 0.33, I² = 0%). Thirty days systolic anterior motion was significantly lower in patients who underwent SM + MV repair compared with SM alone (RR: 0.15, 95%CI: 0.05–0.45, P = 0.0007). Peak pressure left ventricular outflow tract gradient was significantly lower in the SM + MV repair group compared with SM alone (mean difference: −3.47, 95% CI: −5.55 to −1.39, P = 0.001). Current observational evidence suggests an increased risk of in-patient mortality in patients who underwent SM + MVR. SM + MV repair did not affect early mortality but was linked to improved outcomes. Future comprehensive and matched studies are warranted.
Snapping of the Thumb Caused by Supernumerary Extensor Pollicis Longus Tendon
Authors: Oh Sangho , Son Daegu
Published: November 2024

Supernumerary extensor tendons of the hand are relatively common, whereas supernumerary extensor pollicis longus (EPL) tendons are rarely reported. Herein, we present the case of a 17-year-old boy with painful snapping at the anatomical snuffbox after repetitive pushups. Preoperative dynamic ultrasonography and magnetic resonance imaging revealed the bifurcation of EPL tendons. Through explorative surgery under wide-awake anesthesia, we found 2 EPL tendons with a single EPL muscle, which pass through the single extensor compartment and EPL canal distally. Intraoperatively, after releasing the extensor compartment and EPL canal, each EPL tendon was rerouted to a separate gliding plane to resolve the snapping symptom and recurrence. Six months postoperatively, the snapping symptom was resolved, and the patient resumed activities of daily living without any complications. This clinical case may be useful for examining anatomical variations of the thumb extensor tendon and detecting extraordinary pathological symptoms.
Reprogramming macrophages to treat liver diseases
Authors: Simón-Codina Blanca , Cacho-Pujol Júlia , Moles Anna , Melgar-Lesmes Pedro
Published: November 2024

Cutting-edge research has expanded our understanding of the macrophage activation programs in liver diseases making this immune cell type a therapeutic target. Clinical data on macrophage infiltration and polarization states have been used to help predict mortality or poor prognosis in patients with liver cirrhosis and/or HCC. The latest single-cell and spatial transcriptomics studies have dissected unforeseen aspects depicting the immense heterogeneity of macrophages and their multifaceted role in both promoting and resolving hepatic inflammation, injury, and fibrosis. Hepatic macrophages (resident tissue KCs and monocyte-derived macrophages) display such plasticity and phenotypic diversity that macrophages with antagonistic functions may coexist in adjacent regions of the liver. In this scenario, the analysis of macrophage-derived inflammatory and anti-inflammatory circulating soluble markers in patients with liver disease only offers a partial picture of the full complexity of the hepatic macrophage subsets. The reprogramming of macrophages involves understanding the multiple regulatory mechanisms and diverse populations of hepatic macrophages and the design of macrophage-targeted therapeutic interventions to restore hepatic homeostasis. Here we review the potential targets to modulate macrophage behavior in liver diseases and nanoscale therapeutics that aim to target and treat macrophages. We will summarize current knowledge on the diverse macrophage programs activated in chronic liver inflammation, cirrhosis, and HCC that may be of therapeutic interest for precision medicine.
Bilateral Macular Dysplasia in Coffin-Siris Syndrome
Authors: Schumaier Nahrain Putris , Dodaballapur Sneha , Liu Tianyu , Drenser Kimberly , Capone Antonio
Published: November 2024

Purpose:

To report a case of bilateral macular dysplasia without pigmentary retinopathy in a patient with genetically confirmed Coffin-Siris syndrome (CSS) and a co-existing, heterozygous CNGB1 variant.

Methods:

Case report.

Results:

A 7-year-old boy who failed his vision screening was referred for retinal consultation after his eye care provider identified bilateral macular deposits. Past medical history included developmental delay, atypical facial features, uteropelvic junction obstruction, koilonychia, and corpus callosum dysgenesis. The patient underwent whole exome sequencing, which revealed a pathogenic variant in the ARID1A gene consistent with a diagnosis of Coffin-Siris syndrome. Genetic testing also revealed a heterozygous, missense variant in the CNGB1 gene of unknown significance. Fundus examination revealed fine hypopigmented lesions in the macula with surrounding retinal pigment epithelial changes in both eyes. Spectral-domain ocular coherence tomography revealed abnormalities of the ellipsoid and interdigitation zones. The patient’s best-corrected visual acuity and clinical examination remained stable for a decade since his initial examination, with persistent macular dysplasia and no pigmentary retinopathy.

Conclusions:

It is possible that the ocular findings in this case may expand the phenotypes associated with CSS.
Postoperative rhinosinusitis and microbiological outcomes following endoscopic endonasal approaches: A retrospective analysis of 300 patients
Authors: Huang Yu-Wen , Wang Wei-Hsin , Lan Ming-Ying
Published: November 2024

Background:

Endoscopic endonasal approaches (EEAs) are an efficient way to manage skull base lesions; however, studies regarding postoperative rhinosinusitis are limited. This study analyzed the incidence of postoperative rhinosinusitis, the associated risk factors, microbial species, and antibiotic usage in patients who underwent EEA.

Methods:

Patients who underwent EEAs at a tertiary referral hospital between July 2015 and May 2019 were retrospectively evaluated. Postoperative rhinosinusitis was defined as the presence of a purulent nasal discharge on postoperative endoscopic examination. The mucopus was aspirated and subjected to bacterial culture analysis. The culture results of various groups were analyzed.

Results:

This study included 300 patients, and the incidence of post-EEA rhinosinusitis was 59.7%. History of endonasal surgery was an independent predictive factor for post-EEA rhinosinusitis (odds ratio [OR]: 2.54 [1.28-5.05], p = 0.007). Lesions in the anterior skull base were associated with prolonged use of antibiotics for rhinosinusitis during postoperative care (OR: 3.91 [1.32-11.52], p = 0.013). Staphylococcus aureus was the most common causative pathogen (52.3%), followed by methicillin-resistant S. aureus (MRSA) (20.7%), Pantoea dispersa (14.4%), and Pseudomonas aeruginosa (52.3%). P. aeruginosa was more significant in the complex reconstruction group than in the control group. While most patients with post-EEA rhinosinusitis experienced a transient clinical course, one female patient underwent endoscopic sinus surgery (ESS) for prolonged rhinosinusitis.

Conclusion:

Rhinosinusitis is common in the postoperative stage of the EEA. As it usually lasts for a short duration and is treatable with proper medication, aggressive nasal care during the postoperative period is required to prevent related nasal morbidities.
Reflectance Confocal Microscopy and Dermoscopic Imaging Features in Extramammary Paget’s Disease: A Retrospective Study
Authors: Wang Wen-Ju , Liao Yan-Sen , Xu Jing-Kai , Zhou Pei-Mei , Feng Yan-Yan , Cui Yong
Published: November 2024

Objective:

Extramammary Paget’s disease (EMPD) is often misdiagnosed as chronic dermatitis or eczema of the scrotum because of its clinical manifestations, leading to delayed diagnosis and treatment. Reflectance confocal microscopy (RCM) and dermoscopy are widely used in clinical practice, enabling early diagnosis and treatment assessment of skin diseases, particularly which are easily misdiagnosed. This study aimed to summarize the RCM and dermoscopic features of EMPD which may provide evidence for diagnosis and evaluation of treatment effects.

Methods:

A retrospective analysis was conducted on skin lesions from 34 patients diagnosed with EMPD, confirmed through histopathological examination at the dermatology departments of Chengdu Second People’s Hospital and the Japan-China Friendship Hospital between January 2022 and December 2023. The analysis focused on typical changes of lesions, such as blood vessel patterns and background color under dermoscopy, as well as cellular morphology under RCM. Count data were presented as constituent ratios.

Results:

Among the included 34 patients, 28 were male and 6 were female, and 104 skin lesions were identified. The lesions were classified into 3 types: 36 red patches, 41 dark red erosive patches, and 27 brown pigmented patches. Dermoscopic examination of EMPD revealed characteristic features, including milky-white globules (90.4%, 94/104), irregular shiny white streaks (91.3%, 95/104), dotted blood vessels (91.3%, 95/104), and glomerular-like vessels (88.5%, 92/104). RCM demonstrated epidermal structural disorganization (100.0%, 104/104), vacuolated cells in the epidermis (94.2%, 98/104), and Paget cells, either scattered or clustered (88.5%, 92/104). The red macular lesions predominantly contained isolated vacuolated cells in the epidermis, the dark red erosive lesions exhibited Paget cell nests in the basal layer, and the brown pigmented lesions contained numerous dendritic cells. All the patients underwent wide surgical excision followed by RCM and dermoscopic examinations postoperatively.

Conclusion:

This study identified characteristic dermoscopic and RCM features in patients with EMPD, providing a foundation for noninvasive auxiliary diagnosis and guiding postoperative follow-up. Additionally, RCM characteristics of different lesion morphologies can help physicians more accurately assess surgical margins, leading to more precise surgical treatment options.
Heart Transplantation Outcomes in Patients With Hypertrophic Cardiomyopathy in the Era of Mechanical Circulatory Support
Authors: Mazur Matylda , Dowling Robert , Bhat Geetha , Carmona Rubio Andres , Eisen Howard J.
Published: November 2024

Mechanical circulatory support has emerged as a vital therapeutic modality for patients awaiting heart transplantation (HT). However, it is unknown how it affected the characteristics and post-HT outcomes of patients with hypertrophic cardiomyopathy (HCM). This retrospective cohort study analyzed adult HT recipients from the International Society for Heart and Lung Transplantation registry (1998–2017). Two equal-duration eras were defined: era 1 1998–2007 and era 2 2008–2017. Patients with HCM were compared across the two eras (n1 = 742 and n2 = 1,211) and within each era, they were contrasted with individuals with nonischemic (NICM) (n1 = 15,964 and n2 = 20,394) and ischemic cardiomyopathy (ICM) (n1 = 14,140 and n2 = 12,986). Across eras, the number of HTs among patients with HCM increased by 63%. The rate of recipients with HCM in the intensive care unit (ICU) supported with intra-aortic balloon pump (IABP) increased, yet their pre-HT functional status improved, and 5 year post-HT survival remained unchanged and favorable. In era 2, at the time of HT, patients with HCM were more frequently than their NICM and ICM counterparts in the ICU and supported with inotropes. In the same era, 1 and 5 year survival were more favorable in HCM compared to ICM and comparable to NICM.
Oncology Physician Turnover in the United States Based on Medicare Claims Data
Authors: Cornelius Sarah L. , Schaefer Andrew , Tosteson Anna N.A. , O’Malley Alistair James , Wong Sandra L. , Moen Erika L.
Published: November 2024

Objective:

Physician turnover rates are rising in the United States. The cancer workforce, which relies heavily on clinical teamwork and care coordination, may be more greatly impacted by turnover. In this study, we aimed to characterize oncologists who move to identify targets for recruitment and retention efforts.

Methods:

We identified medical, radiation, and surgical oncologists who treated Medicare beneficiaries diagnosed with breast, colorectal, or lung cancer in 2016–2019. We used multivariable logistic regression to identify physician-level and multivariable multinomial regression to identify region-level characteristics associated with turnover. Measures included demographic, practice, and patient-sharing network characteristics.

Results:

Our cohort included 25,012 medical, radiation, and surgical oncologists, of which, 1448 (5.8%) moved. Women [vs men; odds ratio (OR): 1.46; 95% CI: 1.30–1.64] and surgeons (vs medical oncologists; OR: 1.17; 95% CI; 1.04–1.33) had higher odds of moving. Compared with oncologists with moderate patient-sharing ties, those with many ties had lower odds of moving (OR: 0.55; 95% CI: 0.43–0.70). Patient-sharing networks with low efficiency (vs moderate) were more likely to have a net loss in their oncology workforce (OR: 3.06; 95% CI: 1.12–8.35), whereas those with low specialist vulnerability (vs moderate) were less likely to have a net loss (OR: 0.32; 95% CI: 0.1–0.99).

Conclusions:

This study identified novel patient-sharing network characteristics associated with turnover, providing new insights into how the structural features of patient-sharing networks may be related to the recruitment and retention of oncologists.
Higher Percentage of Virtual Primary Care Associated With Minimal Differences in Achievement of Quality Metrics
Authors: Segal Jodi B. , Yanek Lisa , Jager Leah , Okoli Ebele , Hatef Elham , Dada Maqbool , Frick K. Davina
Published: November 2024

Objective:

To test the impact of virtual care usage on quality metrics used for performance measurement.

Background:

Virtual care improves access to primary care; however, the quality of care must not be adversely impacted by its use.

Methods:

This is a mixed-design etiologic study using data from patients receiving primary care in a large, regional health system from January 2020 through December 2021. Eligible patients had at least one primary care contact. Eligible physicians had 10 or more patient contacts. The quartile of virtual visits per physician per month is calculated as the percentage of total visits conducted by phone or video (Q1 is the lowest). Six metrics used for value-based reimbursement were chosen for modeling with generalized linear mixed models.

Results:

The data included 200,090 patients of 683 physicians in 42 clinics over 24 months. Virtual care usage peaked in April 2020 at 78% and then stabilized at 18%. The blood pressure metric was met in 66% (95% CI: 63%–69%) of physician months in Q1 and 65% (95% CI: 63%–68%) in Q4 (P = 0.003). The hemoglobin A1c metric was met in 73% (95% CI: 70%–76%) of physician months in Q1 and 72% (95% CI: 69%–75%) in Q4, not a significant difference. Breast cancer screening completion and colon cancer screening completion did not differ across virtual care quartiles. Medicare annual wellness visits were completed in 55% (95% CI: 50%–60%) of Q1 physician months and 54% in each of Q2, Q3, and Q4 (P < 0.0001).

Conclusions:

Some quality metrics were modestly impacted by high virtual primary care usage; the absolute differences in rates were small. This may provide reassurance to physicians and their health systems that telemedicine use may not adversely impact quality metrics.
Elevated Interleukin-6 Levels as a Potential Marker of Neonatal Morbidity in Full-term Infants With Polycythemia: A Prospective Study
Authors: Tamer Reyhan , Ünal Şerife Suna Oğuz , Yozgat Can Yilmaz
Published: November 2024

Objective:

To research and show that interleukin-6 (IL-6) and c-reactive protein (CRP), which can be used as infection markers, are also higher among newborns with polycythemia. The study took place in the neonatal intensive care unit of Zekai Tahir Burak Maternity Teaching and Research Hospital.

Patients and Methods:

Infants with a gestational age of >37 weeks were included in the study. Infants with chorioamnionitis, perinatal asphyxia, and positive blood culture were excluded from the study. Blood samples were obtained six hours after the delivery from the peripheral vein of the infants for measurements of central hematocrit, blood culture, IL-6, and CRP. Infants with a venous hematocrit value of >65% were grouped as the “polycythemia group,” and the ones with a venous hematocrit value of <65% were designated as the “control group.” Observation of significantly higher levels of CRP and IL-6 among newborns admitted to the neonatal intensive care unit due to different causes (such as respiratory distress, hypoglycemia, and feeding intolerance), but significantly higher IL-6 levels in newborns with polycythemia.

Results:

Thirty-five newborns (18 infants in the polycythemia group and 17 infants in the control group) were enrolled in the study. The IL-6 values for the polycythemia group were higher than the upper normal limits (mean ± 2SD, 37.6 ± 55 vs 12 ± 5 pg/dL, respectively; P = 0.00). The IL-6 values of the polycythemia group were found to be higher than the IL-6 values of the control group, with a mean ± 2SD of 37.6 ± 55 vs 6.3 ± 3.4 pg/dL, respectively; this was significant (P = 0.00). Although the CRP values of the polycythemia group were found to be slightly higher than those of the control group (a mean ± 2SD of 3.06 ± 4.07 vs 1.54 ± 2.21 mg/dL, respectively, P > 0.05), this was not significant.

Conclusions:

This study found a significant and robust statistical correlation between IL-6 and v. Hct values (P = 0.01, rs = 0.641). Contrary to IL-6 levels, however, a meaningful relationship was not found between CRP and v.htc values (P = 0.286; rs = 0.184).
Improving Sickle Cell Patient Appointment Compliance in a Hospital-based Pediatric Ophthalmology Clinic
Authors: Louie Emily , Tang Anthony , Patel Amie , Srinivasan Ragha , Bohn Shiva , Wilson Matthew
Published: November 2024

This quality improvement initiative aimed to reduce the no-show rate at a hospital-based tertiary sickle cell ophthalmology clinic. Missed appointments place a significant burden on the healthcare system, resulting in prolonged waiting times and underutilized clinical resources that impact the quality of care provided. Individuals with sickle cell disease commonly require multiple appointments to address the myriads of comorbidities associated with their disease. Nevertheless, the sickle cell ophthalmology clinic experienced an alarmingly high no-show rate of 49% from June to September of 2021 despite offering same-day appointments with the hematology clinic. To address this issue, we conducted a study in which we compared the baseline no-show rate with the rate after relocating both clinics to the same floor, aiming to overcome patient-related barriers. Following 3.5 months of the clinics sharing the same floor, the no-show rate decreased to 39%, reflecting a 10% improvement from the baseline rate. In summary, co-locating two related clinics can alleviate patient burdens, foster communication between multidisciplinary specialties, and contribute to an overall improvement in the quality of care and treatment provided.
Eltrombopag for Treatment of Thrombocytopenia After Autologous Stem Cell Transplantation in Children: Single Center Experience
Authors: Bayram Nihan , Yaman Yontem , Ozdilli Kursat , Nepesov Serdar , Al Isik Odaman , Elli Murat , Anak Sema
Published: November 2024

Introduction:

Thrombocytopenia is a common clinical problem in cancer patients undergoing high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). It can occur as prolonged isolated thrombocytopenia (PIT) or secondary failure of platelet recovery (SFPR) and may cause potentially fatal bleeding. However, data on the treatment of post-transplant thrombocytopenia is still lacking.

Methods:

We reported our practices involving 15 pediatric patients who received eltrombopag (ELT) treatment for PIT and SFPR after autologous HSCT.

Results:

The overall response was 78.5% (11/14), with 1 patient excluded due to noncompliance. The 12 surviving patients' median follow up was 699 days (range: 167 to 2250 d).

Conclusions:

Our study indicates the efficacy and safety of ELT for treating PIT and SFPR after autologous HSCT in pediatric patients. However, more studies are needed to confirm these findings in children.
Preparing PhD Students for Tenure-Track Faculty Positions
Authors: Killela Mary K. , Adynski Harry , Adynski Gillian , Myer Elizabeth Allen , Dictus Cassandra , Morgan Leah , Hmiel Hayden , Williams Jessica
Published: November 2024

Background

With an increasing number of nursing faculty approaching retirement, it is critical to prepare PhD students to take on tenure-track faculty roles. There are a multitude of competing time demands for nursing faculty, and one way that PhD students can prepare for faculty roles is leading team-based science with their peers during their predoctoral program.

Objectives

To describe the process of PhD students leading an independent research project, in addition to their dissertation work, which aimed to incorporate the tripartite mission- scholarship, teaching, and service.

Methods

This paper outlines the components of the PhD-student-led project, as well as provides recommendations for leadership and schools of nursing as well as sponsors interested in funding this type of work.

Results

Students were able to conduct independent research using diverse research approaches, practice mentoring skills, and provide service and helpful information about the nursing workforce to their academic clinical partner. A key component of this relationship building was incorporating a clinical fellowship during the PhD program for students that directly aided the transition from BSN to PhD programs.

Discussion

PhD students learned valuable lessons about time management and collaborating in a team setting with peers. We recommend school of nursing seek funding opportunities for PhD students to conduct independent team science, encourage academic partnerships with affiliated medical centers and public health settings, and facilitate peer mentorship across cohorts.
Nationwide Analysis of Variables Associated With Sarcoid Inpatient Mortality
Authors: Manansala Michael , Castellino Janelle , Arora Shilpa , Manadan Augustine M.
Published: November 2024

Background

Sarcoidosis is a multisystem autoimmune disease that can result in significant morbidity and mortality. This study aims to identify factors associated with in-hospital death for sarcoid patients on a national level.

Methods

We performed a medical records review study of all adult sarcoid hospitalizations from 2016 to 2020 National Inpatient Sample database. A univariable screen followed by multivariable analysis was completed to identify predictors of in-hospital death among sarcoid patients.

Results

There were 405,650 admissions with a diagnosis of sarcoidosis, 10,210 of whom died. Multivariable analysis showed the following factors were independently associated with a higher odds of in-hospital death: age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.026–1.034), Charlson Comorbidity Index (OR, 1.09; 95% CI, 1.066–1.116), male sex (OR, 1.21; 95% CI, 1.101–1.331), other race (OR, 1.45; 95% CI, 1.073–1.954), arrhythmia/heart blocks (OR, 1.80; 95% CI, 1.617–1.995), cirrhosis/hepatic failure (OR, 8.26; 95% CI, 6.928–9.844), hemophagocytic lymphohistiocytosis (OR, 11.15; 95% CI, 4.172–29.802), infection (OR, 3.31; 95% CI, 3.007–3.633), interstitial lung disease (OR, 1.31; 95% CI, 1.193–1.438), heart failure/myocarditis (OR, 1.29; 95% CI, 1.157–1.436), neurologic diagnoses (OR, 1.37; 95% CI, 1.241–1.502), and pulmonary hypertension (OR, 1.47; 95% CI, 1.305–1.652).

Conclusions

Our multiyear national analysis showed that 2.5% of hospital admissions with a sarcoid diagnosis ended in death. The following factors were associated with death: age, Charlson Comorbidity Index, male sex, other race, arrhythmia/heart blocks, cirrhosis/hepatic failure, hemophagocytic lymphohistiocytosis, infection, interstitial lung disease, heart failure/myocarditis, neurologic diseases, and pulmonary hypertension. This information can help clinicians by improving awareness of these life-threatening complications because early recognition and intervention may improve inpatient sarcoid outcomes.
Scleroderma Renal Crisis and Musculoskeletal Corticosteroid Injections
Authors: Muruganandam Maheswari , Akpan Eyerusalem B. , McElwee Matthew K. , Emil N. Suzanne , Keller Meredith C. , Vangala Adarsh S. , Dihowm Fatmah , Nunez Sharon E. , Gibb James I. , O'Sullivan Frank X. , Fields Roderick A. , Sibbitt Wilmer L.
Published: November 2024

Background/Objective

Inflammatory arthritis frequently affects patients with systemic sclerosis (SSc) but musculoskeletal corticosteroid (MSKC) injections are often avoided due to concerns of scleroderma renal crisis (SRC). This study investigated the incidence of SRC following MSKC injections.

Methods

In a 136-SSc cohort, 46 subjects underwent a total of 330 MSKC injections each receiving a significant dosage of triamcinolone acetonide (mean, 95.2 ± 44.2 mg per injection session). Data on blood pressure (BP), serum creatinine and glucose, urine protein, and complications were obtained before and after injection from the patients’ medical records.

Results

MSKC and control subjects were similar in age (MSKC: 58.9 ± 12.1 vs. 55.5 ± 14.9 years), female (MSKC: 97.8% [45/46] vs. 89.9% [81/90]), antinuclear antibody (MSKC: 71.7% [33/46] vs. 81.1% [73/90]), anti-centromere antibody (MSKC: 47.8% [22/46] vs. 37.8% [34/90]), anti-topoisomerase antibody (MSKC: 26.1% [12/46] vs. 26.7% [24/90]), and anti–RNA polymerase III antibody (MSKC: 17.4.1% [8/46] vs. 24.4% [22/90]) (all p > 0.05). Pre- and post-MSKC demonstrated nonsignificant changes in systolic BP (pre: 127 ± 22 vs. post: 127 ± 21 mm Hg, p = 1.0), diastolic BP (pre: 71 ± 13 vs. post: 71 ± 11 mm Hg, p = 1.0), creatinine (pre: 0.78 ± 0.56 vs. post: 0.76 ± 0.20 mg/dL, p = 0.64), glucose (pre: 100 ± 21 vs. post: 99 ± 24 mg/dL, p = 0.67), and urine protein-creatinine ratio (pre: 0.14 ± 0.12 vs. post: 0.12 ± 0.11 mg/mg, p = 0.41). One case of SRC with mortality occurred in the controls and none in the MSKC group. No infections, hematologic abnormalities, or tendon rupture were noted.

Conclusion

MSKC injections in established SSc are generally safe with low incidences of SRC and complications. However, it is still prudent to monitor high-risk individuals and recent-onset SSc post–MSKC injection.
TRPV4 calcium-permeable channel contributes to valve stiffening in aortic stenosis
Authors: Dutta Bidisha , Rahaman Suneha G. , Mukherjee Pritha , Rahaman Shaik O.
Published: November 2024

Aortic valve stenosis (AVS) is a progressive disease marked by fibrosis, inflammation, calcification, and stiffening of the aortic valve leaflets, leading to disrupted blood flow and left ventricular pressure overload. AVS can result in heart failure and death within 2 to 5 years if left untreated, highlighting its high mortality rate. Understanding the molecular mechanisms of AVS is essential for developing noninvasive treatments. Emerging data suggest that extracellular and intracellular matrix stiffness influences gene expression, inflammation, and cell differentiation. Myofibroblast activation of valvular interstitial cells (VICs) along with excess extracellular matrix (ECM) accumulation and remodeling are primary drivers of AVS progression. Inflammation also plays a critical role, with macrophages accumulating in valve leaflets from AVS patients, promoting inflammation, activating VICs, and synthesizing and remodeling the ECM.

Our lab and others have reported that macrophage and fibroblast activities, including migration, inflammatory gene expression, and myofibroblast activation, are sensitive to matrix stiffness, indicating that valve leaflet stiffening may regulate AVS progression via a cellular stiffness sensor. Our published work shows that mechanosensitive Ca2+-permeable transient receptor potential vanilloid 4 (TRPV4) channels regulate fibrosis in other organs and control macrophage and fibroblast activation, suggesting TRPV4 as the potential stiffness sensor in AVS. This implies that fibrosis and tissue stiffening may reinforce each other, creating a vicious cycle in AVS development, with VICs and macrophages playing central roles. Here, we identify the cellular stiffness sensor mediating the link between stiffness and AVS development using human aortic valve tissues, a murine model of aortic valve stenosis, and atomic force microscopy analysis.
Neutrophil extracellular traps promote tumor chemoresistance to anthracyclines
Authors: Lin Cindy , Herlihy Sarah E. , Li Marina , Deng Hui , Kim Rina , Bernabei Luca , Rosenwasser Matthew , Gabrilovich Dmitry I. , Vogl Dan T. , Nefedova Yulia
Published: November 2024

The microenvironment plays an important role in promoting tumor cell chemoresistance, but the mechanisms responsible for this effect are not clear. Here, using models of multiple myeloma (MM) and solid cancers, we demonstrate a novel mechanism mediated by neutrophils, a major cell population in the bone marrow (BM), that protects cancer cells from chemotherapeutics. We show that in response to tumor-derived soluble factors, BM neutrophils release their DNA in the form of neutrophil extracellular traps (NETs). Cell-free DNA derived from NETs is then taken up by tumor cells via endocytosis and localizes to the cytoplasm. We found that both NETs and cell-free DNA taken up by tumor cells can bind anthracyclines, leading to tumor cell resistance to this class of chemotherapeutic agents. Targeting cell-free DNA with Pulmozyme or blocking NET formation with a PAD4 inhibitor abrogates the chemoprotective effect of neutrophils and restores sensitivity of tumor cells to anthracyclines.
Trends in Coupled Human-Environment Systems Modelling: A Scoping Review
Authors: Thampi Vivek A. , Bauch Chris T. , Anand Madhur
Published: November 2024

Classical environmental models assume the influence of humans on environmental systems is constant. However, human and environmental systems respond to one another. As such, coupled human-environment systems (CHES) models have been developed and are becoming more widely studied. In this review, we analyze CHES modelling techniques and study systems over a decade (May 2009-April 2019). We utilized the PRISMA method to filter publications from both Web of Knowledge and PUBMED, yielding 92 relevant papers for our review. Publications more than doubled from the 5-year interval May 2009-December 2013 (28/92) to the 5-year interval January 2014-April 2019 (64/92). CHES models typically used either differential equations (DEs) (44/92) or agent-based models (ABMs) (28/92). We organized the included literature with respect to the technique used to represent human behaviour. We noticed a diversity of approaches in this respect, but primarily optimization techniques (28/92) and game theory (34/92). We noticed a substantial increase in publications using more highly structured models in the second 5-year interval. We attribute this to reduced technological barriers to developing more detailed models, and greater data availability. We discuss the realism of the models and their ability to capture real-world dynamics. Finally, we explore avenues for future research, and discuss unconventional routes such as online communities and artificial intelligence modelling to expand representation of human behaviour in CHES models.
Increase ofClostridioides difficilePCR ribotype 002 infection coincides with decreased disease severity in hospitalized patients in the Netherlands
Authors: Baktash A , Harmanus C , Goeman J , Brennan W , Cormican M , Corver J , Kuijper EJ , Smits WK
Published: November 2024

Clostridioides difficilePCR ribotype (RT) 002 is the second most prevalent RT in the Netherlands. In 2019, an increase inC. difficileinfections (CDI) due to a clonal RT002 strains was reported in Ireland. In retrospect, a significant increase in the proportion of CDI due to RT002 was detected in the Netherlands between May 2017-May 2018 (11.9% of 683 cases vs 6.5% of 865 in the previous year). Our aim was to analyze and characterize CDI due to RT002 over time and to assess whether RT002 isolates in the Netherlands were related to the Irish RT002 isolates.

Over the period May 2009-April 2021, Dutch patients with CDI due to RT002 showed less severe CDI (22%) in comparison with hypervirulent RTs (RT027; 29% and RT078; 25%), similar to grouped data from other non-hypervirulent ribotypes (21%). However, RT002-associated CDI prior to the increased proportion (2009-2017) showed CDI severity similar to CDI associated with hypervirulent types, whereas this was no longer the case after the increase (2017-2021). Using core genome MLST, Dutch isolates were found not to be related to the Irish outbreak strain. Several Dutch strains clustered together without an evident epidemiological link, suggesting recent emergence.

Importance

Clostridioides difficileis a significant cause of hospital-associated infections, making it relevant to understand the emergence and spread of different ribotypes. This study highlights a rise in cases of PCR ribotype 002 (RT002) in the Netherlands, suggesting changes in its prevalence. Despite the increase in RT002 infections, the severity of disease appears to have decreased and is lower compared to more virulent ribotypes. Further research is needed to understand the factors driving this change. Additionally, this study underscores some limitations of core genome multi-locus sequence typing (cgMLST). cgMLST is valuable for identifying genetic relationships, however it cannot always distinguish between widespread recently emerged strains and local transmission chains, making it challenging to determine the exact sources of infection. Continued surveillance and genetic characterization ofC. difficileare essential to better understand these trends and improve control measures.
Genome-wide association studies and multi-omics integrative analysis reveal novel loci and their molecular mechanisms for circulating polyunsaturated, monounsaturated, and saturated fatty acids
Authors: Sun Yitang , Xu Huifang , Ye Kaixiong
Published: November 2024

Previous genome-wide association studies (GWAS) have identified genetic loci associated with the circulating levels of FAs, but the biological mechanisms of these genetic associations remain largely unexplored. Here, we conducted GWAS to identify additional genetic loci for 19 circulating fatty acid (FA) traits in UK Biobank participants of European ancestry (N = 239,268) and five other ancestries (N = 508 – 4,663). We leveraged the GWAS findings to characterize genetic correlations and colocalized regions among FAs, explore sex differences, examine FA loci influenced by lipoprotein metabolism, and apply statistical fine-mapping to pinpoint putative causal variants. We integrated GWAS signals with multi-omics quantitative trait loci (QTL) to reveal intermediate molecular phenotypes mediating the associations between the genetic loci and FA levels. Altogether, we identified 215 significant loci for polyunsaturated fatty acids (PUFAs)-related traits in European participants, 163 loci for monounsaturated fatty acids (MUFAs)-related traits, and 119 loci for saturated fatty acids (SFAs)-related traits, including 70, 61, and 54 novel loci, respectively. A novel locus for total FAs, the percentage of omega-6 PUFAs in total FAs, and total MUFAs (around genesGSTT1/2/2B) overlapped with QTL signals for all six molecular phenotypes examined, including gene expression, protein abundance, DNA methylation, splicing, histone modification, and chromatin accessibility. Across 19 FA traits, 65% of GWAS loci overlapped with QTL signals for at least one molecular phenotype. Our study identifies novel genetic loci for circulating FA levels and systematically uncovers their underlying molecular mechanisms.
Modified-Mindfulness-Based Stress Reduction as a Treatment for Cognitive Recovery in Patients with Minor Stroke: a Randomized Controlled Pilot Study
Authors: Girgenti Sophia G. , Dallasta Isabella , Lawrence Erin , Merbach Dawn , Simon Jonathan Z. , Llinas Rafael , Gould Neda F. , Marsh Elisabeth Breese
Published: November 2024

Background

Well-developed rehabilitation paradigms exist for post-stroke language and motor impairments. However, no such recovery program has been identified for commonly disabling cognitive deficits in patients following minor stroke. Mindfulness Based Stress Reduction (MBSR) is thought to engage the frontal lobes, improving concentration and attention, and therefore may be an effective option.

Methods

We prospectively enrolled a cohort of patients with subacute minor stroke and randomized them to either an 8-week online modified-MBSR course or online traditional Stroke Support Group (SSG). All patients underwent a battery of cognitive tests and measures of patient reported outcomes (PROs) pre- and post-intervention. ANOVA was used to compare changes in scores over time across both groups, as well as a third group of control patients having received neither intervention (n=128).

Results

A total of 30 patients were randomized (n=16 for m-MBSR; n=14 for SSG). The average age of the cohort was 65.9 years. Both groups scored similarly on assessments one-month post-stroke and demonstrated increased T-scores on cognitive tasks at the 3-month visit. However, the m-MBSR group showed moderately elevated levels of improvement, specifically in processing speed, executive, and global cognitive function. Level of engagement was not associated with better clinical scores, though was unexpectedly low for both groups.

Conclusions

m-MBSR appears to modestly improve frontal lobe activity and demonstrates some success in increasing cognitive performance. However, further studies are needed to determine if it is more efficacious in the chronic stage of recovery when more patients are able to fully engage and actively participate.
Large Language Models Fail to Reproduce Level I Recommendations for Breast Radiotherapy
Authors: Tang Kathleen , Han John , Wu Shengyang
Published: November 2024

This study evaluates the reliability of the largest public-facing large language models in providing accurate breast cancer radiotherapy recommendations. We assessed ChatGPT 3.5, ChatGPT 4, ChatGPT 4o, Claude 3.5 Sonnet, and ChatGPT o1 in three common clinical scenarios. The clinical cases are as follows: post-lumpectomy radiotherapy in a 40 year old woman, (2) postmastectomy radiation in a 40 year old woman with 4+ lymph nodes, and (3) postmastectomy radiation in an 80 year old woman with early stage tumor and negative axillary dissection. Each case was designed to be unambiguous with respect to the Level I evidence and clinical guideline-supported approach. The evidence-supported radiation treatments are as follows: (1) Whole breast with boost (2) Regional nodal irradiation (3) Omission of post-operative radiotherapy. Each prompt is presented to each LLM multiple times to ensure reproducibility. Results indicate that the free, public-facing models often fail to provide accurate treatment recommendations, particularly when omission of radiotherapy was the correct course of action. Many recommendations suggested by the LLMs increase morbidity and mortality in patients. Models only accessible through paid subscription (ChatGPT o1 and o1-mini) demonstrated greatly improved accuracy. Some prompt-engineering techniques, rewording and chain-of-reasoning, enhanced the accuracy of the LLMs, while true/false questioning significantly worsened results. While public-facing LLMs show potential for medical applications, their current reliability is unsuitable for clinical decision-making.