bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating CD1a Immunohistochemistry for Tegumentary Leishmaniasis Diagnosis in the New World: A Focus on Colombia
Authors: Aristizábal-Parra Lucero Katherine , Ospina-Gómez Juan Pablo , Restrepo-Rivera Lina , Ramírez Juan David , Ospina-Varón Carlos Mario , González Juan David , Serrano-Coll Héctor
Published: October 2024

Introduction:

Leishmaniasis, a chronic vector-borne disease caused by parasites of the genus Leishmania, presents diagnostic challenges. Conventional diagnostic methods struggle with accurate visualization of these parasites. Immunostaining with CD1a has demonstrated effectiveness in visualizing Leishmania parasites, particularly in the Old World. However, the application of CD1a immunostaining in Colombian leishmaniasis remains unexplored.

Objective:

To determine the utility of CD1a as an immunomarker in detecting chronic forms of tegumentary leishmaniasis.

Materials and methods:

This proof-of-concept study involved 48 paraffin-embedded samples categorized into 3 groups: moderate-to-high parasite load (n = 15), low load (n = 15), and chronic granulomatous inflammation (n = 13); 5 samples diagnosed with cutaneous histoplasmosis. These samples were stained with the immunomarker CD1a clone EP3622 for comparative analysis. In addition, CD1a immunohistochemistry was compared with 18S rDNA qPCR and hematoxylin–eosin staining to evaluate its performance in relation to these established methods.

Results:

CD1a immunohistochemistry was positive in 46.51% of the samples evaluated. This immunomarker showed lower sensitivity and negative predictive value than 18S rDNA qPCR and hematoxylin–eosin staining; specificity and negative predictive value were consistent. ROC indicated inferior discrimination for leishmaniasis compared with 18 s rDNA qPCR and hematoxylin–eosin staining.

Conclusions:

Immunohistochemistry for CD1a could be a diagnostic support in the detection of chronic forms of tegumentary leishmaniasis.
Topical Therapies for Periorbital Dyschromia: A 30-Year Review of the Literature
Authors: Woolhiser Emily , Sobotka Michelle , Burnette Colin , Gawey Lauren , Dunnick Cory A.
Published: October 2024

BACKGROUND

Periorbital dyschromia (POD) is a prevalent dermatologic problem with multifactorial etiology, making treatment outcomes inconsistent and unclear.

OBJECTIVE

To evaluate and compose a comprehensive review of topical ingredients proven to be effective in the treatment of POD.

MATERIALS AND METHODS

Scopus, PubMed, and OVID databases were searched in a span of 30 years through December 31, 2023, to identify articles with original findings of topical therapies for the treatment of POD. Findings of interest were objectively and subjectively measured regarding pigmentation, skin texture, aesthetic improvement, elasticity, hydration, and eye-bag volume.

RESULTS

The database searches yielded 339 unique studies. After screening and review, 22 studies were included totaling 13 nonrandomized control trials, 7 randomized clinical trials, 1 retrospective case series, and 1 prospective single-arm study. Studies included all reported statistically significant results with topical therapies inclusive of acids, bark extract, bicyclic monoterpene diols, caffeine, combo ingredient serums, ethyl ximenynate, gentiopicroside, glycosaminoglycans, growth factors, topical PRP, and vitamins.

CONCLUSION

The findings of this review suggest that topical therapies can be effective in the treatment of POD. Future trials should focus on delineating specific etiology of POD and evaluation of therapies specific to their cause.
Excimer Laser-Assisted Deep Anterior Lamellar Keratoplasty Versus Penetrating Keratoplasty for Patients With Keratoconus: A Retrospective Analysis From the Homburg Keratoconus Center
Authors: Daas Loay , Aljundi Wissam , Abdin Alaa Din , Munteanu Cristian , Seitz Berthold
Published: October 2024

Purpose:

To evaluate the outcome of excimer laser-assisted deep anterior lamellar keratoplasty (Exc-DALK) and penetrating keratoplasty (Exc-PKP) for keratoconus (KC).

Methods:

We included 123 eyes and compared the outcome of 30 eyes undergoing big-bubble Exc-DALK after stromal debulking (G1) against a matched group of 83 eyes undergoing Exc-PKP (G2) in our department. G2 was created after performing a pseudorandom stratified bootstrapping of our PKP database starting with 2802 surgeries with removal of any bias. Main outcomes included best corrected visual acuity (BCVA), spherical equivalent (SE), tomographic changes, and endothelial cell density (ECD). Data were compared preoperatively, postoperatively with 2 double-running cross-stitch sutures according to Hoffmann [2 and 10 months postoperatively (T1 and T2)], after first suture removal [15 months postoperatively (T3)], and after final suture removal [26 months postoperatively (T4)].

Results:

Preoperatively, all parameters were comparable without significant differences. At T1, G1 showed significantly better BCVA (P = 0.01), lower SE (P = 0.04), lower anterior and posterior topographic astigmatism (ATA and PTA, P < 0.01), lower maximal keratometry (P = 0.02), and lower central corneal thickness (P < 0.01). At T2, G1 showed significantly better BCVA (P = 0.04), lower PTA (P < 0.01), and higher ECD (P < 0.01). At T3, G1 showed significantly lower ATA (P = 0.01) and PTA (P < 0.01) and higher ECD (P = 0.02). At T4, G1 showed significantly lower PTA and higher ECD (P < 0.01) but no significant difference in BCVA (P = 0.07).

Conclusions:

Exc-DALK provided faster visual rehabilitation and represented an endothelial cell-sparing method compared with Exc-PKP. After final suture removal, Exc-DALK showed noninferior outcomes compared with Exc-PKP if the graft was placed on naked Descemet membrane.
Current Scenario and Future Perspectives of Porcine Corneal Xenotransplantation
Authors: Nascimento Heloisa , Martins Thaís M. M. , Moreira Rodrigo , Barbieri Gabriel , Pires Pedro , Carvalho Lucimeire N. , Rosa Larissa R. , Almeida Augusto , Araujo Michelle Silva , Pessuti Carmen Luz , Ferrer Henrique , Pereira Gomes José Álvaro , Belfort Rubens , Raia Silvano
Published: October 2024

Corneal diseases represent a significant cause of blindness worldwide, with corneal transplantation being an effective treatment to prevent vision loss. Despite substantial advances in transplantation techniques, the demand for donor corneas exceeds the available supply, particularly in developing countries. Cornea xenotransplantation has emerged as a promising strategy to address the worldwide scarcity, notably using porcine corneas. In addition to the inherent immune privilege of the cornea, the low cost of porcine breeding and the anatomical and physiological similarities between humans and pigs have made porcine corneas a viable alternative. Nonetheless, ethical concerns, specifically the risk of xenozoonotic transmission and the necessity for stringent biosafety measures, remain significant obstacles. Moreover, the success of xenotransplantation is compromised by innate and adaptive immune responses, which requires meticulous consideration and further studies. Despite these challenges, recent breakthroughs have further contributed to reducing immunogenicity while preserving the corneal architecture. Advances in genetic engineering, such as the use of CRISPR-Cas9 to eliminate critical porcine antigens, have shown promise for mitigating immune reactions. Additionally, new immunosuppressive protocols, such as have techniques like decellularization and the use of porcine-derived acellular matrices, have greatly increased graft survival in preclinical models. Future research must focus on refining immunomodulatory strategies and improving graft preparation techniques to ensure the long-term survival and safety of porcine corneal xenotransplantation in clinical trials in humans.
Advanced biomaterials for regenerative medicine and their possible therapeutic significance in treating COVID-19: a critical overview
Authors: Sarangi Ashish K. , Salem Mohamed A. , Younus Mustafa D. , El-Haroun Hala , Mahal Ahmed , Tripathy Lizaranee , Mishra Rajashree , Shabil Muhammed , Alhumaydhi Fahad A. , Khatib Mahalaqua N. , Bushi Ganesh , Rustagi Sarvesh , Dey Debankur , Satapathy Prakasini , Ballal Suhas , Bansal Pooja , Bhopte Kiran , Tomar Balvir S. , Mishra Snehasish , Alissa Mohammed , Mohapatra Ranjan K. , El-Bahy Zeinhom M.
Published: October 2024

The potential of biomaterials in medical sciences has attracted much interest, especially in promoting tissue regeneration and controlling immune responses. As the COVID-19 pandemic broke out, there was an increased interest in understanding more about how biomaterials could be employed to fight this dreaded disease, especially in the context of regenerative medicine. Out of the numerous regenerative medicine possibilities, stem cells and scaffolding (grafting) technology are two major areas in modern medicine and surgery. Mesenchymal stem cells are useful in tissue repair, tailored therapy and the treatment of COVID-19. Using biomaterials in COVID-19 treatment is intricate and needs multidisciplinary and cross-disciplinary research. Cell-based therapy and organ transplants pose immunological rejection challenges. Immunomodulation enhanced, tumorigenicity decreased, inflammation addressed and tissue damage restricted; bioengineered stem cells need clinical insights and validation. Advanced stem cell-based therapies should ideally be effective, safe and scalable. Cost and scalability shall dictate the dawn of techno-economically feasible regenerative medicine. A globally standard and uniform approval process could accelerate translational regenerative medicine. Researchers, patient advocacy organisations, regulators and biopharmaceutical stakeholders need to join hands for easy navigation of regulatory measures and expeditious market entry of regenerative medicine. This article summarises advances in biomaterials for regenerative medicine and their possible therapeutic benefits in managing infectious diseases like COVID-19. It highlights the significant recent developments in biomaterial design, scaffold construction, and stem cell-based therapies to treat tissue damage and COVID-19-linked immunological dysregulation. It also highlights the potential contribution of biomaterials towards creating novel treatment strategies to manage COVID-19.
An immune signature of postoperative cognitive decline: a prospective cohort study
Authors: Verdonk Franck , Cambriel Amélie , Hedou Julien , Ganio Ed , Bellan Grégoire , Gaudilliere Dyani , Einhaus Jakob , Sabayev Maximilian , Stelzer Ina A. , Feyaerts Dorien , Bonham Adam T. , Ando Kazuo , Choisy Benjamin , Drover David , Heifets Boris , Chretien Fabrice , Aghaeepour Nima , Angst Martin S. , Molliex Serge , Sharshar Tarek , Gaillard Raphael , Gaudilliere Brice
Published: October 2024

Background:

Postoperative cognitive decline (POCD) is the predominant complication affecting patients over 60 years old following major surgery, yet its prediction and prevention remain challenging. Understanding the biological processes underlying the pathogenesis of POCD is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This study aimed to provide a comprehensive analysis of immune cell trajectories differentiating patients with and without POCD and to derive a predictive score enabling the identification of high-risk patients during the preoperative period.

Material and methods:

Twenty-six patients aged 60 years old and older undergoing elective major orthopedic surgery were enrolled in a prospective longitudinal study, and the occurrence of POCD was assessed 7 days after surgery. Serial samples collected before surgery, and 1, 7, and 90 days after surgery were analyzed using a combined single-cell mass cytometry and plasma proteomic approach. Unsupervised clustering of the high-dimensional mass cytometry data was employed to characterize time-dependent trajectories of all major innate and adaptive immune cell frequencies and signaling responses. Sparse machine learning coupled with data-driven feature selection was applied to the presurgery immunological dataset to classify patients at risk for POCD.

Results:

The analysis identified cell-type and signaling-specific immune trajectories differentiating patients with and without POCD. The most prominent trajectory features revealed early exacerbation of JAK/STAT and dampening of inhibitory κB and nuclear factor-κB immune signaling responses in patients with POCD. Further analyses integrating immunological and clinical data collected before surgery identified a preoperative predictive model comprising one plasma protein and 10 immune cell features that classified patients at risk for POCD with excellent accuracy (AUC=0.80, P=2.21e-02 U-test).

Conclusion:

Immune system-wide monitoring of patients over 60 years old undergoing surgery unveiled a peripheral immune signature of POCD. A predictive model built on immunological data collected before surgery demonstrated greater accuracy in predicting POCD compared to known clinical preoperative risk factors, offering a concise list of biomarker candidates to personalize perioperative management.
Preservation of the MMPH and Status of the Notch Configurations Are Important Factors for Successful Revision ACL Reconstruction
Authors: Park Seong Yun , Park Sung Bae , Lee Yong Seuk
Published: October 2024

Objective:

The aim of this study was to identify the differences in anatomical factors between the patients who underwent revision and primary anterior cruciate ligament reconstructions (ACLR) and compare the outcomes between the 2 surgeries.

Design:

Retrospective cohort study.

Setting:

Single institution tertiary academic center between 2014 and 2020.

Patients:

A total of 84 matched patients who underwent revision (group I) or primary ACLR (group II).

Interventions:

Radiological evaluations were performed using side-to-side differences (SS-D), femorotibial angle, and posterior tibial slope. The medial meniscus posterior horn status as width (MMPHW), medial tibial plateau width (MTPW), notch configurations, tunnel positions, and sagittal graft angle were measured using 3D-CT and magnetic resonance imaging (MRI).

Main Outcome Measures:

Graft signals were assessed using MRI. The clinical outcomes were assessed.

Results:

Group I showed larger SS-D and higher mean Howell grade of anterior cruciate ligament (ACL) graft than group II (P = 0.002 and P = 0.004, respectively). Multivariate regression analyses showed that the decreased MMPHW/MTPW ratio (P = 0.010) and notch width index (P < 0.007) were significantly independent factors associated with the higher Howell grade of ACL grafts. The decreased MMPHW/MTPW ratio (P < 0.001) was a significantly independent factor associated with larger SS-D. In the subgroup analysis, all patients in the notchplasty group showed wider notches postoperatively (P < 0.001).

Conclusions:

Revision ACLRs resulted in worse ACL signal intensity and stability outcome. The results of this study suggest that it may be important to preserve the MMPHW as much as possible and check notch configurations, especially during a revision ACLR.
Combination of FDG PET/CT radiomics and clinical parameters for outcome prediction in patients with non-Hodgkin’s lymphoma
Authors: Ortega Claudia , Anconina Reut , Joshi Sayali , Metser Ur , Prica Anca , Johnson Sarah , Liu Zhihui Amy , Keshavarzi Sareh , Veit-Haibach Patrick
Published: October 2024

Purpose

The purposes was to build model incorporating PET +  computed tomography (CT) radiomics features from baseline PET/CT + clinical parameters to predict outcomes in patients with non-Hodgkin lymphomas.

Methods

Cohort of 138 patients with complete clinical parameters and follow up times of 25.3 months recorded. Textural analysis of PET and manual correlating contouring in CT images analyzed using LIFE X software. Defined outcomes were overall survival (OS), disease free-survival, radiotherapy, and unfavorable response (defined as disease progression) assessed by end of therapy PET/CT or contrast CT. Univariable and multivariable analysis performed to assess association between PET, CT, and clinical.

Results

Male (P = 0.030), abnormal lymphocytes (P = 0.030), lower value of PET entropy (P = 0.030), higher value of SHAPE sphericity (P = 0.002) were significantly associated with worse OS. Advanced stage (III or IV, P = 0.013), abnormal lymphocytes (P = 0.032), higher value of CT gray-level run length matrix (GLRLM) LRLGE mean (P = 0.010), higher value of PET gray-level co-occurrence matrix energy angular second moment (P < 0.001), and neighborhood gray-level different matrix (NGLDM) busyness mean (P < 0.001) were significant predictors of shorter DFS. Abnormal lymphocyte (P = 0.033), lower value of CT NGLDM coarseness (P = 0.082), and higher value of PET GLRLM gray-level nonuniformity zone mean (P = 0.040) were significant predictors of unfavorable response to chemotherapy. Area under the curve for the three models (clinical alone, clinical + PET parameters, and clinical + PET + CT parameters) were 0.626, 0.716, and 0.759, respectively.
Radiation exposure in vesicoureteral reflux diagnostics: a comparative study of direct radionuclide cystography and voiding cystourethrogram
Authors: Viljamaa Hanna-Reeta , Ripatti Liisi L.M. , Larjava Heli R.S. , Noponen Tommi E.J. , Saikkonen Aleksi , Rautava Päivi T.K. , Koivisto Mari A. , Pakkasjärvi Niklas A.
Published: October 2024

Introduction

Voiding cystourethrography (VCUG) is the standard method for diagnosing vesicoureteral reflux (VUR) but has been criticized for radiation exposure. Direct radionuclide cystography (DRC) was developed to reduce this risk. We aimed to assess DRC’s efficacy as a screening tool and compare its radiation burden to VCUG.

Materials and methods

We retrospectively analyzed patient records encompassing children who underwent VCUG or DRC to diagnose VUR from 2011 to 2020 at our hospital.

Results

A total of 156 children were included (median age: 0.75 years, 53.8% females). Indications included urinary tract infection in 71.2% of patients and antenatal hydronephrosis in 26.9%. DRC was performed on 122 patients (78.2%) and VCUG on 96 patients (61.5%), with solitary use in 38.5 and 21.8% of cases, respectively, and combined application in 39.7%. DRC detected VUR in 35.3% (43/122) and VCUG in 61.5% (59/96) of patients. Bladder-filling rates differed significantly between DRC (37%) and VCUG (67%) (P < 0.0001). Median radiation doses were lower in VCUG (0.023 mSv) than in DRC (0.073 mSv). For patients requiring complementary VCUG after DRC, the median radiation dose for DRC was 0.063 mSv (P < 0.0001), resulting in a total median dose of 0.098 mSv. Cost analysis revealed VCUG as more cost-effective, with an additional expenditure of approximately 345 euros per patient undergoing DRC in our cohort.

Conclusion

DRC imposed a higher radiation burden on patients than VCUG and often necessitated follow-up VCUG for positive cases. This challenges the utility of DRC as a low-radiation alternative in VUR screening.

Level of evidence

Level 4: cohort study without a control group.
An associate of suspicious axillary node and sentinel node in breast cancer to minimizing axillary surgery, prospective cohort study
Authors: Chirappapha Prakasit , Lertsithichai Panuwat , Adireklarpwong Lakkana , Kaeosuwan Supanat , Wiratkapun Cholatip , Lapkittichot Sarunthorn , Taerakul Navalee , Trimankha Muntana , Nimitkul Kanitha , Pipatsakulroj Wiriya , Sukarayothin Thongchai , Leesombatpaiboon Monchai , Suvikapakornkul Ronnarat , Wasuthit Yodying
Published: October 2024

Background:

Arm morbidity and postoperative complications following sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) are common problems in patients with breast cancer. The de-escalating axillary surgery is increasing; however, there is a lack of patients with suspicious nodes. This study aimed to reduce the need for SLNB in suspicious lymph node cases.

Methods:

A prospective cohort study of women with invasive breast cancer who underwent surgery between January 2021 and December 2022. The study included two cohorts: Cohort A comprised patients with stage cT1-2N0-1M0 cancer who planned upfront surgery, while Cohort B included patients with stages cT1-4N2M0, cT3-4N1M0, or cT1-2N0-1M0 who received neoadjuvant systemic treatment. During the study, a clip was inserted into the suspicious lymph node on imaging to determine whether it could serve as a sentinel node and potentially replace SLNB or reduce the need for axillary surgery.

Result:

In cohort A, 22 surgeries were performed, while in cohort B, seven surgeries were performed. The median follow-up time was 15 months. In cohort A, 71% of the patients had cN0 disease, while 28% had cN1 disease. A suspicious node correlated to a sentinel node was noted in 66.67% of cohort A. The false-negative rate (FNR) was 14.28%. However, when the clip node removal procedure was performed instead of the sentinel node procedure, the FNR was 10%.

Conclusion:

In early breast cancer, suspicious nodes in imaging studies could not currently represent sentinel lymph nodes, and the FNR was still high. Nevertheless, more studies with larger populations will provide a better understanding due to the limited number of patients.
Gastric glomus tumor with a rare presentation: a case report and review of the literature
Authors: Thalji Mariam Mohammed , Alnajjar Yousef A. , Mohammad Maen , Khadra Hala , Bannoura Sami , Al-Ashhab Hazem
Published: October 2024

Introduction and importance:

Gastric glomus tumors (GGT) are rare soft tissue tumors of the gastrointestinal tracts (GIT). It is somewhat challenging to establish the diagnosis of GGT and differentiate it from the more common submucosal neoplasms.

Case presentation:

A 34-year-old female patient presented with upper gastrointestinal bleeding. Extensive workup including endoscopic ultrasonography (EUS) revealed a well-circumscribed isoechoic mass arising from the muscularis propria. Based on fine needle biopsy (FNB) findings, with H&E stains performed only initially, the mass was considered a neuroendocrine tumor (NET). Antrectomy with Billroth II anastomosis was performed. A microscopic and immunohistochemical studies of the resected specimen showed the cells to be positive for smooth muscle actin (SMA) making GGT the final diagnosis.

Clinical discussion:

Of the 116 patients included in our analysis, 56.9% (n=66) were females and age group was between 41 and 64 years old in 63.8% (n=74) of the patients. About 55 cases (47.4%) had abdominal or epigastric pain or discomfort, which was the most frequent clinical symptom. In immunohistochemistry, SMA staining is present in 68.1% of the cases, underscoring its diagnostic significance. Laparotomy with wedge or partial gastrectomy was employed in 46.1% of the recorded cases. Due to malignant potential, long-term follow-up and monitoring are usually recommended.

Conclusion:

Despite the rarity of GGT, they should be included in the differential diagnosis of gastric submucosal tumors, with immunohistochemistry studies playing a major role in the diagnosis. Furthermore, a comprehensive evaluation of the literature in the past 8 years was presented in a table.
Expanding the Spectrum of GLI1-rearranged Neoplasms of the Gastrointestinal Tract to Include Monophasic Keratin-positive Epithelial Neoplasms
Authors: Bahceci Dorukhan , Kim Grace E. , Kakar Sanjay , Balitzer Dana J. , Nguyen Eric D. , Ramachandran Rageshree , Umetsu Sarah E. , Joseph Nancy M.
Published: October 2024

GLI1-altered tumors form a diverse group occurring in various anatomic locations. In the alimentary tract, the most established are gastroblastoma, a biphasic epithelial-mesenchymal neoplasm of the stomach, and plexiform fibromyxoma, a pure spindle cell neoplasm. The spectrum of GLI1-rearranged gastrointestinal tumors has recently expanded with reports of cases in other parts of the GI tract, some exhibiting gastroblastoma-like features and others being pure mesenchymal neoplasms. These tumors often display a nonspecific immunophenotype, with only CD56 and cyclin D1 expression being common. Biphasic GLI1-altered tumors show diffuse keratin positivity in the epithelial component only, and GLI1-altered mesenchymal tumors typically lack or show only focal keratin expression. This study details 2 GLI1-rearranged gastrointestinal tract tumors with diffuse keratin and CD56 expression, composed entirely of epithelial cells with a nested growth pattern and finely stippled monotonous nuclei, leading to an initial suspicion of neuroendocrine tumor in both cases, despite lack of synaptophysin and chromogranin expression. Diffuse strong nuclear cyclin D1 expression was seen in both cases, and conversely, strong cyclin D1 staining was only seen in 5.4% (4/74) of well-differentiated neuroendocrine tumors tested. These 2 GI tract neoplasms highlight a widened spectrum of GLI1-rearranged tumors, now including monophasic epithelial neoplasms with diffuse keratin expression.
Involving Patients and/or Their Next of Kin in Serious Adverse Event Investigations: A Qualitative Study on Hospital Perspectives
Authors: Knap Linda J. , Dijkstra-Eijkemans Rachel I. , Friele Roland D. , Legemaate Johan
Published: October 2024

Background

The involvement of patients or next of kin (P/N) after a serious adverse event (SAE) is evolving. Beyond providing mandatory information, there is growing recognition of the need to incorporate their interests. This study explores practical manifestations of P/N involvement and identifies significant considerations for hospitals.

Methods

The data collection involved various qualitative research methods: 7 focus groups with 56 professionals from 37 hospitals, an interview with 2 representatives from the Dutch Association of Hospitals, and an interactive reflection seminar with over 60 participants from 34 hospitals. Before the focus groups, a brief questionnaire was sent out to survey participants’ practices regarding into SAE investigations. After the study, another questionnaire was distributed to gather suggestions for future improvements and to identify their lessons learned. Thematic analysis was applied to the gathered data to identify key themes.

Results

Hospitals are increasingly acknowledging the interests and perspectives of P/N, recognizing their potential contributions to organizational learning and improvement. P/N involvement following SAEs includes active participation in different stages of the investigation process, not just passive information dissemination. Important factors influencing involvement are the provision of (emotional) support, identification of needs, and transparency of the SAE investigation.

Conclusions

This study enhances understanding of evolving practices surrounding P/N involvement in the context of SAEs in Dutch hospitals. The findings highlight the importance of promoting meaningful involvement, recognizing the significance of P/N experiences, and fostering a culture of transparency and collaboration. By examining the dynamics of involvement, this research aims to inform policy development and facilitate the implementation of patient-centered approaches to post-SAE care.
Enhancing Sepsis Care at an Academic Emergency Department in a Resource-Constrained Setting: A Quality Improvement Initiative
Authors: Noureldeen Haytham , Bakhsh Abdullah , Alshabasy Adel , Alawi Maha , Bakhribah Ahmad , Nasrallah Nihad , Aljuhani Ohoud , Margushi Rahaf , Bantan Rafal , Bokhari Raneem , Idris Sarah , Alshamrani Lamis , Samman Abeer , Alharthi Elaf , Alothman Ali
Published: October 2024

Objectives

The early recognition of sepsis and septic shock is crucial for improved patient outcomes. Quality improvement programs have ameliorated processes and outcomes in the care of patients with sepsis and septic shock. This study aimed to improve the proportion of patients receiving antibiotics within 1 hour of triage and compliance with sepsis bundles.

Methods

A multidisciplinary sepsis task force was created to monitor and improve sepsis care. The program lasted 24 months from January 1, 2018, to December 31, 2019. A unique screening criterion was created by combining items from the systemic inflammatory response syndrome, quick sequential organ failure assessment, and National Early Warning Score systems. Thereafter, a sepsis flowsheet was implemented in the emergency department for monitoring. The measures between the first 12 months and the last 12 months were compared.

Results

The proportion of patients receiving antibiotics within 1 hour of triage improved from 44% to 84%, intravenous crystalloid administration within 3 hours improved from 62% to 94%, serum lactic acid measurement within 3 hours improved from 62% to 94%, and vasopressor initiation within 6 hours improved from 76% to 94%. The mortality rates decreased from 32% to 21% between the 2 study periods.

Conclusions

This program emphasizes the impact of a structured quality improvement program on the process and outcomes of care.
The potential impact of new tuberculosis vaccines on the burden of tuberculosis in people with HIV in South Africa
Authors: Sumner Tom , Clark Rebecca A. , Prys-Jones Tomos O. , Bakker Roel , Churchyard Gavin , White Richard G.
Published: October 2024

Background:

People with HIV (PWH) are at an increased risk of tuberculosis (TB). New TB vaccines may help reduce this burden. New TB vaccine candidates are well tolerated and immunogenic in PWH. There are currently limited data on vaccine efficacy in this population.

Methods:

Using mathematical modeling, we explored the potential impact of a novel TB vaccine on TB burden in PWH in South Africa between 2030 and 2050. We compared the impact of a vaccine delivered irrespective of HIV status to vaccination of either PWH or people without HIV. We explored the impact of reduced vaccine efficacy and duration of protection in PWH relative to people without HIV on our model predictions.

Results:

Vaccination irrespective of HIV status, with a vaccine with equal efficacy and duration in PWH, could avert up to 1.01 (95% range: 0.96–1.22) million TB cases in PWH. Restricting vaccination to PWH or people without HIV would achieve 65% (60–70) and 48% (46–53) of the total impact, respectively. These results are strongly dependent on the assumed efficacy and duration of protection in PWH. Further information on these characteristics is important to identify the most efficient use of new vaccines to reduce TB burden in PWH.

Conclusion:

Our results suggest that new vaccines could play an important role in reducing the TB burden in PWH. Vaccines targeted at people without HIV could provide significant indirect benefit to PWH, but vaccines which are well tolerated and effective in PWH will be critical to maximizing the impact in this population.
Anticoagulant Treatment May Decrease the Relapse Rate of Pulmonary Arterial Involvement in Behçet’s Disease
Authors: Abacar Kerem Yiğit , Boncukcuoglu Ayşe Elif , Aksoy Aysun , Kocakaya Derya , Cimsit Cagatay , Direskeneli Haner , Alibaz-Oner Fatma
Published: October 2024

Objectives

Pulmonary arterial involvement (PAI) is one of the most common causes of mortality in Behçet’s disease (BD). In this study, we aimed to evaluate the clinical features, course, and recurrence risk factors of BD-associated PAI.

Methods

BD patients who were followed up in Marmara University BD outpatient clinic between 1990 and 2023 were included. All data were acquired from the patients' medical records. PAIs were classified according to the type of the vascular involvement as thrombosis or aneurysm. Factors affecting the risk of relapses were determined using multivariate Cox regression analysis.

Results

Among 1350 BD patients, 110 (8.1%) had PAI. The mean age (SD) of patients with PAI was 42.4 (11.6) years, and the male/female ratio was 2.2 (76/34). Thirty-two (29.1%) of 110 patients were asymptomatic. Asymptomatic patients with PAI were significantly younger (p = 0.031) than the symptomatic group. Also, a greater prevalence of females (p = 0.001) and higher recurrence rates (p = 0.019) were observed in the symptomatic group. Pulmonary arterial thrombosis was seen in 104 (94.5%) and aneurysms in 9 patients (6.6%). At least one PAI relapse was observed in 31 patients (28.2%). In multivariate analysis, the Cox regression model was significant (p = 0.013), and not starting anticoagulants independently increased the PAI relapse risk (hazards ratio, 4.36; 95% confidence interval, 1.14–24.1; p = 0.042).

Conclusions

Pulmonary arterial thrombosis is the main presentation type of PAI in BD, whereas aneurysmatic formation is rare. Despite immunosuppressive treatment, relapses occur during follow-up in one third of patients with PAI. When anticoagulant therapy is added to immunosuppressive therapy, the relapse rate in BD patients with PAI is significantly reduced.
Risk Factors for Developing Community-Acquired Hand Infections at a Large-Volume Urban Safety Net Hospital
Authors: Yin Raymond , Rosser Mica , Mclaughlin Matthew F. , Soroudi Daniel , Patel Alap U. , Sadjadi Ryan , Hansen Scott L.
Published: October 2024

Background

Hand infections represent a significant burden for both health care systems and their patients. Epidemiological understanding of community-acquired hand infections is limited. This study examined a cohort of hand infection patients at a large urban safety net hospital for characteristics that were associated with protective and/or risk factors for hand infections.

Methods

We performed a retrospective chart review for all patients who required hand surgery consultation in the emergency department during a 1-year period (2021–2022). County-level population characteristics were obtained through the county-level data sources. We then performed a risk ratio (RR) analysis for demographic and socioeconomic characteristics.

Results

A total of 125 patients were included in the study cohort. Cisgender male (RR, 4.654; P < 0.001), Black (RR, 6.062; P < 0.001) and American Indian/Alaska Native (RR, 3.293; P = 0.041) patients were found to be overrepresented in our cohort when compared to county proportions, indicating an association with increased risk of hand infections. Patients between 35 and 49 years of age were also found to have an increased risk (RR, 1.679; P = 0.005). Age over 65 years, retirement, and employment were found to be protective factors (RR, 0.341 [P = 0.001]; RR, 0.397 [P = 0.043]; RR, 0.197 [P < 0.001]). In contrast, unemployment and unstable housing (unhoused or shelter) were found to have strong harmful risk for necessitating hand infection consults (RR, 7.587 [P < 0.001]; RR, 235.715 [P < 0.001]; RR, 29.990 [P < 0.001]).

Conclusions

There are clear risk factors at play for hand infection incidence. We found that housing status, employment, race, gender, and age were some of the most important contributors for incidence. This information can assist clinicians and public officials in developing more specific screening algorithms and prevention tools to reduce systematic burden. Further studies are required to elucidate specific etiologies associated with hand infection risk.
Seeds of language-like generativity in bird call combinations
Authors: Engesser Sabrina , Ridley Amanda R. , Watson Stuart K. , Kita Sotaro , Townsend Simon W.
Published: October 2024

Language is unbounded in its generativity, enabling the flexible combination of words into novel sentences. Critically, these constructions are intelligible to others due to our ability to derive a sentence’s compositional meaning from the semantic relationships among its components. Some animals also concatenate meaningful calls into compositional-like combinations to communicate more complex information. However, these combinations are structurally highly stereotyped, suggesting a bounded system of holistically perceived signals that impedes the processing of novel variants. Using long-term data and playback experiments on pied babblers, we demonstrate that, despite production stereotypy, they can nevertheless process structurally modified and novel combinations of their calls, demonstrating a capacity for deriving meaning compositionally. Furthermore, differential responses to artificial combinations by fledglings suggest that this compositional sensitivity is acquired ontogenetically. Our findings demonstrate animal combinatorial systems can be flexible at the perceptual level and that such perceptual flexibility may represent a precursor of language-like generativity.
Move less, spend more: the metabolic demands of short walking bouts
Authors: Luciano F. , Ruggiero L. , Minetti A. E. , Pavei G.
Published: October 2024

The metabolic cost of steady-state walking is well known; however, across legged animals, most walking bouts are too short to reach steady state. Here, we investigate how bout duration affects the metabolic cost of human walking with varying mechanical power, metabolic intensity and duration. Ten participants walked for 10- to 240-s bouts on a stair climber at 0.20, 0.25 and 0.36 m s
−1
and on a treadmill at 1.39 m s
−1
. Oxygen uptake was time-integrated and divided by bout duration to get bout average uptake (V̇O
2(b)
). Fitting of oxygen uptake kinetics allowed calculating non-metabolic oxygen exchange during phase-I transient and, hence, non-steady-state metabolic cost (
C
met(b)
) and efficiency. For 240-s bouts, such variables were also calculated at steady state. Across all conditions, shorter bouts had higher V̇O
2(b)
and
C
met(b)
, with proportionally greater non-metabolic oxygen exchange. As the bout duration increased, V̇O
2(b)
,
C
met(b)
and efficiency approached steady-state values. Our findings show that the time-averaged oxygen uptake and metabolic cost are greater for shorter than longer bouts: 30-s bouts consume 20–60% more oxygen than steady-state extrapolations. This is partially explained by the proportionally greater non-metabolic oxygen uptake and leads to lower efficiency for shorter bouts. Inferring metabolic cost from steady state substantially underestimates energy expenditure for short bouts.
The estimated impact of mandatory front-of-pack nutrition labelling policies on adult obesity prevalence and cardiovascular mortality in England: a modelling study
Authors: Evans Rebecca , O’Flaherty Martin , Edi Putra I Gusti Ngurah , Kypridemos Chris , Robinson Eric , Colombet Zoé
Published: October 2024

Objectives

Since 2013, industry-endorsed front-of-pack traffic light labels have been implemented voluntarily on packaged food in the UK. The UK Government is now considering alternative labelling approaches which may be more effective, such as Chile’s mandatory nutrient warning labels. The primary aim of this study was to model the likely impact of implementing mandatory front-of-pack nutrition labels in England on energy intake and consequent population-level obesity, and, secondarily, cardiovascular disease (CVD) mortality.

Design

Microsimulation modelling analysis

Setting

England

Model

A microsimulation model (2024–2043) to estimate the impact of changing front-of-pack nutrition labels in England. The two main policy scenarios tested were mandatory implementation of (i) traffic light labels and (ii) nutrient warning labels. For each scenario, the impact of the policy through assumed changes in energy intake due to consumer behaviour change and reformulation was modelled.

Main outcome measures

Change in obesity prevalence (%) and CVD deaths prevented or postponed.

Results

Compared to the baseline scenario (current voluntary implementation of traffic light labelling), mandatory implementation of traffic light labelling was estimated to reduce obesity prevalence in England by 2.28% (95% UI –4.06 to –0.96) and prevent or postpone 17000 (95% UI 4700 to 48000) CVD deaths. Mandatory implementation of nutrient warning labelling was estimated to have a larger impact; a 3.68% (95% UI –9.94 to –0.18) reduction in obesity prevalence and the prevention/postponement of 29000 (95% UI 1200 to 110000) CVD deaths.

Conclusions

This work offers the first modelled estimation of the impact of introducing mandatory front-of-pack nutrition labels on health outcomes in the adult population in England. Findings suggest that mandatory implementation of nutrient warning labels would reduce rates of obesity and CVD deaths, compared to current voluntary or mandatory implementation of traffic light labelling, and should therefore be considered by the UK government.

Funding

European Research Council (Grant reference: PIDS, 8031940).
Neutrophil gelatinase-associated lipocalin and Fibrinogen-to-albumin ratio are indicators of nephropathy in adult steady state sickle cell disease patients: A multicenter case-control study in Ghana
Authors: Twumasi Stephen , Odame Anto Enoch , Obirikorang Christian , Kobina Dadzie Ephraim Richard , Sackey Benedict , Paintsil Vivian , Owusu Ansah Richard , Effah Alfred , Adofo Ayirebi Allwell , Opoku Angela , Yawson Scott Godfred , Osei Leslie , Duku Joyce , Asafo Adjei Emmanuel , Antwi Boateng Lilian
Published: October 2024

Background

Progressive renal failure is one of the main complications in sickle cell disease. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is present in gelatinase/tertiary granules of neutrophils and it is a relatively newly recognized marker of nephropathy. Fibrinogen increases and albumin decreases in inflammatoy conditions like SCD. This study investigated the diagnostic roles of NGAL and fibrinogen-to-albumin ratio in steady state adult sickle cell disease patients.

Methods

In this study, 104 sickle cell disease participants and 51 healthy subjects were analysed. Participants’ information was thoroughly documented using a structured questionnaire and patient case records. To evaluate the hematobiochemical parameters, 5ml of venous blood was drawn from each participant and a clean catch of mid-stream urine was collected from each participant. Subjects with sickle cell disease were further classified as SCD nephropathy and SCD non- nephropathy subjects based on reduced estimated Glomerular Filtration Rate (eGFR) and microalbuminuria.

Results

Prevalence of nephropathy was 32.7% among adult steady state SCD patients. Significant high levels of Urine Albumin-to-Creatinine Ratio (UACR), NGAL and fibrinogen-to-albumin ratio (FAR) were seen in SCD patients with nephropathy compared to those without nephropathy (p<0.001). NGAL levels significantly increased along with increased urine albumin-to-creatinine ratio (r=0.28,p<0.005) in both SCD with nephropathy and those without nephropathy. There was a significant negative correlation between creatinine (r=-0.90,p<0.0005), urea (r=-0.50,p<0.0005) and eGFR in SCD subjects. Similarly, a significant negative relationship existed between UACR and eGFR (r=-0.34,p<0.0005). Creatinine also had a significant positive correlation with UACR (r=0.27,p<0.005 and urea (r=0.56,p<0.0005) in SCD subjects. NGAL was found to be a good predictor of nephropathy in steady state SCD patients with AUC=0.742,p<0.0001 when compared with creatinine and urea with AUC=0.618,p=0.048 and AUC=0.531,p=0.647 respectively. However, FAR could not be used as a predictive marker since it had non-significant poor performance (AUC=0.462,p=0.536).

Conclusion

NGAL as independent marker, is an early predictor of kidney disease as compared to urea and creatinine. Fibrinogen-to-albumin ratio can be used to track nephropathy treatment in steady state sickle cell disease patients since it is elevated in those with sickle cell nephropathy compared to healthy individuals. These two markers can be added to the available array of test in the management of nephropathy among steady SCD patients.
Development and Validation of Automated Software for the Detection of Large Vessel Occlusion on Noncontrast CT
Authors: Tsuji Hirofumi , Ishii Akira , Abekura Yu , Nishi Hidehisa , Fuchigami Takuya , Tachibana Atsushi , Ito Hirotaka , Arakawa Yoshiki
Published: October 2024

Background

Reliable detection of large-vessel occlusion (LVO) via medical-image analysis has significant advantages in cases of acute ischemic stroke (AIS). In recent years, convolutional neural network (CNN)-based technologies for automated LVO detection have been developed. However, the pros and cons of CNN-based assistance in clinical practice remain poorly understood. The purpose of this study was to develop and validate a deep learning-based model to detect the hyperdense-artery sign (HAS) as a proxy for LVO and to investigate its impact on neurosurgeons’ diagnostic accuracy.

Methods

We conducted a multicenter, retrospective study of patients with LVO due to anterior-circulation AIS who underwent computed tomography angiography or magnetic resonance angiography on admission, as well as patients without LVO (patients with no indicative angiography features and patients with cerebral infarction without LVO), who were admitted from 2006 to 2022. A CNN algorithm for LVO detection was developed using data from four institutions (n=690), and model performance was validated using data from five institutions (n=129). For further investigation, five board-certified and five non-board-certified neurosurgeons performed two separate observer-performance studies with a 4-week interval, with and without the CNN for each image.

Results

The HAS was detected in the correct location with a sensitivity and specificity of 0.79 and 0.87 by the CNN, 0.61 and 0.60 by board-certified neurosurgeons, and 0.61 and 0.66 by non-board-certified neurosurgeons, respectively. With the CNN, the mean area under the curve and figure of merit significantly increased for all readers (from 0.72 to 0.81, p<0.001, and from 0.71 to 0.77, p=0.005, respectively).

Conclusions

Our deep learning-based automated LVO-detection model for non-contrast-enhanced computed tomographic images significantly improved neurosurgeons’ diagnostic performance. Further studies are needed to clarify the usefulness of the CNN in clinical practice.
Searching for Sulfotyrosines (sY) in a HA(pY)STACK
Authors: Tzvetkov Jordan , Eyers Claire E , Eyers Patrick A , Ramsbottom Kerry A , Oswald Sally O , Harris John A , Sun Zhi , Deutsch Eric W , Jones Andrew R
Published: October 2024

Protein sulfation can be crucial in regulating protein-protein interactions but remains largely underexplored. Sulfation is near-isobaric to phosphorylation, making it particularly challenging to investigate using mass spectrometry. The degree to which tyrosine sulfation (sY) is misidentified as phosphorylation (pY) is thus an unresolved concern. This study explores the extent of sY misidentification within the human phosphoproteome by distinguishing between sulfation and phosphorylation based on their mass difference.

Using Gaussian mixture models (GMMs), we screened ∼45M peptide-spectrum matches (PSMs) from the PeptideAtlas Human Phosphoproteome build for peptidoforms with mass error shifts indicative of sulfation. This analysis pinpointed 104 candidate sulfated peptidoforms, backed-up by Gene Ontology (GO) terms and custom terms linked to sulfation. False positive filtering by manual annotation resulted in 31 convincing peptidoforms spanning 7 known and 7 novel sY sites. Y47 in Calumenin was particularly intriguing since mass error shifts, acidic motif conservation, and MS2neutral loss patterns characteristic of sulfation provided strong evidence that this site is sulfated rather than phosphorylated.

Overall, although misidentification of sulfation in phosphoproteomics datasets derived from cell and tissue intracellular extracts can occur, it appears relatively rare and should not be considered a substantive confounding factor in high-quality phosphoproteomics datasets.