bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Quadriceps Strength at 6 Months Postoperatively and Improvement in Patient-Reported Knee Function After Anterior Cruciate Ligament Reconstruction
Authors: Ishida Tomoya , Suzuki Makoto , Matsumoto Hisashi , Samukawa Mina , Kaneko Satoru , Inoue Chiharu , Aoki Yoshimitsu , Tohyama Harukazu
Published: January 2025

Background:

Understanding the factors associated with poor recovery over time after anterior cruciate ligament reconstruction (ACLR) helps clinicians identify patients who are at risk and targets for an intervention.

Purpose:

To determine the factors associated with improvement in subjective knee function from 6 to 12 months after ACLR.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

A total of 91 patients undergoing primary unilateral ACLR were included. Subjective knee function was assessed using the International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) at 6 and 12 months postoperatively. Isokinetic knee strength (quadriceps and hamstring) and Anterior Cruciate Ligament–Return to Sport After Injury (ACL-RSI) scale scores were also assessed. Patients were included in the poor recovery group if their improvement in the IKDC-SKF score from 6 to 12 months was <15.5 points (minimal detectable change) and their IKDC-SKF score at 12 months was <90 points (maximum, 100 points). The IKDC-SKF score, knee strength, and the ACL-RSI score were compared between the poor recovery and good recovery groups with and without propensity score matching. Matched variables included age, sex, and IKDC-SKF score at 6 months after ACLR. In addition, logistic regression analysis was performed to identify factors that discriminated between the poor recovery and good recovery groups.

Results:

There were 32 participants (35%) allocated to the poor recovery group. Before propensity score matching, the poor recovery group had a significantly older age, lower IKDC-SKF scores at 6 and 12 months, and a lower limb symmetry index (LSI) for quadriceps strength at 6 months. After propensity score matching, the LSI for quadriceps strength at 6 months was significantly different between the poor recovery and good recovery groups (73.0 ± 17.4 vs 83.3 ± 18.2, respectively; P = .039). Logistic regression analysis showed that a lower LSI for quadriceps strength at 6 months was significantly associated with poor recovery of the IKDC-SKF score (odds ratio, 0.96 [95% CI, 0.93-0.98]), and receiver operating characteristic curve analysis identified 80.9% as a cutoff value of the LSI for quadriceps strength with 75.0% sensitivity and 61.0% specificity.

Conclusion:

A lower LSI for quadriceps strength at 6 months postoperatively was associated with poor recovery of the IKDC-SKF score from 6 to 12 months after ACLR, even after adjusting for confounders.
Evaluation of Thigh Muscle Strength in Adolescent Patients After Anterior Cruciate Ligament Reconstruction With Lateral Extra-articular Tenodesis or Anterolateral Ligament Reconstruction
Authors: Weaver Adam P. , Harkey Matthew S. , Pacicca Donna M. , Crepeau Allison E. , Brown Matthew J. , Werner Brian C. , Diduch David R. , Kuenze Christopher
Published: January 2025

Background:

There has been increased interest in lateral extra-articular procedures, such as anterolateral ligament reconstruction (ALLR) or lateral extra-articular tenodesis (LET), to reduce anterolateral rotation instability of the knee after anterior cruciate ligament reconstruction (ACLR). Despite promising surgical outcomes with these techniques, their impact on knee strength recovery is unknown.

Hypothesis:

Patients undergoing lateral extra-articular procedures at the time of ACLR would have impaired thigh muscle strength at 6 to 9 months after surgery.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Adolescent patients who had undergone primary unilateral ACLR with lateral extra-articular augmentation between 2017 and 2023 were identified. Patients were included if they were aged between 12 and 20 years at the time of surgery and had completed an isokinetic strength assessment at 6 to 9 months after surgery. A total of 104 participants (mean age, 16.5 ± 1.7 years; 63 female) were included in this analysis: 25 who underwent ACLR+ALLR, 17 who underwent ACLR+LET, and 62 who underwent isolated ACLR. Isokinetic knee extension and flexion strength normalized to body weight, as well as the bilateral limb symmetry index (LSI), were assessed. One-way analysis of variance and analysis of covariance were used to compare differences between surgical techniques.

Results:

After adjusting for age, graft type, and time since surgery, the ACLR+LET (1.36 ± 0.52 N·m/kg) and ACLR+ALLR (1.61 ± 0.53 N·m/kg) groups had significantly less involved limb knee extension strength ( P = .025), uninvolved limb knee extension strength ( P = .046), and LSI for knee extension strength ( P = .040) compared to the isolated ACLR group. There were no differences between the 3 groups regarding involved limb knee flexion strength ( P = .222) or uninvolved limb knee flexion strength ( P = .984), but the isolated ACLR group displayed a greater LSI for knee flexion strength (96.6% ± 17.8%; P = .012).

Conclusion:

The addition of lateral extra-articular procedures at the time of ACLR was associated with decreased quadriceps strength at 6 to 9 months after ACLR. While lateral extra-articular procedures may enhance knee rotary stability after ACLR, prolonged rehabilitation may be needed to re-establish adequate quadriceps strength before return to sports.
Neural-WDRC: A Deep Learning Wide Dynamic Range Compression Method Combined With Controllable Noise Reduction for Hearing Aids
Authors: Zhang Huiyong , Moore Brian C. J. , Jiang Feng , Diao Mingfang , Ji Fei , Li Xiaodong , Zheng Chengshi
Published: January 2025

Wide dynamic range compression (WDRC) and noise reduction both play important roles in hearing aids. WDRC provides level-dependent amplification so that the level of sound produced by the hearing aid falls between the hearing threshold and the highest comfortable level of the listener, while noise reduction reduces ambient noise with the goal of improving intelligibility and listening comfort and reducing effort. In most current hearing aids, noise reduction and WDRC are implemented sequentially, but this may lead to distortion of the amplitude modulation patterns of both the speech and the noise. This paper describes a deep learning method, called Neural-WDRC, for implementing both noise reduction and WDRC, employing a two-stage low-complexity network. The network initially estimates the noise alone and the speech alone. Fast-acting compression is applied to the estimated speech and slow-acting compression to the estimated noise, but with a controllable residual noise level to help the user to perceive natural environmental sounds. Neural-WDRC is frame-based, and the output of the current frame is determined only by the current and preceding frames. Neural-WDRC was compared with conventional slow- and fast-acting compression and with signal-to-noise ratio (SNR)-aware compression using objective measures and listening tests based on normal-hearing participants listening to signals processed to simulate the effects of hearing loss and hearing-impaired participants. The objective measures demonstrated that Neural-WDRC effectively reduced negative interactions of speech and noise in highly non-stationary noise scenarios. The listening tests showed that Neural-WDRC was preferred over the other compression methods for speech in non-stationary noises.
Do Public School Choice Policies Segregate Schools? Dynamic Effects in Michigan
Authors: Edwards Danielle Sanderson , Anderson Kaitlin P.
Published: January 2025

Interdistrict choice has the potential to exacerbate or alleviate between-district segregation—an increasingly pervasive form of U.S. school segregation—by allowing students to attend schools in districts where they do not reside. Prior research concentrates on the effects of charter schooling on segregation within districts and counties. We used longitudinal enrollment and demographic data from Michigan to examine the impacts of both interdistrict and charter school choice on racial and economic segregation within and between districts in a single setting. We estimated these effects by leveraging between-grade differences in choice use within school systems and years. We confirmed findings from previous research that increases in charter school enrollment increase within-district racial and economic segregation. We also found that the effects of interdistrict choice on both within- and between-district segregation vary with the presence of charter schools.
Mitochondria-Associated Endoplasmic Reticulum Membranes in Microglia: One Contact Site to Rule Them all
Authors: Navarro Elisa , Montesinos Jorge
Published: January 2025

Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in maintaining tissue homeostasis by monitoring and responding to environmental changes through processes such as phagocytosis, cytokine production or synapse remodeling. Their dynamic nature and diverse functions are supported by the regulation of multiple metabolic pathways, enabling microglia to efficiently adapt to fluctuating signals. A key aspect of this regulation occurs at mitochondria-associated ER membranes (MAM), specialized contact sites between the ER and mitochondria. These structures facilitate the exchange of calcium, lipids, and metabolites and serve as metabolic and signaling hubs. This review synthesizes current research on how MAM influence microglial physiology, with an emphasis on their role in immunometabolism, offering new insights into the integration of metabolic and immune functions in the CNS and its impact in the context of neurodegeneration.
Integration of social work into specialist palliative home service
Authors: Wartchow Janice Lee , Bär Stefan , Alt-Epping Bernd , Gerlach Christina
Published: January 2025

Background:

The specialist palliative home service (SAPV) federal framework contract for adults, to be enacted in Germany until 2028, does not legally mandate the hiring of a third professional group beyond specialist nurses and physicians, although palliative care embraces the psychosocial dimension and an interprofessional approach.

Objectives:

This article aims to explore the role of medical staff in integrating social work (SW) into SAPV.

Design:

Qualitative case study.

Methods:

The study utilised theoretical and qualitative quota sampling to explore barriers to integrating SW into SAPV-teams, ensuring diverse perspectives. Sequential analysis was applied to uncover collective interpretations, generating and validating interpretive hypotheses directly from the data.

Results:

Four physicians and four nurses from the SAPV-team based at Heidelberg University Hospital participated. The medical staff’s attributions to SW significantly impact its integration into SAPV. Their perception of the SW profession determines the extent and manner of its integration into daily practices. Attributions on SW in SAPV as determined by nurses and physicians were social-medical knowledge, counselling, being a core competence in SAPV and similarities to the profession of psychologists. In the examined case, the integration was effective, and there was a desire for an increased presence of SW because there is still a lack of their working hours, and the medical staff wished for the social workers’ presence during home visits.

Conclusion:

This study highlights that SAPV requires SW to be effective, nonetheless, not being considered in the new federal contract to allocate resources. Possible barriers against the integration of SW within the real-world clinical practice of palliative care should be further investigated in future studies by involving social workers’ and healthcare managers’ experiences and strategies to understand why the employment of social workers in SAPV is progressing slowly and inform strategies to enhance their integration.
Important factors in municipality-based pediatric palliation from healthcare professionals’ perspective: A qualitative study
Authors: Skjærseth Kristin , Preminger Natalie , Hauken May Aasebø
Published: January 2025

Background:

Municipality-based pediatric palliative care (PPC) is recommended to promote the quality of life for the child and family by enabling them to stay at home as much as possible. However, municipality-based PPC presents complex challenges and places significant demands on healthcare professionals. Yet, it remains an underexplored field.

Objectives:

Semi-structured and individual interviews with 16 healthcare professionals with experiences from PPC were conducted and transcribed. Data was analyzed using systematic text condensation.

Results:

To increase the knowledge base and understanding of important factors for municipality-based PPC from healthcare professionals’ perspective.

Design:

A qualitative method with an interpretive descriptive design was applied.

Methods:

The bridging theme “Establishing a sense of security and predictability for the family and healthcare professionals” emerged from the analysis. This was elaborated by three main themes: (1) “A comprehensive approach to the family,” (2) “Establishing and maintaining a dedicated, multidisciplinary pediatric palliative team in the municipality,” and (3) “Collaboration and communication between involved services.” Each main theme was further elaborated by subthemes.

Conclusion:

The importance of establishing security and predictability in municipality-based PPC was emphasized. To achieve this, holistic support for the entire family and ensuring sufficient competence in the municipality seem crucial. Establishing municipality PPC teams is proposed, and the need for early referral, routines for collaboration, and a designated coordinator appear to be key systemic factors.

Registration and reporting guidelines:

The study is registered in the institutional system for research project (RETTE ID: R2082), and the study is reported according to the COREQ checklist for qualitative studies.
Assessing and comparing compassionate communities benefits across cities in diverse cultural contexts: a step toward the identification of the most important ones
Authors: González-Jaramillo Valentina , Krikorian Alicia , Tripodoro Vilma , Jorge Margarita , Orellana Sebastián , López Francy , Vélez Maria Clara , Noguera Tatiana , Montilla Silvina , Felber Sibylle , Zambrano Sofía C. , Eychmüller Steffen
Published: January 2025

Background:

As Compassionate Communities (CCs) are developing worldwide, there is a growing need to systematically assess if they are having the expected effects on the community. Although having a single strategy would be ideal in terms of standardization and comparison, due to the inherent heterogeneity of CCs, it is not known how feasible this would be.

Objectives:

To assess the feasibility of creating a general strategy, based on the results of a series of focus groups conducted across three diverse CCs, to guide the evaluation of already existing programs and the development of new ones.

Design:

Focus groups in three cities, including different types of stakeholders, were conducted to identify potential outcomes (benefits) from CCs, as the base of a general strategy to assess CCs.

Methods:

We coded the discussions and built a list of the outcomes mentioned. Then, we merged those similar enough into a more general one that encompassed the others. We extracted from reviews all the CCs outcomes that have been measured. We merged the outcomes from the focus groups and the reviews and built a single list.

Results:

We obtained a final list of 46 outcomes; 44 were reported from the focus groups, and two more were added from the reviews. Of the 44 from the focus groups, 22 (50%) were present in the three CCs, 14(32%) were present in two CCs, and the remaining 8 (18%) were present only in one compassionate community. There were outcomes commonly reported both in the three CCs and in the literature reviews related to training the general community in compassion and end-of-life topics, facilitating the development of community networks, and generating public spaces for social integration.

Conclusion:

Half of the identified outcomes were reported in the three CCs. This indicates the feasibility of creating a single strategy but also reflects the need to leave room to include other aspects specific to each community according to its context in the assessment.
Demographic and clinical characteristics of older people with multimorbidity accessing primary healthcare in Malawi: A cross-sectional study
Authors: Kwaitana Duncan , Jafali James , Bates Maya Jane , van Breevoort Dorothee , Mildestvedt Thomas , Meland Eivind , Umar Eric
Published: January 2025

Background

Multimorbidity is a growing global concern, affecting patient outcomes and healthcare costs. In low- and middle-income countries, data on multimorbidity in primary care beyond prevalence is limited. Our study explored the demographic and clinical characteristics of multimorbidity among older people attending primary health care in Malawi.

Methods

We conducted a cross-sectional analysis on medical records from 15,009 older patients aged ≥50 years across three hospitals in Malawi (one tertiary, two district). Data from 2019-2021 was analyzed using R statistical software to examine patterns of multimorbidity (two or more chronic conditions). Outcome estimates were adjusted for sex, age, location, and year of clinic visit.

Results

The overall prevalence of multimorbidity, defined across 17 recorded chronic conditions, was 19.6%. Among the 2,941 cases of multimorbidity, 2,708 (92.0%) involved two chronic conditions, while 233 (8.0%) involved three. While most conditions increased steadily in prevalence with age, diabetes followed a different pattern, with higher prevalence among individuals aged 50–59 years (53.9%) and 60–69 years (52.4%) compared to those 70 years and older (40.3%). After adjusting for clinic visit year, gender, and study location, individuals aged 70 years and older were significantly less likely to have multimorbidity compared to those aged 50–59 years (AOR = 0.57, 95% CI: 0.52–0.62, p < 0.001).

Conclusion

The study revealed a wide range of multimorbidity combinations among older people attending primary health care. Strategies to address multimorbidity in older people should include efforts to identify other, less common clusters of chronic conditions.
Correlation between process conditions and mechanical film properties in foamed multilayer blown films
Authors: Stieglitz Marius , Hopmann Christian , Leuchtenberger-Engel Lisa , Junge Henrik
Published: January 2025

In the context of packaging with films, specific mechanical properties are of paramount importance. This can be achieved through the implementation of optimized manufacturing processes and the efficient utilization of raw materials. The foam extrusion process has the potential to enhance material efficiency. The foam structure impacts the mechanical properties due to replacing force-conducting material. Blown film extrusion represents a predominant production process in the packaging field, offering the potential for cost-effective mass production. Integration of these processes gives rise to intricate behavior patterns, attributable to interactions between the conditions governing the blown film and those governing foam extrusion. This affects the density reduction and the mechanical properties of the material. This study’s objective was to identify the significant parameters affecting mechanical properties and to gain insight into the mechanisms influencing the foam blown film process. The results demonstrated that combining foam and blown film extrusion markedly reduces the resulting film density, with a potential savings of up to 40% in plastic at 7% blowing agent content. The optimal conditions to produce small-cell foam structures include high die pressure gradients, which can be achieved by lowering the blown film die head temperature or increasing the mass flow rate of the foamed middle layer. Tensile stress and Youngs modulus decrease with increasing blowing agent content, as the gas-filled cells reduce structural integrity. Thinner films often show higher tensile strength due to better molecular orientation. At the same time, the mass ratio influences the mechanical properties by changing the polymer structure and cell distribution, which optimizes or weakens the mechanical properties. The study presents significant insights into the blown film foam extrusion process and investigates the correlations between density reduction and the resulting mechanical properties.
Sodium butyrate regulates macrophage polarization by TGR5/β-arrestin2 in vitro
Authors: Liu Miao , Xie Wen-jie , Zhang Xu , Wu Wei , Li Guang , Wang Lu
Published: January 2025

Background

Macrophages play an important role in the pathogenesis of ulcerative colitis (UC). We will explore the effects of sodium butyrate (SB) on macrophage function.

Methods

The targets of butyric acid were identified using SwissTargetPrediction database and surface plasmon resonance (SPR). Limited proteolysis mass spectrometry (Lip-MS) was used to further investigate the binding sites of butyric acid with its targets and molecular docking was employed to simulate their binding modes. Macrophage polarization model was established with lipopolysaccharide (LPS) in vitro. Takeda G protein-coupled receptor 5 (TGR5) and β-arrestin2 expression and macrophage polarization markers were detected with or without SB.

Results

TGR5 was identified as the target of butyric acid. Moreover, the amino acid regions 275–286 and 321–330 of TGR5 (GPBAR1 [275–286] and GPBAR1 [321–330]) were the potential binding regions for butyric acid. Based on molecular docking analysis, butyric acid formed effective hydrogen-bonding interactions with ASP-284 and TYR-287 of TGR5. In cell experiments, LPS inhibited the expression of TGR5, β-arrestin2, IL-10, ARG1, and CD206 and increased the expression of IL-1β, iNOS, and CD86, while SB reversed the effect of LPS. SBI-115, a TGR5 antagonist, and knockdown of β-arrestin2 inhibited the effect of sodium butyrate. INT-777, a TGR5 agonist, reversed the inhibitory effect of knockdown of β-arrestin2.

Conclusion

SB inhibited M1-like polarization and promoted M2-like polarization induced by LPS via TGR5/β-arrestin2 in RAW264.7 cells and TGR5 was the target of SB.
Defective Slc7a7 transport reduces erythropoietin compromising erythropoiesis
Authors: Giroud-Gerbetant Judith , Sotillo Fernando , Hernández Gonzalo , Ruano Irene , Sebastián David , Fort Joana , Sánchez Mayka , Weiss Günter , Prats Neus , Zorzano Antonio , Palacín Manuel , Bodoy Susanna
Published: January 2025

Background

Lysinuric protein intolerance is a rare autosomal disorder caused by mutations in the Slc7a7 gene that lead to impaired transport of neutral and basic amino acids. The gold standard treatment for lysinuric protein intolerance involves a low-protein diet and citrulline supplementation. While this approach partially improves cationic amino acid plasma levels and alleviates some symptoms, long-term treatment is suggested to be detrimental and may lead to life-threatening complications characterized by a wide range of hematological and immunological abnormalities. The specific cause of these hematopoietic defects—whether intrinsic to hematopoietic cells or driven by external factors—remains unclear. Given the limitations of current citrulline-based treatments and the unknown role of SLC7A7 in red blood cell production, there is an urgent need to investigate the pathways affected by SLC7A7 deficiency.

Methods

We employed total inducible and cell type-specific Slc7a7 knockout mouse models to determine whether the hematological abnormalities observed in LPI are due to the loss of Slc7a7 function in hematopoietic cells. We analyzed erythropoiesis in these mice and performed bone marrow transplantation experiments to assess the role of Slc7a7 in erythroblasts and myeloid cells. The statistical significance of differences between groups was evaluated via standard statistical tests, including Student’s t test and ANOVA.

Results

Whole-body Slc7a7 knockout mice presented impaired erythropoiesis. However, this defect was not replicated in mice with Slc7a7 deficiency restricted to erythroblasts or myeloid cells, suggesting that the observed hematopoietic abnormalities are not due to intrinsic Slc7a7 loss in these cell types. Additionally, bone marrow transplants from control mice did not rescue the hematopoietic defects in Slc7a7-deficient mice, nor did the transplantation of Slc7a7-deficient cells induce defects in control recipients. Further investigation indicated that defective erythropoiesis is linked to impaired erythropoietin production in the kidney and subsequent iron overload.

Conclusions

The hematopoietic defects in the Lysinuric protein intolerance mouse model are not caused by intrinsic Slc7a7 loss in hematopoietic cells but rather by impaired erythropoietin production in the kidney. This finding opens potential avenues for therapeutic strategies targeting erythropoietin production to address hematological abnormalities in humans with lysinuric protein intolerance.
Impact of the new hazard classes in the CLP regulation on EU chemicals legislation
Authors: Kättström Diana , Beronius Anna , Boije af Gennäs Urban , Rudén Christina , Ågerstrand Marlene
Published: January 2025

The EU recently introduced four new hazard classes to the Classification, Labelling and Packaging Regulation (CLP) (EC) 1272/2008. The classes are endocrine disruption for human health (ED HH) and the environment (ED ENV), persistent, bioaccumulative and toxic (PBT) or very persistent and very bioaccumulative (vPvB), and persistent, mobile and toxic (PMT) or very persistent and very mobile (vPvM). This action was a direct consequence of the EU’s Chemicals Strategy for Sustainability, which aims at strengthening the protection of human health and the environment, as well as reinforcing the CLP Regulation as the central piece of the chemicals legislation. This study examined the regulatory obligations triggered by these new hazard classes, as well as the existing obligations for endocrine disrupters and PBT/vPvB substances identified in other EU regulations. In addition, we compared the CLP criteria for endocrine disruption and PBT/vPvB to criteria existing in other EU regulations and investigated how these criteria are used in the EU chemicals legislation. We found that the implementation of the new hazard classes under the CLP into existing EU chemicals legislation will require the revision of all regulations that rely on the CLP hazard criteria for risk management. Without revision, the immediate impact of the new hazard classes will only extend to six regulations and the regulatory obligations they contain, all of which apply to substances classified under any of the CLP hazard classes. Meanwhile, substances with endocrine disrupting and PBT/vPvB properties are already being identified and regulated using criteria from regulations other than the CLP. When comparing the criteria for identification of endocrine disrupters and PBT/vPvB substances across the chemicals legislation, we found that the criteria differed between regulations. The findings aim to support the efficient implementation of the new CLP hazard classes and harmonization of criteria across regulations, in line with the Chemicals Strategy for Sustainability.
Sustainable utilization of bovine adipose tissue derivatives as robust antimicrobial agents against Methicillin-resistant Staphylococcus aureus
Authors: Alcici Muhammed Abdelhameed Ismael , Abdelhaleem Salma Waheed , Fahim Karima Mogahed , Saleh Neveen Mohamed , Farag Heba Saeed
Published: January 2025

Background

The excessive use of antibiotics is a major contributor to the global issue of antimicrobial resistance (AMR), a significant threat to human and animal health. Hence, assessing new strategies for managing Multi-Drug Resistant (MDR) microorganisms is vital. In this study, the use of mechanically isolated mature adipose cells (MIMACs) and their lysate (Adipolysate) as a new sustainable antimicrobial agent was assessed against Methicillin-resistant Staphylococcus aureus (MRSA).

Conclusions

The minimum volume of MIMACs achieved complete bacterial inhibition (Minimum Lethal volume) was 75 µl and 100 µl for bacterial concentration of 1010 and 1012 cfu/ml, respectively. Direct bacterial membrane attachment and intracellular capture was visualized under light and electron microscopy. Adipolysate was characterized via GC–MS, the fatty acid profile demonstrated several components with known antimicrobial properties. The tested Adipolysate revealed inhibition zone of diameter 25.33 ± 0.88 mm against the tested S. aureus strain, compared with the inhibition zone of Vancomycin (24.0 ± 0.00 mm) and Erythromycin (30.0 ± 0.00). The study revealed the potential effects of MIMACs and Adipolysate as sustainable, natural, and robust antimicrobial agents. However, these preliminary results will be further investigated to understand the mechanism of action and explore possible applications in various fields.
The implementation and side effect management of immune checkpoint inhibitors in gynecologic oncology: a JAGO/NOGGO survey
Authors: Riedel Maximilian , Herrmann Helene , Bartl Thomas , Rossner Anna-Maria , Tatzber Anna , Flethe Chiara , Zocholl Dario , Schmalfeldt Barbara , Sehouli Jalid , Pietzner Klaus
Published: January 2025

Background

The integration of immune checkpoint inhibitors (ICIs) into routine gynecologic cancer treatment requires a thorough understanding of how to manage immune-related adverse events (irAEs) to ensure patient safety. However, reports on real-world clinical experience in the management of ICIs in gynecologic oncology are very limited. The aim of this survey was to provide a real-world overview of the experiences and the current state of irAE management of ICIs in Germany, Switzerland, and Austria.

Methods

We designed a questionnaire consisting of 34 items focused on physicans’ clinical experiences with ICIs and their management of irAEs. The survey was distributed between October 2022 and May 2023 to medical professionals with experience in the field of gynecologic oncology.

Results

A total of 221 gynecologists participated in the study. Most respondents (n = 130, 59.1%) were primarily engaged in gynecologic oncology at the time of the survey, with an average of ten years of clinical experience. Individual experiences with regard to irAEs varied significantly. When asked which irAEs they had observed “frequently” or “very frequently”, respondents most commonly reported thyroiditis (37.2%), followed by skin reactions (23.6%), and pneumonitis (10.6%). A total of n = 16 (7.4%) reported at least one death of a patient due to irAEs. Feeling “unconfident” or “very unconfident” about managing irAEs was reported by 35.6% (n = 78). With regard to clinical management of adverse events after discontinuation of treatment, 32.4% (n = 68) ceased to inquire about irAEs after six months.

Conclusion

The results of this survey provide valuable insights into physicians’ real-world experiences with irAEs associated with ICI treatment. Dealing with serious immune-related and potentially life-threatening side effects has become a routine aspect of clinical practice. Many physicians, however, express a lack of sufficient familiarity with irAEs and their management. Therefore, it is essential to improve medical education, specialized oncological training, and close interdisciplinary collaboration to improve patient care.
Knights in shining armour and (M)others in life jackets: Women’s experiences of advocating for care alone when suffering recurrent early pregnancy loss during the SARS-CoV-2 pandemic
Authors: Kent-Nye Flora E. , Sheen Kayleigh S. , Burgess Karen , Oza Munira , Magee Laura A. , Jurković Davor , Silverio Sergio A.
Published: January 2025

Background

Recurrent early pregnancy loss [rEPL] is a traumatic experience, marked by feelings such as grief and depression, and often anxiety. Despite this, the psychological consequences of rEPL are often overlooked, particularly when considering future reproductive health or approaching subsequent pregnancies. The SARS-CoV-2 pandemic led to significant reconfiguration of maternity care and a negative impact on the perinatal experience, but the specific impact on women’s experience of rEPL has yet to be explored. This study aimed to examine the impact of changes to early pregnancy loss care and social restrictions during the pandemic on women’s experience of rEPL.

Methods

A qualitative interview study design was employed, with semi-structured interviews conducted virtually. A total of 16 women who had suffered two or more early pregnancy losses (≤ 14 weeks gestation) during the SARS-CoV-2 pandemic in the United Kingdom participated. Data were recorded, transcribed, and analysed by hand, following a Classical Grounded Theory Analysis, appropriate for cross-disciplinary health research.

Results

Iterative and inductive analysis generated the theory ‘Knights in Shining Armour and (M)others in Life Jackets’, which describes women’s experience of advocating for care alone, when suffering rEPL during the pandemic. This theory was derived from the way in which three emergent themes inter-related: (1) Dismantling Validation; (2) Preserving an Identity of Motherhood; and (3) Support Waning.

Conclusions

This study affirms recent findings of devalued maternity care during the pandemic, and magnification of pre-pandemic issues with EPL care, such as a lack of support or perceived empathy.
Oral health in patients with cleft lip and palate: a systematic literature review and meta-analysis of periodontal and dental disease and oral microbiota (part 1)
Authors: Pardo A. , Vanti V. , Lonardi F. , Signoriello A. , Lobbia G. , Lombardo G. , Trevisiol L. , D’Agostino A.
Published: January 2025

Introduction

Orofacial cleft impacts jawbone and dental development and function, often with consequences for oral health. The first in this two-part systematic review of the literature on oral health in persons with cleft lip and/or palate focuses on periodontal parameters and composition of oral bacterial flora, while the second analyzes data on dental caries.

Materials and Methods

Four databases (PubMed, Cochrane, Scopus, Web of Science) were searched for studies that compared periodontal parameters, caries index, and microbiota composition between persons with cleft lip and/or palate and healthy controls. The Newcastle–Ottawa scale and the Joanna Briggs Institute checklist were applied to evaluate study quality.

Results

A total of 24 studies underwent systematic review, 18 of which entered meta-analysis. Twenty studies included a control group, while four included only persons with orofacial cleft. The first part (18 studies) compared periodontal parameters and oral microbiota.

Conclusions

Meta-analysis of periodontal parameters (plaque index, gingival index, bleeding index, probing pocket depth, clinical attachment level) revealed an association between orofacial cleft and greater risk for poor oral health and periodontal disease. Good oral health relies on correct home oral hygiene and regular visits to the dentist starting at an early age.
Medical Student Musculoskeletal Knowledge: Examining the Impact and Value of an Orthopaedic Surgery Clerkship Using the Freedman and Bernstein Examination
Authors: Nishime Nicole , Seibel Mary , Lindskog Dieter , Wiznia Daniel
Published: January 2025

Purpose

Given the importance of musculoskeletal knowledge but the limited orthopaedic instruction offered in medical school, our Orthopaedic Surgery Department developed a three-week clerkship for interested students. This study assesses the clerkship’s impact on medical student musculoskeletal knowledge through administration of the Freedman and Bernstein Basic Cognitive Musculoskeletal Examination.

Methods

Medical students enrolled in the orthopaedic surgery clerkship between February 2019 and May 2024 were asked to participate in pre- and post-clerkship surveys using the Freedman and Bernstein Basic Cognitive Musculoskeletal Examination. Raw and weighted scores were computed according to the guidelines provided by Freedman and Bernstein. Averaged scores were used to compute mean pre- and post-test scores.

Results

There were 64 responses to the pre-test and 33 responses to the post-test. The mean pre-test weighted score was 54% with 12 students (18.8%) passing. The mean post-test score was 70% with 17 students (51.5%) passing. Raw scores showed that musculoskeletal knowledge improved from pre-test (M = 55.13, SD = 19.90) to post-test (M = 70.22, SD = 14.70; p < .001). The results comparing weighted scores showed that the participants’ musculoskeletal knowledge also improved from pre-test (M = 52.86, SD = 21.12) to post-test (M = 67.11, SD = 19.02; p < .001).

Conclusion

While students demonstrated improved musculoskeletal knowledge after completing our institution’s orthopaedic surgery clerkship, almost half of the students did not pass the post-test. Most of the students who did not pass the post-test expressed definite or possible interest in pursuing an orthopaedic surgery residency.
Pharmacological pain management in patients with rheumatoid arthritis: a narrative literature review
Authors: Cox Natasha , Mallen Christian D. , Scott Ian C.
Published: January 2025

Background

Pain is a major challenge for patients with rheumatoid arthritis (RA), with many people suffering chronic pain. Current RA management guidelines focus on assessing and reducing disease activity using disease-modifying anti-rheumatic drugs (DMARDs). Consequently, pain care is often suboptimal, with growing evidence that analgesics are widely prescribed to patients with RA, despite potential toxicities and limited evidence for efficacy. Our review provides an overview of pharmacological treatments for pain in patients with RA, summarising their efficacy and use.

Findings

Thirteen systematic reviews of drug efficacy for pain in patients with RA were included in this review. These showed moderate- to high-quality evidence from clinical trials in more contemporary time-periods (mainly 1990s/2000s for synthetic DMARDs and post-2000 for biological/targeted synthetic DMARDs) that, in patients with active RA, short-term glucocorticoids and synthetic, biologic, and targeted synthetic DMARDs have efficacy at reducing pain intensity relative to placebo. In contrast, they showed low-quality evidence from trials in more historical time-periods (mainly in the 1960s–1990s for opioids and paracetamol) that (aside from naproxen) analgesics/neuromodulators provide any improvements in pain relative to placebo, and no supportive evidence for gabapentinoids, or long-term opioids. Despite this evidence base, 21 studies of analgesic prescribing in patients with RA consistently showed substantial and sustained prescribing of analgesics, particularly opioids, with approximately one quarter and > 40% of patients receiving chronic opioid prescriptions in each year in England and North America, respectively. Whilst NSAID prescribing had fallen over time across countries, gabapentinoid prescribing in England had risen from < 1% of patients in 2004 to approximately 10% in 2020. Prescribing levels varied substantially between individual clinicians and groups of patients.

Conclusions

In patients with active RA, DMARDs have efficacy at reducing pain, supporting the role of treat-to-target strategies. Despite limited evidence that analgesics improve pain in patients with RA, these medicines are widely prescribed. The reasons for this are unclear. We consider that closing this evidence-to-practice gap requires qualitative research exploring the drivers of this practice, high-quality trials of analgesic efficacy in contemporary RA populations, alongside an increased focus on pain management (including pharmacological and non-pharmacological options) within RA guidelines.
Diagnostic utility of LEF1 and β-catenin in WNT pathway tumors with CTNNB1 mutation
Authors: Li Can , Dong Lingdan , Zhu Li , Guan Wenbin
Published: January 2025

Objective

This study aimed to compare the expression of lymphoid enhancer factor 1 (LEF1) and β-catenin in basal cell adenoma (BA), desmoid-type fibromatosis (DF), and pancreatic solid pseudopapillary neoplasm (SPN) to evaluate their diagnostic utility in tumors associated with the WNT/β-catenin signaling pathway harboring the mutation of CTNNB1 gene 3 exon.

Methods

Eighty tumor patients, including 26 BAs, 30 DFs, and 24 SPNs, were analyzed. Immunohistochemical staining was identified positive (nuclear staining of LEF1 and β-catenin in > 50% of tumor cells). The diagnostic rate of LEF1 alone, β-catenin alone, and their combination were compared for each tumor type and all patients.

Results

Compared to β-catenin, when LEF1 alone was used for diagnosis, the diagnostic rate increased by 46.16% for BA, 16.67% for SPN, and 11.25% for all patients, but decreased by 23.34% for DF. The combined use of β-catenin and LEF1 significantly increased the diagnostic ratio in BA (46.16%), SPN (16.67%), and all patients (21.25%), but only marginally in DF (3.33%). In terms of all WNT pathway tumors with CTNNB1 gene mutation encompassed by our study, statistical analysis revealed no significant difference between LEF1 alone and β-catenin alone. However, their combined application was highly significant (P = 0.001) .

Conclusion

While β-catenin is commonly used as a marker for WNT pathway tumors, its variable expression and localization can be challenging for diagnosis. Our study emphasizes the importance of LEF1 as a complementary marker to β-catenin in diagnosing BA, DF, SPN, and other WNT pathway tumors activated by exon 3 CTNNB1 gene mutation. The combined use of LEF1 and β-catenin enhances diagnostic accuracy and may help the identification of these tumor types.
Neurocognitive impact of different irradiation modalities for patients with grade I-II skull base meningioma: a prospective multi-arm cohort study (CANCER COG)
Authors: Lesueur Paul , Joly Florence , Clarisse Benedicte , Lequesne Justine , Stefan Dinu , Balosso Jacques , Lange Marie , Thureau Sebastien , Capel Aurelie , Castera Marie , Legrand Berenice , Goliot Nicolas , Grellard Jean Michel , Tessonier Thomas , Castel Helene , Valable Samuel
Published: January 2025

Background

Radiotherapy as a complement or an alternative to neurosurgery has a central role in the treatment of skull base grade I-II meningiomas. Radiotherapy techniques have improved considerably over the last two decades, becoming more effective and sparing more and more the healthy tissue surrounding the tumour. Currently, hypo-fractionated stereotactic radiotherapy (SRT) for small tumours and normo-fractionated intensity-modulated radiotherapy (IMRT) or proton-therapy (PT) for larger tumours are the most widely used techniques. It is expected a decrease of the risk of cognitive impairment with these modern techniques. However prospective data about cognitive long-term consequences of partial brain irradiation with SRT, PT, or IMRT remain very scarce to date.

Methods

CANCER COG is one of the first multicentric study in the world to prospectively assess the cognitive performances of patients following different modalities of cerebral radiotherapy (stereotactic radiotherapy, proton therapy, intensity modulated radiotherapy) for the treatment of grade I-II skull base meningioma, up to at least 10 years after the end of radiotherapy. This longitudinal study includes the follow-up of 3 cohorts, including: patients treated with PRT, IMRT, and SRT. An additionally control group will be formed. The primary objective is to report long-term cognitive deterioration in each cohort until 10 years after the end of irradiation. The rate of clinical symptomatology improvement over time after irradiation, the evolution of health-related quality-of-life, anxiety/depression, fatigue, over time after irradiation, the tumoral local control after irradiation, the progression-free survival (PFS), the professional reintegration for working-age patients will also be assessed. CANCER COG aims to help clinicians to choose the best irradiation techniques with the best benefit/risk ratio. Inclusions started on september 2023.

Trial registration

The study was registered on clinicaltrials.gov with the following number: NCT 06036706.
The psychometric properties of the child anxiety and depression life interference scale (CADLIS)
Authors: O’Gradey-Lee Maddison , Jones Alana , Gandhi Esther , Lyneham Heidi , M. Rapee Ronald , Hudson Jennifer L.
Published: January 2025

Objective

Life interference is a key diagnostic feature for anxiety and depressive disorders. Measures focusing on life interference caused by anxiety and depressive disorders in children and adolescents have received minimal attention. This study evaluated the psychometric properties of the Child Anxiety and Depression Life Interference Scale (CADLIS), a brief child (CADLIS-C) and parent-report (CADLIS-P) measure designed to assess life interference from anxiety and depressive disorders in both the child and parent’s life.

Method

A total of 672 parents of children aged 4–18 years completed the CADLIS-P, and 627 children aged 7–18 years completed the CADLIS-C.

Results

The proposed two-factor CADLIS-C model was not supported, instead, due to high inter-factor covariance a one-factor model of life interference was proposed. The one-factor model demonstrated better model fit. The proposed three-factor model for the CADLIS-P was not supported, instead, an exploratory factor analysis found a two-factor model differentiating life interference into child and parent life interference a better model fit. The CADLIS demonstrated excellent internal consistency, good convergent and divergent validity, interrater correlations and was able to differentiate between children with and without clinical levels of anxiety and depressive symptoms.

Limitations

Limitations of the study included the sample population which consisted of a small clinical sample, an over-representation of high-income families and the use of a panel provider.

Conclusions

Overall, the CADLIS demonstrated sound psychometric properties. The CADLIS is a reliable measure that demonstrates evidence of convergent validity for the assessment of life interference associated with anxiety and depressive symptoms in children.