Advances in meniscus tissue engineering: Towards bridging the gaps from bench to bedside.

Meniscus is vital for maintaining the anatomical and functional integrity of knee. Injuries to meniscus, commonly caused by trauma or degenerative processes, can result in knee joint dysfunction and secondary osteoarthritis, while current conservative and surgical interventions for meniscus injuries bear suboptimal outcomes. In the past decade, there has been a significant focus on advancing meniscus tissue engineering, encompassing isolated scaffold strategies, biological augmentation, physical stimulus, and meniscus organoids, to improve the prognosis of meniscus injuries. Despite noteworthy promising preclinical results, translational gaps and inconsistencies in the therapeutic efficiency between preclinical and clinical studies exist. This review comprehensively outlines the developments in meniscus tissue engineering over the past decade (Scheme 1). Reasons for the discordant results between preclinical and clinical trials, as well as potential strategies to expedite the translation of bench-to-bedside approaches are analyzed and discussed.

Escala de alerta precoce na identificação de pacientes com risco de deterioração clínica / Early warning scale for identifying patients at risk of clinical deterioration / Escala de alerta temprana en la identificación de pacientes con riesgo de deterioro clínico

Objetivo: avaliar pontuação da National Early Warning Score (NEWS) em relação ao tipo de desfecho e perfil dos pacientes da enfermaria clínica médica de um hospital em Teresina, Piauí, Brasil. Método: estudo quantitativo realizado num hospital público, em Teresina, com 150 prontuários de pacientes internados no setor clínica médica de fevereiro de 2022 a dezembro de 2022, a partir de registros demográficos, clínicos e valores da escala na admissão e desfecho. Resultados: houve associação dos valores da escala com a faixa etária (p=0,029), tempo de internação (p=0,023) e tipo de desfecho (p < 0,001). Alto risco clínico prevaleceu entre pacientes do sexo masculino (13%), na faixa etária de 60 a 94 anos (13%), com permanência de 21 a 57 dias (19,2%) e óbito como desfecho (100%). Conclusão: implementação da referida escala evidenciou ser fundamental para prever agravos clínicos e melhorar qualidade da assistência.

Objective: to evaluate the National Early Warning Score (NEWS) in relation to the type of outcome and profile of patients in the medical clinical ward of a hospital in Teresina, Piauí, Brazil. Method: a quantitative study conducted in a public hospital in Teresina, with 150 medical records of patients admitted to the medical clinic sector from February 2022 to December 2022, based on demographic and clinical records and scale values at admission and outcome. Results: there was an association between the scale values and the age group (p=0.029), length of stay (p=0.023) and type of outcome (p < 0.001). High clinical risk prevailed among male patients (13%), aged between 60 and 94 years (13%), with a stay of 21 to 57 days (19.2%), and death as an outcome (100%). Conclusion: implementation of the aforementioned scale proved to be fundamental for predicting clinical problems and improving care quality.

Objetivo: evaluar el puntaje de la National Early Warning Score (NEWS) con respecto al tipo de desenlace y el perfil de los pacientes de la enfermería clínica médica de un hospital en Teresina, Piauí, Brasil. Método: estudio cuantitativo realizado en un hospital público en Teresina, con 150 historiales médicos de pacientes internados en el sector de clínica médica desde febrero de 2022 hasta diciembre de 2022, a partir de registros demográficos, clínicos y valores de la escala en la admisión y desenlace. Resultados: hubo asociación de los valores de la escala con la edad (p=0,029), tiempo de internación (p=0,023) y tipo de desenlace (p < 0,001). El alto riesgo clínico prevaleció entre los pacientes del sexo masculino (13%), en la franja de edad entre 60 y 94 años (13%), con una estancia de 21 a 57 días (19,2%) y fallecimiento como desenlace (100%). Conclusión: la implementación de dicha escala demostró ser fundamental para prever agravios clínicos y mejorar la calidad de la asistencia.

Mecánica y energética durante la marcha en cinta caminadora en Adultos Uruguayos Saludables: efecto del IMC y la edad

La evaluación de la marcha en cinta caminadora puede resultar relevante para la toma de decisiones clínicas. No obstante, factores demográficos como la edad y el IMC pueden alterar la interpretación de los resultados. Nuestro objetivo fue obtener variables espacio- temporales, energéticas y costo de transporte durante la velocidad autoseleccionada en cinta caminadora para una muestra representativa de adultos uruguayos (n=28) y evaluar si diferentes rangos de edades e IMC pueden ser factores a tener en cuenta en pruebas clínicas donde se consideren dichas variables. Participaron 17 hombres y 11 mujeres (39,3 ± 14,8 años, 75,9 ± 12,5 kg, 1,74 ± 0,09 m, IMC 25,2 ± 4,06). Se realizó una reconstrucción 3D del movimiento en forma sincronizada con el consumo energético. Se obtuvieron valores de referencia y luego de agrupar los participantes según su IMC y rango de edad se compararon los datos mediante test de t (p≤0.05). Los resultados revelaron discrepancias significativas en las medidas espacio-temporales y energéticas de los adultos uruguayos al caminar en cinta con respecto a la literatura. La marcha difiere entre adultos jóvenes y de mediana edad en su velocidad autoseleccionada (p=0,03), longitud de zancada (p=0,01), trabajo mecánico externo (<0,001) y recuperación de energía mecánica (0,009), destacando la importancia de considerar la edad en evaluaciones clínicas. El IMC no influyó significativamente en estas variables. Estos hallazgos subrayan la necesidad de ajustar las interpretaciones de las pruebas clínicas de la marcha sobre cinta caminadora en adultos uruguayos de mediana edad (45 a 65 años).

Treadmill gait assessment can be relevant for clinical decision-making. However, demographic factors such as age and BMI may alter result interpretation. Our aim was to obtain spatiotemporal, energetic, and cost of transport variables during self-selected treadmill walking speed for a representative sample of Uruguayan adults (n=28) and to assess if different age ranges and BMI could be factors to consider in clinical tests involving these variables. Seventeen men and eleven women participated (39.3 ± 14.8 years, 75.9 ± 12.5 kg, 1.74 ± 0.09 m, BMI 25.2 ± 4.06). A synchronized 3D motion reconstruction was performed with energy consumption. Reference values were obtained and data were compared using t-tests (p≤0.05), after grouping participants by BMI and age range. Results revealed significant discrepancies in spatiotemporal and energetic measures of Uruguayan adults walking on the treadmill, compared to the literature. Gait differed between young and middle-aged adults in their self-selected speed (p=0.03), stride length (p=0.01), external mechanical work (p<0.001), and mechanical energy recovery (0.009), emphasizing the importance of considering age in clinical evaluations. BMI did not significantly influence these variables. These findings underscore the need to adjust interpretations of treadmill gait clinical tests in middle-aged Uruguayan adults (45 to 65 years).

A avaliação da marcha na esteira pode ser relevante para a tomada de decisões clínicas. No entanto, fatores demográficos como idade e IMC podem alterar a interpretação dos resultados. Nosso objetivo foi obter variáveis espaço-temporais, energéticas e custo de transporte durante a velocidade de caminhada autoselecionada na esteira para uma amostra representativa de adultos uruguaios (n = 28) e avaliar se diferentes faixas etárias e IMC podem ser fatores a serem considerados em testes clínicos que envolvam essas variáveis. Dezessete homens e onze mulheres participaram (39,3 ± 14,8 anos, 75,9 ± 12,5 kg, 1,74 ± 0,09 m, IMC 25,2 ± 4,06). Foi realizada uma reconstrução tridimensional do movimento sincronizada com o consumo de energia. Foram obtidos valores de referência e os dados foram comparados usando testes t (p≤0,05), após agrupar os participantes por IMC e faixa etária. Os resultados revelaram discrepâncias significativas nas medidas espaço-temporais e energéticas dos adultos uruguaios ao caminhar na esteira, em comparação com a literatura. A marcha diferiu entre adultos jovens e de meia-idade em sua velocidade autoselecionada (p=0,03), comprimento da passada (p=0,01), trabalho mecânico externo (<0,001) e recuperação de energia mecânica (0,009), destacando a importância de considerar a idade em avaliações clínicas. O IMC não influenciou significativamente essas variáveis. Esses achados destacam a necessidade de ajustar as interpretações dos testes clínicos de marcha na esteira em adultos uruguaios de meia- idade (45 a 65 anos).

Engineering therapeutical extracellular vesicles for clinical translation.

Cell-based therapies are revolutionizing medicine by replacing or modifying dysfunctional cells with healthy cells or engineered derivatives, offering disease reversal and cure. One promising approach is using cell-derived extracellular vesicles (EVs), which offer therapeutic benefits similar to cell transplants without the biosafety risks. Although EV applications face challenges like limited production, inadequate therapeutic loading, and poor targeting efficiency, recent advances in bioengineering have enhanced their effectiveness. Herein, we summarize technological breakthroughs in EV bioengineering over the past 5 years, highlighting their improved therapeutic functionalities and potential clinical prospects. We also discuss biomanufacturing processes, regulation, and safety considerations for bioengineered EV therapies, emphasizing the significance of establishing robust frameworks to ensure translation capability, safety, and therapeutic effectiveness for successful clinical adoption.

A Preliminary Report of Developing Performer-Centered Vocal Injury Rehabilitation: An Interprofessional Collaborative Practice for Graduate Students in Speech-Language Pathology and Acting.

OBJECTIVES: Acting voice coaches (AVCs) and speech-language pathologists (SLPs) use dynamic teaching methods and intervene using motor learning principles. Both display instructional flexibility based on the actor/client's needs. With these criteria, we developed a virtual 3-hour professional voice lab to promote team-based learning between SLP graduate students and Master of Fine Arts (MFA) student actors. METHODS: The lab contained three phases: prebrief (50 minutes), case-study simulation (1.5 hours), and debrief (30 minutes). The students completed pre and postevaluation surveys to reflect on their learning experience. During the prebrief, the roles of AVCs and SLPs in actor's voice habilitation and rehabilitation, respectively, were discussed along with the special vocal needs of stage actors. The learners completed a comprehensive voice evaluation on "Maria Horseman," a 23-year-old professional actor with a voice disorder, in small interprofessional groups. The provided template offered a holistic approach to explore speaking-singing-acting vocal activities, vocal behaviors, physical demands/cardiorespiratory load, training/practice regimen, lifestyle changes including medication effect, and voice ergonomics. A customized client-centered voice intervention plan was developed by considering Maria's best interests and stimulability. RESULTS: Two different surveys, 15 items in Performance Voice Diagnostics for SLP students and Voice-Related Self-Perception for MFA students, and 20 items in modified Casey-Fink Readiness to Practice, were used to compare differences in self-confidence levels intervening professional voice disorders. Comparison of pre and postevaluation data revealed a statistically significant difference in learner self-confidence and readiness levels. CONCLUSIONS: A team-based, interprofessional learning approach on voice rehabilitation would help SLPs to consider special vocal demands of professional voice users in their evaluation methods. This may also lead to preventive early intervention by increasing vocal awareness and knowledge on phonatory function in professional actors from the beginning of their careers.

Advances in Functionalized Hydrogels in the Treatment of Myocardial Infarction and Drug-Delivery Strategies.

Myocardial infarction (MI) is a serious cardiovascular disease with high morbidity and mortality rates, posing a significant threat to patient's health and quality of life. Following a MI, the damaged myocardial tissue is typically not fully repaired, leading to permanent impairment of myocardial function. While traditional treatments can alleviate symptoms and reduce pain, their ability to repair damaged heart muscle tissue is limited. Functionalized hydrogels, a broad category of materials with diverse functionalities, can enhance the properties of hydrogels to cater to the needs of tissue engineering, drug delivery, medical dressings, and other applications. Recently, functionalized hydrogels have emerged as a promising new therapeutic approach for the treatment of MI. Functionalized hydrogels possess outstanding biocompatibility, customizable mechanical properties, and drug-release capabilities. These properties enable them to offer scaffold support, drug release, and tissue regeneration promotion, making them a promising approach for treating MI. This paper aims to evaluate the advancements and delivery methods of functionalized hydrogels for treating MI, while also discussing their potential and the challenges they may pose for future clinical use.

DNAJB6 is expressed in neurons and oligodendrocytes of the human brain.

DNAJB6 is a suppressor of α-synuclein aggregation in vivo and in vitro. DNAJB6 is strongly expressed in the brain, and its overall protein expression is altered in neurodegenerative conditions such as Parkinson's Disease (PD) and Multiple System Atrophy (MSA). These two diseases are characterized by accumulation of aggregated α-synuclein in neurons and oligodendrocytes, respectively. To further explore this, we employed post-mortem normal human brain material to investigate the regional and cell type specific protein expression of DNAJB6. We found that the DNAJB6 protein is ubiquitously expressed across various regions of the brain. Notably, we demonstrate for the first time that DNAJB6 is present in nearly half (41%-53%) of the oligodendrocyte population and in the majority (68%-80%) of neurons. However, DNAJB6 was only sparsely present in other cell types such as astrocytes and microglia. Given that α-synuclein aggregation in oligodendrocytes is a hallmark of MSA, we investigated DNAJB6 presence in MSA brains compared to control brains. We found no significant difference in the percentage of oligodendrocytes where DNAJB6 was present in MSA brains relative to control brains. In conclusion, our results reveal an expression of the DNAJB6 protein across various regions of the human brain, and that DNAJB6 is almost exclusively present in neurons and oligodendrocytes. Since prior studies have shown that PD and MSA brains have altered levels of DNAJB6 relative to control brains, DNAJB6 may be an interesting target for drug development.

Guided bone regeneration at dehiscence comparing synthetic bone substitute versus bovine bone mineral: A multicenter, noninferiority, randomized trial.

AIM: To evaluate the efficacy of guided bone regeneration (GBR) for the treatment of peri-implant dehiscence defects using a synthetic bone substitute (SBS) or a deproteinized bovine bone mineral (DBBM) as a bone substitute. METHODS: Patients with expected dehiscence defects following implant placement were randomized to use either SBS or DBBM together with a bioabsorbable collagen membrane over dehiscenced implant surfaces aimed for GBR. The changes in the bone defect size were measured before the GBR procedure and 6 months after implant placement at the re-entry surgery. Secondary outcomes included peri-implant health outcomes, implant cumulative survival rates, bone level changes, and patient-reported outcomes (PROMs) at prosthesis delivery and 1-year follow-up. RESULTS: Of the 49 included patients, 24 were treated with SBS and 25 with DBBM. In the SBS group, the defect height (DH) at implant insertion was 5.1 ± 2.6 mm and was reduced at re-entry to 1.3 ± 2.0 mm (74.5%). In the DBBM group, the respective changes in DH were 4.1 ± 1.7 mm and 1.5 ± 1.9 mm (63.4%). These differences were not statistically significant (p = 0.216). The complete defect resolution rate was also comparable in both groups without statistical difference (62.5% of patients (15/24) vs. 44% of patients (11/25)). Overall, the marginal bone levels remained stable during the 1-year follow-up in both groups. CONCLUSION: The SBS is noninferior to DBBM for simultaneous GBR to implant placement at implant sites with buccal dehiscences in terms of defect resolution and evaluated secondary outcomes (KCT0008393 - this clinical trial was not registered before participant recruitment and randomization).

How to optimise medicines management for people with Parkinson's disease in hospital.

RATIONALE AND KEY POINTS: Hospital admissions can be challenging for people with Parkinson's disease, in part because of the lack of understanding, among some healthcare professionals, of the importance of administering antiparkinsonian medicines on time. This article outlines the steps that nurses can take to optimise medicines management for people with Parkinson's disease who are admitted to hospital. • Pharmacotherapy is the primary treatment for Parkinson's disease and aims to increase dopamine levels in the brain to relieve symptoms. • People with Parkinson's disease require careful administration, titration, adjustment and monitoring of their antiparkinsonian medicines regimen, which is highly individualised. • It is crucial that people with Parkinson's disease take their antiparkinsonian medicines at exactly the right time, since the inaccurate timing of these medicines can have significant adverse health implications. REFLECTIVE ACTIVITY: 'How to' articles can help to update your practice and ensure it remains evidence-based. Apply this article to your practice. Reflect on and write a short account of: • How this article might improve your practice when undertaking medicines management for people with Parkinson's disease in hospital. • How you could use this information to educate nursing students or your colleagues on optimising medicines management for people with Parkinson's disease in hospital.

The Use of Art to Develop Holistic Nurses and Clinical Judgment: An Educational Intervention.

Background: Artwork can be used to practice the development of holistic care for nursing students. This activity was designed for senior nursing students to develop their holistic nursing skills through a series of in-class activities while viewing Frida Kahlo's The Broken Column. Aim: This study's aim was to design an educational experience to develop a more holistic approach to caring for patients for nursing students. Method: Students submitted their initial impressions of the painting via an anonymous quiz. After a guided Visual Thinking Strategies (VTS) session, students submitted impressions of the artwork. A VTS facilitator read a history of an accident which revealed the cause of Kahlo's medical and emotional pain. Students then wrote about their perceptions of the painting's meaning and how they might use VTS in caring for their patients. Answers were analyzed using Braun and Clark's thematic analysis. Results: The themes identified were emotions and feelings, metaphor, life/story, and listening to inform perspective. Most found that VTS changed their impressions and enhanced their ability to question patients and inform their care. Conclusion: Students found that VTS expanded their view of patient care and helped them see the patient more holistically, aligning with the development of clinical judgment.

Vascular Calcification: Where is the Cure?

With the progress of aging, the incidence of vascular calcification (VC) gradually increases, which is correlated with cardiovascular events and all-cause death, aggravating global clinical burden. Over the past several decades, accumulating approaches targeting the underlying pathogenesis of VC have provided some possibilities for the treatment of VC. Unfortunately, none of the current interventions have achieved clinical effectiveness on reversing or curing VC. The purpose of this review is to make a summary of novel perspectives on the interventions of VC and provide reference for clinical decision-making.

Inflammatory Signaling via PEIZO1 Engages and Enhances the LPS-Mediated Apoptosis during Clinical Mastitis.

Bovine clinical mastitis is characterized by inflammation and immune responses, with apoptosis of mammary epithelial cells as a cellular reaction to infection. PIEZO1, identified as a mechanotransduction effector channel in nonruminant animals and sensitive to both mechanical stimuli or inflammatory signals like lipopolysaccharide (LPS). However, its role in inflammatory processes in cattle has not been well-documented. The aim of this study was to elucidate the in situ expression of PIEZO1 in bovine mammary gland and its potential involvement in clinical mastitis. We observed widespread distribution and upregulation of PIEZO1 in mammary epithelial cells in clinical mastitis cows and LPS-induced mouse models, indicating a conserved role across species. In vitro studies using mammary epithelial cells (MAC-T) revealed that LPS upregulates PIEZO1. Notably, the effects of PIEZO1 artificial activator Yoda1 increased apoptosis and NLRP3 expression, effects mitigated by PIEZO1 silencing or NLRP3 inhibition. In conclusion, the activation of the PIEZO1-NLRP3 pathway induces abnormal apoptosis in mammary epithelial cells, potentially serving as a regulatory mechanism to combat inflammatory responses to abnormal stimuli.

Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable esophageal squamous cell carcinoma: A pooled analysis of randomized clinical trials.

BACKGROUND: The comparison of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) for locally advanced esophageal squamous cell carcinoma (ESCC) remains inconclusive, and the optimal regimen is still under investigation. METHODS: Prospective randomized clinical trials were systematically searched in electronic databases from inception to Oct 2023. A graphical reconstructive algorithm was employed to extract time-to-event outcomes from Kaplan-Meier curves presented in the original studies. Using reconstructed individual patient data, summary overall survival (OS) and disease progression-free survival (DFS) for nCRT versus nCT, primarily doublet chemotherapy were recalculated. Hazard Ratios (HRs) of OS and DFS reported were also pooled by the fixed-effects model. RESULTS: A total of 6 randomized clinical trials comprising 1162 patients were included in our analysis. In the individual patient data (IPD) pooled analysis, a significant OS benefit was found for nCRT in ESCC (HR=0.81, 95 %CI:0.67-0.98, p=0.029), compared with the treatment of nCT. The median overall survival time were 53 months (95 %CI:41.9-67.7 m) and 66 months(95 %CI:57.2-NA) respectively in the nCT and nCRT groups. Additionally, a significant improvement in PFS for nCRT compared to nCT in the IPD pooled analysis (HR=0.79,95 %CI:0.64-0.98; p=0.027). Consistent with above results, the pooled HRs of OS and DFS for nCRT versus nCT were 0.78 (95 % CI 0.65-0.92, p=0.004) and 0.79 (95 % CI: 0.65-0.97, p=0.02), respectively. Notably, no substantial heterogeneity across studies was observed. CONCLUSIONS: Our findings indicate that nCRT offers better survival outcomes for ESCC, at least when compared to neoadjuvant doublet chemotherapy.This evidence continues to support the clinical practice of employing nCRT in locally advanced resectable ESCC.

Clinical supervisor's experiences of peer group clinical supervision during COVID-19: a mixed methods study.

BACKGROUND: Providing positive and supportive environments for nurses and midwives working in ever-changing and complex healthcare services is paramount. Clinical supervision is one approach that nurtures and supports professional guidance, ethical practice, and personal development, which impacts positively on staff morale and standards of care delivery. In the context of this study, peer group clinical supervision provides allocated time to reflect and discuss care provided and facilitated by clinical supervisors who are at the same grade/level as the supervisees. METHODS: To explore the clinical supervisor's experiences of peer group clinical supervision a mixed methods study design was utilised within Irish health services (midwifery, intellectual disability, general, mental health). The Manchester Clinical Supervision Scale was used to survey clinical supervisors (n = 36) and semi-structured interviews (n = 10) with clinical supervisors were conducted. Survey data were analysed through SPSS and interview data were analysed utilising content analysis. The qualitative and quantitative data's reporting rigour was guided by the CROSS and SRQR guidelines. RESULTS: Participants generally had a positive encounter when providing clinical supervision. They highly appreciated the value of clinical supervision and expressed a considerable degree of contentment with the supervision they provided to supervisees. The advantages of peer group clinical supervision encompass aspects related to self (such as confidence, leadership, personal development, and resilience), service and organisation (including a positive working environment, employee retention, and safety), and patient care (involving critical thinking and evaluation, patient safety, adherence to quality standards, and elevated levels of care). CONCLUSION: There are many benefits of peer group clinical supervision at an individual, service, organisation, and patient level. Nevertheless, there is a need to address a lack of awareness and misconceptions surrounding clinical supervision to create an environment and culture conducive to realising its full potential. It is crucial that clinical supervision be accessible to nurses and midwives of all grades across all healthcare services, with national planning to address capacity and sustainability.

Moderating effect of family structure on the relationship between early clinical exposure and emotional labor of nursing students: a cross-sectional study.

BACKGROUND: Emotional labor is an essential component of nursing practice and is important for Generation Z nursing students born from the mid-1990s to early 2010s. They will become the backbone of the nursing workforce but present more emotional regulation problems. Studies on emotional labor are limited to clinical nurses and influencing factors at the individual level. The impacts of external systems on emotional labor of nursing students have not been explored. This study aimed to quantify the relationship between early clinical exposure and emotional labor and test the moderating effect of family structure on the relationship. METHODS: The cross-sectional study recruited 467 nursing students using convenience sampling from seven colleges and universities in mainland China. An e-survey created on WJX.CN was used to collect data in January 2023. Emotional labor (surface acting and deep acting) was measured with the Emotional Labor scale. Early clinical exposure (exposure or not and times of exposure) and family structure (nuclear family, extended family, and single-parent family) were assessed with self-reported questions. Descriptive statistics and the linear mixed-effects modeling were used to do the analyses. RESULTS: The mean scores of surface acting and deep acting were 26.66 ± 5.66 and 13.90 ± 2.40, respectively. A significant difference in scores of surface acting was not observed for exposure or not, whereas such a significant difference was found for times of exposure. Nursing students from extended families demonstrated significantly lower scores on surface acting while exposed to clinical practice compared with those from nuclear families. Family structure moderated the relationship between times of exposure and surface acting of nursing students when exposed to clinical practice for one time, but the significance disappeared when the times of exposure increased. No significant findings of early clinical exposure on deep acting were observed. CONCLUSIONS: Early clinical exposure influenced emotional labor, and students from extended families were more likely to get benefits from early clinical exposure. Studies are needed to help students from nuclear families get comparable benefits on emotional labor as those from extended families, and improve deep acting by early clinical exposure.

New strategies in soft tissue sarcoma treatment.

Soft tissue sarcomas (STS) have long been a formidable challenge in oncology, partly because of their rarity and diversity, which complicates large-scale studies and slows the advent of new treatments. Traditionally anchored by anthracycline-based chemotherapy, the landscape of STS treatment hasn't shifted dramatically in the past twenty years. However, recent strides in research are starting to paint a more hopeful picture. Leveraging advanced molecular profiling, researchers are now tailoring treatments to the unique genetic makeup of tumors, with targeted therapies showing promise. Innovations such as NTRK inhibitors for NTRK-rearranged sarcomas and gamma-secretase inhibitors for desmoid tumors are changing clinical practices. The rise of immunotherapy, including novel agents like LAG-3 inhibitors and bifunctional proteins that target both TGF-ß and PD-L1, offers new avenues for treatment, particularly when combined with traditional therapies like chemotherapy. Meanwhile, the approval of epigenetic treatments for specific sarcoma subtypes heralds a new wave of strategy based on histological specificity, which could lead to more personalized and effective care. While challenges remain, the field of STS treatment is evolving, driven by a deeper understanding of the disease's biological underpinnings and a commitment to innovative research approaches.

Epithelial­derived head and neck squamous tumourigenesis (Review).

Head and neck squamous cell carcinomas (HNSCCs), a heterogeneous group of cancers that arise from the mucosal epithelia cells in the head and neck areas, present great challenges in diagnosis, treatment and prognosis due to their complex aetiology and various clinical manifestations. Several factors, including smoking, alcohol consumption, oncogenic genes, growth factors, Epstein­Barr virus and human papillomavirus infections can contribute to HNSCC development. The unpredictable tumour microenvironment adds to the complexity of managing HNSCC. Despite significant advances in therapies, the prediction of outcome after treatment for patients with HNSCC remains poor, and the 5­year overall survival rate is low due to late diagnosis. Early detection greatly increases the chances of successful treatment. The present review aimed to bring together the latest findings related to the molecular mechanisms of HNSCC carcinogenesis and progression. Comprehensive genomic, transcriptomic, metabolomic, microbiome and proteomic analyses allow researchers to identify important biological markers such as genetic alterations, gene expression signatures and protein markers that drive HNSCC tumours. These biomarkers associated with the stages of initiation, progression and metastasis of cancer are useful in the management of patients with cancer in order to improve their life expectancy and quality of life.

Anatomic femoral tunnel and satisfactory clinical outcomes achieved with the modified transtibial technique in anterior cruciate ligament reconstruction: A systematic review and meta-analysis.

Background: Anatomic anterior cruciate ligament (ACL) reconstruction is considered the gold standard treatment for ACL injuries because it aims to restore the knee's normal anatomy and stability, while also protecting long-term knee health. Long-term clinical and radiological outcomes after ACL reconstruction using the modified TT technique are unclear. Objective: To assess the clinical and radiological outcomes following ACL reconstruction using modified transtibial (TT) techniques at a minimum 12-month follow-up. Design: A systematic review with meta-analysis. Methods: PubMed, EMBASE, Web of Science, the Cochrane Library, and MEDLINE databases were searched from the inception to December 1, 2022. PICO search strategy was used to identify studies applying modified TT techniques on patients with ACL reconstruction and a minimum follow-up of 12 months. Eligible studies were identified independently by two reviewers. We extracted data on patient demographics, surgical characteristics, patient reported outcomes including subjective evaluations and clinical outcomes. Radiological data including femoral and tibial tunnel position, femoral and tibial tunnel length, and femoral tunnel angle were also extracted. The tunnel position was evaluated using the quadrant method based on three-dimensional computed tomography (3D CT) images. The standardized mean difference (SMD) and 95 % confidence interval (CI) were calculated for clinical and radiological outcomes. Results: Sixteen studies involving 628 patients were finally included. The SMD of Lysholm (90.39; 95 % CI 83.41-97.38), IKDC (86.07; 95 % CI 79.84-92.31), and Tegner (6.15; 95 % CI 3.96-8.33) scores were considered satisfactory. The depth of the femoral tunnel showed a pooled SMD of 30.08 % (95 % CI 28.25-31.91 %), and the height showed a pooled SMD of 37.72 % (95 % CI 35.75-39.70 %). The pooled SMD for the femoral tunnel angle in the coronal plane was 48.27°(95 % CI 43.14-53.40°), and the pooled SMD for the femoral tunnel length was 33.98 mm (95 % CI 29.03-38.93 mm). Conclusions: This investigation has shown that modified TT technique can create an anatomic femoral tunnel and maintain optimal tunnel length and angulation. Most patients had satisfactory subjective outcomes and physical examinations after ACL reconstruction using modified TT technique. This information may assist in guiding expectations of clinicians and patients following ACL reconstruction with modified TT technique.

Clinical value of γ-glutamyl transpeptidase to platelet ratio and triglyceride measurement in the diagnosis of nonalcoholic fatty liver disease: A cross-sectional study.

Objective: In clinical practice, there are few effective biomarkers for identifying non-alcoholic fatty liver disease (NAFLD). The aim of this study is to investigate the diagnostic value of γ-glutamyl transpeptidase to platelet ratio (GPR) combined with triglyceride (TG) in NAFLD. Methods: A total of 14,415 individuals participated in the annual physical examination. Multivariate logistic regression analysis was conducted to investigate the exposure factors associated with NAFLD. Spearman's analysis was performed to assess the correlation among the exposure factors of NAFLD. Furthermore, the diagnostic efficacy of the combination of GPR and TG in NAFLD was analyzed using the receiver operating characteristic curve (ROC). Results: The results of the multivariate logistic regression analysis showed that BMI (OR = 1.619), Systolic Blood Pressure (SBP) (OR = 1.014), Diastolic Blood Pressure (DBP) (OR = 1.028), GPR (OR = 12.809), and TG (OR = 2.936) were all risk factors for NAFLD, while HDL-C (OR = 0.215) was a protective factor. Spearman correlation analysis revealed significant positive correlations between GPR and SBP, DBP, BMI, TG (p < 0.01), but a negative correlation between GPR and HDL-C (p < 0.01). TG was only positively correlated with GPR (p < 0.001). ROC curve analysis demonstrated that the area under the curve (AUC) of GPR combined with TG for diagnosis of NAFLD was 0.855 (95 % CI: 0.819-0.891), sensitivity was 83.45 % and specificity was 73.56 %. Conclusion: This study indicated that high levels of GPR and TG were risk factors for NAFLD and demonstrated good clinical value in diagnosing NAFLD.