bluuebunny/crossref_metadata_2025 huggingface dataset:
VALUABLE INTERACTION WITH COGNITIVE REMEDIATION AND OPTIMAL ANTIPSYCHOTICS FOR RECOVERY IN SCHIZOPHRENIA (VICTORY-S): STUDY PROTOCOL FOR AN INTERVENTIONAL, OPEN-LABEL, RATER- BLINDED, RANDOMIZED COMPARISON OF COMBINED TREATMENT WITH COGNITIVE REMEDIATION AND LURASIDONE OR PALIPERIDONE
Authors: Kubota *Ryotaro , Ikezawa Satoru , Oi Hideki , Oba Mari S , Izumi Shoki , Adachi Leona , Miwa Mako , Tsuno Ryoko , Toya Shunji , Nishizato Yohei , Haga Daisuke , Iwane Tatsuro , Nakagome Kazuyuki
Published: February 2025

Background

Cognitive impairment, a core feature of schizophrenia, is associated with poor functional outcomes. Available interventions include both pharmacotherapy and psychosocial treatment. However, each of these interventions, when used alone, have often inadequate effect sizes.

Aims & Objectives

This study aims to compare the effects of lurasidone combined with cognitive remediation (the Neuropsychological Educational Approach to Remediation [NEAR]) and paliperidone combined with NEAR on cognitive function in patients with schizophrenia.

Methods

The valuable interaction with cognitive remediation and optimal antipsychotics for recovery in schizophrenia (VICTORY-S) study is a multicenter, interventional, open-label, rater-blinded, randomized comparison study, comparing the effect of lurasidone plus cognitive remediation with that of paliperidone plus cognitive remediation in patients with schizophrenia. The NEAR will be used for cognitive remediation. Eligible patients will be randomized 1:1 to receive lurasidone or paliperidone combined with NEAR (6 weeks antipsychotic alone followed by 24 weeks combination antipsychotic plus NEAR). The primary endpoint is the change from baseline in the tablet-based Brief Assessment of Cognition in Schizophrenia composite T-score at the end of the 24-week NEAR combination treatment period. Secondary endpoints will include change from baseline in various measures of social function, positive and negative symptoms, depression, defeatist beliefs, and quality of life at the end of the 24- week NEAR combination treatment period. Furthermore, change from the end of the 6-week antipsychotic alone period to the end of the 24-week NEAR combination treatment period will be assessed for all endpoints. Safety will also be evaluated. (Japan Registry of Clinical Trials ID is jRCTs031200338)

Results

This study is currently recruiting participants.

Discussion & Conclusion: Achievement of adequate cognitive function is central to supporting social function, which is one of the key treatment goals for patients with schizophrenia. A previous study investigated the combined effect of lurasidone and cognitive remediation in patients with schizophrenia. However, cognitive function had recovered by the start of cognitive remediation and there was no antipsychotic control. We think that this study will fill in the gaps of the previous study and provide useful information to clinicians regarding treatment decisions for patients with schizophrenia.
CHILDHOOD EMOTIONAL MALTREATMENT INCREASES THE “WEAR-AND- TEAR” OF PHYSIOLOGICAL SYSTEMS, ESPECIALLY NEUROENDOCRINE CHANGES IN SCHIZOPHRENIA
Authors: Wang *Ran , Xu Shuqi , Yang Xue , Jiao Lihuan
Published: February 2025

Background

A body of experimental data and clinical investigations suggests that childhood adversity permanently affects the plasticity of multiple brain circuits, including the processing of environmental stimuli, the regulation of autonomic nervous, cardiovascular and endocrine responses.

Aim

To quantify the “wear and tear” on physiological systems in schizophrenia, we introduced the concept of allostatic load (AL) index,which covers multiple physiological indicators and is a useful framework for predicting stress-related dysbiosis. Adverse childhood experiences, especially sexual and emotional abuse, could lead to elevated levels of AL index in patients with schizophrenia. We aimed to determine whether childhood trauma affects physiological indicators of schizophrenia in adulthood, particularly indicators of stress. Improved understanding of the relationship between childhood maltreatment and stress- related pathophysiology could strengthen multidisciplinary interventions and further comprehensive the healthcare system for people with schizophrenia.

Method

Using the Childhood Trauma Questionnaire (CTQ) and the allostatic load (AL) index. First-episode drug-naï ve schizophrenia patients (n=56) and healthy controls (n=53) were evaluated. Pearson correlation analysis was employed to explore the relationship between childhood traumatic experiences and the AL index in schizophrenia patients.

Results

Schizophrenia patients exhibited significantly higher scores for childhood trauma compared to healthy controls. Emotional abuse was found to correlate positively with the neuroendocrine-related AL index in schizophrenia patients (r=0.471, p<0.001). Multivariate linear regression further confirmed that emotional abuse was a significant predictor for the neuroendocrine-related AL index, accounting for 20.6% of its variance.

Conclusion

The findings of this study suggest that emotional abuse during childhood is associated with an elevated neuroendocrine-related AL index in adulthood among patients with schizophrenia. This offers new insights for clinical assessment and intervention in schizophrenia.
ACUTE AND CHRONIC EFFECT OF ESSENTIAL OIL BLEND ON PHYSIOLOGICAL RESPONSE OF STRESS
Authors: Saiyudthong *Somrudee , Chansiri Kosum , Lee Brian , Sittiprapaporn Phakkharawat , Sathirachawan Kanchanapa
Published: February 2025

Background

Prolonged stress is a major cause of mental and physical illness (Mariotti A, 2015). Aromatherapy, using essential oil, has been widely used to relieve stress (Farrar AJ and Farrar FC, 2020).

Aims & Objectives

The aim of this study was to investigate the effects of Thai aromatherapy formulations, including bergamot oil, ylang-ylang oil, Litsea cubeba Pers. oil, peppermint oil and sandalwood oil on relaxation.

Method

Firstly, essential oil formulation used for reducing stress was developed in order to choose the most satisfying blend. The selected blend was identified the main component by using gas chromatography mass spectrometry (GC– MS). Then, this blend was used to investigate the acute effect of essential oil inhalation on physiological stress by assessing vital sign, salivary α-amylase and salivary cortisol. Subsequently, the effect of long-term treatment with stickers made with the selected blend was investigated.

Results

The result showed that the volunteers were satisfied with the essential oils blend containing menthol, isomenthone and limonene. Acute inhalation of this blend did not lower blood pressure including systolic blood pressure, diastolic blood pressure and mean arterial pressure, heart rate, salivary α-amylase and salivary cortisol level compared to pre- inhalation. After 2 weeks of using sticker containing essential oil blend, there was a significant reduction in stress score, systolic blood pressure and salivary cortisol (p<0.05).

Discussion & Conclusion

This study indicated that long-term inhalation of Thai essential oil blend reduced stress by reducing the hypothalamic-pituitary-adrenal axis (HPA) activity.

References

Mariotti, A. (2015) ‘The effects of chronic stress on health: new insights into the molecular mechanisms of brain– body communication’ Future Sci OA., 1(3), Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137920/pdf/fso-01-23.pdf (Accessed: 30 October 2023).

Farrar AJ, Farrar FC. (2020) Clinical Aromatherapy. Nurs Clin North Am. 2020 Dec;55(4): pp. 489- 504. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520654/pdf/main.pdf (Accessed: 10 September 2020).
BIDIRECTIONAL RELATIONSHIP BETWEEN DISABILITY AND COGNITIVE IMPAIRMENT: A LONGITUDINAL STUDY AMONG TAIWANESE OLDER ADULTS
Authors: Hung *Tsung-Hsuan , Tsai Tsung-Yu , Chiu Ching-Ju
Published: February 2025

Background

Cognitive impairment and disability are two significant age-related health issues in older adults, but the relationship between each other remains unclear. Several cross-sectional studies have established the associations between cognitive impairment and disability. While the previous longitudinal studies reported inconsistent results.

Aims & Objectives

We aim to simultaneously explore the relationship between cognitive impairment and disability and further pinpoint which one holds a more pivotal role in the relationship.

Method

628 participants aged 66.0 (SD=7.3) were retrieved from the Social Environment and Biomarkers of Aging Study, a nationally representative longitudinal survey of Taiwanese study, conducted in 2000. Cognition was evaluated by using a modified Short Portable Mental Status Questionnaire (SPMSQ), and disability was indicated by Activity of daily living (ADL), Instrumental activity of daily living (IADL), and Mobility. Structural equation models with cross-lagged analysis were performed for path analysis.

Results

The cross-lagged model was well constructed (χ2 (9)=34.5941, p<0.0001, RMSEA=0.0673, CFI=0.99, SRMR=0.03). Baseline disability in 2000 significantly predicted future cognitive impairment (β=−0.25, p<0.05) in 2006, and baseline cognitive impairment in 2000 also significantly predicted future disability (β=−0.03, p<0.05) 6 years later. Fisher’ s Z test, examining difference of the standardized coefficients from two cross-lagged paths, showed statistically significance(p<0.001).

Discussion & Conclusion

The findings suggested the relationships between cognition and disability are bidirectional in older adults. Compared to the impact of cognitive function on disability, disability presented a greater influence on subsequent cognitive impairment. The potential mechanisms of such kinds of associations might be complicated. To explain the mechanism, future research, focusing on comorbidities, physical and mental capacities, social interactions, unhealthy lifestyles, and the inflammation process, is warranted.
Body composition and checkpoint inhibitor treatment outcomes in advanced melanoma: a multicenter cohort study
Authors: Schuiveling Mark , Ter Maat Laurens S , Van Duin Isabella A J , Verheijden Rik J , Troenokarso Max F , Moeskops Pim , Verhoeff Joost J C , Elias Sjoerd G , Van Amsterdam Wouter A C , Burgers Femke , Van Den Berkmortel Franchette W P J , Boers-Sonderen Marye J , Boomsma Martijn F , De Groot Jan Willem , Haanen John B A G , Hospers Geke A P , Piersma djura , Vreugdenhil Gerard , Westgeest Hans M , Kapiteijn Ellen , Labots Mariette , Veldhuis Wouter B , Van Diest Paul J , De Jong Pim A , Pluim Josien P W , Leiner Tim , Veta Mitko , Suijkerbuijk Karijn P M
Published: February 2025

Introduction

The association of body composition with checkpoint inhibitor outcomes in melanoma is a matter of ongoing debate. In this study, we aim to investigate body mass index (BMI) alongside CT-derived body composition metrics in the largest cohort to date.

Methods

Patients treated with first-line anti-PD1 ± anti-CTLA4 for advanced melanoma were retrospectively identified from 11 melanoma centers in The Netherlands. From baseline CT scans, five body composition metrics were extracted: subcutaneous adipose tissue index, visceral adipose tissue index and skeletal muscle index, density and gauge. These metrics were correlated in uni- and multivariable Cox proportional hazards analysis with progression-free, overall and melanoma-specific survival (PFS, OS and MSS).

Results

A total of 1471 eligible patients were included. Median PFS and OS were 9.1 and 38.1 months, respectively. Worse PFS was observed in underweight patients (multivariable HR = 1.86, 95% CI 1.14–3.06). Furthermore, prolonged OS was observed in patients with higher skeletal muscle density (multivariable HR = 0.88, 95% CI 0.81-0.97) and gauge (multivariable HR = 0.61, 95% CI 0.82-0.998), whereas higher visceral adipose tissue index was associated with worse OS (multivariable HR = 1.12, 95% CI 1.04-1.22). No association with survival outcomes was found for overweight, obesity or subcutaneous adipose tissue.

Discussion

Our findings suggest that underweight BMI is associated with worse PFS, whereas higher skeletal muscle density and lower visceral adipose tissue index were associated with improved OS. These associations were independent of known prognostic factors, including sex, age, performance status and extent of disease. No significant association between higher BMI and survival outcomes was observed.
High-throughput in vitro drug screening and in vivo studies identify fenretinide as a brain-penetrant DMG therapeutic
Authors: Upton Dannielle H , Liu Jie , George Sandra M , Valvi Santosh , Ung Caitlin , Rayner Benjamin S , Gopalakrishnan Anjana , Pandher Ruby , Khan Aaminah , Venkat Pooja , Mayoh Chelsea , Holliday Holly , Yeung Nicole , Nguyen Hieu , Franshaw Laura , Ehteda Anahid , Shen Han , Farruggia Giovanna , Orienti Isabella , Reynolds C Patrick , Tsoli Maria , Ziegler David S
Published: February 2025

Background

Diffuse midline glioma, characterised by H3K27 alteration (DMG), is the predominant high-grade glioma in children. It commonly originates in the brainstem, yet effective treatments for these patients remain elusive.

Methods

To identify novel therapies for DMG, we conducted high-throughput drug screens (HTS) using biologically active, clinically approved compounds against DMG neurospheres. Multiple primary DMG cultures were utilised in conjunction with in vitro cytotoxicity and clonogenic assays to validate the efficacy of top compounds. Molecularly diverse patient-derived and transgenic DMG orthotopic models were employed to assess therapeutic efficacy alongside pharmacokinetic and immunohistochemical analyses. Mechanistic studies, including RNA sequencing, western blotting, and flow cytometry, were conducted to elucidate the antitumour efficacy of the most promising compound, fenretinide, in DMG cells.

Results

Through HTS, six compounds were identified and validated for their potent cytotoxic activity. However, most of these compounds failed to improve survival in an orthotopic Diffuse Midline Glioma (DMG) model due to limited blood-brain barrier (BBB) penetration. In contrast, fenretinide exhibited effective BBB penetration, significantly enhancing the survival of tumour-bearing animals. Mechanistic studies revealed that fenretinide increased reactive oxygen species (ROS) generation and induced apoptosis by inhibiting PDGFRα. RNA-sequencing further elucidated that fenretinide upregulates the Unfolded Protein Response (UPR) and endoplasmic reticulum (ER) stress pathways while downregulating neurogenesis. The in vivo antitumour efficacy of two fenretinide formulations was demonstrated in PDGFRα-amplified and transgenic DMG models.

Conclusion

This comprehensive study has identified new DMG therapeutic vulnerabilities and highlights fenretinide as a brain-penetrant, anti-DMG agent.
Automated longitudinal treatment response assessment of brain tumors: a systematic review
Authors: Shi Tangqi , Kujawa Aaron , Linares Christian , Vercauteren Tom , Booth Thomas C
Published: February 2025

Background

Longitudinal assessment of tumor burden using imaging helps to determine whether there has been a response to treatment both in trial and real-world settings. From a patient and clinical trial perspective alike, the time to develop disease progression, or progression-free survival, is an important endpoint. However, manual longitudinal response assessment is time-consuming and subject to interobserver variability. Automated response assessment techniques based on machine learning (ML) promise to enhance accuracy and reduce reliance on manual measurement. This paper evaluates the quality and performance accuracy of recently published studies.

Methods

Following PRISMA guidelines and the CLAIM checklist, we searched PUBMED, EMBASE, and Web of Science for articles (January 2010-November 2024). Our PROSPERO-registered study (CRD42024496126) focused on adult brain tumor automated treatment response assessment studies using ML methodologies. We determined the extent of development and validation of the tools and employed QUADAS-2 for study appraisal.

Results

Twenty (including seventeen retrospective and three prospective) studies were included. Data extracted included information on the dataset, automated response assessment including pertinent steps within the pipeline (index tests), and reference standards. Only limited conclusions are appropriate given the high bias risk and applicability concerns (particularly regarding reference standards and patient selection), and the low-level evidence. There was insufficient homogenous data for meta-analysis.

Conclusion

The study highlights the potential of ML to improve brain tumor longitudinal treatment response assessment. Interpretation is limited due to study bias and limited evidence of generalizability. Prospective studies with external datasets validating the latest neuro-oncology criteria are now required.
Dietary intake of whale oil–containing ω‐3 long‐chain polyunsaturated fatty acids attenuates choroidal neovascularization in mice
Authors: Yanai Ryoji , Yasunaga Genta , Tsuji Shunya , Honda Takeshi , Iwata Arihiro , Miyagawa Eiji , Yoshida Koji , Kishimoto Mitsuhiro , Sakai Hiroki , Fujise Yoshihiro , Asagiri Masataka , Mitamura Yoshinori
Published: February 2025

Age‐related macular degeneration (AMD) is a leading cause of blindness in Western and developing countries. Since antivascular endothelial growth factor (VEGF) therapy is available for the regression of choroidal neovascularization (CNV), it does not work for the pathophysiology of AMD so a cure is increasingly demanded. Whale oil promotes various bodily functions, such as anti‐inflammatory effects for cardiovascular disease, but its physiological mechanisms are still unclarified. Here, we examined the effects of whale oil on a mouse model of AMD. The area of CNV measured in choroidal flat‐mount preparations at 7 days after laser photocoagulation was significantly smaller in mice fed whale oil compared with control mice free of ω‐3 long‐chain polyunsaturated fatty acids (LCPUFAs). The plasma concentrations of ω‐3 LCPUFAs were higher, whereas those of ω‐6 LCPUFAs were lower in mice fed the diet containing whale oil than in those fed the control diet. The concentrations of various inflammatory cytokines and chemokines in the retina or choroid at 3 or 7 days after CNV induction differed between the two groups of mice. Furthermore, the concentration of VEGF was decreased in the retina but increased in the choroid at 7 or 3 days after photocoagulation, respectively. Our results thus show that dietary intake of whale oil–containing ω‐3 LCPUFAs attenuated CNV in association with changes in inflammatory mediator levels and VEGF expression in the retina and choroid of mice, and it, therefore, warrants further study as a means to protect against AMD in humans.
TMBIM1 ameliorates sepsis‐induced cardiac dysfunction by promoting Parkin‐mediated mitophagy
Authors: Huang Weichang , Lou Anni , Wang Jun , Wang Yuegang , Zhang Wenyong , Li Jierui , Wang Shuanghu , Geng Shiyu , Wang Guozhen , Li Xu
Published: February 2025

Myocardial dysfunction is a significant complication of sepsis that is associated with elevated mortality rates. Transmembrane BAX inhibitor motif containing 1 (TMBIM1), a stress‐responsive protein, has garnered interest in the field of cardiovascular disease for its cardioprotective properties. Nevertheless, the role of TMBIM1 on sepsis‐induced cardiac dysfunction (SICD) remains unknown. Here, our findings revealed a significant elevation in TMBIM1 expression within the myocardium following endotoxin challenge and further demonstrate the cardioprotective effects of TMBIM1 through adenovirus‐mediated gene manipulation. Notably, lipopolysaccharide exposure markedly induced mitochondrial dysfunction in cardiomyocytes, which was effectively alleviated by TMBIM1 overexpression, while TMBIM1 knockdown exacerbated this dysfunction. Moreover, in cardiomyocytes subjected to endotoxin challenge, TMBIM1 was observed to interact with Parkin, facilitating its translocation from the cytosol to damaged mitochondria. This interaction enhanced the activation of mitophagy, thereby promoting the clearance of dysfunctional mitochondria and subsequently mitigating cellular injury. Hence, targeting TMBIM1 could be a novel therapeutic strategy for treating SICD.
Vasopressin in traumatic hemorrhagic shock
Authors: Voelckel Wolfgang G.
Published: February 2025

Purpose of review

Hemorrhage and subsequent development of therapy refractory shock are the major cause of death in potentially salvageable trauma victims. Recent scientific work recognizes that there is an urgent need to develop new life-support strategies. From a variety of interventions and drugs with the potential to prolong the compensation phase or to reverse the decompensation phase of shock, arginine vasopressin (AVP) is one of the most promising and best evaluated drugs. Nonetheless, the efficacy of AVP administration in hemorrhagic shock is still to be proven. Thus, this umbrella review summarizes the current evidence of AVP in hemorrhagic shock.

Recent findings

Fifteen short reviews, narrative reviews, systematic reviews and meta-analysis addressing AVP in traumatic hemorrhagic shock were identified and included in this umbrella review. There is robust evidence deriving form 23 animal studies that AVP administration is effective in hemorrhagic shock, resulting in hemodynamic stabilization and improved survival. This observation is supported by six case reports but not confirmed by two retrospective observational studies and two randomized control trials.

In uncontrolled hemorrhagic shock, arginine vasopressin might be considered as a therapy of last resort in shock patients not responding to conventional therapy. Further research is needed to determine the potential benefits and optimal dosage/timing of vasopressin use in hemorrhagic shock.
The integration of telehealth in antenatal anesthesia consults
Authors: Scharf Katelyn , Toledo Paloma
Published: February 2025

Purpose of review

Telehealth is a popular way for health care providers to connect with patients and is utilized by anesthesiologists across the world for preoperative evaluations. The purpose of this review is to outline the latest literature about telehealth use within obstetric anesthesia.

Recent findings

Utilization of telehealth significantly increased during the Coronavirus disease 2019 (COVID-19) pandemic and has proven to be a useful and reliable way to conduct antenatal obstetric anesthesia consultations in high-risk patient groups. Recent publications indicate the reliability and utility of telehealth, especially to reach remote patient populations. This can help anesthesiologists reach patients referred to tertiary centers from remote areas, which can improve the quality and safety of patient care. Furthermore, with hospital-provided infrastructure, the majority of obstetric patients are able to connect with providers via telehealth.

Obstetric anesthesiologists play a pivotal role in the perioperative planning for high-risk pregnant women, and telehealth can serve as a tool to make this easier and more efficient with high patient and provider satisfaction.
Restoring hemostasis with prothrombin complex concentrate: benefits and risks in trauma-induced coagulopathy
Authors: Grottke Oliver , Heubner Lars
Published: February 2025

Purpose of this review

To provide evidence for the use of prothrombin complex concentrate (PCC) as a potential hemostatic treatment for trauma-induced coagulopathy with and without anticoagulants.

Recent findings

PCC is effective in enhancing thrombin generation and achieving hemostasis in traumatized patients under anticoagulants. For vitamin K antagonist (VKA) reversal, it shows superior efficacy over fresh frozen plasma, achieving rapid normalization of the international normalized ratio normalization and reduced transfusion needs. In direct oral anticoagulant (DOAC)-associated bleeding, PCC offers an alternative when specific antidotes are unavailable. However, evidence from randomized trials in the field of trauma and coagulopathy is limited, and the results have shown conflicting outcomes in terms of mortality reduction. Further, following PCC application, thromboembolic risks remain a particular concern. Monitoring tools such as thrombin generation assays and point-of-care tests show promise but are not universally available.

PCC is a valuable option for managing coagulopathy in specific settings, especially VKA and DOAC reversal. Based on current evidence, we caution against the use of PCC as a versatile hemostatic agent suitable for indications involving multiple clotting factor deficiencies for uncontrolled coagulopathic bleeding in trauma or other clinical settings outside anticoagulation reversal. The risk vs. benefit profile should be carefully examined, similar to any other agent.
Outcomes, cost-effectiveness, and ethics in patient blood management
Authors: Bolliger Daniel , Buser Andreas , Tanaka Kenichi A.
Published: February 2025

Purpose of the review

In this narrative review, we evaluate the recent evidence for benefits, cost-effectiveness, and ethical considerations of patient blood management (PBM) programs.

Recent findings

PBM programs are able to reduce the amount of red blood cell transfusion by 20–40% and the risk of reoperation. Lower morbidity and mortality due to PBM implementation were only shown in retrospective studies with a before-and-after design but not in randomized controlled trials. PBM is very likely to be cost-effective when reduced blood transfusion can be accomplished through low-cost interventions, such as administration of oral iron or antifibrinolytics. Further, cost-efficacy can also be achieved by reducing postoperative morbidity and length of hospital stay. Of note, cost-efficacy of PBM interventions might be better in patients at high bleeding risk. Finally, aiming to improve patient’s outcome while minimizing transfusion-induced complications, PBM seems highly ethical.

PBM is an important concept as it promotes the rational use of allogeneic blood products and reduces transfusion and wastage of precious and limited blood products.
Update on traumatic brain injury in the ICU
Authors: Slot Rosalinde E.R. , Helbok Raimund , van der Jagt Mathieu
Published: February 2025

Purpose of review

This review aims to summarize recent developments for the management of severe traumatic brain injury (TBI) in the ICU. Recent advancements in TBI ICU management emphasize a progression toward more multimodal approaches and mitigating secondary brain injury by increased focus on careful systemic management.

Recent findings

Invasive monitoring techniques such as continuous intracranial pressure (ICP) and brain tissue oxygen pressure (PbtO2) monitoring are considered standard of care or may become crucial, respectively, for managing severe TBI. Technological advances in noninvasive techniques (e.g. quantitative pupillometry) are likely to advance our diagnostic and prognostic ability. Blood biomarkers, including glial fibrillary acidic protein, neurofilament light chain, and ubiquitin carboxy-terminal hydrolase L1, provide minimally invasive ways to better assess injury severity and predict outcomes. These advancements support personalized care, which will likely influence clinical management strategies in the future.

ICP monitoring remains a key component of severe TBI management in ICU. Emerging evidence is slowly changing and improving intensive care and patient outcomes and include both brain-targeted therapies and careful systemic intensive care management.
The utility of wearable devices in the perioperative period
Authors: Xiang Alexander J. , Hu Jenny Xinye , Ladha Karim S.
Published: February 2025

Purpose of review

Improved perioperative patient monitoring is a crucial step toward better predicting postoperative outcomes. Wearable devices capable of measuring various health-related metrics represent a novel tool that can assist healthcare providers. However, the literature surrounding wearables is wide-ranging, preventing clinicians from drawing definitive conclusions regarding their utility. This review intends to consolidate the recent literature on perioperative wearables and summarize the most salient information.

Recent findings

Wearable devices measuring cardiac output and colonic motility have recently been piloted with mixed results. Novel measurement techniques for established metrics have also been studied, including photoplethysmography devices for heart rate and blood pressure along with resistance thermometers for temperature. Nuanced methods of synthesizing data have been piloted, including machine-learning algorithms for predicting adverse events and trajectory curves for step count progression. Wearable devices are generally well accepted, although adjuvant support systems have improved patient satisfaction.

Perioperative wearables are valuable tools for tracking postoperative health metrics, predicting adverse events, and improving patient satisfaction. Future research on removing barriers such as technological illiteracy, artifact generation, and false-positive alarms would enable better integration of wearables into the hospital setting.
Personal Public Disclosure: A New Paradigm for Meeting Regulatory Requirements Under Exception From Informed Consent
Authors: Ross Catherine E. , Kleinman Monica E. , Donnino Michael W.
Published: February 2025

Objectives:

To describe a novel approach to the requirement for public disclosure under regulations for Exception From Informed Consent (EFIC) in an inpatient clinical trial.

Design:

Single-arm intervention study within a clinical trial.

Setting:

Medical and medical/surgical PICUs at an academic children’s hospital.

Participants:

Families of children and young adults younger than 26 years old receiving care in a PICU.

Interventions:

As part of a multipronged approach to meeting requirements for public disclosure for EFIC, we developed and implemented a process termed “personal public disclosure,” in which a member of the study team notifies all potentially eligible patients/families in-person or by phone about the trial as soon as possible upon PICU admission. Patients/families may choose to opt out of future participation in the trial.

Measurements and Main Results:

Over a 16-month period, 1577 potentially eligible patients/families were successfully contacted for personal public disclosure. Of these, 473 (30%) opted out of future participation in the trial. In the same period, 64 patients developed the emergent event of interest for the primary trial. Of these, only 9 (14%) were enrolled. Upon notification of enrollment, all 9 (100%) agreed to continue in the data collection phase of the study. Of the remaining 55 missed enrollments, 38 (69%) were due to the event occurring before personal public disclosure had been completed.

Conclusions:

Personal public disclosure supports patient/family autonomy within an EFIC trial; however, this approach is limited by low cost-effectiveness, feasibility and appropriateness in many circumstances.
External Evaluation of Longitudinal Population Pharmacokinetic Models of Vancomycin in Patients With Osteoarticular Infections
Authors: Nguyen Van Dong , Côté Alice , Marsot Amélie
Published: February 2025

Background:

Osteoarticular infections pose a challenge for therapeutic drug monitoring of vancomycin because they often require prolonged treatment. Given the extensive renal elimination of vancomycin, its pharmacokinetic properties are difficult to predict in the later stages of treatment because the risk of nephrotoxicity increases with the duration of treatment. In this study, published longitudinal population pharmacokinetic (popPK) models were externally evaluated in a cohort of patients with osteoarticular infections.

Methods:

A literature search was performed in PubMed/EMBASE and published reviews. The predictive performance of the selected models was assessed through prediction- and simulation-based diagnostics using NONMEM software. Data were collected during both the retrospective and prospective phases, during which prospectively recruited patients provided additional vancomycin concentrations.

Results:

The external validation dataset comprised 525 vancomycin concentrations obtained from 73 patients treated for osteoarticular infections at Montréal General Hospital. Two published popPK models that provided different approaches for integrating a longitudinal structure were identified. Both failed to meet the clinically acceptable threshold of imprecision in population predictions. The weighted median absolute prediction error ranged from 34.9% to 48.3% before re-estimation of model parameters and from 33.5% to 35.2% after re-estimation. The re-estimated models tended to underpredict vancomycin concentrations in the later stages of treatment.

Conclusions:

The 2 evaluated models showed poor predictive performance in our local study population. Further studies should explore new strategies to incorporate a longitudinal component and consider other relevant clinical covariates to develop improved longitudinal popPK models for vancomycin.
Reconstruction of Complex Nasal Defect With Anterolateral Thigh Chimeric Flap
Authors: Sơn Trần Thiết , Dung Phạm Thị Việt , Nghĩa Phan Tuấn , Thuý Tạ Thị Hồng , Nhật Phạm Kiến , Anh Hoàng Tuấn
Published: February 2025

Total nasal defects, including adjacent soft tissue damage, present a challenge for plastic surgeons, and in this case, free flaps should be an alternative when local flaps are limited. However, the importance of donor site morbidity must be taken into account for free flaps. Due to flap bulkiness, the anterolateral thigh (ALT) free flaps are less commonly used to restore nasal structures. Our case used a thinned ALT flap to reconstruct the entire nasal defect and part of the upper lip due to the resection of poorly differentiated squamous cell carcinoma. Two ALT flaps were harvested to reconstruct a 10 × 6 cm defect spanning the entire nose and part of the upper lip. Both skin paddles were thinned to a minimum of 4 mm thickness. A costal cartilage graft was used to create a framework for structural support. The donor site was closed with local flaps and skin grafts. No complications were noted during follow-ups. After 24 months, the patient had an excellent nasal contour that matched her skin tone and had no airway obstruction. The thinned ALT chimeric flap can be ideal for large defects composed of multiple anatomical units, even in the facial region. Its advantages are that it is thin, flexible, and well vascularized and can provide favorable aesthetic results with minimal donor site morbidity.
Outcomes of a Tenon Patch Graft for Corneal Perforations in Resolving Infective Keratitis
Authors: Heroor Aniruddh , Dandekar Prajakta , Murthy Somasheila I.
Published: February 2025

Purpose:

To report the outcomes of a Tenon patch graft (TPG) in sealing corneal perforations in cases with resolving infective keratitis.

Methods:

This retrospective interventional study was conducted at a tertiary eye care center. All patients who underwent a TPG for corneal perforations because of clinically or/and microbiologically diagnosed infective keratitis between 2021 and 2023 were included. The surgical technique was consistent with that used in noninfective etiology. Out of 100 cases undergoing a TPG during the same period, 15 eyes of 14 patients had corneal perforations secondary to infective keratitis.

Results:

The etiological profile included bacterial keratitis in 8, viral and fungal keratitis in 3, and Pythium keratitis in 1 eye of 15 eyes. One patient had bilateral infective keratitis after refractive surgery. The perforations were central in 7 and paracentral in 8 eyes. Successful restoration of tectonic integrity at 1 month was achieved in 14/15 eyes (93%). One patient had a repeat perforation at 3 weeks postoperatively, which was managed with a cyanoacrylate glue application. Infection control was achieved in all cases with adjunctive topical antimicrobial therapy.

Conclusions:

A TPG is a viable option for restoring globe integrity in corneal perforations encountered in resolving infective keratitis.
Humpback whale song complexity and evolution on a northwestern Pacific breeding ground: Okinawa, Japan
Authors: Marwood Eleanor M. , Eichenberger Franca , Kobayashi Nozomi , Okabe Haruna , Ozawa Sachie , Rendell Luke , Garland Ellen C.
Published: February 2025

Male humpback whales (
Megaptera novaeangliae
) sing a slowly evolving, sexually selected song display socially learned from conspecifics. Within an ocean basin, song similarity between breeding populations can reveal the degree of connectivity among them. In the northwestern Pacific Ocean, there is a paucity of information on song dynamics and linkages across the ocean basin. Here, we quantified fine-scale song evolution in whales near Okinawa, Japan, using similarity indices (Levenshtein distance and Dice’s similarity) and song complexity measures to investigate three consecutive years (2011–2013) of song dynamics on this breeding ground. Matched song themes revealed minimal evolution between 2011 and 2012, while the 2013 song was more distinct, as singers sang both new and evolved versions of themes. This was mirrored by the song complexity scores, which decreased and then increased over time. Qualitative comparisons of Okinawa song themes to other published North Pacific breeding ground songs revealed many themes were shared across the North Pacific, contributing to the growing body of evidence of a single panmictic song lineage across the North Pacific Ocean basin, in contrast to the South Pacific. Understanding geographically differing song dynamics is essential to revealing the underlying drivers of this ocean basin-wide non-human culture.
Total acoustic transmission between fluids using a solid material with emphasis on the air–water interface
Authors: Bakhtiary Yekta Hesam , Norris Andrew N.
Published: February 2025

Total acoustic transmission between water and air is modelled using a purely solid interface comprising two elastic plates separated by periodically spaced ribs. The frequency of full transmission depends only on, and is inversely proportional to, the areal density of the plate facing the air. The total transmission also requires a specific dependence of the rib spacing on the bending stiffness of the two plates. These relations are the result of an explicit analytical solution for the transmitted and reflected acoustic waves combined with asymptotic approximations based on the small parameter defined by the air-to-water impedance ratio. Surprisingly, the total transmission effect is almost independent of the angle of incidence, even though the transmission conditions are predicated on normal incidence. Parametric studies are performed to examine the effect on the frequency bandwidth and Q-factor of the acoustic transmissivity. A lower bound for the Q-factor of

30.6

is simply related to the water–air impedance ratio.
Multi-Omics Analysis of Red Blood Cells Reveals Molecular Pathways Underlying Thalassemia Severity Beyond Globin Gene Mutations
Authors: Mitra Nibedita , Bhattacharyya Upasana , Chowdhury Prosanto , Pal Arijit , Korwar Arvind , Bhattacharjee Samsidhhi , Basu Anupam
Published: February 2025

Background

Hemoglobinopathies are the most common monogenic genetic disorders, primarily managed through blood transfusions or bone marrow transplantation. Clinical severity other than mutational effect not well investigated and still unknown. This study aims to identify dysregulated molecular pathways in red blood cells contributing to thalassemia severity.

Method

From a cohort of 285 hemoglobinopathy patients, 10 age-matched individuals with identical compound heterozygous mutations (IVS 1-5 G>C and CD 26 G>A) were screened. Five had severe thalassemia requiring regular transfusions, while five had a non-severe form requiring fewer transfusions. RNA sequencing and proteome analysis were conducted on isolated RBCs, through Novaseq and Orbitrap MS platform respectively. Bioconductor-R and different bioinformatics tools were utilized subsequently.

Results

Transcriptome analysis revealed an increased percentage of snRNA transcripts in all over thalassemia group. Pathways related to autophagy, mitophagy, and chaperone-mediated folding were enriched in the severe group. Thus, dysregulated genes, linked to ineffective erythropoiesis were fished out also.

Conclusion

In this this study, thalassemia subjects were of same mutational genotype, but clinically opposite severity. Accordingly, first time identified six pathways which are responsible for thalassemia severity independent of mutational burden. These dysregulated pathways can be further be explored and targeted experimentally for drug development.
Spatially resolved proteomic signatures of atherosclerotic carotid artery disease
Authors: Sinha Ankit , Sachs Nadja , Kratz Elena , Pauli Jessica , Steigerwald Sophia , Albrecht Vincent , Nordmann Thierry , Ugur Enes , Rodriguez Edwin H , Engl Marie-Luise , Skowronek Patricia , von Scheidt Moritz , Winter Hanna , Branzan Daniela , Schunkert Heribert , Maegdefessel Lars , Mann Matthias
Published: February 2025

Atherosclerotic plaque rupture remains a leading cause of adverse cardiovascular events, yet the molecular drivers of plaque vulnerability are incompletely understood. To address this challenge, we developed an integrated approach that combines histomorphology-guided spatial proteomics with machine learning to map protein signatures across spatially distinct plaque subregions. Our analysis revealed that vulnerability signatures concentrate in the necrotic core and fibrous cap subregions, and are significantly enriched for ossification, inflammation, cholesterol metabolism, and extracellular matrix degradation pathways. When comparing the vulnerability status across subregions, we found that the necrotic core has the most distinctive vulnerability-associated proteome, with 454 proteins significantly altered between stable and vulnerable states. We identified a mechanistic link between inflammation and oxidative stress, PCSK9 upregulation, and vascular smooth muscle cell dysfunction in vulnerable plaques. This finding suggests arterial PCSK9 as a therapeutic target beyond its established role in hepatic lipid metabolism. By employing machine learning, we developed and independently validated a seven-protein tissue panel (receiver operating characteristic– area under the curve = 0.86) and found a 12-protein serum panel to predict plaque vulnerability status. Thus, plaque vulnerability signatures are spatially concentrated in specific subregions and highlight actionable biomarkers and therapeutic targets for advanced carotid artery disease.
The impact of medication reconciliation on discrepancies and all-cause readmission among hospitalized patients with chronic kidney disease: A quasi-experimental study
Authors: Altawalbeh Shoroq M. , Sallam Nahlah M. , Alshogran Osama Y. , Al-Khatib Minas , Bani Amer Mohammad S. , Tahaineh Linda , Albsoul-Younes Abla
Published: February 2025

Introduction

Chronic kidney disease (CKD) with its associated comorbidities and pill burden can expose patients to a heightened risk of drug-related problems, including medication discrepancies.

This study aimed to evaluate the impact of medication reconciliation supplemented with medication review on the number of medication discrepancies at discharge and all-cause readmission among CKD patients.

Methods

This was a quasi-experimental trial among adult CKD patients admitted into two major referral hospitals in northern Jordan. Patients in the intervention group received medication reconciliation supplemented with medication review by a clinical pharmacist, while those in the control group received the usual care. The recognized discrepancies were evaluated at admission and at discharge in both groups. Participants were followed for 90-day readmission.

Results

Among patients in the intervention group, the average number of discrepancies was 2.5±2.2 per CKD patient. Compared to the control group, the reduction in discrepancy numbers between admission and discharge was higher in the intervention group by 1.66 discrepancies. The likelihood of 90-day readmission was significantly lower in the intervention group (OR=0.41; P=0.002).

Conclusion

Supplemented medication reconciliation among CKD patients reveals a favorable impact on medication discrepancies and readmission rates. Optimizing medication management during transitions of care can improve overall health outcomes.

Impact of findings on practice statements

Activating the role of clinical pharmacists in providing medication reconciliation can decrease medication discrepancies and enhance clinical outcomes particularly in hospitalized CKD patients.

Designing and implementing an effective interprofessional collaborative approach in the hospital settings might boost the benefits achieved from transition-of-care services.
Screening rare genetic diagnoses for amenability to bespoke antisense oligonucleotide therapy development: a retrospective cohort study
Authors: Cheerie David , Lauffer Marlen C. , Newton Logan , Amburgey Kimberly , Beijer Danique , Haque Bushra , Kalish Brian T. , Meserve Margaret , Oh Rachel Y. , Pan Amy Y. , Reuter Miriam , Szego Michael J. , Szuto Anna ,   N=1 Collaborative, Aartsma-Rus Annemieke , Axford Michelle M. , Deshwar Ashish R. , Dowling James J. , Marshall Christian R. , Ivakine Zhenya , Synofzik Matthis , Yu Timothy W. , Costain Gregory
Published: February 2025

Purpose

To estimate the proportion of molecular genetic diagnoses in a real-world, phenotypically heterogeneous patient cohort that are amenable to antisense oligonucleotide (ASO) treatment.

Methods

We retrospectively applied the N=1 Collaborative’s VARIANT (VariantAssessments towards Eligibility forAntisense OligonucleotideTreatment) guidelines to all diagnostic variants found by clinical genome-wide sequencing at a single pediatric hospital in 532 patients over a 6-year period. Variants were classified as either “eligible”, “likely eligible”, “unlikely eligible”, or “not eligible” in relation to the different ASO approaches, or “unable to assess”.

Results

In total, 25 unique variants across 26 patients (4.9% of 532 patients) were eligible or likely eligible for ASO treatment at a molecular genetic level, via canonical exon skipping (4), splice correction (3), or mRNA knockdown (18). Only eight of these molecular genetic diagnoses were made within a year of symptom onset. After considering disease and delivery related factors, 11 diagnoses were still considered candidates for bespoke ASO development.

Conclusion

A meaningful proportion of genetic diagnoses identified by genome-wide sequencing may be amenable to ASO treatment. These results underscore the importance of timely diagnosis, and the proactive identification and accelerated functional testing of genetic variants amenable to ASO treatments.