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32 pages, 5469 KB  
Systematic Review
Systematic Review and Meta-Analysis of RCTs on Efficacy of Conventional vs. Emerging Treatments for Amblyopia
by Clara Martinez-Perez and Ana Paula Oliveira
Life 2026, 16(2), 222; https://doi.org/10.3390/life16020222 - 28 Jan 2026
Abstract
Amblyopia affects 1–4% of the population and remains a leading cause of unilateral visual impairment, with adherence and residual deficits limiting outcomes of standard therapies. This systematic review and meta-analysis compared the effectiveness of conventional and emerging amblyopia treatments in children, adolescents, and [...] Read more.
Amblyopia affects 1–4% of the population and remains a leading cause of unilateral visual impairment, with adherence and residual deficits limiting outcomes of standard therapies. This systematic review and meta-analysis compared the effectiveness of conventional and emerging amblyopia treatments in children, adolescents, and adults with anisometropic, strabismic, or mixed amblyopia. Following PRISMA guidelines and PROSPERO registration (CRD420251123552), PubMed, Web of Science, and Scopus were searched up to 5 August 2025 for randomized controlled trials. Sixty-six trials (sample sizes 7–404) were included, with thirty-six contributing to the meta-analysis. Primary outcomes were best-corrected visual acuity (logMAR) and stereopsis. Risk of bias was assessed using the Cochrane tool, and certainty of evidence was assessed using GRADE. Atropine penalization and occlusion demonstrated equivalent effects on visual acuity (mean difference 0.04 logMAR; 95% CI −0.04 to 0.12; moderate-certainty evidence). Digital, dichoptic, binocular, and virtual reality therapies showed a statistically significant but small improvement over patching (mean difference 0.02 logMAR; 95% CI 0.00–0.04; low-certainty evidence). Pharmacological adjuvants combined with patching yielded slightly larger gains (mean difference 0.08 logMAR; 95% CI 0.03–0.13; low-to-moderate certainty). No consistent benefit was observed for stereopsis outcomes. Overall, the certainty of evidence ranged from low to moderate, and most pooled effects were below commonly accepted thresholds for clinically meaningful visual acuity improvement (≈0.1 logMAR, one line). Atropine and occlusion remain equivalent first-line treatments, while adjunctive and multimodal approaches may offer limited additional benefit in selected patients when adherence, tolerability, and engagement are prioritized. Full article
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19 pages, 1224 KB  
Article
Detection of HIV-1 Resistance Mutations to Antiretroviral Therapy and Cell Tropism in Russian Patients Using Next-Generation Sequencing
by Artem Fadeev, Veronika Eder, Maria Pisareva, Valery Tsvetkov, Alexey Masharskiy, Kseniya Komissarova, Anna Ivanova, Nikita Yolshin, Andrey Komissarov, Alexey Mazus and Dmitry Lioznov
Pathogens 2026, 15(2), 144; https://doi.org/10.3390/pathogens15020144 - 28 Jan 2026
Abstract
The use of antiretroviral therapy (ART) as the only effective way to control human immunodeficiency virus (HIV) infection results in HIV drug resistance. Next-generation sequencing (NGS) has become a common method for identifying drug-resistant variants and reducing analysis costs. The aim of this [...] Read more.
The use of antiretroviral therapy (ART) as the only effective way to control human immunodeficiency virus (HIV) infection results in HIV drug resistance. Next-generation sequencing (NGS) has become a common method for identifying drug-resistant variants and reducing analysis costs. The aim of this study was to develop an NGS-based protocol for identifying resistance mutations and cell tropism of HIV-1 in adult patients with and without treatment experience in Russia in 2024–2025. Plasma samples from adult HIV-infected patients from Russia were analyzed. Consensus nucleotide sequences of pol and env genes were obtained using NGS. HIV-1 drug resistance analysis was conducted using the Stanford University HIVdb database. CXCR4 cell tropism was predicted using an empirical rule classifier. A protocol for NGS of HIV-1 pol and env genes was developed. The most common HIV-1 surveillance mutations were in the reverse transcriptase. High levels of resistance were observed to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced patients and to NNRTIs in treatment-naïve patients. Low levels of resistance were observed to protease and integrase strand transfer inhibitors (INSTIs). CXCR4 cell tropism was extremely rare. NGS allows for the simultaneous processing of large data sets during epidemiological studies. The introduction of NGS-based protocols allows for performing ART efficiency and tropism monitoring at scale. Full article
(This article belongs to the Section Epidemiology of Infectious Diseases)
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24 pages, 845 KB  
Review
Global Warming and the Elderly: A Socio-Ecological Framework
by Nina Hanenson Russin, Matthew P. Martin and Megan McElhinny
Int. J. Environ. Res. Public Health 2026, 23(2), 164; https://doi.org/10.3390/ijerph23020164 - 28 Jan 2026
Abstract
Problem Statement: Two global trends, including aging populations and the acceleration of global warming, are increasing the risk of heat-related illness, challenging the health of populations, and the sustainability of healthcare systems. Global warming refers to the increase in the Earth’s average surface [...] Read more.
Problem Statement: Two global trends, including aging populations and the acceleration of global warming, are increasing the risk of heat-related illness, challenging the health of populations, and the sustainability of healthcare systems. Global warming refers to the increase in the Earth’s average surface temperature, generally attributed to the greenhouse effect, which is occurring at three times the rate of the pre-industrial era. The global population of older adults, defined here as individuals aged 60 and over, is expected to reach over 2 billion by mid-century. This population is particularly vulnerable to heat-related illness, specifically disruption of thermoregulation from excessive exposure to environmental heat due to metabolic and cognitive changes associated with aging. Objectives: This review examines heat-related illness and its impact on older adults within a socio-ecological framework, considering both drivers and mitigation strategies related to global warming, the built environment, social determinants of health, healthcare system responses, and the individual. The authors were motivated to create a conceptual model within this framework drawing on their lived experiences as healthcare providers interacting with older adults in a large urban area of the southwestern US, known for its extreme heat and extensive heat island effects. Based on this framework, the authors suggest actionable strategies supported by the literature to reduce the risks of morbidity and mortality. Methods: The literature search utilized a wide lens to identify evidence supporting various aspects of the hypothesized framework. In this sense, this review differs from systematic and scoping reviews, which seek a complete synthesis of the available literature or a mapping of the evidence. The first author conducted the literature search and synthesis, while the second and third authors reviewed and added publications to the initial search and conceptualized the socio-ecological framework. Discussion: This study is unique in its focus on a global trend that threatens the well-being of a growing population. The population health focus underscores social determinants of health and limitations of existing healthcare systems to guide healthcare providers in reducing older adults’ vulnerability to heat-related illness. This includes patient education regarding age-related declines in extreme heat tolerance, safe and unsafe physical activity habits, the impact of prescription drugs on heat tolerance, and, importantly, identifying the symptoms of heatstroke, which is a medical emergency. Additional strategies for improving survivability and quality of life for this vulnerable population include improved emergency response systems, better social support, and closer attention to evidence-based treatment for heat-related health conditions. Full article
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30 pages, 1026 KB  
Review
The Natural History of Obstructive Sleep Apnea: A Scoping Review
by Alexandros Kalkanis, Theodoros Panou, Kostas Archontogeorgis and Paschalis Steiropoulos
Healthcare 2026, 14(3), 325; https://doi.org/10.3390/healthcare14030325 - 27 Jan 2026
Abstract
Obstructive sleep apnea (OSA) is a common disorder caused by recurrent upper airway obstruction during sleep, affecting individuals across the lifespan. In children, OSA commonly results from adenotonsillar hypertrophy and may resolve spontaneously or following surgical intervention. Among adolescents and adults, OSA is [...] Read more.
Obstructive sleep apnea (OSA) is a common disorder caused by recurrent upper airway obstruction during sleep, affecting individuals across the lifespan. In children, OSA commonly results from adenotonsillar hypertrophy and may resolve spontaneously or following surgical intervention. Among adolescents and adults, OSA is more frequently associated with modifiable lifestyle factors, particularly obesity. The natural history of OSA may evolve from intermittent snoring and mild disease to moderate or severe forms if left untreated, leading to reduced health-related quality of life and overall health deterioration. Early identification of OSA, especially in mild and moderate cases, allows timely interventions to improve OSA-associated indices and may prevent progression to severe disease. Continuous positive airway pressure therapy remains the treatment of choice for adults, providing effective symptom control and reducing long-term complications, although adherence rates vary. In obese patients, sustained weight reduction represents the most effective disease-modifying strategy: a ≥5% weight loss is associated with an approximately 80% reduction in progression risk, while bariatric surgery achieves remission in up to 60–65% of cases at one year. Emerging anti-obesity pharmacotherapies have also demonstrated clinically meaningful reductions in the apnea–hypopnea index. Comorbid conditions such as hypertension, type 2 diabetes, and depression exacerbate OSA severity, impair treatment response, and complicate overall disease management. This review uniquely integrates pediatric and adult longitudinal data, treatment-modified trajectories, and emerging therapeutic approaches to provide a life-course perspective on OSA natural history, highlighting opportunities for early, phenotype-directed intervention to possibly alter disease course and long-term outcomes. Full article
(This article belongs to the Special Issue Sleep Disorders Management in Primary Care—Second Edition)
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12 pages, 990 KB  
Article
Analysis of Factors Affecting Postoperative Opioid Requirement in Adult Patients Undergoing Minimally Invasive Repair of Pectus Excavatum
by Minju Kim, Saewon Park, Seung Keun Yoon and Wonjung Hwang
J. Clin. Med. 2026, 15(3), 1023; https://doi.org/10.3390/jcm15031023 - 27 Jan 2026
Abstract
Background/Objectives: Minimally invasive repair of pectus excavatum (MIRPE) is an established surgical treatment for adult pectus excavatum (PE). Compared with pediatric patients, adults generally have a more rigid chest wall and greater costal cartilage ossification, often resulting in more severe postoperative pain. [...] Read more.
Background/Objectives: Minimally invasive repair of pectus excavatum (MIRPE) is an established surgical treatment for adult pectus excavatum (PE). Compared with pediatric patients, adults generally have a more rigid chest wall and greater costal cartilage ossification, often resulting in more severe postoperative pain. However, most previous studies have focused on pediatric patients with PE and on evaluating effective analgesic methods. This study aimed to investigate perioperative factors associated with postoperative opioid requirements and pain intensity in adult patients undergoing MIRPE. Methods: This study was a single-center retrospective study of adult PE patients who underwent MIRPE between March 2011 and January 2023. The primary outcome was total opioid consumption during the first 24 postoperative hours. Secondary outcomes included opioid and rescue analgesic use within 0–6, 6–24, and 24–48 h, as well as pain intensity during each interval. Multivariable linear regression analysis was performed to identify factors associated with postoperative opioid consumption. Results: A total of 382 patients were analyzed. Pain intensity peaked within the first 6 postoperative hours, decreased during the 6–24 h and increased during 24–48 h period. Higher BMI and placement of more than three bars were independently associated with greater opioid consumption during the first 6 h (p < 0.001). Within 24 and 48 h, male sex, longer operation time and higher BMI were independently associated with opioid consumption (p < 0.001). During 6–24 and 24–48 h period, VAS severity was significantly higher in male patients and those with longer operation times. Conclusions: Male sex, higher BMI, prolonged operation time, and multiple bar insertion may contribute to greater postoperative opioid requirements during the early postoperative phase in adult patients undergoing MIRPE. Full article
(This article belongs to the Special Issue Clinical Updates on Perioperative Pain Management: 3rd Edition)
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15 pages, 2854 KB  
Article
Impact of Fusion Partners and Transplantation Benefit in Intensively Treated KMT2A-Rearranged Acute Myeloid Leukemia
by Heng Shen, Jiayuan Chen, Xiaoyuan Gong, Chunlin Zhou, Dong Lin, Kaiqi Liu, Benfa Gong, Guangji Zhang, Yan Li, Yuntao Liu, Shaowei Qiu, Bingcheng Liu, Ying Wang, Yingchang Mi, Qiuyun Fang, Jianxiang Wang and Hui Wei
Cancers 2026, 18(3), 401; https://doi.org/10.3390/cancers18030401 - 27 Jan 2026
Abstract
Background: KMT2A rearrangements are a frequent genetic abnormality associated with Acute myeloid leukemia (AML), historically linked to varied prognoses and outcomes. The prognosis for patients with this rearrangement remains controversial, necessitating further research to stratify risk and guide treatment. Methods: In this retrospective [...] Read more.
Background: KMT2A rearrangements are a frequent genetic abnormality associated with Acute myeloid leukemia (AML), historically linked to varied prognoses and outcomes. The prognosis for patients with this rearrangement remains controversial, necessitating further research to stratify risk and guide treatment. Methods: In this retrospective study, a total of 3468 adolescent and adult AML patients were screened, and 181 patients harboring KMT2A rearrangements were analyzed. We used FISH, RT-PCR, and next-generation sequencing, including transcriptome and targeted panels, for diagnosis and mutation profiling. All patients received intensive chemotherapy. We evaluated overall survival and event-free survival using Kaplan–Meier and Cox regression models, with HSCT analyzed as a time-dependent variable. Results: The incidence of KMT2A-rearranged AML in our newly diagnosed cohort was 5.9%. Among the 181 patients included in the final analysis, 89 (49.2%) were male and 92 (50.8%) were female, with a median age of 33 years (range: 13–65). The distribution of fusion partners included KMT2A::MLLT3 (n = 39), KMT2A::AFDN (n = 27), KMT2A::MLLT10 (n = 25), KMT2A::ELL (n = 24), and others (n = 12). Seventy-four patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). The median follow-up for survivors was 17.53 months (range 1.47–112.57), and the 3-year overall survival (OS) and event-free survival (EFS) for the entire cohort were 42.0% and 32.1%, respectively. Patients with KMT2A::ELL exhibited superior OS compared to other subtypes (3-year OS [ELL vs. non-ELL]: 59.8% vs. 39.3%, p = 0.023). Concomitant mutations did not significantly impact the prognosis of KMT2A-rearranged AML patients. In multivariate analysis, age and HSCT in CR1 were independently associated with OS and EFS (OS: HR = 1.022, p = 0.026 [age]; HR = 0.238, p < 0.001 [HSCT]; EFS: HR = 1.027, p = 0.002 [age]; HR = 0.155, p < 0.001 [HSCT]). Patients aged over 20 years were more likely to benefit from HSCT than those aged 20 years or younger (p < 0.001 [age > 20], p = 0.780 [age ≤ 20]). Conclusions: Our study revealed the heterogeneous outcomes of KMT2A-rearranged AML patients and clarified the impact of HSCT across different age groups. Full article
(This article belongs to the Special Issue Acute Myeloid Leukemia in Adults (2nd Edition))
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15 pages, 1858 KB  
Article
Leptospirosis in Central Romania: A 17-Year Single-Center Cohort Study of Hospitalized Adults
by Victoria Birlutiu and Rares-Mircea Birlutiu
Microorganisms 2026, 14(2), 298; https://doi.org/10.3390/microorganisms14020298 - 27 Jan 2026
Abstract
Background: Leptospirosis is an important zoonosis that can present as a self-limited influenza-like illness or progress to severe, including life-threatening multiorgan dysfunction. We report the epidemiology, clinical profile, and correlates of severity among adults hospitalized patients with leptospirosis diagnosed in central Romania over [...] Read more.
Background: Leptospirosis is an important zoonosis that can present as a self-limited influenza-like illness or progress to severe, including life-threatening multiorgan dysfunction. We report the epidemiology, clinical profile, and correlates of severity among adults hospitalized patients with leptospirosis diagnosed in central Romania over a period of 17 years. Methods: We conducted a retrospective, single-center cohort study of adults admitted between 1 January 2008 and 1 December 2025 with laboratory-confirmed leptospirosis. Confirmation was based on positive anti-Leptospira IgM serology, with repeat testing when the initial result was equivocal and confirmation with a microscopic agglutination test. We extracted demographic, exposure, clinical, laboratory, treatment, and outcome data from medical records. The modified Faine score was also calculated using admission data. Results: Sixty-four patients were included in this analysis, of which 53 (82.8%) were male patients. Admissions peaked in 2023–2025 (34/64, 53.1%) and in the August–September months. Reported exposures were predominantly peri-domestic (46.9%), followed by rural/animal-related occupations (20.3%) and freshwater contact (17.2%). Severe disease occurred in 26/64 (40.6%), was more frequent in men (p = 0.021), and was more common pre-pandemic than during/after the pandemic (p < 0.001). Severe cases were associated with oliguria/anuria, hematuria, and jaundice, alongside higher urea/creatinine and bilirubin, lower hemoglobin and lymphocyte percentages, and a longer hospitalization period. One in-hospital death occurred (1.6%). Serogroup identification was available for 10 patients (15.6%) (pre-pandemic only). The mean modified Faine score was 27.5 ± 6.0. Conclusions: In this temperate-region cohort study, hospitalized leptospirosis showed a marked male predominance, a late-summer peak, and a substantial burden of severe disease. Early renal and hepatobiliary manifestations with concordant laboratory abnormalities may support timely risk stratification and escalation of care, while expanded molecular diagnostics and systematic typing are needed to clarify temporal trends and guide prevention. Full article
(This article belongs to the Special Issue Infectious Disease Surveillance in Romania: Second Edition)
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19 pages, 735 KB  
Review
Neurochemical and Energetic Alterations in Depression: A Narrative Review of Potential PET Biomarkers
by Santiago Jose Cornejo Schmiedl, Bryan Astudillo Ortega, Bernardo Sosa-Moscoso, Gabriela González de Armas, Jose Ignacio Montenegro Galarza, Jose A. Rodas and Jose E. Leon-Rojas
Int. J. Mol. Sci. 2026, 27(3), 1267; https://doi.org/10.3390/ijms27031267 - 27 Jan 2026
Abstract
Depression is a heterogeneous neuropsychiatric disorder with variable clinical presentation and response to treatment. This variability has motivated interest in neuroimaging biomarkers capable of disease characterization and therapeutic prediction. Positron emission tomography (PET) enables in vivo assessment of cerebral glucose utilization, neurochemical targets, [...] Read more.
Depression is a heterogeneous neuropsychiatric disorder with variable clinical presentation and response to treatment. This variability has motivated interest in neuroimaging biomarkers capable of disease characterization and therapeutic prediction. Positron emission tomography (PET) enables in vivo assessment of cerebral glucose utilization, neurochemical targets, inflammatory markers, and cerebral blood flow. This narrative review synthesizes PET studies conducted predominantly in adults with major depressive disorder diagnosed using DSM-based criteria, with bipolar disorder included only when imaging was performed during a depressive episode. Studies were identified through a structured, non-systematic literature search of major databases. Depression is consistently associated with regionally specific PET alterations within cortico-limbic and cortico-striatal circuits; studies most frequently report reduced glucose-derived PET measures in prefrontal and anterior cingulate regions at baseline, with treatment responders showing relative increases or redistribution of these measures following interventions. Neurochemical PET studies demonstrate altered receptor, transporter, or enzyme-related binding in serotonergic, dopaminergic, and noradrenergic systems, while neuroinflammatory and perfusion studies reveal regionally increased PET signals in subsets of patients. Overall, PET findings indicate convergent, region-specific and neurochemical alterations associated with depressive episodes and treatment response. Interpretation is constrained by methodological and clinical heterogeneity, underscoring the need for harmonized, longitudinal PET studies. Full article
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32 pages, 1547 KB  
Article
Bifunctional Metformin–Phenolic Hybrids with Improved Anticancer and Antioxidant Properties: Evaluation on Glioma Cells
by Caroline Delehedde, Mathieu Chocry, Camille Nguyen, Alice Asteian, Maxime Robin, Ludovic Leloup, Mathieu Cassien, Anne Mercier, Marcel Culcasi, Hervé Kovacic and Sylvia Pietri
Int. J. Mol. Sci. 2026, 27(3), 1259; https://doi.org/10.3390/ijms27031259 - 27 Jan 2026
Abstract
Glioblastoma is one of the most highly aggressive types of brain tumor in adults. With limited treatment options, current therapies remain insufficient due to its invasiveness and immune evasion, highlighting the urgent need for new treatments. Bifunctional molecules targeting multiple aspects of the [...] Read more.
Glioblastoma is one of the most highly aggressive types of brain tumor in adults. With limited treatment options, current therapies remain insufficient due to its invasiveness and immune evasion, highlighting the urgent need for new treatments. Bifunctional molecules targeting multiple aspects of the disease could be promising to overcome drug resistance and tumor heterogeneity. Metformin has demonstrated protective effects against brain tumors but requires high doses for efficacy, making it of great interest for molecular optimization. In this context, we synthesized a series of nine metformin–phenolic molecules, combining the metformin guanidine framework with phenolic acids, which have well-established properties in inhibiting cancer cell migration and adhesion. Their impact on cytotoxicity, reactive oxygen species inhibition, and signaling pathways was investigated for glioma cell lines and stem cells. Two of these hybrids, 5a and 5h, particularly enhanced cytotoxicity in glioblastoma cells, selectively targeting cancer cells while sparing healthy ones. Their mechanism of action differed significantly from metformin. Unlike metformin, which mainly triggers metabolic stress, the hybrids broadly inhibit RTK–MAPK–PI3K signaling, leading to cell cycle arrest and apoptosis. The results suggest that these compounds could offer a more effective and synergistic approach for glioblastoma treatment. Full article
(This article belongs to the Special Issue Biomechanics and Molecular Research on Glioblastoma: 2nd Edition)
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13 pages, 493 KB  
Article
Emergency and Non-Referral Admissions as Predictors of Hospital Mortality Among Adults with Congenital Heart Diseases: A Nationwide Claim-Based Registry Study in Japan
by Yoshihide Mitani, Michikazu Nakai, Isao Shiraishi, Hiroyuki Ohashi, Hirofumi Sawada and Hideo Ohuchi
Healthcare 2026, 14(3), 315; https://doi.org/10.3390/healthcare14030315 - 27 Jan 2026
Abstract
Background: Improved pediatric cardiac care has markedly increased the adult congenital heart disease (ACHD) population worldwide, creating new clinical and healthcare delivery challenges. However, nationwide evidence on predictors of acute outcomes in ACHD patients, particularly the impact of disrupted specialist care under universal [...] Read more.
Background: Improved pediatric cardiac care has markedly increased the adult congenital heart disease (ACHD) population worldwide, creating new clinical and healthcare delivery challenges. However, nationwide evidence on predictors of acute outcomes in ACHD patients, particularly the impact of disrupted specialist care under universal healthcare systems, remains limited. Methods: We conducted a retrospective analysis using Japan’s nationwide administrative database from 2013 to 2022, evaluating hospital admissions of ACHD patients aged ≥15 years. Patients were categorized into surgical, catheter-based, and medical treatment groups. Multilevel logistic regression models identified predictors of in-hospital mortality, including emergency and non-referral admissions as indicators of impaired continuity of specialist care. Results: A total of 27,754 admissions were analyzed (median age 59 years; 49% male). Emergency admissions accounted for 35.2%, non-referral admissions for 9.9%, and overall in-hospital mortality was 5.0%. Older age, admission to non-ACHD centers, higher CHD complexity, emergency admissions, and non-referral admissions were independently associated with increased mortality. In addition, older age, CHD complexity, and admission to non-ACHD centers predicted emergency and non-referral admissions. Conclusions: These findings show persistent gaps in specialist care continuity for ACHD patients despite universal healthcare coverage and support the need for integrated ACHD care networks to improve outcomes in this aging population in Japan. Full article
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15 pages, 590 KB  
Article
Epidemiology of Short-Stay Unit Emergency Calls in a Tertiary Emergency Department: A TECOR Study
by Giles Barrington, Toni Dunbabin, Simone Page, Lauren Thurlow, Lizette Tredoux and Viet Tran
Emerg. Care Med. 2026, 3(1), 4; https://doi.org/10.3390/ecm3010004 - 27 Jan 2026
Abstract
Background/Objectives: Emergency department short-stay units (ED SSUs) manage patients requiring short-term observation and treatment. For a small number of patients, a longer hospital admission is required. Care for these patients is provided by an inpatient team and the responsibility for managing acute [...] Read more.
Background/Objectives: Emergency department short-stay units (ED SSUs) manage patients requiring short-term observation and treatment. For a small number of patients, a longer hospital admission is required. Care for these patients is provided by an inpatient team and the responsibility for managing acute clinical deterioration falls to a rapid response team, activated by an emergency call. While emergency calls have primarily been a feature of the inpatient setting, admitted patients are increasingly boarding within ED SSUs and the occurrence and impact of emergency calls in this setting remains largely unreported. This study aimed to determine the incidence and characteristics of emergency calls within an ED SSU, describing patient demographics, clinical triggers, and outcomes. Methods: This retrospective cohort study utilised the Tasmanian Emergency Care Outcomes Registry (TECOR) to analyse emergency calls in the ED SSU of a tertiary emergency department between 1 February 2024 and 28 February 2025. Inclusion criteria were defined as adult patients (≥14 years) admitted to an inpatient service who had emergency calls whilst in the ED SSU. Descriptive statistics were used to characterise this cohort. Results: Of 83,238 ED presentations, 11,775 adult patients were transferred to the ED SSU. 1464 (12.4%) of these patients were subsequently admitted under an inpatient service but remained boarding in the ED SSU, with 54 emergency calls occurring in 38 unique patients (2.6%). The median age was 81.5 years (IQR 65–86), older than both the main ED cohort with a median age of 71 years, and median ages of 65 to 69.5 years reported in ward-based cohorts. Most calls were medical emergency team (MET) activations (52, 96.30%) with only 2 (3.7%) code blues. The most common triggers were hypotension (20, 37.04%), reduced level of consciousness (7, 12.96%) and serious concern (7, 12.96%). Delays occurred in 18.52% of calls (mean 82 min). The median ED SSU length of stay for patients having an emergency call was 40.15 h, substantially exceeding the intended ED SSU admission criteria threshold of 24 h. Goals of care remained incomplete in 33.33% of calls, even after emergency team review. Conclusions: ED SSU emergency calls are infrequent but clinically significant, involving an elderly, vulnerable population with late sign triggers and prolonged boarding. These findings highlight fundamental mismatches between patient acuity and ED SSU environment capabilities, emphasising the need for improved monitoring, more selective admission criteria, and enhanced systems for recognising deterioration for patients boarding in ED SSUs. Full article
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12 pages, 261 KB  
Study Protocol
Longitudinal Predictors of Pain and Physical Function Trajectories over 12 Months in Older Adults with Knee Osteoarthritis Receiving an Education and Exercise Program: Statistical Analysis Protocol
by Mar Flores-Cortés, Ferran Cuenca-Martínez and Tasha R. Stanton
Disabilities 2026, 6(1), 14; https://doi.org/10.3390/disabilities6010014 - 27 Jan 2026
Abstract
Knee osteoarthritis (KOA) is a leading cause of disability in older adults, characterized by persistent pain and reduced physical function. Beyond localized joint pathology, many individuals with knee osteoarthritis experience multisite pain and live with multiple comorbidities, reflecting a heterogeneous and multifactorial pain [...] Read more.
Knee osteoarthritis (KOA) is a leading cause of disability in older adults, characterized by persistent pain and reduced physical function. Beyond localized joint pathology, many individuals with knee osteoarthritis experience multisite pain and live with multiple comorbidities, reflecting a heterogeneous and multifactorial pain condition. Prognostic models based primarily on biomedical variables have shown limited ability to explain long-term outcomes, partly due to insufficient integration of pain chronicity, comorbidity count and psychosocial determinants such as treatment expectations and pain self-efficacy. While exercise and education are commonly recommended as primary non-surgical treatments, people often respond to them very differently. This study protocol describes a secondary longitudinal observational analysis of data from the EPIPHA-KNEE two-arm, multicentre randomized controlled trial. The primary outcomes will be knee OA pain intensity and physical function, assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire at baseline, 3, 6 and 12 months. Baseline prognostic factors will include pain duration, pain distribution, comorbidity count and patient expectations, including treatment expectations and pain self-efficacy. Linear mixed-effects models will be used to examine longitudinal associations between these predictors and pain and function trajectories, with particular emphasis on predictor-by-time interactions to characterize differential patterns of change over time. The planned analyses aim to improve understanding of how clinical characteristics and expectancy-related factors jointly shape 12-month pain and physical function trajectories in older adults with knee osteoarthritis receiving education and exercise-based care, thereby informing prognostic stratification within non-surgical management. Full article
13 pages, 904 KB  
Article
Impact of Early Versus Late Treatment with Botulinum Toxin A on Goal Attainment in Post-Stroke Spasticity: A Retrospective Cohort Study
by Atul Patel, Jinming Zhang, Simon Page, Sarah Harding, Mathieu Beneteau, Colin Navickas and Alberto Esquenazi
Toxins 2026, 18(2), 68; https://doi.org/10.3390/toxins18020068 - 27 Jan 2026
Abstract
This study evaluated the effect of time of botulinum toxin A (BoNT-A) treatment on clinical outcomes in adults with post-stroke spasticity (PSS). Individual data were pooled from five studies. Eligible patients received ≥1 BoNT-A injection(s) for PSS and had goal attainment scaling (GAS) [...] Read more.
This study evaluated the effect of time of botulinum toxin A (BoNT-A) treatment on clinical outcomes in adults with post-stroke spasticity (PSS). Individual data were pooled from five studies. Eligible patients received ≥1 BoNT-A injection(s) for PSS and had goal attainment scaling (GAS) scores measured at baseline and 12 weeks. Patients were grouped according to time of treatment post-stroke: early (<1 year) or late (≥1 year). The primary endpoint was the total GAS (GAS-T) score change from baseline to 12 weeks. Secondary outcomes included the proportion of patients with a GAS-T score ≥ 50. Overall, 968 patients were included (166 early and 802 late). Median time post-stroke to BoNT-A treatment was 0.5 (early) versus 5.4 (late) years. Mean (standard deviation [SD]) baseline GAS scores were similar between cohorts (early: 36.9 [3.5]; late: 36.9 [3.6]). The mean (SD) change in the GAS-T score from baseline to 12 weeks was greater in the early versus late cohort (15.7 [8.9] vs. 13.1 [8.9]; p < 0.001). More patients in the early versus late cohort had a GAS-T score ≥ 50 (63.9% vs. 47.4%; p < 0.001) at 12 weeks. No new safety concerns were reported. Early treatment of PSS with BoNT-A has a positive impact on patients’ ability to achieve treatment goals. Plain Language Summary: After a stroke, people can experience muscle stiffness in their limbs, called post-stroke spasticity (PSS), which can lead to pain and make movement difficult. Treatment can include botulinum toxin A (BoNT-A) injections given directly into affected muscles. The aim of our study was to assess whether giving BoNT-A within a year after experiencing a stroke was more effective in treating PSS than delaying treatment. We combined data from 968 patients across five different studies. Most people (802 patients) received BoNT-A treatment 1 year or more after their stroke (late treatment group), while 166 people received treatment within a year of their stroke (early treatment group). In the studies, patients set treatment goals with their physician, for example being able to hold an object or walk a certain distance. After treatment, the extent to which each goal was achieved was assessed and scored based on whether the result was less than expected, as expected, or better than expected by the patient and physician. The scores from the two treatment groups were compared. People in the early treatment group did better in achieving their treatment goals compared with those in the late treatment group. We also looked at any side effects patients experienced. No unexpected side effects were reported. BoNT-A treatment of PSS can help patients achieve their treatment goals, and patients treated early (within 1 year after stroke) may do better than those treated later. This information may help in rehabilitation planning for stroke patients. Full article
(This article belongs to the Section Bacterial Toxins)
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24 pages, 3379 KB  
Article
The Effects of ACTH and Dexamethasone on the Transcriptomic Profile of the Rat Adrenal Gland: An In Vivo Study
by Emilia Cicha, Małgorzata Blatkiewicz, Karol Jopek, Marta Szyszka, Piotr W. Malendowicz, Anna Olechnowicz, Ludwik K. Malendowicz and Marcin Rucinski
Curr. Issues Mol. Biol. 2026, 48(2), 135; https://doi.org/10.3390/cimb48020135 - 27 Jan 2026
Abstract
The hypothalamic–pituitary–adrenal (HPA) axis plays a pivotal role in regulating stress responses through ACTH-stimulated glucocorticoid production. The transcriptional programmes underlying temporal adaptation to prolonged ACTH exposure and glucocorticoid feedback remain incompletely characterized. Adult male Wistar rats were subjected to acute ACTH stimulation (single [...] Read more.
The hypothalamic–pituitary–adrenal (HPA) axis plays a pivotal role in regulating stress responses through ACTH-stimulated glucocorticoid production. The transcriptional programmes underlying temporal adaptation to prolonged ACTH exposure and glucocorticoid feedback remain incompletely characterized. Adult male Wistar rats were subjected to acute ACTH stimulation (single injection, 1 h) to elicit an immediate transcriptional response, prolonged ACTH exposure (three injections over 36 h) as a repeated exposure, or Dexamethasone treatment (three injections over 36 h). Plasma corticosterone levels were subsequently measured using an enzyme-linked immunosorbent assay (ELISA). The adrenal transcriptome profiling was performed using Affymetrix arrays. Differentially expressed genes (DEGs; |fold change| ≥ 1.8, adjusted p < 0.05) were analyzed using limma, followed by pathway and network analyses. Acute ACTH exposure resulted in the induction of 569 DEGs (357 upregulated), including immediate-early genes (Nr4a family, AP-1 factors), cAMP-PKA-CREB signalling components, and heat shock proteins. Prolonged ACTH resulted in 98 DEGs (predominantly downregulated), including the suppression of mitochondrial genes and upregulation of Polycomb repressive complex 2 components, suggesting epigenetic transcriptional attenuation. Dexamethasone treatment yielded 75 DEGs with selective suppression of SREBP-mediated cholesterol biosynthesis and uptake pathways. Twelve genes were downregulated by both prolonged ACTH and Dexamethasone, including sterol metabolism and interferon-stimulated genes. Acute and prolonged ACTH exposure engage distinct transcriptional programmes. Acute stimulation activates immediate-early genes and stress responses, while prolonged exposure suppresses mitochondrial gene expression through transcriptional dampening mechanisms. Dexamethasone is associated with the inhibition of cholesterol metabolism via SREBP pathway suppression. These findings illuminate HPA axis adaptation and glucocorticoid-induced adrenal suppression. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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10 pages, 212 KB  
Article
The Prognostic Significance of Bronchoalveolar Lavage Cellular Analysis in Evaluating Disease Burden in Non-Cystic Fibrosis Bronchiectasis
by Ahmet Yurttaş, Deniz Çelik, Sertan Bulut, Özkan Yetkin and Hüseyin Lakadamyalı
Life 2026, 16(2), 206; https://doi.org/10.3390/life16020206 - 27 Jan 2026
Abstract
Objective: This study aimed to investigate the relationship between bronchoalveolar lavage (BAL) cellular profiles, microbiological status, and clinical outcomes such as hospital admission in adult patients with non-cystic fibrosis bronchiectasis. Methods: A retrospective cross-sectional study was conducted on thirty adult bronchiectasis patients. Demographic, [...] Read more.
Objective: This study aimed to investigate the relationship between bronchoalveolar lavage (BAL) cellular profiles, microbiological status, and clinical outcomes such as hospital admission in adult patients with non-cystic fibrosis bronchiectasis. Methods: A retrospective cross-sectional study was conducted on thirty adult bronchiectasis patients. Demographic, clinical, and laboratory data were collected. The cellular components of BAL fluid (macrophages, neutrophils, lymphocytes, and eosinophils) were analyzed. Patients were grouped according to the presence of microbial culture growth and history of hospitalization in the past year. Statistical analyses were performed to determine significant relationships. Results: The median age was 57 years, and the gender distribution was equal. There was no significant difference in BAL cellular profiles between groups with and without culture growth. However, in the group with a hospital admission in the past year, BAL showed a significantly lower percentage of alveolar macrophages (20% vs. 47%, p = 0.011) and a higher percentage of eosinophils (5% vs. 1%, p = 0.036). The hospitalized group also showed a trend toward a higher neutrophil percentage and a lower lymphocyte/neutrophil ratio. Furthermore, surprising associations were noted, such as a higher BAL macrophage count in married individuals and higher BAL eosinophilia in patients with diabetes. Conclusions: BAL cellular analysis provides valuable information beyond routine microbiological investigations in bronchiectasis. The low-alveolar-macrophage and high-eosinophil profile was found to be significantly associated with hospitalization, and this profile has the potential to serve as a prognostic biomarker in defining the “high-risk” phenotype. These findings highlight the complexity of the local inflammatory response and reveal the potential role of BAL in developing personalized treatment strategies for patients with bronchiectasis. Full article
(This article belongs to the Special Issue Pathology, Diagnosis, and Treatments of Airway Diseases)
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