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Search Results (363)

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14 pages, 926 KiB  
Article
The Effectiveness of Manual Therapy in the Cervical Spine and Diaphragm, in Combination with Breathing Re-Education Exercises, on the Range of Motion and Forward Head Posture in Patients with Non-Specific Chronic Neck Pain: A Randomized Controlled Trial
by Petros I. Tatsios, Eirini Grammatopoulou, Zacharias Dimitriadis and George A. Koumantakis
Healthcare 2025, 13(14), 1765; https://doi.org/10.3390/healthcare13141765 - 21 Jul 2025
Viewed by 428
Abstract
Background/Objectives: A randomized controlled trial (RCT) was designed to test the emerging role of respiratory mechanics as part of physiotherapy in patients with non-specific chronic neck pain (NSCNP). Methods: Ninety patients with NSCNP and symptom duration >3 months were randomly allocated to three [...] Read more.
Background/Objectives: A randomized controlled trial (RCT) was designed to test the emerging role of respiratory mechanics as part of physiotherapy in patients with non-specific chronic neck pain (NSCNP). Methods: Ninety patients with NSCNP and symptom duration >3 months were randomly allocated to three intervention groups of equal size, receiving either cervical spine (according to the Mulligan Concept) and diaphragm manual therapy plus breathing reeducation exercises (experimental group—EG1), cervical spine manual therapy plus sham diaphragmatic manual techniques (EG2), or conventional physiotherapy (control group—CG). The treatment period lasted one month (10 sessions) for all groups. The effect on the cervical spine range of motion (CS-ROM) and on the craniovertebral angle (CVA) was examined. Outcomes were collected before treatment (0/12), after treatment (1/12), and three months after the end of treatment (4/12). The main analysis comprised a two-way mixed ANOVA with a repeated measures factor (time) and a between-groups factor (group). Post hoc tests assessed the source of significant interactions detected. The significance level was set at p = 0.05. Results: No significant between-group baseline differences were identified. Increases in CS-ROM and in CVA were registered mainly post-treatment, with improvements maintained at follow-up for CS-ROM. EG1 significantly improved over CG in all movement directions except for flexion and over EG2 for extension only, at 1/12 and 4/12. All groups improved by the same amount for CVA. Conclusions: EG1, which included diaphragm manual therapy and breathing re-education exercises, registered the largest overall improvement over CG (except for flexion and CVA), and for extension over EG2. The interaction between respiratory mechanics and neck mobility may provide new therapeutic and assessment insights of patients with NSCNP. Full article
(This article belongs to the Special Issue Future Trends of Physical Activity in Health Promotion)
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12 pages, 455 KiB  
Article
A Bayesian Structural Equation Model to Predict Quality of Life in European Older Adults
by José M. Tomás, Aitana Sanz and Zaira Torres
Eur. J. Investig. Health Psychol. Educ. 2025, 15(7), 127; https://doi.org/10.3390/ejihpe15070127 - 9 Jul 2025
Viewed by 302
Abstract
The ultimate goal of developed societies is to age with quality of life, but this concept is broad, and few studies have addressed which variables specifically affect its dimensions. This study aims to test a model for predicting the impact of frailty, pain, [...] Read more.
The ultimate goal of developed societies is to age with quality of life, but this concept is broad, and few studies have addressed which variables specifically affect its dimensions. This study aims to test a model for predicting the impact of frailty, pain, and loneliness on the four dimensions of quality of life (control, autonomy, pleasure, and self-realization). Data were drawn from a sample of 61,355 Europeans from the Wave 7 of the SHARE project, aged 60 or older (M = 71.87, SD = 8.22), from which 55.9% were females. Statistical analyses included a fully Bayesian structural equation model that evidences the significant effect of loneliness, frailty, and pain on the four dimensions of quality of life. The variables have an unequal impact on the different dimensions’ loneliness was the main predictor for the dimensions control, autonomy, and pleasure, while frailty was the main predictor to self-realization. This study supports the need to address these variables to intervene on the different aspects of quality of life in old age. Full article
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25 pages, 1127 KiB  
Review
Ozone Treatment in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Review of Rationale and Research Directions
by Bernardino Clavo, Angeles Cánovas-Molina, Mario Federico, Gregorio Martínez-Sánchez, Gretel Benítez, Saray Galván, Yolanda Ramallo-Fariña, Himar Fabelo, Sara Cazorla-Rivero, Elba Lago-Moreno, Carla Antonilli, Juan A. Díaz-Garrido, Ignacio J. Jorge, Gustavo Marrero-Callico, Delvys Rodríguez-Abreu and Francisco Rodríguez-Esparragón
Cancers 2025, 17(14), 2278; https://doi.org/10.3390/cancers17142278 - 8 Jul 2025
Viewed by 750
Abstract
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. CIPN can lead to a dose reduction and/or the interruption of chemotherapy, limiting its effectiveness, while chronic CIPN decreases patients’ quality of life. Improvements in cancer treatment and patients’ survival have [...] Read more.
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. CIPN can lead to a dose reduction and/or the interruption of chemotherapy, limiting its effectiveness, while chronic CIPN decreases patients’ quality of life. Improvements in cancer treatment and patients’ survival have increased the number of patients living with CIPN. The only evidence-based treatment for CIPN-related pain, duloxetine, provides only modest clinical benefit, and there is no effective clinical management option for numbness and tingling. Several experimental studies and clinical reports suggest that adjuvant ozone treatment may be beneficial in managing CIPN. Methods: This narrative review aims to provide an overview of current knowledge regarding CIPN and ozone therapy. Specifically, it summarizes experimental studies (18) and clinical reports (27) published between 1995 and 2025 that offer preliminary evidence supporting the potential role of ozone treatment in managing CIPN, highlighting the need for ongoing randomized clinical trials to establish its efficacy. Additionally, this review highlights existing gaps in the literature and proposes directions for future research. Results: The hypothesized mechanisms of action and experimental findings suggest that ozone therapy may be a valuable intervention for CIPN, a concept supported by preliminary clinical observations. Conclusions: Clinically relevant approaches for established CIPN are currently unavailable. While preliminary data suggest a potential role of ozone therapy, clinical evidence remains limited. Further high-quality randomized controlled trials are needed to confirm its efficacy and safety in this context; several trials are currently ongoing. Full article
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22 pages, 533 KiB  
Article
Exploring Emotional Conflicts and Pain Experience in Patients with Non-Specific Chronic Neck Pain: A Qualitative Study
by Yolanda Pérez-Martín, Milagros Pérez-Muñoz, Beatriz Martín-Castro, Susana Nunez-Nagy, Belén Díaz-Pulido and Isabel Rodríguez-Costa
J. Clin. Med. 2025, 14(13), 4748; https://doi.org/10.3390/jcm14134748 - 4 Jul 2025
Viewed by 417
Abstract
Background/Objective: Non-specific chronic neck pain (CNP) greatly affects the social dynamics, the work performance, and the personal independence of patients. Research emphasizes the significant role of sociological factors, psychological stress, and emotional conflicts in the development, regulation, and endurance of chronic pain. [...] Read more.
Background/Objective: Non-specific chronic neck pain (CNP) greatly affects the social dynamics, the work performance, and the personal independence of patients. Research emphasizes the significant role of sociological factors, psychological stress, and emotional conflicts in the development, regulation, and endurance of chronic pain. This study aims to explore the influence of emotional conflicts on pain experience among CNP patients, drawing from their experiences. Methods: A phenomenological investigation was conducted, grounded in Heideggerian philosophy, involving CNP patients and healthcare professionals in Madrid, Spain. Participants were recruited from Primary Health Care centers. Data collection methods included semi-structured in-depth interviews, focus groups with patients, focus groups with healthcare providers, participant observation, and reflective diaries. Hermeneutic phenomenology guided the data interpretation. Thematic analysis was applied to transcribed audio recordings. Results: This study included 12 patients with CNP who participated in two in-depth interviews conducted at different time points—before and after receiving physiotherapy treatment. Additionally, 23 CNP patients took part in four focus groups, and 46 healthcare professionals (including physicians, nurses, and physiotherapists) participated in three focus groups. A hermeneutic analysis revealed the following three main categories: “Self-concept and pain experience”, “Daily life obligations and pain perception”, and “Emotional conflicts related to CNP”. Patients described themselves as nervous, having communication difficulties, and often prioritizing family or work tasks, leading to stress. They indicated that their interpersonal conflicts with close relations intensified their perceived pain in the neck, head, shoulders, and arms. Conclusions: From the perspective of the participants in this study, interpersonal and emotional conflicts appear to influence their perception of CNP. Full article
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13 pages, 1364 KiB  
Article
Risk Factors for Common Bile Duct Stones in Patients with Previous Cholecystectomy: A Multicenter Prospective Proof-of-Concept Study
by Andrea Lisotti, Thomas Togliani, Graziella Masciangelo, Angelo Bruni, Emilija Rakichevikj, Peter Vilmann, Vincenzo Giorgio Mirante and Pietro Fusaroli
J. Clin. Med. 2025, 14(13), 4532; https://doi.org/10.3390/jcm14134532 - 26 Jun 2025
Viewed by 551
Abstract
Objectives: Most studies assess risk factors for common bile duct (CBD) stones in patients with gallbladder in situ. We aimed to assess risk factors for CBD stones in patients with previous cholecystectomy in a proof-of-concept study. Methods: We enrolled consecutive patients undergoing EUS [...] Read more.
Objectives: Most studies assess risk factors for common bile duct (CBD) stones in patients with gallbladder in situ. We aimed to assess risk factors for CBD stones in patients with previous cholecystectomy in a proof-of-concept study. Methods: We enrolled consecutive patients undergoing EUS for suspected symptomatic CBD stones and recorded demographic variables, clinical presentation, liver function tests (LFTs), and transabdominal ultrasound (US) findings. EUS was used as gold standard for CBD stones. Multivariate analysis was used to identify risk factors in the training set; a model was created and tested on the validation set. Results: A total of 211 patients (25.6% male; median age, 66 [49–75] years old) were enrolled; 77.7% presented with abdominal pain, 30.3% with hyperbilirubinemia, 26.5% with pancreatitis, and 61.1% with LFT alterations. Ultrasound showed CBD dilation in 37.4% patients. Overall, 96 (45.5%) patients had CBD stones. According to multivariate analysis, male gender (OR 2.54 [1.26–5.09]; p = 0.009), age > 63 years (OR 3.06 [1.63–5.72]; p < 0.001), LFT alteration (OR 2.62 [1.40–4.91]; p = 0.003), and CBD dilation (OR 2.46 [1.31–4.65]; p = 0.005) were independently related to CBD stones. A model was created based on the number of risk factors on admission; patients with no risk factor had a 9.5% prevalence of CBD stones; those with one risk factor, 26.7%; two risk factors, 53.2%; three risk factors, 66.7%; and four risk factors, 100%. Conclusions: The results of this proof-of-concept study identify male gender, age, LFT alteration, and CBD dilation as risk factors for CBD stones in patients with previous cholecystectomy. An adequate assessment of the pre-test probability will guide patients’ subsequent management. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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15 pages, 284 KiB  
Article
The Relationship Between Binge Eating Behavior and Psychological Pain in Patients with Major Depressive Disorder
by Aynur Özbay, Mehmet Emin Demirkol, Lut Tamam, Zeynep Namlı, Mahmut Onur Karaytuğ and Caner Yeşiloğlu
Behav. Sci. 2025, 15(7), 842; https://doi.org/10.3390/bs15070842 - 22 Jun 2025
Viewed by 374
Abstract
Major Depressive Disorder (MDD) is a chronic mental disorder characterized by anhedonia, loss of desire, guilt, suicidal thoughts, and appetite changes. It is reported that individuals with MDD resort to binge eating to escape from negative feelings. In this study, we aimed to [...] Read more.
Major Depressive Disorder (MDD) is a chronic mental disorder characterized by anhedonia, loss of desire, guilt, suicidal thoughts, and appetite changes. It is reported that individuals with MDD resort to binge eating to escape from negative feelings. In this study, we aimed to determine the relationship between binge eating behavior and the concept of psychological pain associated with emotions such as shame, guilt, and anger in individuals with MDD. We conducted the study in the Psychiatry Outpatient Clinics of Balcalı Hospital, Çukurova University Faculty of Medicine. The sample consisted of 147 individuals with MDD without psychotic symptoms and 128 healthy controls with sociodemographic characteristics similar to the MDD group. We administered a sociodemographic data form, the Hamilton Depression Rating Scale (HDRS), Psychache Scale (PS), Tolerance for Mental Pain Scale-10 (TMPS-10), Barratt Impulsiveness Scale (BIS-11), and Eating Disorder Examination Questionnaire (EDE-Q-13). Eighty-two (55.7%) of the patients with MDD were diagnosed with binge eating disorder (BED). In the group of MDD patients with BED comorbidity, the EDE-Q-13 total, binging subscale, and HDRS scores were significantly higher than those of the other groups (p < 0.05 for each group), with large to very large effect sizes (e.g., EDE-Q-13 binging d = 1.04; HDRS d = 1.91; PS d = 1.22). There was no significant difference between the MDD groups (with and without BED) regarding the BIS and BIS subscales’ subscores, PS, and TMPS scores. For participants with MDD, there was a significant same-directional correlation between EDE-Q-13 binging, HDRS, BIS, and PS scores (p < 0.05 for each), with moderate to strong effect sizes (EDE-Q-13 binging and HDRS: r = 0.398, p < 0.001; binging and PS: r = 0.273, p < 0.001; binging and BIS: r = 0.233, p = 0.005; binging and TMPS-10: r = –0.257, p = 0.002). Additionally, a negative correlation was observed between TMPS and the scores for EDE-Q-13 binging, HDRS, BIS, and PS. A linear regression analysis indicated that depression severity and BMI were the strongest predictors of binge eating behavior (R2 = 0.243; f2 = 0.32). Based on our results, we concluded that the presence of binge eating behavior in patients with MDD is associated with more severe depressive symptoms, psychological pain, impulsivity, and lower tolerance to psychological pain. The finding that binge eating behavior was most strongly associated with depression severity and body mass index (BMI) supports the notion that binge eating behavior is a maladaptive attitude. Longitudinal studies comparing individuals with different BMIs in different clinical samples are needed to confirm our results. Full article
(This article belongs to the Section Psychiatric, Emotional and Behavioral Disorders)
16 pages, 2453 KiB  
Systematic Review
The Neuroanatomical Correlates of Visceral Pain: An Activation Likelihood Estimation Meta-Analysis
by Christoph Müller and Hagen Maxeiner
Brain Sci. 2025, 15(6), 651; https://doi.org/10.3390/brainsci15060651 - 17 Jun 2025
Viewed by 503
Abstract
Background: Acute visceral pain is among the most common symptoms of patients seeking in-hospital treatment and is related to various thoracic, abdominal, and pelvic diseases. It is characterized by distinguishable sensory qualities and can be described on a sensory-discriminative and affective-motivational level. These [...] Read more.
Background: Acute visceral pain is among the most common symptoms of patients seeking in-hospital treatment and is related to various thoracic, abdominal, and pelvic diseases. It is characterized by distinguishable sensory qualities and can be described on a sensory-discriminative and affective-motivational level. These sensory qualities correlate with the activation of cerebral areas involved in the neuronal processing of visceral pain and can be visualized using functional neuroimaging. Methods: An ALE (activation likelihood estimation) meta-analysis of a total of 21 studies investigating different balloon distention paradigms during either PET or fMRI was performed to demonstrate the neuroanatomical correlates of visceral pain. The ALE meta-analysis was performed using the GingerAle software version 3.0.2 and was displayed with the Mango software 4.1 on an anatomical MNI template. Results: Summarizing studies investigating the functional neuroanatomy of visceral pain, bihemispheric activation of the insula, the thalamus, and clusters involving the right inferior parietal lobe/postcentral gyrus as well as the left postcentral gyrus/parietal inferior lobe were observed. Conclusions: This ALE meta-analysis substantiates the concept of two distinguishable neuroanatomical pathways of visceral pain which are related to either the sensory-discriminative or the affective-motivational dimension of pain processing. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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14 pages, 1027 KiB  
Review
Seronegative Sicca Syndrome: Diagnostic Considerations and Management Strategies
by Yordanka M. Basheva-Kraeva, Krasimir I. Kraev, Petar A. Uchikov, Maria I. Kraeva, Bozhidar K. Hristov, Nina St. Stoyanova, Vesela T. Mitkova-Hristova, Borislav Ivanov, Stanislav S. Karamitev, Nina Koleva, Aleksandar Marinkov and Veselin A. Vassilev
Life 2025, 15(6), 966; https://doi.org/10.3390/life15060966 - 17 Jun 2025
Viewed by 625
Abstract
Seronegative sicca syndrome encompasses patients who present with xerostomia and/or keratoconjunctivitis sicca but lack anti-SSA/SSB antibodies and do not fulfill current classification criteria for primary Sjögren’s syndrome (pSS). Despite symptom overlap with pSS, these individuals remain diagnostically and therapeutically unclassified. This review studies [...] Read more.
Seronegative sicca syndrome encompasses patients who present with xerostomia and/or keratoconjunctivitis sicca but lack anti-SSA/SSB antibodies and do not fulfill current classification criteria for primary Sjögren’s syndrome (pSS). Despite symptom overlap with pSS, these individuals remain diagnostically and therapeutically unclassified. This review studies the clinical, immunological, and pathological spectrum of seronegative sicca, highlighting its heterogeneity and the limitations of antibody-centric diagnostic frameworks. Histopathologic findings in some seronegative patients—including focal lymphocytic sialadenitis—mirror those seen in pSS, suggesting underlying immune-mediated glandular damage. In others, nonspecific or normal biopsy findings suggest non-immune mechanisms. New evidence of immune activity, such as elevated cytokines (BAFF, IFN-α), and novel autoantibodies (SP-1, CA-VI), further supports the concept of subclinical autoimmunity in a subset of these patients. Clinically, they often face significant burden, including dryness, fatigue, and pain, yet remain excluded from most research cohorts, therapeutic trials, and clinical guidelines. Their management is often individualized, relying on symptomatic therapies rather than immunomodulatory agents. The lack of validated diagnostic criteria and prognostic markers compounds the uncertainty surrounding disease evolution, as some patients may later seroconvert or develop systemic features. To address these gaps, a paradigm shift is needed—one that embraces the spectrum of sicca syndromes, incorporates advanced immunophenotyping, and allows inclusion of seronegative patients in research and care algorithms. Full article
(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)
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18 pages, 916 KiB  
Review
Physical Activity as a Central Pillar of Lifestyle Modification in the Management of Chronic Musculoskeletal Pain: A Narrative Review
by Rodrigo Núñez-Cortés, Joaquín Salazar-Méndez and Jo Nijs
J. Funct. Morphol. Kinesiol. 2025, 10(2), 183; https://doi.org/10.3390/jfmk10020183 - 20 May 2025
Viewed by 4569
Abstract
Objective: This narrative review aims to analyze physical activity as a central pillar of lifestyle modification in the management of chronic musculoskeletal pain by examining its effects on pain modulation as well as related lifestyle domains, including sleep, stress regulation, dietary habits, [...] Read more.
Objective: This narrative review aims to analyze physical activity as a central pillar of lifestyle modification in the management of chronic musculoskeletal pain by examining its effects on pain modulation as well as related lifestyle domains, including sleep, stress regulation, dietary habits, and smoking behavior. Methods: A narrative structured review was conducted. We searched MEDLINE/PubMed, Embase, and Cochrane Reviews using terms related to chronic pain and lifestyle. Randomized controlled trials, observational studies, systematic reviews, and narrative reviews reporting on the concepts of interest were included. The results were synthesized and described narratively. Results: Through the release of neuromodulatory compounds such as endorphins, endocannabinoids, dopamine, and serotonin, exercise improves analgesia, promotes emotional resilience, and reduces the reward response associated with addictive behaviors such as smoking. Its effects on the hypothalamic–pituitary–adrenal axis reduce cortisol levels, while melatonin regulation promotes circadian synchronization and deeper sleep stages. In addition, exercise modulates appetite by increasing insulin sensitivity and altering hormones such as leptin and ghrelin, contributing to appetite control and energy balance. These mechanisms support a comprehensive approach to chronic pain management. Conclusions: Physical activity is a core component of lifestyle-based chronic pain management, not only because of its analgesic effects, but also because of its positive influence on sleep, stress regulation, dietary habits, and smoking reduction. Although the available evidence is promising, more randomized controlled trials are needed to examine the effects of exercise on other healthy lifestyle behaviors, such as stress reduction, dietary modification, and smoking cessation, to consolidate its role in the comprehensive prevention and management of chronic pain. Full article
(This article belongs to the Special Issue Sports Medicine and Public Health)
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12 pages, 236 KiB  
Article
Inxeba Elinga Phakathi: The Danger of Mental Health Invisibility and the Role of Social Community Caregiving
by Nobuntu Penxa-Matholeni
Int. J. Environ. Res. Public Health 2025, 22(5), 786; https://doi.org/10.3390/ijerph22050786 - 16 May 2025
Viewed by 425
Abstract
The stigma and invisibility surrounding mental health often lead to alienation and reinforce societal misconceptions. This paper examines how the concept of inxeba elingaphakathi (the invisible wound) in isiXhosa encapsulates the emotional and psychological pain frequently overlooked in mental health discussions, particularly among [...] Read more.
The stigma and invisibility surrounding mental health often lead to alienation and reinforce societal misconceptions. This paper examines how the concept of inxeba elingaphakathi (the invisible wound) in isiXhosa encapsulates the emotional and psychological pain frequently overlooked in mental health discussions, particularly among Black South African women. Employing an Indigenous storytelling methodology, the study explores how social community caregiving can illuminate these hidden wounds and challenge prevailing stigma. By analyzing the societal factors shaping mental health perceptions, this research advocates for a culturally grounded approach to healing and belonging. Full article
(This article belongs to the Special Issue SDG 3 in Sub-Saharan Africa: Emerging Public Health Issues)
13 pages, 5681 KiB  
Article
Intermittent Pneumatic Impulse Compression in the Treatment of Stasis Dermatitis—A Monocenter Randomized Controlled Trial
by Sarah Janßen, Julia Schmölders, Theresa Maria Jansen, Neslihan Ertas, Julian-Dario Rembe, Bernhard Homey and Norman-Philipp Hoff
J. Clin. Med. 2025, 14(10), 3321; https://doi.org/10.3390/jcm14103321 - 9 May 2025
Viewed by 565
Abstract
Background/Objectives: Intermittent pneumatic impulse compression (IIC) is a well-established drainage treatment that reduces edema and enhances arterial blood flow. While widely utilized in various medical fields, its efficacy in dermatology, particularly for stasis dermatitis, remains underexplored. This study evaluates the effectiveness of IIC [...] Read more.
Background/Objectives: Intermittent pneumatic impulse compression (IIC) is a well-established drainage treatment that reduces edema and enhances arterial blood flow. While widely utilized in various medical fields, its efficacy in dermatology, particularly for stasis dermatitis, remains underexplored. This study evaluates the effectiveness of IIC in inpatients with bilateral stasis dermatitis by comparing standard therapy alone versus standard therapy with additional IIC on one leg over five days. Methods: Seventeen patients from the Dermatology Department at University Hospital Duesseldorf were enrolled. Both legs received standard therapy, while one randomized leg received additional IIC for four hours daily. Measurements, including transcutaneous oxygen pressure (tcpO2), leg circumference, and pain sensation, were taken at baseline, the first day post-IIC, and after five days. Statistical analysis included paired t-tests, with significance set at p < 0.05. Results: The IIC-treated legs exhibited significant improvements in tissue oxygen saturation (MD = 19.87 mmHg, SD = 27.82, p = 0.012) and reduced ankle circumference (MD = −2.125 cm, SD = 1.593, p < 0.0001). No significant changes were observed in tcpO2 or circumference in the non-IIC-treated legs. Other leg circumference measurements (calf, above the knee) did not demonstrate significant improvements in either group. Pain levels remained stable under IIC therapy. Conclusions: This proof-of-concept study provides evidence supporting IIC as a beneficial adjunct therapy for stasis dermatitis, demonstrating significant edema reduction and enhanced oxygenation. Further investigations are warranted to confirm these findings and expand clinical applicability. Full article
(This article belongs to the Special Issue Tissue Scarring, Fibrosis and Regeneration)
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15 pages, 816 KiB  
Study Protocol
The Effect of Fremanezumab on Pain in Patients with Complex Regional Pain Syndrome: Study Protocol of a Randomized, Double-Blind, Proof-of-Concept, Placebo-Controlled Trial
by Abarajitha Thiyagarajah, Astrid Juhl Terkelsen, Frank Birklein, Nanna Brix Finnerup and Sandra Sif Gylfadottir
Brain Sci. 2025, 15(5), 468; https://doi.org/10.3390/brainsci15050468 - 28 Apr 2025
Viewed by 782
Abstract
Background/Objectives: Complex regional pain syndrome (CRPS) is a primary pain condition that can develop in a limb after a trauma. Although the condition is rare, it may cause lifelong pain and disability. Evidence-based treatments are limited. Neurogenic inflammation induced by the release of [...] Read more.
Background/Objectives: Complex regional pain syndrome (CRPS) is a primary pain condition that can develop in a limb after a trauma. Although the condition is rare, it may cause lifelong pain and disability. Evidence-based treatments are limited. Neurogenic inflammation induced by the release of neuropeptides, such as calcitonin gene-related peptide (CGRP), is thought to play an important role in the pathophysiology of CRPS. Recently, drugs targeting CGRP have proven to be effective and well tolerated in the treatment of migraine, but their efficacy in other pain conditions, including CRPS, is unclear. The aim of this study is to assess the efficacy of the anti-CGRP antibody fremanezumab on pain in CRPS. Methods: In this randomized, double-blind, placebo-controlled, proof-of-concept study, 60 adult patients with CRPS with a disease duration of 3–36 months are randomized to treatment for eight weeks with fremanezumab 225 mg or placebo administered subcutaneously at a 1:1 rate. The primary objective is to compare the change in pain intensity from baseline to the last week of treatment between fremanezumab and the placebo. Other objectives are to assess pain relief and differences in clinical signs between the groups and to examine if the effect can be predicted by CGRP biomarkers. Adverse events and blinding will also be assessed. Conclusions: If found effective, fremanezumab and other anti-CGRP antibodies may emerge as a mechanism-based treatment option for patients with CRPS, which could hopefully improve the overall care of patients with this devastating disease. Full article
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16 pages, 3745 KiB  
Review
The Role of MDCT Coronary Angiography in the Detection of Benign Varieties and Anomalies of Coronary Blood Vessels—A Narrative Review
by Ana Mladenovic Markovic, Ana Tomic, Miodrag Nisevic, Biljana Parapid, Nikola Boskovic, Marina Vitas, Miona Jevtovic and Sandra Grujicic
Medicina 2025, 61(4), 765; https://doi.org/10.3390/medicina61040765 - 21 Apr 2025
Viewed by 701
Abstract
Coronary arteries may vary in quantity, point of origin, or course. These variations fall under the category of anatomical variants/anomalies of the coronary arteries, representing congenital abnormalities of the coronary vascular system. Generally, they are benign, asymptomatic, and identified inadvertently during coronary angiography [...] Read more.
Coronary arteries may vary in quantity, point of origin, or course. These variations fall under the category of anatomical variants/anomalies of the coronary arteries, representing congenital abnormalities of the coronary vascular system. Generally, they are benign, asymptomatic, and identified inadvertently during coronary angiography conducted for alternative indications. However, in some cases, the anomaly’s characteristics or its interaction with surrounding structures may cause hemodynamic disturbances. These disturbances can lead to turbulent blood flow, which in turn poses an increased likelihood for the development of atherosclerosis and myocardial ischemia. If symptomatic, potential manifestations include chest pain, arrhythmias, syncope, myocardial infarction, and sudden cardiac death. Given the potential for life-threatening complications in certain cases, the early and accurate diagnosis of coronary artery anomalies is of paramount importance. The most common diagnostic procedures used for the evaluation of coronary vessels are coronary angiography and multi-detector row computed tomography (MDCT) coronary angiography. MDCT angiography is a non-invasive, dependable, safe, and sensitive method for the detailed visualization of coronary anatomy. It offers high-resolution imaging that enables precise assessment of congenital coronary variations, aiding in both clinical decision-making and long-term patient management. We conducted a narrative review to analyze and integrate the body of literature on coronary artery varieties and anomalies. Our objective was to provide a comprehensive, albeit non-exhaustive, overview of essential concepts and findings related to their definition, classification, and detection with MDCT angiography. By integrating current knowledge in MDCT imaging, we seek to contribute to a better understanding of the clinical implications of coronary artery variations and their role in cardiovascular health. Full article
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19 pages, 2608 KiB  
Article
Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response
by Emmanuel Adediran, Tanisha Arte, Dedeepya Pasupuleti, Sharon Vijayanand, Revanth Singh, Parth Patel, Mahek Gulani, Amarae Ferguson, Mohammad Uddin, Susu M. Zughaier and Martin J. D’Souza
Pharmaceutics 2025, 17(4), 510; https://doi.org/10.3390/pharmaceutics17040510 - 12 Apr 2025
Viewed by 1045
Abstract
Background: Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the [...] Read more.
Background: Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the non-invasive, transdermal vaccination route using dissolving microneedles would significantly improve vaccine compliance. Research on innovative vaccine delivery systems, such as antigen-loaded PLGA microparticles, has the potential to pave the way for a broader range of vaccine candidates. Methods: In this proof-of-concept study, a combination of the inactivated influenza A H1N1 virus and inactivated influenza A H3N2 virus were encapsulated in a biodegradable poly (lactic-co-glycolic acid) (PLGA) polymeric matrix within microparticles, which enhanced antigen presentation. The antigen PLGA microparticles were prepared separately using a double emulsion (w/o/w), lyophilized, and characterized. Next, the vaccine microparticles were assessed in vitro in dendritic cells (DC 2.4) for immunogenicity. To explore pain-free transdermal vaccination, the vaccine microparticles were loaded into dissolving microneedles and administered in mice (n = 5). Results: Our vaccination study demonstrated that the microneedle-based vaccine elicited strong humoral responses as demonstrated by high antigen-specific IgA, IgG, IgG1, and IgG2a antibodies in serum samples and IgA in lung supernatant. Further, the vaccine also elicited a strong cellular response as evidenced by high levels of CD4+ and CD8a+ T cells in lymphoid organs such as the lymph nodes and spleen. Conclusion: The delivery of influenza vaccine-loaded PLGA microparticles using microneedles would be beneficial to individuals experiencing needle-phobia, as well as the geriatric and pediatric population. Full article
(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)
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22 pages, 332 KiB  
Review
Modern Treatment of Skeletal Metastases: Multidisciplinarity and the Concept of Oligometastasis in the Recent Literature
by Giulia Trovarelli, Arianna Rizzo, Felicia Deborah Zinnarello, Mariachiara Cerchiaro, Andrea Angelini, Elisa Pala and Pietro Ruggieri
Curr. Oncol. 2025, 32(4), 226; https://doi.org/10.3390/curroncol32040226 - 11 Apr 2025
Cited by 1 | Viewed by 1210
Abstract
Bone metastases are a major concern in cancer management since they significantly contribute to morbidity and mortality. Metastatic lesions, commonly arising from breast, prostate, lung, and kidney cancers, affect approximately 25% of cancer patients, leading to severe complications such as pain, fractures, and [...] Read more.
Bone metastases are a major concern in cancer management since they significantly contribute to morbidity and mortality. Metastatic lesions, commonly arising from breast, prostate, lung, and kidney cancers, affect approximately 25% of cancer patients, leading to severe complications such as pain, fractures, and neurological deficits. This narrative review explores contemporary approaches to bone metastases, emphasizing a multidisciplinary strategy and the evolving concept of oligometastatic disease. Oligometastases, defined by limited metastatic spread (1–5 lesions), offer a potential window for curative treatment through aggressive interventions, including stereotactic ablative radiotherapy and resection surgery. Tumor boards, integrating systemic therapies with local interventions, are crucial to optimize treatment. Despite promising results, gaps remain in defining optimal treatment sequences and refining patient selection criteria. Future research should focus on personalized approaches, leveraging biomarkers and advanced imaging to enhance outcomes and the quality of life in patients with bone metastases. Full article
(This article belongs to the Special Issue 2nd Edition: Treatment of Bone Metastasis)
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