Journal of Clinical Medicine

14 pages, 3756 KiB

Open AccessArticle

The Prognostic Implication of Late Gadolinium Enhancement Quantification and Syncope in Hypertrophic Cardiomyopathy

by Christopher Mann, Theresa M. Dachs, Diana Gharib, Katalin Widmann, Rodi Tosun, Marc Srdits, Christina Kronberger, Dietrich Beitzke, Christian Loewe, Andreas A. Kammerlander, Marianne Gwechenberger, Irene M. Lang, Christian Hengstenberg, Thomas A. Zelniker and Daniel Dalos

J. Clin. Med. 2025, 14(5), 1781; https://doi.org/10.3390/jcm14051781 - 6 Mar 2025

Abstract

Background: Risk stratification for sudden cardiac death in hypertrophic cardiomyopathy (HCM) remains challenging. Late gadolinium enhancement (LGE) on cardiac MRI signifies myocardial fibrosis and is linked to adverse outcomes in HCM. However, the threshold of LGE that is clinically significant remains a subject [...] Read more.

Background: Risk stratification for sudden cardiac death in hypertrophic cardiomyopathy (HCM) remains challenging. Late gadolinium enhancement (LGE) on cardiac MRI signifies myocardial fibrosis and is linked to adverse outcomes in HCM. However, the threshold of LGE that is clinically significant remains a subject of debate. We hypothesized that even small amounts of LGE (≥ 5%) or a history of syncope are associated with worse outcomes. Methods: Between May 2018 and June 2023, HCM patients were prospectively enrolled at the Medical University of Vienna, Austria, a tertiary referral center. The primary endpoint was a composite of new-onset ventricular tachycardia, appropriate ICD therapy, and all-cause mortality. Results: In total, 230 patients were included. The median age of patients was 56 (IQR 44, 64) years, 40% (n = 94) were female, and 43% (n = 84) had significant left ventricular outflow tract obstruction (LVOTO). Over a median follow-up of 3.2 years, 29 patients (13%) met the composite endpoint. While the ESC HCM risk score was not associated with the primary endpoint, both LGE > 5% (Adj. HR 6.16) and a history of at least one syncope (Adj. HR 3.40) were independently associated with the primary endpoint. These associations were consistent across patients with and without LVOTO. Conclusions: In conclusion, our findings indicate that the combination of a history of syncope together with small amounts of LGE (≥ 5%) in cardiac MRI are associated with unfavorable clinical outcomes in HCM patients Full article

(This article belongs to the Section Cardiology)

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20 pages, 585 KiB

Open AccessReview

Frozen Shoulder as a Metabolic and Immune Disorder: Potential Roles of Leptin Resistance, JAK-STAT Dysregulation, and Fibrosis

by Santiago Navarro-Ledesma

J. Clin. Med. 2025, 14(5), 1780; https://doi.org/10.3390/jcm14051780 - 6 Mar 2025

Abstract

Frozen shoulder (FS) is a complex and multifactorial condition characterized by persistent inflammation, fibrosis, and metabolic dysregulation. Despite extensive research, the underlying drivers of FS remain poorly understood. Recent findings indicate the coexistence of pro-inflammatory and fibrosis-resolving macrophages within affected tissues, suggesting a [...] Read more.

Frozen shoulder (FS) is a complex and multifactorial condition characterized by persistent inflammation, fibrosis, and metabolic dysregulation. Despite extensive research, the underlying drivers of FS remain poorly understood. Recent findings indicate the coexistence of pro-inflammatory and fibrosis-resolving macrophages within affected tissues, suggesting a dysregulated immune response influenced by metabolic and neuroendocrine factors. This review proposes that leptin resistance, a hallmark of metabolic syndrome and chronic inflammation, may play a central role in FS pathogenesis by impairing macrophage polarization, perpetuating inflammation, and disrupting fibrosis resolution. The JAK-STAT signaling pathway, critically modulated by leptin resistance, may further contribute to immune dysregulation by sustaining inflammatory macrophage activation and interfering with tissue remodeling. Additionally, FS shares pathogenic features with fibrotic diseases driven by TGF-β signaling, mitochondrial dysfunction, and circadian disruption, further linking systemic metabolic dysfunction to localized fibrotic pathology. Beyond immune and metabolic regulation, alterations in gut microbiota, bacterial translocation, and chronic psychosocial stress may further exacerbate systemic inflammation and neuroendocrine imbalances, intensifying JAK-STAT dysregulation and leptin resistance. By examining the intricate interplay between metabolism, immune function, and fibrotic remodeling, this review highlights targeting leptin sensitivity, JAK-STAT modulation, and mitochondrial restoration as novel therapeutic strategies for FS treatment. Future research should explore these interconnections to develop integrative interventions that address both the metabolic and immune dysregulation underlying FS, ultimately improving clinical outcomes. Full article

(This article belongs to the Special Issue Clinical Updates in Physiotherapy for Musculoskeletal Disorders)

17 pages, 4765 KiB

Open AccessSystematic Review

Posterior Hypopharyngeal/Upper Esophageal Wall Reconstruction Using a Double-Island Free Fasciocutaneous Anterolateral Thigh Flap: A Case Report and Scoping Review of the Literature

by Léna G. Dietrich, Vera A. Paulus, Mihai A. Constantinescu, Moritz C. Deml, Roland Giger and Ioana Lese

J. Clin. Med. 2025, 14(5), 1779; https://doi.org/10.3390/jcm14051779 - 6 Mar 2025

Abstract

Background/Objectives: Isolated defects of the posterior hypopharyngeal/upper esophageal wall are rare, typically arising after cancer resection or complications following cervical spine osteosynthesis. Various local and free flaps are available for reconstruction, but we opted for a double-island anterolateral thigh (ALT) flap in [...] Read more.

Background/Objectives: Isolated defects of the posterior hypopharyngeal/upper esophageal wall are rare, typically arising after cancer resection or complications following cervical spine osteosynthesis. Various local and free flaps are available for reconstruction, but we opted for a double-island anterolateral thigh (ALT) flap in this case. Methods: A scoping review was conducted (June 2024) following PRISMAScR 2018 guidelines in order to examine the coverage options available in the literature for posterior hypopharyngeal/upper esophagus wall defects while also presenting a case where such a defect was covered with a double-island anterolateral thigh (ALT) flap. Eligibility criteria: Human studies describing defect coverage of the posterior hypopharyngeal/upper esophagus wall were included. Sources of evidence: A literature search was conducted in PubMed, Cochrane Library, and Google Scholar, following PRISMAScR guidelines. Charting methods: Data on surgical techniques, outcomes, and complications were extracted and analyzed by two independent reviewers. Case report: A 57-year-old female developed a chronic posterior wall perforation following Zenker’s diverticulum treatment and C5/6 cage osteosynthesis. Reconstruction was performed using a free fasciocutaneous ALT flap with two skin paddles: one (2 × 2 cm) for the esophageal mucosa and an additional vascularized fascia layer (4 × 8 cm) to separate the cage from the hypopharyngeal defect. To enable flap monitoring in the otherwise hidden defect, a second skin island was externalized cervically. Results: Postoperative recovery was uneventful, with a continuous viable flap signal. A Gastrografin swallow test confirmed an intact esophagus without leaks or dehiscences. Oral intake resumed after 10 days. The literature review highlighted 239 cases with multiple reconstructive techniques, each with advantages and limitations. Conclusions: The double-paddle free fasciocutaneous ALT flap is a viable option for posterior hypopharyngeal/upper esophageal wall reconstruction, allowing effective postoperative monitoring. This approach offers a valuable modification for complex cases requiring enhanced structural integrity and flap assessment. Full article

(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)

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10 pages, 868 KiB

Open AccessArticle

Outcomes and Predictive Factors of I-125 Plaque Therapy for Refractory Retinoblastoma

by Yacoub A. Yousef, Farah Halawa, Mona Mohammad, Lama Al-Fahoum, Rama Soudi, Mustafa Mehyar, Reem AlJabari, Hadeel Halalsheh, Ibrahim AlNawaiseh and Imad Jaradat

J. Clin. Med. 2025, 14(5), 1778; https://doi.org/10.3390/jcm14051778 - 6 Mar 2025

Abstract

Objective: This study aimed to evaluate the outcomes and predictive factors of I-125 radioactive plaque therapy for recurrent and refractory retinoblastoma (Rb) cases that failed primary systemic chemotherapy and focal therapies. Methods: A retrospective study of 20 eyes with intraocular Rb [...] Read more.

Objective: This study aimed to evaluate the outcomes and predictive factors of I-125 radioactive plaque therapy for recurrent and refractory retinoblastoma (Rb) cases that failed primary systemic chemotherapy and focal therapies. Methods: A retrospective study of 20 eyes with intraocular Rb treated with I-125 radioactive plaque therapy (Apex dose 45 Gy) from 2013 to 2023 was conducted. Data on tumor characteristics, treatments, and outcomes were collected over a follow-up period of at least one year. Results: There were 11 (55%) males and 8 (40%) patients who had bilateral disease. All 20 treated eyes (100%) showed initial tumor regression, while long-term tumor control and eye salvage were achieved in 14 eyes (70%). Six eyes (30%) experienced uncontrollable tumor recurrence after a mean of 6 months (range: 3–12 months) after plaque therapy. Recurrence included main tumor activity in six eyes and additional resistant vitreous seeds in two of them. Poor predictive factors for eye salvage included Group D at diagnosis (p = 0.044), active vitreous seeds at the time of plaque therapy ((p = 0.045), tumor thickness >5.0 mm (p = 0.045), and tumor base dimension >12 mm (p = 0.023). Post-plaque complications included cataracts in seven eyes (35%), tumor hemorrhage in six eyes (30%), retinal detachment in four eyes (20%), radiation retinopathy in three eyes (15%), and neovascular glaucoma in one eye (5%). Five (83%) of those with tumor hemorrhage had plaque surgery performed within less than 6 months of the last cycle of systemic chemotherapy. At a mean follow-up of 36 months (range: 12–96 months), five eyes (25%) were enucleated, and high-risk pathological features were identified in three eyes, including post-laminar optic nerve infiltration (one eye) and massive choroidal invasion (two eyes). All patients were alive and free of metastasis except one patient (5%) whose parents refused enucleation and came back with extra-scleral extension and bone marrow metastasis and eventually passed away. Conclusions: I-125 radioactive plaque therapy is a valuable salvage treatment for recurrent and refractory retinoblastoma, achieving tumor control and eye salvage in 70% of cases with an acceptable safety profile. However, the observed recurrence rate (30%) at an apex dose of 45 Gy suggests a need for dose optimization and individualized treatment strategies. Identifying high-risk features, such as Group D disease, active vitreous seeds, and larger tumors, is crucial for patient selection and outcome prediction. Future research should explore alternative dosing strategies, combination therapies, and improved predictive models to enhance long-term tumor control while minimizing complications. Full article

(This article belongs to the Section Ophthalmology)

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13 pages, 559 KiB

Open AccessArticle

Effects of Walking and Barre Exercise on CES-D, Stress Hormones, hs-CRP, and Immunoglobulins in Elderly Women

by Min-Kyo Kim, Su-Han Koh and Tae-Kyu Kim

J. Clin. Med. 2025, 14(5), 1777; https://doi.org/10.3390/jcm14051777 - 6 Mar 2025

Abstract

Objectives: This study explored the impact of a 12-week walking and barre exercise program on depression levels (CES-D), stress hormones (dopamine, epinephrine, norepinephrine, cortisol, serotonin), high-sensitivity C-reactive protein (hs-CRP), and immunoglobulins (IgA, IgG, IgM) in women aged 65 and above. Methods: Twenty-seven participants [...] Read more.

Objectives: This study explored the impact of a 12-week walking and barre exercise program on depression levels (CES-D), stress hormones (dopamine, epinephrine, norepinephrine, cortisol, serotonin), high-sensitivity C-reactive protein (hs-CRP), and immunoglobulins (IgA, IgG, IgM) in women aged 65 and above. Methods: Twenty-seven participants were divided into a walking exercise group (WG), barre exercise group (BG) and control group (CG), each comprising nine individuals. Sessions lasted 50 min, thrice weekly, with intensity progressing every 4 weeks. Two-way repeated measures of ANOVA assessed time–group interactions and main effects, and paired t-tests and one-way ANOVA were used post hoc with significance set at 0.05. Results: The CES-D scores demonstrated significant interaction (p < 0.001), decreasing significantly in the BG and WG (p < 0.01) while rising in the CG (p < 0.05). Post hoc analysis revealed significantly lower depression levels in the BG compared to the CG (p < 0.01). Stress hormones epinephrine and cortisol showed a main effect of time (p < 0.05), with epinephrine increasing significantly in the BG (p < 0.05) and cortisol decreasing in the BG and WG (p < 0.05). An interaction effect emerged in hs-CRP levels (p < 0.05), while IgA and IgM displayed interaction effects (p < 0.05 and p < 0.01, respectively), both significantly increasing in the BG (p < 0.05). Conclusions: In summary, regular exercise positively impacted depression, stress hormones, and immune functions in older women. Full article

(This article belongs to the Special Issue Physical Activity, Exercise and Health: Clinical Management and Research)

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13 pages, 8983 KiB

Open AccessSystematic Review

Efficacy and Safety of Combination Therapy with PARP Inhibitors and Anti-Angiogenic Agents in Ovarian Cancer: A Systematic Review and Meta-Analysis

by István Baradács, Brigitta Teutsch, Ádám Vincze, Péter Hegyi, Bence Szabó, Péter Nyirády, Nándor Ács, Zsolt Melczer, Ferenc Bánhidy and Balázs Lintner

J. Clin. Med. 2025, 14(5), 1776; https://doi.org/10.3390/jcm14051776 - 6 Mar 2025

Abstract

Introduction: Ovarian cancer is a significant contributor to gynecological cancer-related mortality, necessitating innovative treatment strategies. This systematic review and meta-analysis aimed to assess the efficacy and safety of combining PARP inhibitors with anti-angiogenic agents (AAAs) in the treatment of ovarian cancer. Methods: This [...] Read more.

Introduction: Ovarian cancer is a significant contributor to gynecological cancer-related mortality, necessitating innovative treatment strategies. This systematic review and meta-analysis aimed to assess the efficacy and safety of combining PARP inhibitors with anti-angiogenic agents (AAAs) in the treatment of ovarian cancer. Methods: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered on PROSPERO (CRD42022319461). A systematic search of three electronic databases, including MEDLINE (via PubMed), EMBASE, and Cochrane Library was conducted to identify relevant randomized controlled trials (RCT) that evaluated the efficacy and safety of the combination therapy. Subgroup analyses were based on BRCA mutation status. Meta-analysis was conducted to estimate pooled hazard ratios (HR) and risk ratios (RR) for progression-free survival (PFS) and adverse events, respectively. The combination therapy was compared to PARP inhibitors alone and to chemotherapy. Heterogeneity was assessed using Higgins and Thompson’s I² statistic where applicable. Results: Seven RCTs involving 2397 patients were included. Combination therapy did not show a statistically significant improvement in PFS compared to PARP inhibitor monotherapy in the general population (HR 0.63, CI 0.37–1.06), or in BRCA-mutated (HR 0.70, CI 0.30–1.63) and BRCA wild-type subgroups (HR 0.39, CI 0.14–1.07). When compared to chemotherapy, combination therapy produced no significant PFS benefit in recurrent ovarian cancer (HR 0.83, CI 0.42–1.63) in the total population. Safety analysis revealed that hypertension and diarrhea were significantly more frequent in combination therapy compared with PARP inhibitors alone (RR 6.80, CI 2.87–16.06 and RR 10.04, CI 2.25–44.75) or chemotherapy alone (RR 13.80, CI 3.43–55.57 and RR 6.57, CI 2.84–15.24). Conclusions: The combination of PARP inhibitors and AAAs did not demonstrate a statistically significant benefit in PFS compared to PARP inhibitors or chemotherapy alone in recurrent ovarian cancer. While the combination therapy was generally well tolerated, hypertension and diarrhea occurred significantly. These findings suggest that combination therapy may not provide a clear survival advantage in the recurrent setting. Further high-quality, biomarker-driven clinical trials are needed to refine patient selection, optimize toxicity management, and determine the potential role of combination therapy in ovarian cancer treatment. Full article

(This article belongs to the Section Obstetrics & Gynecology)

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14 pages, 550 KiB

Open AccessFeature PaperArticle

Effectiveness of Etanercept Biosimilar Initiating for Etanercept-Naive Patients, Using Ultrasound, Clinical, and Biomarker Assessments in Outcomes of Real-World Therapy (ENPORT-NGSK Study): An Interventional, Multicenter, Open-Label, Single-Arm Clinical Trial

by Remi Sumiyoshi, Shin-ya Kawashiri, Toshimasa Shimizu, Tomohiro Koga, Rieko Kiya, Shigeki Tashiro, Yurika Kawazoe, Shuntaro Sato, Yukitaka Ueki, Takahisa Suzuki, Tamami Yoshitama, Yoshifumi Tada, Naoki Hosogaya, Hiroshi Yamamoto and Atsushi Kawakami

J. Clin. Med. 2025, 14(5), 1775; https://doi.org/10.3390/jcm14051775 - 6 Mar 2025

Abstract

Background/Objectives: This study aimed to investigate the effectiveness of etanercept biosimilar 1 under real-world clinical conditions in patients with rheumatoid arthritis (RA), using not only clinical evaluation but also musculoskeletal ultrasound (MSUS). Methods: This multicenter, interventional, open-label, single-arm clinical trial conducted [...] Read more.

Background/Objectives: This study aimed to investigate the effectiveness of etanercept biosimilar 1 under real-world clinical conditions in patients with rheumatoid arthritis (RA), using not only clinical evaluation but also musculoskeletal ultrasound (MSUS). Methods: This multicenter, interventional, open-label, single-arm clinical trial conducted a 24-week follow-up. Patients with RA with moderate to high disease activity received weekly subcutaneous injections of etanercept biosimilar 1 at 50 mg/dose for 24 weeks. The effectiveness was evaluated with clinical indices and MSUS. Results: Twenty-three patients were evaluated during the study period. The primary endpoint involves a change in the Global OMERACT-EULAR Synovitis Score by MSUS in bilateral second–fifth metacarpophalangeal joints from baseline, demonstrating median (IQR) values of 0 (−4, 1), including 4 (1, 9.8) and 2 (0, 5) at baseline and 24 weeks, respectively. The clinical endpoints exhibited a good treatment response, with 15 (68%) and 18 (86%) patients achieving low disease activity or remission at 12 weeks and 24 weeks, respectively. Additionally, MSUS scores improved at both 12 and 24 weeks compared to baseline. The patients who achieved power doppler remission (total power doppler score = 0) at 24 weeks demonstrated a shorter disease duration and no previous use of biological disease-modifying antirheumatic drugs compared to those with no power doppler remission. Conclusions: Etanercept biosimilar 1 exhibited significant improvements not only in clinical indices but also in MSUS assessment, indicating its effectiveness at the structural level. Full article

(This article belongs to the Section Pharmacology)

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15 pages, 835 KiB

Open AccessReview

The Relationship Between Chronic Pruritus, Attention-Deficit/Hyperactivity Disorder, and Skin Picking—A Case Series and Narrative Review

by Eva Loos, Suzan Sekar, Christiane Rosin, Alexander A. Navarini, Chrysovalandis Schwale, Rainer Schaefert and Simon Müller

J. Clin. Med. 2025, 14(5), 1774; https://doi.org/10.3390/jcm14051774 - 6 Mar 2025

Abstract

Chronic pruritus (CP), attention-deficit/hyperactivity disorder (ADHD), and skin picking disorder (SPD) are medical conditions that involve both somatic and psychosocial dimensions, posing unique challenges in clinical management. While CP and SPD are often observed together, the link between ADHD and these conditions is [...] Read more.

Chronic pruritus (CP), attention-deficit/hyperactivity disorder (ADHD), and skin picking disorder (SPD) are medical conditions that involve both somatic and psychosocial dimensions, posing unique challenges in clinical management. While CP and SPD are often observed together, the link between ADHD and these conditions is less recognized. This conceptual work describes three women who suffered from a complex interplay of CP, ADHD, and SPD treated at our specialized bi-disciplinary psychodermatological pruritus clinic. Based on our clinical observation and a narrative review of the literature, we assume a bidirectional, triangular relationship between CP, ADHD, and SPD. To support this assumption, we propose two hypotheses: (1) a neurodevelopmental hypothesis, emphasizing that an underlying neurodevelopmental disorder, in this case, ADHD, might present with symptoms like dysfunction of sensory processing, impulsivity, and attention deficits as shared features that reinforce CP and SPD, and (2) a neuroinflammatory hypothesis, suggesting that similar neuroinflammatory signatures promote the co-occurrence of CP, ADHD, and SPD. In addition, we provide specific suggestions derived from our clinical experience on how to manage patients with this complex combination of conditions. Elucidating the interplay between CP, ADHD, and SPD might help develop personalized treatment strategies and improve outcomes. Full article

(This article belongs to the Special Issue Pruritus and Psyche: An Update on Clinical Management)

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16 pages, 3299 KiB

Open AccessSystematic Review

Comminuted Mason III/IV Radial Head Fractures: What Is the Best Treatment Between Prosthesis and Radial Head Resection? A Systematic Review and Meta-Analysis

by Luca Bianco Prevot, Livio Pietro Tronconi, Vittorio Bolcato, Riccardo Accetta, Stefania Fozzato and Giuseppe Basile

J. Clin. Med. 2025, 14(5), 1773; https://doi.org/10.3390/jcm14051773 - 6 Mar 2025

Abstract

Background/Objectives: Various surgical methods have been proposed for the treatment of comminuted Mason III/IV radial head fractures. In particular, the advantages and disadvantages between prosthesis implantation (RHA) or radial head resection (RHR) are not sufficiently quantified in the current literature. Methods: [...] Read more.

Background/Objectives: Various surgical methods have been proposed for the treatment of comminuted Mason III/IV radial head fractures. In particular, the advantages and disadvantages between prosthesis implantation (RHA) or radial head resection (RHR) are not sufficiently quantified in the current literature. Methods: A systematic literature search was conducted using PubMed Web of Science, Cochrane Library, and Embase in February 2024. Studies conducted on patients with Mason type III or IV radial head fractures and studies relating to surgical methods, including radial head resection or Radial head prosthesis implantation, were included. The two methods were evaluated in terms of clinical and functional results through the DASH score (Disability of the arm, shoulder, and hand), Mayo Elbow Performance Index (MEPI), and flexion-extension range of motion. The onset of osteoarthritis and complications were also assessed. Risk of bias and quality of evidence were assessed using Cochrane guidelines. Results: A total of 345 articles were evaluated and, of these, 21 were included in the study for a total of 552 patients. The results of the meta-analysis showed no significant differences in favor of RHA or RHR in terms of Mayo Elbow Performance (p = 0.58), degrees of flexion (p = 0.689), degrees of extension deficit (p = 0.697), and overall incidence of complications (p = 0.389), while it highlighted a statistically significant difference in terms of DASH score (19.2 vs. 16.2, respectively; p = 0.008) and subjects who developed osteoarthritis (13.4% vs. 47.3%, respectively; p = 0.046). Conclusions: The results of this meta-analysis confirm that both surgical methods provide good functional outcomes, with no significant differences in MEPI, DASH, and range of motion. However, a higher incidence of post-traumatic osteoarthritis was observed in patients undergoing RHR. Additionally, RHR patients exhibited slightly worse functional outcomes in the DASH score; however, this difference is not substantial enough to be considered clinically significant. These findings suggest that while both techniques are viable, RHA may be preferable in patients at higher risk of joint degeneration and instability, and the choice of treatment should be tailored to individual patient characteristics. Full article

(This article belongs to the Special Issue Trends and Prospects in Shoulder and Elbow Surgery)

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12 pages, 1367 KiB

Open AccessArticle

Investigation of MicroRNA-17 Expression, Tumor Necrosis Factor-α, and Interleukin-6 Levels in Lumbar Degenerative Disc Disease: Case–Control Study

by Luay Şerifoğlu, Müge Kopuz Álvarez Noval, Selvi Duman Bakırezer, Seda Güleç Yılmaz, Eyüp Varol, Muhittin Emre Altunrende, Ali Haluk Düzkalır and Selçuk Özdoğan

J. Clin. Med. 2025, 14(5), 1772; https://doi.org/10.3390/jcm14051772 - 6 Mar 2025

Abstract

Background/Objectives: The aim of the study is to investigate the role of microRNA-17 (miRNA-17), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in the pathogenesis of lumbar degenerative disc disease (LDDD). The goal is to explore how miRNA-17 regulates inflammation and apoptosis within the [...] Read more.

Background/Objectives: The aim of the study is to investigate the role of microRNA-17 (miRNA-17), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in the pathogenesis of lumbar degenerative disc disease (LDDD). The goal is to explore how miRNA-17 regulates inflammation and apoptosis within the intervertebral discs, with a particular focus on its involvement in inflammatory pathways via NF-κB signaling. This research seeks to uncover the molecular mechanisms that contribute to LDDD and its associated chronic lower back pain and disability. Methods: A case–control study was conducted, involving 110 patients diagnosed with LDDD and 17 healthy control individuals. Serum levels of miRNA-17, TNF-α, and IL-6 were measured using quantitative real-time PCR and enzyme-linked immunosorbent assays (ELISAs). The patients were further categorized based on the severity of their condition using the Oswestry Disability Index (ODI), which classified them into five subgroups. The correlation between miRNA-17 expression, pro-inflammatory cytokines, and disease severity was analyzed statistically. Results: The results demonstrated a significant downregulation of microRNA-17 in patients with LDDD compared to healthy controls. Inflammatory markers TNF-α and IL-6 were found to be significantly elevated in the patient group. A peak in inflammation and miRNA-17 expression was observed in patients with moderate to severe disability (ODI Grade 3), while inflammation levels decreased in more advanced stages of the disease (ODI Grades 4 and 5), suggesting a possible shift in disease dynamics. Conclusions: This study demonstrates that miRNA-17 plays a regulatory role in inflammation during the progression of LDDD, particularly through the modulation of TNF-α and IL-6 levels. The findings indicate that inflammation is most pronounced in the mid-stages of LDDD, while the later stages are characterized by structural damage rather than ongoing inflammation. These insights could help guide future therapeutic strategies aimed at targeting the molecular mechanisms underlying LDDD, potentially improving patient outcomes. Full article

(This article belongs to the Section Clinical Neurology)

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20 pages, 2984 KiB

Open AccessSystematic Review

Digital Cognitive Behavioral Therapy for Panic Disorder and Agoraphobia: A Meta-Analytic Review of Clinical Components to Maximize Efficacy

by Han Wool Jung, Ki Won Jang, Sangkyu Nam, Areum Kim, Junghoon Lee, Moo Eob Ahn, Sang-Kyu Lee, Yeo Jin Kim, Jae-Kyoung Shin and Daeyoung Roh

J. Clin. Med. 2025, 14(5), 1771; https://doi.org/10.3390/jcm14051771 - 6 Mar 2025

Abstract

Background: Although digital cognitive behavioral therapy (dCBT) is considered effective for anxiety disorders, there is considerable heterogeneity in its efficacy across studies, and its varied treatment content and clinical components may explain such heterogeneity. Objective: This review aimed to identify the [...] Read more.

Background: Although digital cognitive behavioral therapy (dCBT) is considered effective for anxiety disorders, there is considerable heterogeneity in its efficacy across studies, and its varied treatment content and clinical components may explain such heterogeneity. Objective: This review aimed to identify the efficacy of digital cognitive behavioral therapy for panic disorder and agoraphobia, and examine whether applying relevant clinical components of interoceptive exposure, inhibitory-learning-based exposure, and personalization of treatment enhances its efficacy. Methods: Randomized controlled trials of dCBT for panic disorder and agoraphobia with passive or active controls were identified from OVID Medline, Embase, Cochrane Library, and PsycINFO. The overall effect sizes for dCBT groups (interventions through digital platforms based on the internet, mobile, computers, VR, etc.) were aggregated against passive control (placebo/sham) and active control (traditional CBT) groups. For subgroup analysis, key intervention components such as interoceptive exposure, inhibitory learning, and personalization were assessed dichotomously (0 or 1) along with other study characteristics. The stepwise meta-regression models were applied with traditional and Bayesian statistical testing. The risk of bias and publication bias of included studies were assessed. Results: Among the 31 selected studies, dCBT had an overall effect size of g = 0.70 against passive control and g = −0.05 against active control. In subgroup analysis, interoceptive exposure improved the clinical effects for both controls, and inhibitory learning and personalization increased the clinical effects for passive control along with therapist guide/support and the length of sessions. Many studies were vulnerable to therapist bias and attrition bias. No publication bias was detected. Conclusions: The heterogeneity in clinical effects of dCBT for panic and agoraphobia can be explained by the different intervention factors they include. For effective dCBT, therapists should consider the clinical components relevant to the treatment. Full article

(This article belongs to the Special Issue Treatment Personalization in Clinical Psychology and Psychotherapy)

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14 pages, 599 KiB

Open AccessArticle

Cardiometabolic Markers in Algerian Obese Subjects with and Without Type 2 Diabetes: Adipocytokine Imbalance as a Risk Factor

by Hassiba Benbaibeche, Abdenour Bounihi, Hamza Saidi, Elhadj Ahmed Koceir and Naim Akhtar Khan

J. Clin. Med. 2025, 14(5), 1770; https://doi.org/10.3390/jcm14051770 - 6 Mar 2025

Abstract

Background/Objectives: An increase in body fat is linked to abnormalities in energy metabolism. We aimed at determining cardiometabolic risk in Algerian participants with obesity alone and with or without type 2 diabetes. The study measured the concentrations of circulating adipocytokines (leptin, adiponectin, [...] Read more.

Background/Objectives: An increase in body fat is linked to abnormalities in energy metabolism. We aimed at determining cardiometabolic risk in Algerian participants with obesity alone and with or without type 2 diabetes. The study measured the concentrations of circulating adipocytokines (leptin, adiponectin, resistin), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) to identify and examine how imbalances in adipocytokines may affect the parameters of cardiometabolic health. Methods: Algerian participants (n = 300) were recruited and divided into three groups: control, obese, and type 2 diabetics (with two sub-groups: with and without obesity). Insulin resistance was evaluated using HOMA-IR, while ELISA was used to measure adipocytokines. Atherogenic index in plasma (AIP), adiponectin-leptin ratio (ALR), and visceral adiposity index (VAI) were also assessed. One-way ANOVA was used to compare obesity and diabetes groups to the control one (p < 0.05). Logistic regression analysis was conducted to strengthen the robustness of statistical correlations. Results: Participants with reduced adiponectin-leptin ratio (ALR) and elevated levels of resistin, TNF-α, and IL-6 are found to be at higher risk of cardiovascular diseases. An imbalance in adipocytokine levels is caused by a decrease in adiponectin concentrations, and an increase in pro-inflammatory adipocytokines that maintain and exacerbate energy imbalance and induces hyperinsulinemia, exposing individuals to a high risk of cardiovascular diseases. Conclusions: Given that ALR is a functional biomarker of inflammation, insulin resistance, and adipose tissue dysfunction, targeting ALR could potentially be a therapeutic approach to coping with obesity-related cardiometabolic risks. Mediterranean diet, weight loss, and increased physical activity can be key components to promote healthy adipose tissue through the increase in ALR. Full article

(This article belongs to the Topic Biomarkers in Cardiovascular Disease—Chances and Risks, 2nd Volume)

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14 pages, 6317 KiB

Open AccessArticle

The Human Disharmony Loop: A Case Series Proposing the Unique Role of the Pectoralis Minor in a Unifying Syndrome of Chronic Pain, Neuropathy, and Weakness

by Ketan Sharma and James M. Friedman

J. Clin. Med. 2025, 14(5), 1769; https://doi.org/10.3390/jcm14051769 - 6 Mar 2025

Abstract

Background/Objectives: Many patients evaluated by shoulder specialists suffer from intractable pain, neuropathy, and weakness. The pectoralis minor (PM) remains the only scapula muscle to receive lower trunk (C8-T1) input. We propose a novel syndrome: the Human Disharmony Loop. This model portrays how [...] Read more.

Background/Objectives: Many patients evaluated by shoulder specialists suffer from intractable pain, neuropathy, and weakness. The pectoralis minor (PM) remains the only scapula muscle to receive lower trunk (C8-T1) input. We propose a novel syndrome: the Human Disharmony Loop. This model portrays how this unique PM innervation causes scapular dyskinesia, which deranges the anatomy of the upper limb girdle and produces a refractory symptom complex of pain, neuropathy, and weakness. We hypothesize that certain patients with historically intractable symptoms of the upper limb girdle may benefit from PM tenotomy. Methods: Ten patients of diverse etiologies presented with a similar constellation of complaints. The patients included a female athlete, a female with macromastia, a male bodybuilder, and patients with post-radiation breast cancer, post-operative shoulder arthroplasty, interscalene block injury, cervical spine disease, persistent impingement after rotator cuff repair, direct traction injury, and occupational disorder. All patients exhibited coracoid tenderness, scapula protraction with internal rotation and anterior tilt, and pain involving the neck, shoulder, and upper back. The patients demonstrated varying degrees of arm neuropathy, subacromial impingement, and occipital headaches. The patients failed all prior treatments by multiple subspecialists, including surgery. Each patient underwent isolated open PM tenotomy. Results: In all ten patients, PM tenotomy substantially reduced shoulder, upper back, and neck pain, cleared concomitant neuropathy, restored full motion, and eradicated occipital headaches. The response to surgery was rapid, dramatic, and durable. Conclusions: The unique asymmetric neurologic innervation to the sole ventral stabilizer of the scapula, the pectoralis minor, predisposes the human shoulder to neurologic and musculoskeletal imbalance. This produces the Human Disharmony Loop: a clinical syndrome spanning from the neck to the fingertips, with chronic pain, neuropathy, and weakness. These challenging patients may benefit dramatically from isolated PM tenotomy. Full article

(This article belongs to the Section Clinical Neurology)

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15 pages, 847 KiB

Open AccessArticle

Enhanced Recovery After Surgery (ERAS) Protocols in Cardiac Surgery: Impact on Opioid Consumption

by Alexandra Othenin-Girard, Zied Ltaief, Mario Verdugo-Marchese, Luc Lavanchy, Patrice Vuadens, Anna Nowacka, Ziyad Gunga, Valentine Melly, Tamila Abdurashidova, Caroline Botteau, Marius Hennemann, Jérôme Graf, Patrick Schoettker, Matthias Kirsch and Valentina Rancati

J. Clin. Med. 2025, 14(5), 1768; https://doi.org/10.3390/jcm14051768 - 6 Mar 2025

Abstract

Background: Enhanced Recovery After Surgery (ERAS) protocols have been implemented in various surgical specialties to improve patient outcomes and reduce opioid consumption. In cardiac surgery, the traditionally high-dose opioid use is associated with prolonged ventilation, intensive care unit (ICU) stays, and opioid-related [...] Read more.

Background: Enhanced Recovery After Surgery (ERAS) protocols have been implemented in various surgical specialties to improve patient outcomes and reduce opioid consumption. In cardiac surgery, the traditionally high-dose opioid use is associated with prolonged ventilation, intensive care unit (ICU) stays, and opioid-related adverse drug events (ORADEs). This study evaluates the impact of an ERAS^® Society-certified program on opioid consumption in patients undergoing elective cardiac surgery at Lausanne University Hospital. Methods: A retrospective, monocentric observational study was conducted comparing two patient cohorts: one treated with ERAS protocols (2023–2024) and a retrospective control group from 2019. Data were collected from the hospital’s electronic medical records and the ERAS program database. The primary outcome was total opioid consumption, measured intraoperatively and postoperatively (postoperative day (POD) 0–3). Secondary outcomes included pain control, length of stay, complications, and recovery parameters. Statistical analyses included multivariate logistic regression to identify factors associated with reduced opioid consumption. Results: Patients in the ERAS group demonstrated significantly lower total opioid consumption, whether intraoperatively (median sufentanil: 40 mcg vs. 51 mcg, p < 0.0001) or postoperatively (POD 0–3: p < 0.001). The ERAS group had faster extubation times, earlier mobilization and pain control with non-opioid analgesics, fewer complications, and shorter hospital stays (9 vs. 12 days, p < 0.001). Logistic regression identified fast-track extubation and absence of complications as strong predictors of reduced opioid use. Conclusions: The implementation of an ERAS protocol in cardiac surgery significantly reduces opioid consumption while enhancing recovery. Full article

(This article belongs to the Special Issue Clinical Advances in Cardiothoracic Anesthesia)

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13 pages, 1704 KiB

Open AccessArticle

Broad-Spectrum Adverse Events of Special Interests Based on Immune Response Following COVID-19 Vaccination: A Large-Scale Population-Based Cohort Study

by Hong Jin Kim, Jee Hyun Suh, Min-Ho Kim, Myeong Geun Choi and Eun Mi Chun

J. Clin. Med. 2025, 14(5), 1767; https://doi.org/10.3390/jcm14051767 - 6 Mar 2025

Abstract

Background/Objectives: Current studies on adverse events related to the COVID-19 vaccine have predominantly focused on severe, life-threatening side effects. However, numerous less severe but common adverse events (AEs) remain underreported and insufficiently investigated despite their potential impact. Methods: This population-based cohort study investigated [...] Read more.

Background/Objectives: Current studies on adverse events related to the COVID-19 vaccine have predominantly focused on severe, life-threatening side effects. However, numerous less severe but common adverse events (AEs) remain underreported and insufficiently investigated despite their potential impact. Methods: This population-based cohort study investigated the cumulative incidence rate (cIR) and risk of the broad-spectrum AEs of special interests (AESIs) based on immune response, including gynecological, dermatological, ophthalmological, otologic, and dental problems, following COVID-19 vaccination. Results: Among 4,203,887 individuals in Seoul, South Korea, the final analysis included 1,458,557 vaccinated subjects and 289,579 non-vaccinated subjects after the exclusion of underlying diseases. The cIR of AESIs for three months was significantly higher in vaccinated subjects than in non-vaccinated subjects, except for endometriosis. The vaccination significantly increased the risks of all the AESIs except for visual impairment. The risk of alopecia showed the highest HRs (HR [95% CI] = 2.40 [1.90–3.03]) among the AESIs following COVID-19 vaccination. Among the vaccinated subjects, heterologous vaccination was associated with the increased risk of most of the AESIs. Conclusions: Our findings suggest that clinicians should closely recognize and follow up on various COVID-19 vaccine-related AEs due to their unknown impact, even if they may not be serious at present. Full article

(This article belongs to the Special Issue Novel Insights into COVID-19-Associated Complications and Sequelae)

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18 pages, 905 KiB

Open AccessSystematic Review

Efficacy of Transcranial Direct Current Stimulation and Photobiomodulation in Improving Cognitive Abilities for Alzheimer’s Disease: A Systematic Review

by Monica Cornea, Bogdan Ioan Vintilă, Mihaela Bucuța, Laura Ștef, Claudia Elena Anghel, Andreea Maria Grama, Andrei Lomnasan, Andreea Angela Stetiu, Adrian Boicean, Mihai Sava, Lucian Constantin Paziuc, Mihnea Costin Manea, Andrian Tîbîrnă and Ciprian-Ionuț Băcilă

J. Clin. Med. 2025, 14(5), 1766; https://doi.org/10.3390/jcm14051766 - 6 Mar 2025

Abstract

Background: Due to the increasing global prevalence of Alzheimer’s dementia (AD), neuromodulation techniques such as transcranial direct current stimulation (tDCS) and photobiomodulation (PBM) are considered potential complementary therapies. Objective: We assessed the efficacy and safety of tDCS and PBM and their potential to [...] Read more.

Background: Due to the increasing global prevalence of Alzheimer’s dementia (AD), neuromodulation techniques such as transcranial direct current stimulation (tDCS) and photobiomodulation (PBM) are considered potential complementary therapies. Objective: We assessed the efficacy and safety of tDCS and PBM and their potential to enhance cognitive functions in individuals with AD. Methods: This review primarily examined studies designed to evaluate the efficacy, followed by an assessment of the safety of tDCS and PBM for people with AD. The databases searched were PubMed, Scopus, and Web of Science Core Collection, resulting in 17 published randomized and controlled trials. References were screened over 5 years (2020–2024). The research design used PRISMA guidelines. Results: Fourteen studies were considered for tDCS, and the current literature supports efficacy and safety at an amperage of 2 mA, with electrodes placed on the dorsolateral prefrontal cortex (DLPFC). Three studies were included for PBM. The heterogeneity of these study measures made them unsuitable for combined efficacy analysis, and they did not provide a safety evaluation. Conclusions: Despite differences in efficacy assessments, tDCS and PBM improved cognitive abilities. There is an urgent need to standardize metrics for evaluating efficacy and safety, particularly for PBM. Future research is encouraged. Full article

(This article belongs to the Special Issue Potential Cures of Alzheimer's Dementia)

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16 pages, 901 KiB

Open AccessPerspective

Shaping the Future of Chronic Kidney Disease Management in Spain: Insights from the CARABELA-CKD Initiative

by Javier Escalada, Patricia de Sequera, Jesús Ignacio Diago, CARABELA-CKD Scientific Committee and Pedro Ruiz

J. Clin. Med. 2025, 14(5), 1765; https://doi.org/10.3390/jcm14051765 - 6 Mar 2025

Abstract

Chronic kidney disease (CKD) is a growing public health challenge in Spain, driven by population ageing and increasing risk factors. In this context, the CARABELA-CKD initiative brought together over 100 representatives from the CKD healthcare ecosystem in Spain to address this critical issue [...] Read more.

Chronic kidney disease (CKD) is a growing public health challenge in Spain, driven by population ageing and increasing risk factors. In this context, the CARABELA-CKD initiative brought together over 100 representatives from the CKD healthcare ecosystem in Spain to address this critical issue by identifying needs and improvement areas in the current management of CKD patients and proposing a comprehensive optimization of the Spanish CKD care process. This collaborative initiative involves leading scientific societies including the S.E.N. (Spanish Society of Nephrology), the SEEN (Spanish Society of Endocrinology and Nutrition), and the SECA (Spanish Society of Quality of Care), in partnership with AstraZeneca. CARABELA-CKD emphasizes data-driven decision-making and continuous quality improvement to identify and deliver innovative solutions that enhance patient care. Building on existing CKD care models, we performed an in-depth analysis of the current barriers in enhanced care and determined a series of healthcare quality indicators and areas for improvement. These areas encompass standardized protocols for care delivery, patient empowerment through education, and fostering collaboration among healthcare professionals and authorities. The CARABELA-CKD framework promotes a holistic, multidisciplinary approach, treating CKD management as a cross-functional process. As a result of this collaborative effort, a series of interventions are proposed, oriented to empower healthcare professionals to deliver personalized, high-quality care with the ultimate aim of improving patient outcomes and quality of life. Full article

(This article belongs to the Section Nephrology & Urology)

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13 pages, 1444 KiB

Open AccessArticle

Bone Changes During Growth in Patients with Osteogenesis Imperfecta

by Laura Burgueño-Torres, Lara García-Boedo and Manuel Joaquín de Nova-García

J. Clin. Med. 2025, 14(5), 1764; https://doi.org/10.3390/jcm14051764 - 6 Mar 2025

Abstract

Background/Objectives: Osteogenesis Imperfecta (OI) is a congenital disorder, in which the production of collagen, mainly type I, is altered, leading to a decrease in bone mineral density, increasing the risk of fracture with minimal trauma. Several studies have analyzed bone mineral density [...] Read more.

Background/Objectives: Osteogenesis Imperfecta (OI) is a congenital disorder, in which the production of collagen, mainly type I, is altered, leading to a decrease in bone mineral density, increasing the risk of fracture with minimal trauma. Several studies have analyzed bone mineral density in osteoporotic patients based on linear measurements such as radiomorphometric indices measured with panoramic radiographs, although few studies have investigated bone trabeculation in children diagnosed with OI. Therefore, the aim of the present investigation was to analyze the dental panoramic indices in panoramic radiographs in the cortical and trabeculated bone of children with OI. Methods: Thus, 66 pediatric patients diagnosed with OI under antiresorptive treatment were compared with a sample of controls matched for sex and age. Using Image J software (version: 1.54d), three radiomorphometric indices were analyzed in orthopantomographies of the study and control groups, evaluating the influence of disease severity as well as the type of antiresorptive treatment administered. Results: Patients with OI had a higher presence of type C2 and C3 MCI (mandibular cortical index) than their matched controls (p < 0.05), although no differences were found for the visual estimation of cortical width (SVE) and mandibular cortical width (MCW). Treatment with zoledronic acid was associated with a higher number of cases of type C1 MCI, in terms of sample description, while patients treated with a combination of pamidronate and zoledronic acid had a higher rate of type C1 and C2 MCI, with no statistical differences. Conclusions: In the overall sample, most patients showed a thin SVE index (59.1%), a C2 or C1 type MCI (46.2% and 42.4%) and an MCW of 2.9 mm. Differences in bone mineral density were also observed throughout growth and the different antiresorptive treatments. Zoledronic acid has been associated with a higher percentage of C1 and C3 ICM, and pamidronate alone or in combination is associated with a C1 and C2 MCI index. Full article

(This article belongs to the Section Orthopedics)

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9 pages, 197 KiB

Open AccessArticle

Diagnostic Accuracy of Artificial Intelligence vs. Oncologist Interpretation in Digital Cervicography for Abnormal Cervical Cytology

by Kyeong-A So, Eun-Bi Jang, Seung-Hyuk Shim, Sun-Joo Lee and Tae-Jin Kim

J. Clin. Med. 2025, 14(5), 1763; https://doi.org/10.3390/jcm14051763 - 6 Mar 2025

Abstract

Objective: We compared the diagnostic performance of artificial intelligence (AI) with that of a gynecologic oncologist during digital cervicography. Methods: Women with abnormal cytology who underwent cervicography between January 2019 and December 2023 were included. A gynecologic oncologist interpreted the digital cervicography and [...] Read more.

Objective: We compared the diagnostic performance of artificial intelligence (AI) with that of a gynecologic oncologist during digital cervicography. Methods: Women with abnormal cytology who underwent cervicography between January 2019 and December 2023 were included. A gynecologic oncologist interpreted the digital cervicography and the results were compared with those of the AI system. Diagnostic performances were assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy for low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs)/cancer. Cohen’s kappa quantified agreement. Results: This study included 449 women (mean age, 41.0 years). A Cohen’s kappa of 0.511 (p < 0.0001) indicated moderate agreement between the oncologist and AI. Among 226 cases of HSILs/cancer, the oncologist’s sensitivity was 62.8%, compared to 47.8% for AI, with similar specificity (81.2% vs. 83.5%). The oncologist’s PPV and NPV were 85.0% and 56.3%, respectively, whereas AI’s were 83.1% and 48.5%, respectively. For LSILs/HSILs/cancer (n = 283), the oncologist achieved 98.2% sensitivity and 44.7% specificity, compared to AI’s 93.3% sensitivity and 46.1% specificity. Both had a similar PPV (86.9% vs. 86.6%); however, the oncologist’s NPV (87.2%) exceeded AI’s 64.8%. Diagnostic accuracy for LSILs/HSILs/cancer was 86.9% for the oncologist and 82.3% for AI, whereas for HSILs/cancer, it was 69.6% and 61.0%, respectively. Conclusions: Moderate agreement was observed between the oncologist and AI. Although AI demonstrated similar performance in diagnosing cervical lesions, the oncologist achieved higher diagnostic accuracy. AI is a complementary tool and future research should refine AI algorithms to align with clinical performance. Full article

(This article belongs to the Special Issue Recent Issues in Gynecologic Cancer Prevention and Screening)

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