Journal of Clinical Medicine

21 pages, 826 KB

Open AccessArticle

Association Between Postoperative Pain Intensity and Delirium in Cardiac and Neurosurgical Patients: A Retrospective Pilot Study

by Mateusz Szczupak, Jacek Kobak, Jakub Wiśniewski, Jolanta Wierzchowska and Sabina Krupa-Nurcek

J. Clin. Med. 2025, 14(24), 8840; https://doi.org/10.3390/jcm14248840 (registering DOI) - 13 Dec 2025

Abstract

Background/Objective: Postoperative pain and delirium are frequent and clinically relevant complications in patients undergoing major cardiac or neurosurgical procedures. The interaction between these conditions remains insufficiently characterized, particularly across heterogeneous surgical populations. This study aimed to investigate the relationship between postoperative pain [...] Read more.

Background/Objective: Postoperative pain and delirium are frequent and clinically relevant complications in patients undergoing major cardiac or neurosurgical procedures. The interaction between these conditions remains insufficiently characterized, particularly across heterogeneous surgical populations. This study aimed to investigate the relationship between postoperative pain intensity and delirium severity within the first 48 h after surgery in cardiac and neurosurgical patients. Methods: This retrospective observational analysis included 408 individuals—202 following cardiac surgery and 206 after neurosurgical procedures. Pain intensity was measured using the Numerical Rating Scale (NRS), while delirium presence and severity were assessed using the CAM-ICU and CAM-ICU-7 instruments. Associations between NRS scores, delirium severity, demographic characteristics, and ICU length of stay were examined. Results: Cardiac surgery patients experienced higher pain levels on postoperative day 1 compared with neurosurgical patients; this difference was not observed on day 2. In the cardiac cohort, higher NRS scores were positively associated with greater delirium severity on both postoperative days. No such association was detected in the neurosurgical group. Pain scores also differed across procedure types within each specialty, and several demographic variables (age, sex, ICU stay duration) were linked with variations in pain intensity. On postoperative day 1, pain intensity showed a moderate association with delirium severity (Spearman ρ = 0.23; 95% CI 0.14–0.32). Patients who developed delirium had higher pain scores (r = 0.25). In ordinal logistic regression, greater pain on postoperative day 1 independently predicted higher delirium severity (OR 2.24; 95% CI 1.70–2.94). Conclusions: Significant associations between postoperative pain intensity and delirium severity were identified in cardiac surgery patients, whereas no similar pattern emerged among neurosurgical patients. Given the retrospective design and incomplete data on perioperative pharmacotherapy, the findings should be interpreted descriptively and do not support causal conclusions. These results underscore the importance of systematic monitoring of pain and cognitive function in high-risk postoperative populations and highlight the need for prospective studies to elucidate the complex interplay between pain, perioperative factors, and postoperative delirium. Full article

(This article belongs to the Special Issue Clinical Management and Long-Term Prognosis in Intensive Care)

11 pages, 657 KB

Open AccessCase Report

Malignant Syphilis in an Immunocompetent Patient: A Case Report and Review of the Literature

by Chiara Vincenza Mazzola, Eleonora Bono, Ilenia Giacchino, Cinzia Calà, Luca Pipitò and Antonio Cascio

J. Clin. Med. 2025, 14(24), 8839; https://doi.org/10.3390/jcm14248839 (registering DOI) - 13 Dec 2025

Abstract

Background: Syphilis can present with diverse clinical manifestations, earning the name “great imitator.” Malignant syphilis (MS) is a rare, severe form of secondary syphilis, typically reported in immunocompromised patients, particularly those living with HIV. However, MS can occasionally occur in immunocompetent individuals, [...] Read more.

Background: Syphilis can present with diverse clinical manifestations, earning the name “great imitator.” Malignant syphilis (MS) is a rare, severe form of secondary syphilis, typically reported in immunocompromised patients, particularly those living with HIV. However, MS can occasionally occur in immunocompetent individuals, posing diagnostic challenges due to its atypical presentation. Methods: A case report is presented alongside a PubMed literature search using the terms “(malignant syphilis OR lues maligna) AND (immunocompetent) AND (case report OR case series).” No language or temporal restrictions were applied, yielding 18 relevant publications. Results: A 60-year-old HIV-negative man presented with fever, weight loss, papular lesions, and a single ulcer on the sternum. Serology was positive for syphilis, and PCR confirmed T. pallidum DNA in the lesion. Treatment with a single intramuscular dose of benzathine penicillin G led to prompt clinical and serological improvement. Literature review (n = 18) showed that MS in immunocompetent patients affects both sexes (55% male; mean age 37.1 years), often presents with ulceronodular or rupioid crusted lesions, and frequently involves systemic symptoms. Molecular diagnostics were rarely reported, with most diagnoses relying on histopathology and serology. Treatment with benzathine penicillin G was effective in all cases, and full recovery was achieved. Conclusions: MS can occur in immunocompetent, HIV-negative individuals without obvious risk factors. Clinicians should maintain a high index of suspicion in cases of systemic, cutaneous, or ocular manifestations suggestive of MS. Molecular assays can facilitate diagnosis and prevent unnecessary invasive procedures. Benzathine penicillin G remains the treatment of choice, demonstrating high therapeutic effectiveness. MS should be considered in the differential diagnosis of ulcerative or nodular dermatoses, regardless of immune status. Full article

(This article belongs to the Special Issue Sexually Transmitted Infections as a Challenge of Modern Society: Old Problems and Modern Solutions)

11 pages, 225 KB

Open AccessArticle

Long-Term Safety and Efficacy of Partially Absorbable Transobturator Mid-Urethral Sling in Women Aged 65 Years and Older

by Réka Fábián-Kovács, Asnat Groutz, Jonatan Neuman, Menahem Neuman, Yoav Baruch and Ronen S. Gold

J. Clin. Med. 2025, 14(24), 8838; https://doi.org/10.3390/jcm14248838 (registering DOI) - 13 Dec 2025

Abstract

Objectives: To assess the long-term safety and efficacy of the Serasis^® partially absorbable transobturator mid-urethral sling (MUS) in women aged ≥65 years compared to younger women. Methods: A retrospective comparative study of 375 consecutive women who underwent Serasis^® MUS for stress [...] Read more.

Objectives: To assess the long-term safety and efficacy of the Serasis^® partially absorbable transobturator mid-urethral sling (MUS) in women aged ≥65 years compared to younger women. Methods: A retrospective comparative study of 375 consecutive women who underwent Serasis^® MUS for stress urinary incontinence (SUI). Patients were stratified into two age groups: 45–64 years (N = 118) and ≥65 years (N = 257), with further subdivision of the elderly cohort into 65–74 years (N = 208) and 75–84 years (N = 49). Primary outcomes included perioperative safety and long-term subjective cure rates, assessed via standardized telephone survey at a mean follow-up of 8.5 years (range, 6.8–10.9 years). Results: Perioperative outcomes were comparable across age groups. At 4 months postoperatively, subjective cure was achieved in 82.9% of elderly and 86.4% of younger patients. Long-term subjective cure rates were 79.6% and 85.4%, respectively (p = 0.27). Elderly patients experienced higher rates of postoperative voiding dysfunction and persistent overactive bladder symptoms, though subjective satisfaction remained high. Long-term mesh-related complications were infrequent across age groups. Specifically, vaginal mesh erosion requiring surgical removal occurred in three elderly patients (1.6%) and in only one younger patient (1.1%). A multivariate logistic regression analysis identified preoperative mixed urinary incontinence, BMI >30 kg/m² and concomitant pelvic organ prolapse repair as independent predictors of surgical failure. Age ≥65 years was not an independent predictor of surgical failure (OR 1.3, 95% CI 0.8–2.1, p = 0.31). Conclusions: The use of a partially absorbable MUS in elderly women with SUI is a safe and effective surgical approach, associated with a significant reduction in long-term mesh-related complications. Full article

(This article belongs to the Section Obstetrics & Gynecology)

16 pages, 346 KB

Open AccessReview

Exposure-Based Intervention in Virtual Reality to Address Kinesiophobia in Parkinson’s Disease: A Narrative Review

by Alice Jeanningros, Stéphane Bouchard and Alexandra Potvin-Desrochers

J. Clin. Med. 2025, 14(24), 8837; https://doi.org/10.3390/jcm14248837 (registering DOI) - 13 Dec 2025

Abstract

Background/Objectives: Physical activity alleviates symptoms and may slow Parkinson’s disease (PD) progression, yet many individuals with PD remain sedentary. Kinesiophobia, the fear of movement, may represent a significant but underexplored psychological barrier to physical activity in this population. Virtual reality (VR), already [...] Read more.

Background/Objectives: Physical activity alleviates symptoms and may slow Parkinson’s disease (PD) progression, yet many individuals with PD remain sedentary. Kinesiophobia, the fear of movement, may represent a significant but underexplored psychological barrier to physical activity in this population. Virtual reality (VR), already effective in phobias, may represent a promising approach to address this challenge. This review initially aimed to systematically examine exposure-based interventions in VR (E-IVR) directly targeting kinesiophobia in PD. Methods: Database searches using keywords such as “kinesiophobia,” “fear of movement,” and “VR” combined with “PD” yielded no eligible studies. Consequently, the scope was broadened to include populations with neurological or musculoskeletal conditions, and a narrative review format was adopted to synthesize the available evidence. Furthermore, relevant studies of interventions in VR applied in PD, although not specifically addressing kinesiophobia, are detailed to provide evidence of efficacy and feasibility of VR interventions in PD. Finally, directions are offered to support the creation of E-IVR targeting kinesiophobia in individuals with PD. Results: Meta-analyses in neurological and musculoskeletal populations demonstrate moderate to large reductions in kinesiophobia following VR interventions, although effects vary depending on assessment tools, degree of immersion, and exposure design. In PD, VR has been applied to rehabilitation, anxiety reduction, and quality of life enhancement. These interventions achieved high adherence (≥90%), were well tolerated, and reported no major adverse events. Conclusions: Kinesiophobia is prevalent in PD and could contribute to physical inactivity. E-IVR appears feasible, safe, and innovative for addressing kinesiophobia in people living with PD. Full article

(This article belongs to the Section Clinical Neurology)

15 pages, 1225 KB

Open AccessArticle

Three Decades of Spinal Cord Injury in Saudi Arabia: Trends in Incidence, Prevalence, and Disability Outcomes

by Ahmad F. Alahmary, Mishal M. Aldaihan, Vishal Vennu and Saad M. Bindawas

J. Clin. Med. 2025, 14(24), 8836; https://doi.org/10.3390/jcm14248836 (registering DOI) - 13 Dec 2025

Abstract

Background/Objective: Spinal cord injury (SCI) is a life-altering condition representing a major cause of long-term disability and substantial health burden worldwide. In the Middle East, including Saudi Arabia, rapid urbanization and evolving injury patterns may have influenced SCI trends; however, national data remain [...] Read more.

Background/Objective: Spinal cord injury (SCI) is a life-altering condition representing a major cause of long-term disability and substantial health burden worldwide. In the Middle East, including Saudi Arabia, rapid urbanization and evolving injury patterns may have influenced SCI trends; however, national data remain limited. This study aimed to examine age-standardized trends in SCI incidence, prevalence, and years lived with disability (YLDs) in Saudi Arabia from 1990 to 2021, comparing transport-related and non-transport unintentional injuries, and describing age- and sex-specific SCI patterns in 2021. Methods: Using data from the Global Burden of Diseases (GBD) 2021 study, we conducted a population-based trend analysis for Saudi Arabia from 1990 to 2021, stratified by age, sex, and injury cause. Outcomes included age-standardized incidence, prevalence, and YLD rates per 100,000 population, along with percentage changes, average annual percentage changes, and rate ratios with 95% uncertainty intervals (UIs). Results: Between 1990 and 2021, age-standardized SCI showed a point estimate increase in incidence (25.0%; 95% UI: −28.3 to 116.8) and prevalence (24.3%; 95% UI: 0.8 to 53.4), while YLDs showed a modest rise (1.4%; 95% UI: −44.5 to 83.9). Males experienced greater increases in incidence (31.9%) and prevalence (32.3%) than females. Non-transport unintentional injuries surpassed transport-related causes, accounting for nearly 75% of SCI-related YLDs in 2021. The highest burden occurred among young adult males (highest incidence) and older adults (peak prevalence). Conclusion: The burden of SCI in Saudi Arabia has increased over the past three decades, with a shift toward non-transport unintentional injuries. Because wide uncertainty intervals limit definitive conclusions on trend direction, strengthening injury prevention, rehabilitation, and surveillance programs is crucial to mitigate this growing burden. Full article

(This article belongs to the Special Issue State of the Art in Spinal Cord Injuries: Clinical Rehabilitation and Management)

15 pages, 3379 KB

Open AccessReview

The Role of Endoscopic Sinus Surgery in Children with Cystic Fibrosis

by Francesca Galluzzi, Werner Garavello, Gianluca Dalfino, Francesca De Bernardi, Paolo Castelnuovo and Mario Turri-Zanoni

J. Clin. Med. 2025, 14(24), 8835; https://doi.org/10.3390/jcm14248835 (registering DOI) - 13 Dec 2025

Abstract

Objectives: The aim of this study was to assess the role of functional endoscopic sinus surgery (FESS) in the treatment of chronic rhinosinusitis (CRS) in children with cystic fibrosis (CF). Methods: We performed a comprehensive review of the literature by searching PubMed/MEDLINE. Results: [...] Read more.

Objectives: The aim of this study was to assess the role of functional endoscopic sinus surgery (FESS) in the treatment of chronic rhinosinusitis (CRS) in children with cystic fibrosis (CF). Methods: We performed a comprehensive review of the literature by searching PubMed/MEDLINE. Results: CRS affects most children with CF. Though subjective symptoms are variable, radiological and endoscopic examination demonstrated typical objective findings. FESS is recommended for children with significant nasal symptoms that do not respond to medical treatment. At present, there are no uniform criteria for timing and extension of surgery. Primary surgery includes nasal polypectomy and correction of any bone anatomical variants that reduce ventilation of paranasal sinuses predisposing to recurrent sinusitis and complications. In case of recurrences, revision surgery supports a more expanded surgical approach. Moreover, FESS can relieve symptoms, improve patients’ quality of life, manage complications, ameliorate the delivery of medical therapy, and reduce sinonasal and lung superinfections. Conclusions: FESS has emerged as a safe and effective procedure for the treatment of CRS in children with CF. Since children with CF and CRS are difficult-to-treat patients, a multidisciplinary approach in tertiary-care referral centers is required. Full article

(This article belongs to the Section Otolaryngology)

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11 pages, 468 KB

Open AccessArticle

A Prophylactic Noninvasive Ventilation Reduces Complications Following Minimally Invasive Coronary Surgery

by Janusz Konstanty-Kalandyk, Anna Kędziora, Dominika Batycka-Stachnik, Piotr Śliwiński, Przemysław Ptak, Dorota Sobczyk and Jacek Piątek

J. Clin. Med. 2025, 14(24), 8834; https://doi.org/10.3390/jcm14248834 (registering DOI) - 13 Dec 2025

Abstract

Objective: Postoperative pulmonary complications (PPCs) remain a significant source of morbidity and mortality in patients undergoing minimally invasive cardiothoracic procedures. Noninvasive ventilation (NIV) is frequently employed as adjunctive therapy to manage respiratory insufficiency. This study evaluated the implementation of prophylactic NIV immediately following [...] Read more.

Objective: Postoperative pulmonary complications (PPCs) remain a significant source of morbidity and mortality in patients undergoing minimally invasive cardiothoracic procedures. Noninvasive ventilation (NIV) is frequently employed as adjunctive therapy to manage respiratory insufficiency. This study evaluated the implementation of prophylactic NIV immediately following extubation after minimally invasive direct coronary artery bypass (MIDCAB) surgery. Methods: A total of 454 consecutive patients undergoing MIDCAB were included. In total, 139 patients received prophylactic NIV (P-NIV)—postoperative management, 315 patients formed a historical control group treated according to the previous standard of care. Clinical outcomes assessed postoperative pulmonary complications, in-hospital mortality, and one-year survival. Results: The incidence of PPCs was significantly lower in the P-NIV group compared with the control cohort (6.5% vs. 14.9%; p = 0.012). Unadjusted analyses demonstrated a significant reduction in the odds of PPCs with P-NIV (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.17–0.85). Using inverse probability of treatment weighting, prophylactic NIV was associated with an absolute reduction of 8.0 percentage points in PPC risk across the entire cohort (average treatment effect [ATE], −0.080; 95% CI, −0.136 to −0.024; z = −2.80; p = 0.005). Kaplan–Meier analysis demonstrated significantly improved one-year survival in the P-NIV group (log-rank p = 0.047). Conclusions: The implementation of prophylactic NIV following MIDCAB was associated with a greater than 50% reduction in the odds of PPCs in both unadjusted and adjusted analyses and improved one-year survival. These results support the adoption of routine prophylactic NIV in the postoperative management of patients undergoing minimally invasive coronary surgery. Full article

(This article belongs to the Special Issue State-of-the-Art in Cardiac Surgery: Progress, Challenges and Opportunities)

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19 pages, 1046 KB

Open AccessReview

Ovarian Neuroendocrine Neoplasms: Challenges and Future Perspectives

by Valentina Di Vito, Gabriele Veroi, Laura Rizza, Francesca Rota, Andrea Baiocchini, Maria Cristina Macciomei, Carla Lubrano, Anna La Salvia, Andrea Lania, Lucia Rosalba Grillo, Silvia Migliaccio, Guido Rindi and Roberto Baldelli

J. Clin. Med. 2025, 14(24), 8833; https://doi.org/10.3390/jcm14248833 (registering DOI) - 13 Dec 2025

Abstract

Background: Ovarian neuroendocrine neoplasms (O-NENs) are extremely rare, representing less than 1% of all ovarian neoplasms and under 5% of all neuroendocrine tumors (NETs). They encompass two primary histological subtypes: well-differentiated carcinoids and poorly differentiated neuroendocrine carcinomas, which display distinct biological behaviors [...] Read more.

Background: Ovarian neuroendocrine neoplasms (O-NENs) are extremely rare, representing less than 1% of all ovarian neoplasms and under 5% of all neuroendocrine tumors (NETs). They encompass two primary histological subtypes: well-differentiated carcinoids and poorly differentiated neuroendocrine carcinomas, which display distinct biological behaviors and prognoses. The ovary can also be a site of metastasis from extra-ovarian NETs. Owing to their rarity, clinical management lacks standardization, and diagnosis is often incidental following surgery for presumed epithelial ovarian neoplasms. Objectives: This review aims to provide an updated synthesis of current evidence on the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment strategies, and prognosis of O-NENs, highlighting unmet clinical needs. Methods: A literature search was performed on PubMed for the years 2014–2024 using the keywords: “ovarian neuroendocrine tumor”, “ovarian neuroendocrine neoplasm”, “ovarian neuroendocrine carcinoma”, and “ovarian carcinoid”. Only articles published in English were considered. Given the rarity of the disease, in addition to meta-analyses and systematic reviews, relevant case reports and case series were also included to provide a comprehensive clinical picture, yielding 32 eligible articles. Results: Evidence indicates that O-NENs remain understudied, with most data derived from case reports and small series. Clinical presentations vary from asymptomatic masses to hormone-related syndromes, often mimicking other ovarian pathologies. Diagnostic work-up typically follows the same protocol as epithelial ovarian cancer, with the neuroendocrine nature only recognized postoperatively. Treatment strategies are empirical and largely extrapolated from extra-ovarian NETs due to the absence of specific guidelines. Prognosis varies widely depending on histotype, stage, and secretory activity. Conclusions: O-NENs pose significant diagnostic and therapeutic challenges due to their rarity and heterogeneity. Greater clinical awareness, multidisciplinary management, and multicenter research are essential to establish evidence-based protocols and improve patient outcomes. Full article

(This article belongs to the Section Oncology)

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15 pages, 1251 KB

Open AccessArticle

Multicentre Trial Evaluating the Safety and Tolerability of Estetrol-Drospirenone Combined Oral Contraceptive in Postmenarchal Female Adolescents

by Angelica Lindén Hirschberg, Lali Pkhaladze, Kristina Gemzell-Danielsson, Kai Haldre, Kateryna Ruban, Nina Flerin, Guillaume Chatel and Dan Apter

J. Clin. Med. 2025, 14(24), 8832; https://doi.org/10.3390/jcm14248832 (registering DOI) - 13 Dec 2025

Abstract

Objectives: This study aims to evaluate the safety and tolerability of estetrol/drospirenone in adolescents. Methods: In this Phase 3 open-label study, postmenarchal adolescents (12–17 years) received estetrol (E4)/drospirenone (DRSP) 15 mg/3 mg orally for six cycles (24 active/4 placebo regimen). Safety [...] Read more.

Objectives: This study aims to evaluate the safety and tolerability of estetrol/drospirenone in adolescents. Methods: In this Phase 3 open-label study, postmenarchal adolescents (12–17 years) received estetrol (E4)/drospirenone (DRSP) 15 mg/3 mg orally for six cycles (24 active/4 placebo regimen). Safety was evaluated through adverse event (AE) reporting. Participants also recorded daily pill intake, bleeding/spotting, dysmenorrhea, and pain medication use in e-diaries. Descriptive statistics were used. Results: Of 112 enrolled participants, 105 received treatment (mean age: 15.2 years), and 84.8% were completers. No serious treatment-related AEs or safety concerns were observed. Nausea and dysmenorrhea (each 1.9%) were the most common treatment-related AEs. Over 71% of participants took all tablets in each cycle. The percentage of participants with unscheduled bleeding and/or spotting decreased from 45.8% (Cycle 1) to 14.5% (Cycle 5), and the number of days with unscheduled bleeding and/or spotting decreased from nine to six days per cycle. The scheduled bleeding and/or spotting rate ranged between 77.4% and 90.5%, with a duration decreasing from six to four days in Cycle 1 to Cycle 5. Absence of scheduled bleeding increased from 9.5% in Cycle 3 to 22.6% in Cycle 5. The proportion of participants reporting dysmenorrhea decreased by 34.8%, with a median visual analogue scale score dropping from 5.0 at baseline to 3.7 at Cycle 6. Pain medication use decreased from 63.9% to 31.6% in Cycle 6. Conclusions: The use of E4/DRSP in adolescents raised no safety concerns, was well tolerated, resulted in a clear and stable cyclic bleeding pattern, and reduced pain associated with dysmenorrhea. Full article

(This article belongs to the Collection Pediatric and Adolescent Gynecology)

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12 pages, 531 KB

Open AccessBrief Report

Combination Treatment of Persistent SARS-CoV-2 Infection with Dual Antiviral Therapy and Intravenous Immunoglobulin: A Novel Approach

by Myrto Blizou, Stefanos Lampadakis, Emmanouil Karofylakis, Andromachi Blizou, Konstantinos Thomas, Spyridon Prountzos, Vasileios Papavasileiou, Thomas Raptakis, Effrosyni D. Manali, Spyros A. Papiris, Stelios Loukides and Elvira-Markela Antonogiannaki

J. Clin. Med. 2025, 14(24), 8831; https://doi.org/10.3390/jcm14248831 (registering DOI) - 13 Dec 2025

Abstract

Background: Immunocompromised patients, particularly those with humoral immune deficiencies or receiving B-cell-targeted therapies, are at increased risk of persistent SARS-CoV-2 infection, a condition often underrecognized and lacking standardized treatment. Methods: We present a case series of patients with persistent SARS-CoV-2 infection and underlying [...] Read more.

Background: Immunocompromised patients, particularly those with humoral immune deficiencies or receiving B-cell-targeted therapies, are at increased risk of persistent SARS-CoV-2 infection, a condition often underrecognized and lacking standardized treatment. Methods: We present a case series of patients with persistent SARS-CoV-2 infection and underlying humoral immunodeficiency, treated at the General University Hospital “Attikon” from February 2023 to September 2024. Persistent infection was defined by prolonged symptoms, compatible imaging findings, and RT-PCR positivity beyond 21 days. All patients received combination antiviral therapy with remdesivir and nirmatrelvir/ritonavir, and intravenous immunoglobulin (IVIG), using a structured diagnostic and therapeutic algorithm. Results: Eleven patients (55% male), median age 56 [IQR 50–66] years, were included. Seven (64%) had hematologic malignancy, 10 (91%) received anti-CD20 therapy, and 6 (55%) had both. Median symptom duration before diagnosis was 63 [58–135] days. Ten (91%) experienced recurrent symptoms; one (9%) had progressive symptoms with severe respiratory failure requiring high-flow nasal cannula. Persistent infection was confirmed via bronchoscopy with bronchoalveolar lavage in 6 patients (55%). Prior to diagnosis, 5 patients (45%) required one hospitalization, 1 (9%) was hospitalized twice, and 2 (18%) had more than two hospitalizations. Following combination therapy, 10 (91%) achieved complete response at 180-day follow-up. Conclusions: The proposed diagnostic and therapeutic algorithm combining remdesivir, nirmatrelvir/ritonavir, and IVIG enhanced diagnostic value and therapeutic outcomes in this high-risk population. Full article

(This article belongs to the Collection Coronavirus Disease 2019: Clinical Presentation, Pathogenesis and Treatment)

13 pages, 385 KB

Open AccessArticle

Immediate Loading of Implants Placed Immediately in Fresh Sockets: A 10-Year Single-Arm Prospective Case Series Follow-Up

by Eugenio Velasco-Ortega, Ivan Ortiz-Garcia, Loreto Monsalve-Guil, José López-López, Enrique Núñez-Márquez, Nuno Matos-Garrido, José Luis Rondón-Romero, Álvaro Jiménez-Guerra and Jesús Moreno-Muñoz

J. Clin. Med. 2025, 14(24), 8830; https://doi.org/10.3390/jcm14248830 (registering DOI) - 13 Dec 2025

Abstract

Implant dentistry is an important treatment option for patients requiring prosthetic rehabilitation after tooth loss. This study reports the evaluation of immediately loaded, immediately placed implants in fresh extraction sockets. Methods. Fifty-two partially edentulous patients (27 females and 25 males with mean [...] Read more.

Implant dentistry is an important treatment option for patients requiring prosthetic rehabilitation after tooth loss. This study reports the evaluation of immediately loaded, immediately placed implants in fresh extraction sockets. Methods. Fifty-two partially edentulous patients (27 females and 25 males with mean age of 53.6 years), were treated with 112 Galimplant ^® implants placed immediately into fresh sockets for prosthodontic rehabilitation. All implants were loaded immediately. Clinical and radiographic parameters related to both the implants and the prosthodontic restorations were followed for 10 years. Results. Nine patients (17.3%) had a history of periodontitis, 26.9% were smokers, and 21.1% presented with chronic systemic conditions. The outcomes demonstrated an implant survival and success rate of 97.1%, indicating that immediately placed implants with immediate loading can achieve and maintain successful osseointegration. Three implants were lost during the healing period. The mean marginal bone loss was 1.09 ± 0.75 mm. Mucositis affected 21.4% of implants, and peri-implantitis was observed in 11.6% of implants. Fourteen implants (7.1%) were associated with technical complications, including screw loosening and ceramic chipping. Conclusions. The clinical findings of this study indicate favorable long-term outcomes for immediately loaded implants placed in fresh extraction sockets. Both implants and prosthetic restorations demonstrated a success rate of over 92.9% during the observation period. Full article

(This article belongs to the Special Issue Clinical Updates on Prosthodontics)

13 pages, 330 KB

Open AccessArticle

Prognostic Role of Lesion Morphology in Patellar Osteochondral Fixation: Influence of Localization and Size on Functional and Pain Outcomes

by Yunus Emre Bulum, Abdullah Burak Kara, Muhammed Enes Karataş, Mehmet Mete Oruç, Abdullah Demirtaş and Oğuz Şükrü Poyanlı

J. Clin. Med. 2025, 14(24), 8829; https://doi.org/10.3390/jcm14248829 (registering DOI) - 13 Dec 2025

Abstract

Background/Objectives: Osteochondral lesions are common after acute patellar dislocation, particularly in young, active individuals. Although fixation of osteochondral fragments is a preferred treatment to restore joint congruence and prevent cartilage degeneration, the prognostic effect of lesion localization and size on postoperative outcomes [...] Read more.

Background/Objectives: Osteochondral lesions are common after acute patellar dislocation, particularly in young, active individuals. Although fixation of osteochondral fragments is a preferred treatment to restore joint congruence and prevent cartilage degeneration, the prognostic effect of lesion localization and size on postoperative outcomes remains unclear. Methods: This retrospective clinical study included 75 patients (mean age 23.8 ± 6.1 years) who underwent osteochondral fixation after patellar dislocation between 2018 and 2024. Lesions were classified by location—medial patellar facet, lateral facet, trochlear groove/lateral femoral condyle, or multiple regions—and measured on preoperative MRI for size and depth. Functional outcomes were assessed using Kujala, Lysholm, Tegner, and VAS pain scores preoperatively and 12 months postoperatively. Associations between lesion characteristics and postoperative results were analyzed using t-tests, ANOVA, and Pearson correlation. Results: Lesions were most frequently located on the medial patellar facet (42.7%), followed by the trochlear groove/lateral femoral condyle (34.7%). Larger and deeper lesions were more common in trochlear or multiple-site involvement (p = 0.002 and p = 0.031, respectively). At final follow-up, all functional scores improved significantly (Kujala: 62.4 ± 11.3 to 86.7 ± 9.1; Lysholm: 64.1 ± 12.0 to 88.2 ± 8.3; VAS: 6.2 ± 1.3 to 2.1 ± 1.1; all p < 0.001). Patients with smaller lesions (<100 mm²) and medial facet involvement achieved higher Kujala scores (p = 0.020) and lower postoperative pain (p = 0.001). The overall return-to-sport rate was 78.7%, and postoperative complications occurred in 10.7% of cases, mainly recurrent dislocation or implant irritation. Conclusions: Lesion localization and size significantly affect postoperative outcomes after osteochondral fixation for patellar dislocation. Medial facet and smaller lesions are associated with better pain relief and functional recovery, whereas large or trochlear lesions carry a less favorable prognosis. Morphological assessment of lesion characteristics should therefore guide surgical planning, fixation strategy, and postoperative rehabilitation to optimize clinical outcomes. Full article

(This article belongs to the Section Orthopedics)

27 pages, 1606 KB

Open AccessReview

Non-Surgical Correction of Facial Asymmetry: A Narrative Review of Non-Surgical Modalities and Clinical Case Examples

by Clara Lee, Sumin Chae, Han-Jin Kwon, Wonwoo Jeong, Kyung Kwan Lee and Minsuk Chae

J. Clin. Med. 2025, 14(24), 8828; https://doi.org/10.3390/jcm14248828 (registering DOI) - 13 Dec 2025

Abstract

Facial asymmetry significantly affects aesthetic appearance, essential functions such as mastication and speech, and psychological well-being. While traditional surgical interventions effectively address significant facial asymmetry, they are often associated with considerable morbidity, prolonged recovery periods, and potential complications. Consequently, interest in minimally invasive, [...] Read more.

Facial asymmetry significantly affects aesthetic appearance, essential functions such as mastication and speech, and psychological well-being. While traditional surgical interventions effectively address significant facial asymmetry, they are often associated with considerable morbidity, prolonged recovery periods, and potential complications. Consequently, interest in minimally invasive, non-surgical techniques has substantially increased, driven by advantages including reduced downtime, rapid recovery, and immediate aesthetic results. This narrative review critically evaluates contemporary non-surgical techniques for correcting facial asymmetry, focusing specifically on dermal fillers, collagen stimulators (polydioxanone powder), polydioxanone thread lifting, energy-based non-invasive devices (radiofrequency, ultrasound, and laser therapies), and extracorporeal shockwave therapy. The review is based on a structured literature search of PubMed/MEDLINE, Embase, and Google Scholar up to October 2025, focusing on human clinical studies and review articles on non-surgical correction of facial asymmetry and related facial contouring. We provide a detailed analysis of each treatment modality’s underlying mechanisms, clinical efficacy, advantages, limitations, and safety profiles. Current evidence suggests that these non-surgical methods effectively enhance facial symmetry by offering immediate visible improvements and progressive enhancements through natural collagen regeneration, thereby significantly improving patient satisfaction and overall quality of life. Clinicians are encouraged to incorporate these versatile, minimally invasive interventions into clinical practice, carefully tailoring treatments according to individual patient characteristics and specific aesthetic goals. Further research should aim to refine existing treatment protocols, evaluate long-term efficacy and safety, and establish standardized guidelines to optimize outcomes in facial asymmetry correction. Full article

(This article belongs to the Special Issue Facial Plastic and Cosmetic Medicine)

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22 pages, 2533 KB

Open AccessArticle

A Double-Blind Randomized Active-Controlled Trial Evaluating the Short-Term Efficacy of a Single Intramuscular Injection of a Fixed-Dose Combination Product Containing Diclofenac and Thiocolchicoside in Patients with Acute Moderate to Severe Low Back Pain

by Ioannis Oikonomou, Maria Panagiotopoulou, Nikolaos Christopoulos, Eleni Loukeri, Georgios Christodoulakis, Georgios Kountis, Stamatios A. Papadakis, Ioannis Chiotis, Athanasios Georgokostas, Nikolaos Garantziotis, Christos Loukas, Dimitrios Pallis, Petros Nikolakakos and Yiannis C. Bassiakos

J. Clin. Med. 2025, 14(24), 8827; https://doi.org/10.3390/jcm14248827 (registering DOI) - 13 Dec 2025

Abstract

Background/Objectives: Acute low back pain (LBP) is a prevalent cause of disability worldwide. If often involves both inflammation and reflex muscle spasm, suggesting combined therapy with a non-steroidal anti-inflammatory drug (NSAID) and a muscle relaxant may provide superior relief. This study aimed [...] Read more.

Background/Objectives: Acute low back pain (LBP) is a prevalent cause of disability worldwide. If often involves both inflammation and reflex muscle spasm, suggesting combined therapy with a non-steroidal anti-inflammatory drug (NSAID) and a muscle relaxant may provide superior relief. This study aimed to evaluate the short-term efficacy and safety of a single intramuscular (IM) injection of a fixed-dose combination (FDC) product containing Diclofenac and Thiocolchicoside versus Diclofenac monotherapy in adults with acute LBP. Methods: We conducted a phase III multicenter, randomized, double-blind, parallel-group trial in 140 patients with acute LBP of moderate to severe intensity. Patients were allocated 1:1 to receive either the combination of Diclofenac sodium 75 mg + Thiocolchicoside 4 mg (FDC product, Test Group) or Diclofenac sodium 75 mg alone (Diclofenac monotherapy, Reference Group) via a single IM injection. The primary outcome was the change in patient-reported pain intensity using the Visual Analogue Scale (VAS) from baseline to 3 h post-dose. Key secondary outcomes included pain change at 1 h in the VAS, improvement in lumbar mobility (finger-to-floor distance test, FTF), the proportion of patients achieving >30% pain reduction, and the incidence of adverse events (AEs). Randomization was centralized and both investigators and patients were blinded to the treatment. Results: All 140 randomized patients completed the trial. At 3 h post-injection, the combination therapy produced a significantly greater mean pain reduction than monotherapy (41.52 mm vs. 28.13 mm on the 100 mm VAS; p < 0.0001). Superiority of the combination was already evident at 1 h post-dose (VAS reduction 27.61 mm vs. 20.40 mm; p = 0.0089). Lumbar flexion improved more with the combination at 3 h (mean FTF distance improvement 14.52 cm vs. 7.94 cm; p < 0.0001) and at 1 h (9.21 cm vs. 4.62 cm; p < 0.0001). A higher proportion of patients achieved >30% pain relief with the combination (45.7% vs. 27.2% at 3 h, p < 0.0001; 31.4% vs. 18.6% at 1 h, p = 0.0066). Only one mild, transient adverse event (headache) was reported in the combination group (1.4% of patients) and none in the diclofenac-only group. No serious AEs occurred. Conclusions: A single intramuscular dose of diclofenac plus thiocolchicoside provided faster, greater relief of acute LBP than diclofenac alone, without compromising safety. The combination therapy significantly reduced pain and muscle spasm-related mobility limitations within 1–3 h and was well tolerated. These results support the combined use of an NSAID and muscle relaxant as an effective and safe option for acute moderate-to-severe LBP management. Full article

(This article belongs to the Special Issue Low Back Pain: Clinical Treatment and Management)

15 pages, 356 KB

Open AccessArticle

Clinical and Prognostic Differences Between Mechanical Versus Biological Prosthetic Infective Endocarditis—A Nationwide Database Study

by Juan Esteban de Villarreal-Soto, Jorge Calderón Parra, Patricia Muñoz García, Gregorio Cuerpo Caballero, Marina Machado Vílchez, Maria Ángeles Rodríguez-Esteban, Raquel Rodriguez-Garcia, Valentín Tascon-Quevedo, Ane Josune Goikoetxea-Agirre, Eduard Quintana Obrador, Miguel Angel Goenaga-Sanchez, Elisa Garcia-Vazquez, Rafael Hernandez-Estefania, Antonio Ramos Martínez and Carlos Esteban Martin-López

J. Clin. Med. 2025, 14(24), 8826; https://doi.org/10.3390/jcm14248826 (registering DOI) - 13 Dec 2025

Abstract

Objectives: Infective endocarditis (IE) is a feared and life-threatening complication, requiring a multidisciplinary approach. Prosthetic valve endocarditis (PVE) accounts for 20–30% of IE, is one of the most severe forms of IE, and is associated with high morbidity and mortality. We aim [...] Read more.

Objectives: Infective endocarditis (IE) is a feared and life-threatening complication, requiring a multidisciplinary approach. Prosthetic valve endocarditis (PVE) accounts for 20–30% of IE, is one of the most severe forms of IE, and is associated with high morbidity and mortality. We aim to compare and analyze baseline characteristics, microbiology, clinical presentation, complications, and prognosis between biological and mechanical PVE; we also carried out a subgroup analysis of patients aged 45–65 at the time of onset of prosthetic surgery. Methods: The present study is a post hoc analysis of a prospective multicenter cohort of patients with PVE between January 2008 and December 2023. Patients were divided into two groups regarding the type of prosthesis, mechanical vs. biological. Results: A total of 1544 patients were included. 733 (47.47%) patients with mechanical PVE (mPVE) and 811 (52.52) with biological PVE (bPVE). We found that bPVE appeared earlier than mPVE, had more healthcare-related infections and paravalvular complications. Both groups had similar clinical presentations; moreover, there was no difference in surgical indication and if surgery was performed. On the other hand, mPVE has a higher incidence of Staphylococcus aureus (SA) and Gram-negative bacteria, while bPVE has more coagulase-negative staphylococci. Multivariable logistic regression identified the following independent risk factors of mortality: EuroSCORE I, age, mPVE, SA, IE comprising two valves, and severe sepsis. mPVE had a higher mortality on admission, probably due to a higher incidence of septic shock and CNS embolism. The subgroup analysis of patients between 45 and 65 years at the time of prosthesis implantation showed similar results. Conclusions: The present analysis shows that bPVE appears earlier than mPVE, even in the subgroup of patients aged 45–65. bPVE has more healthcare-related infections and more paravalvular complications. After adjusting for baseline differences, mPVE had higher in-hospital mortality. Full article

(This article belongs to the Section Cardiology)

21 pages, 9141 KB

Open AccessArticle

AI vs. MD: Benchmarking ChatGPT and Gemini for Complex Wound Management

by Luca Corradini, Gianluca Marcaccini, Ishith Seth, Warren M. Rozen, Camilla Biagiotti, Roberto Cuomo and Francesco Ruben Giardino

J. Clin. Med. 2025, 14(24), 8825; https://doi.org/10.3390/jcm14248825 (registering DOI) - 13 Dec 2025

Abstract

Background: The management of hard-to-heal wounds poses a major clinical challenge due to heterogeneous etiology and significant global healthcare costs (estimated at USD 148.64 billion in 2022). Large Language Models (LLMs), such as ChatGPT and Gemini, are emerging as potential decision-support tools. This [...] Read more.

Background: The management of hard-to-heal wounds poses a major clinical challenge due to heterogeneous etiology and significant global healthcare costs (estimated at USD 148.64 billion in 2022). Large Language Models (LLMs), such as ChatGPT and Gemini, are emerging as potential decision-support tools. This study aimed to rigorously assess the accuracy and reliability of ChatGPT and Gemini in the visual description and initial therapeutic management of complex wounds based solely on clinical images. Methods: Twenty clinical images of complex wounds from diverse etiologies were independently analyzed by ChatGPT (version dated 15 October 2025) and Gemini (version dated 15 October 2025). The models were queried using two standardized, concise prompts. The AI responses were compared against a clinical gold standard established by the unanimous consensus of an expert panel of three plastic surgeons. Results: Statistical analysis showed no significant difference in overall performance between the two models and the expert consensus. Gemini achieved a slightly higher percentage of perfect agreement in management recommendations (75.0% vs. 60.0% for ChatGPT). Both LLMs demonstrated high proficiency in identifying the etiology of vascular lesions and recognizing critical “red flags,” such as signs of ischemia requiring urgent vascular assessment. Noted divergences included Gemini’s greater suspicion of potential neoplastic etiology and the models’ shared error in suggesting Negative Pressure Wound Therapy (NPWT) in a case potentially contraindicated by severe infection. Conclusions: LLMs, particularly ChatGPT and Gemini, demonstrate significant potential as decision-support systems and educational tools in wound care, offering rapid diagnosis and standardized initial management, especially in non-specialist settings. Instances of divergence in systemic treatments or in atypical presentations highlight the limitations of relying on image-based reasoning alone. Ultimately, LLMs serve as powerful, scalable assets that, under professional supervision, can enhance diagnostic speed and improve care pathways. Full article

(This article belongs to the Special Issue Integrating Artificial Intelligence into Plastic, Reconstructive, and Aesthetic Surgery: Innovations, Challenges, and Clinical Application)

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16 pages, 1776 KB

Open AccessReview

Artificial Intelligence and the Future of Cardiac Implantable Electronic Devices: Diagnostics, Monitoring, and Therapy

by Ibrahim Antoun, Alkassem Alkhayer, Ahmed Abdelrazik, Mahmoud Eldesouky, Kaung Myat Thu, Harshil Dhutia, Riyaz Somani and G. André Ng

J. Clin. Med. 2025, 14(24), 8824; https://doi.org/10.3390/jcm14248824 (registering DOI) - 13 Dec 2025

Abstract

Cardiac implantable electronic devices (CIEDs) such as pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronisation therapy (CRT) devices are generating unprecedented volumes of data in both inpatient and remote settings. Artificial intelligence (AI) techniques are increasingly being applied to enhance the management of these [...] Read more.

Cardiac implantable electronic devices (CIEDs) such as pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronisation therapy (CRT) devices are generating unprecedented volumes of data in both inpatient and remote settings. Artificial intelligence (AI) techniques are increasingly being applied to enhance the management of these devices and the patients who rely on them. Recent advances demonstrate that machine learning (ML) and deep learning (DL) can improve diagnostic capabilities (for example, by detecting arrhythmias and predicting clinical events), streamline remote monitoring workflows, and optimise device-based therapies. Key applications include AI-driven algorithms that accurately detect true arrhythmias while filtering out false alerts from pacemakers and implantable monitors, neural network models that predict ventricular arrhythmias weeks before ICD shocks, and personalised models that forecast which heart failure patients will respond to CRT. Moreover, novel approaches such as natural language processing (NLP) and reinforcement learning are being explored to integrate diverse data sources and to enable devices to self-adjust their programming. This narrative review summarises the major applications of AI in the CIED domain—diagnostics, remote monitoring, and therapy optimisation—with an emphasis on the recent literature over the past five years. The review highlights important studies and randomised trials in each area, discusses the variety of AI techniques employed, and outlines future directions and challenges (including data standardisation, validation in clinical trials, and regulatory considerations) for translating these innovations into routine clinical care. Full article

(This article belongs to the Special Issue Application of Artificial Intelligence in Cardiology)

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13 pages, 233 KB

Open AccessArticle

Sex Differences in Continuous Glucose Monitoring Metrics and Glucose Variability in Subjects with Type 1 Diabetes Treated with Advanced Hybrid Closed Loop Therapy: An Observational, Retrospective, One-Year Follow-Up Study

by Matteo Conti, Ilaria Gironi, Elena Meneghini, Elena Mion, Giacoma Di Vieste, Federico Bertuzzi and Basilio Pintaudi

J. Clin. Med. 2025, 14(24), 8823; https://doi.org/10.3390/jcm14248823 (registering DOI) - 13 Dec 2025

Abstract

Background: Advanced hybrid closed-loop (aHCL) systems have improved glycemic control in individuals with type 1 diabetes (T1DM). However, it remains unclear whether their efficacy and safety differ by patient’s sex, in view of known sex-related physiological and behavioral differences in disease control [...] Read more.

Background: Advanced hybrid closed-loop (aHCL) systems have improved glycemic control in individuals with type 1 diabetes (T1DM). However, it remains unclear whether their efficacy and safety differ by patient’s sex, in view of known sex-related physiological and behavioral differences in disease control and management. Methods: This retrospective, single-center study included 176 adults with T1DM starting aHCL therapy with Medtronic MiniMed™ 780G. Continuous glucose monitoring (CGM) metrics, glycated hemoglobin (HbA1c), and glycemic variability (GV) indexes were collected at baseline, 6 months, and 12 months after starting aHCL therapy. Only patients with at least 70% sensor usage were included at each time point. The primary outcome was the assessment of sex-related differences in CGM metrics at 12 months. Secondary outcomes included changes in HbA1c and GV indexes by sex and over time. Results: TIR increased significantly at 6 (+6.6%, p < 0.001) and 12 months (+5.4%, p < 0.001), TAR decreased, and TBR remained stable. HbA1c was significantly reduced at both 6 and 12 months (−0.6%, p < 0.001). Improvements were consistent in both males and females, with females exhibiting better improvement in HbA1c compared to males (−0.4%, p = 0.049). No significant sex differences were found in CGM metrics at 12 months. GV indexes improved significantly in both groups, regardless of sex. At the multivariable analysis, only HbA1c <7.0% at baseline was associated with the achievement of the composite outcome (TIR > 70%, TBR < 4%, HbA1c < 7.0%). Conclusions: aHCL therapy improved glycemic control and GV in adults with T1DM, regardless of the patient’s sex. These results support the generalizability of aHCL therapy and underscore the need to ensure equitable access to technologies rather than sex-specific adjustments. Full article

(This article belongs to the Section Immunology & Rheumatology)

9 pages, 607 KB

Open AccessBrief Report

Enhanced Benefits of Prone Positioning Combined with Lung Recruitment Maneuver in Patients with COVID-19 and Non-COVID-19 ARDS: A Secondary Analysis of a Randomized Clinical Trial

by Lan Lan, Yuenan Ni, Yubei Zhou, Ping Li, Faping Wang and Fengming Luo

J. Clin. Med. 2025, 14(24), 8822; https://doi.org/10.3390/jcm14248822 (registering DOI) - 13 Dec 2025

Abstract

Background: Early reports highlighted unique features of COVID-19-associated ARDS. The combination of prone position (PP) and positive end-expiratory pressure (PEEP)-induced lung recruitment maneuver (LRM) has demonstrated efficacy in enhancing oxygenation and improving outcomes in patients with ARDS, but it remains unknown whether there [...] Read more.

Background: Early reports highlighted unique features of COVID-19-associated ARDS. The combination of prone position (PP) and positive end-expiratory pressure (PEEP)-induced lung recruitment maneuver (LRM) has demonstrated efficacy in enhancing oxygenation and improving outcomes in patients with ARDS, but it remains unknown whether there is a difference between COVID-19 ARDS and non-COVID-19 ARDS. Method: This study is a secondary analysis of a previously conducted randomized controlled trial. Patients with moderate to severe ARDS were consecutively enrolled during the study period (June–December 2023). After initiation of PP, patients received a PEEP-induced LRM followed by 12 h of daily PP. The interventions were repeated at least three times over the subsequent 3 days. Clinical outcomes, respiratory mechanics, and electrical impedance tomography (EIT) results were evaluated. Results: Twenty-eight patients were included in the final analysis, half of whom were infected with COVID-19 (50%). The PEEP-induced LRM led to greater improvement in oxygenation among COVID-19 ARDS than non-COVID-19 ARDS (∆PaO₂/FiO₂ ratio 90.5 mmHg vs. 65.5 mmHg, p < 0.05). Based on EIT measurement, compared with the non-COVID-19 ARDS group, PEEP-induced LRM resulted in a greater increase in ventilation distribution, mainly in the dorsal regions of interest 4 (ROI 4) ventilation distribution (∆ROI4 4.5% vs. 1.0%, p = 0.01) and in dorsal regional ventilation (∆dorsal regional ventilation 10.0% vs. 5.5%, p = 0.04) in the COVID-19 ARDS group. Conclusions: Compared to typical ARDS, PEEP-induced LRM combined with PP may be more effective in enhancing oxygenation in COVID-19-related ARDS. Full article

(This article belongs to the Section Intensive Care)

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