Medicina

13 pages, 657 KB

Open AccessArticle

Risk of Severe Acute Kidney Injury According to the Presence of Nephrotic-Range Proteinuria in Patients with Liver Cirrhosis: A Retrospective Cohort Study (2016–2025)

by Seong Gyu Kim and Sang Gyu Kwak

Medicina 2026, 62(4), 797; https://doi.org/10.3390/medicina62040797 (registering DOI) - 21 Apr 2026

Abstract

Background and Objectives: Acute kidney injury (AKI) is a frequent and life-threatening complication in patients with liver cirrhosis (LC). Nephrotic-range proteinuria may reflect underlying structural renal vulnerability; however, its association with AKI severity in cirrhosis remains unclear. Materials and Methods: We conducted a [...] Read more.

Background and Objectives: Acute kidney injury (AKI) is a frequent and life-threatening complication in patients with liver cirrhosis (LC). Nephrotic-range proteinuria may reflect underlying structural renal vulnerability; however, its association with AKI severity in cirrhosis remains unclear. Materials and Methods: We conducted a retrospective cohort study of 408 adults with LC admitted to a tertiary referral hospital between January 2016 and December 2025. Nephrotic-range proteinuria was defined as a urine protein-to-creatinine ratio (UPCR) ≥3.5 g/g measured within 7 days before or at admission. AKI was staged using serum creatinine-based Kidney Disease: Improving Global Outcomes criteria. Baseline creatinine was defined as the lowest value within 7 days before admission; if unavailable, the lowest stable value within the preceding 3 months was used. Severe AKI was defined as KDIGO stage 2–3. Multivariable logistic regression was performed to evaluate the association between nephrotic-range proteinuria and severe AKI after adjustment for age, sex, diabetes mellitus, hypertension, chronic kidney disease (CKD), sepsis, ICU admission, and Child–Pugh class. Results: Of the 408 patients, 56 (13.7%) had nephrotic-range proteinuria. Severe AKI occurred more frequently in patients with nephrotic-range proteinuria than in those without (39.3% vs. 21.9%), corresponding to an absolute risk difference of 17.4 percentage points (p = 0.008). In the adjusted model, nephrotic-range proteinuria was associated with a higher likelihood of severe AKI (adjusted odds ratio [OR], 2.27; 95% confidence interval [CI], 1.17–4.41; p = 0.015). CKD (adjusted OR, 2.26; 95% CI, 1.33–3.81; p = 0.002), ICU admission (adjusted OR, 2.03; 95% CI, 1.22–3.39; p = 0.007), and Child–Pugh class C versus A (adjusted OR, 3.50; 95% CI, 1.37–8.93; p = 0.009) were also significantly associated with severe AKI. Conclusions: Among hospitalized patients with LC, nephrotic-range proteinuria was associated with a higher likelihood of severe AKI. Quantitative proteinuria assessment may help identify patients at increased risk of advanced renal dysfunction, although causal inference is limited by the retrospective observational design. Full article

(This article belongs to the Section Gastroenterology & Hepatology)

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29 pages, 1027 KB

Open AccessReview

The Impact of Dementia Caregiving on the Health of the Spousal Caregiver

by Donna de Levante Raphael, Lora J. Kasselman, Wendy Drewes, Isabella Wolff, Luke Betlow, Joshua De Leon and Allison B. Reiss

Medicina 2026, 62(4), 796; https://doi.org/10.3390/medicina62040796 (registering DOI) - 21 Apr 2026

Abstract

Dementia caregiving represents a major public health challenge, with spousal caregivers assuming the greatest burden. Spouses, themselves typically older adults, provide high intensity, long-term, and largely unpaid care across all stages of cognitive decline. Despite their central role in dementia care, the health [...] Read more.

Dementia caregiving represents a major public health challenge, with spousal caregivers assuming the greatest burden. Spouses, themselves typically older adults, provide high intensity, long-term, and largely unpaid care across all stages of cognitive decline. Despite their central role in dementia care, the health consequences experienced by spousal caregivers remain insufficiently characterized in the literature and inadequately addressed in clinical and public health practice. This structured narrative review synthesizes current evidence on the multidimensional impact of dementia caregiving on the physical, psychological, cognitive, social, and financial health of spousal caregivers. It further contextualizes these consequences within the trajectory of dementia progression, and identifies interventions, support systems, and policy considerations necessary to mitigate caregiver burden. Spousal caregivers experience disproportionate burden due to continuous, escalating responsibilities that often mirror the progressive deterioration of their partners. Emotional burdens, including uncertainty during pre-diagnostic stages, role strain, conflict, loss of intimacy, and anticipatory grief. Physically, spouses endure musculoskeletal strain, sleep disruption, poor nutrition, and heightened frailty risk. Psychologically, spousal caregivers exhibit elevated rates of depression, anxiety, loneliness, and stress-related disorders. Socially, caregivers experience substantial isolation, stigma, and erosion of social networks. Financial hardship, including early retirement, reduced employment, and uncompensated care hours, further exacerbate stress. Evidence suggests that chronic caregiving stress contributes to biological changes such as immune dysregulation, inflammation, acceleration, aging, and potential cognitive decline in caregivers themselves. Caregiver burden influences patient outcomes as evidenced by increased emergency department use, falls, and earlier institutionalization in persons with dementia whose caregiver is subjected to a high burden. Current care models rarely include routine, caregiver assessment or structured guidance following diagnosis, resulting in substantial unmet needs. Effective mitigation requires integrated, stage-sensitive interventions, including psychosocial support, caregiver education, respite services, culturally tailored programs, and digital health tools, alongside broader policy reforms to reduce financial and structural barriers. Full article

(This article belongs to the Section Neurology)

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11 pages, 467 KB

Open AccessArticle

Predictive Utility of EROA/LVEDV Ratio in Mitraclip Outcomes: Retrospective Multicenter Cohort Study

by Vivek Joseph Varughese, Chandler Richardson, James Pollock, Patryk Czyzewski, Ashley Lyons, Hata Mujadzic, Deborah M. Hurley, Michael Cryer, Sunil V. Rao and Akshay Kumar

Medicina 2026, 62(4), 795; https://doi.org/10.3390/medicina62040795 (registering DOI) - 21 Apr 2026

Abstract

Background: The effective regurgitant orifice area to left ventricular end-diastolic volume (EROA/LVEDV) ratio has been proposed to distinguish proportionate from disproportionate functional mitral regurgitation and to guide patient selection for transcatheter edge-to-edge repair (TEER). Methods: We conducted a multicenter, retrospective cohort [...] Read more.

Background: The effective regurgitant orifice area to left ventricular end-diastolic volume (EROA/LVEDV) ratio has been proposed to distinguish proportionate from disproportionate functional mitral regurgitation and to guide patient selection for transcatheter edge-to-edge repair (TEER). Methods: We conducted a multicenter, retrospective cohort study of 221 patients undergoing TEER with the Mitraclip system. Preprocedural echocardiographic parameters, including EROA, LVEDV, diastolic indices, and chamber volumes, were systematically collected. The primary outcome indicative of symptom worsening was defined as Heart Failure Hospitalizations (HFH) requiring IV diuresis/death in the one year following clip placement. Association of the preprocedural EROA/LVEDV ratio and symptom worsening was assessed using multivariate regression models and ROC-AUC. Results: In the one-year follow-up, 87 patients (39.36%) had symptom worsening. In the multivariate regression analysis, preprocedural EROA/LVEDV ratio was associated with symptom worsening at one year (OR: 0.95 (0.92–0.97, p value < 0.01). In the ROC model, the pre-procedural EROA/LVEDV ratio had an AUC value of 0.74 (0.69–0.83), with a moderate value for predicting symptom worsening at one year. Conclusions: Results of the study proved that a lower pre-procedural EROA/LVEDV ratio had a significant association with symptom worsening, with the ratio proving to have a moderate value for predicting symptom worsening/death at one year. Full article

(This article belongs to the Section Cardiology)

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31 pages, 4715 KB

Open AccessReview

The Overlap Between Crohn’s Disease and Intestinal Tuberculosis: A Never-Ending Story

by Sergiu Marian Cazacu, Costin Teodor Streba, Cristian Constantin, Claudiu Marinel Ionele, Ion Rogoveanu, Alexandru Valentin Popescu and Mirela-Marinela Florescu

Medicina 2026, 62(4), 794; https://doi.org/10.3390/medicina62040794 (registering DOI) - 21 Apr 2026

Abstract

The prevalence of Crohn’s disease has increased over the last few decades, even in developing countries, whereas that of intestinal tuberculosis has decreased, which places both diseases at an epidemiological crossroads. Crohn’s disease and intestinal tuberculosis share many clinical, endoscopic, imaging, and pathological [...] Read more.

The prevalence of Crohn’s disease has increased over the last few decades, even in developing countries, whereas that of intestinal tuberculosis has decreased, which places both diseases at an epidemiological crossroads. Crohn’s disease and intestinal tuberculosis share many clinical, endoscopic, imaging, and pathological features, which sometimes make differential diagnosis very difficult; an accurate diagnosis is, however, very important since an erroneous treatment can worsen the evolution or delay proper therapy. The association between past TB infection and Crohn’s disease can make the diagnosis especially hard. This review summarizes current data on specific features that allow differentiation between Crohn’s disease and intestinal tuberculosis, paying particular attention to the microbiome, clinical signs, endoscopy, cross-sectional imaging, bacteriological, and immunological findings detailed. The importance of computerized models and scores for the differentiation is also detailed, because common features may make the differentiation based on a single criterion difficult. Full article

(This article belongs to the Special Issue New Advances in Inflammatory Bowel Disease and Diarrheal Disorders)

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15 pages, 337 KB

Open AccessArticle

Neoadjuvant Therapy in Locally Advanced Rectal Cancer—What Result Should We Expect?

by Roxana-Elena Stefan, Adrian Constantin, Daniela Dinu, Florin Achim, Alexandru Rotariu, Florin Grama, Horia-Dan Liscu, Lucian Iordache, Dragos-Viorel Scripcariu, Anthony Rasuceanu, Silviu Constantinoiu and Dragos Predescu

Medicina 2026, 62(4), 793; https://doi.org/10.3390/medicina62040793 (registering DOI) - 21 Apr 2026

Abstract

Background and Objectives: Neoadjuvant chemoradiotherapy is a key component of the treatment strategy for locally advanced rectal cancer (LARC), both through its direct impact on oncological prognosis and by increasing the likelihood of sphincter-preserving surgery. Oncological prognosis improves dramatically following a complete [...] Read more.

Background and Objectives: Neoadjuvant chemoradiotherapy is a key component of the treatment strategy for locally advanced rectal cancer (LARC), both through its direct impact on oncological prognosis and by increasing the likelihood of sphincter-preserving surgery. Oncological prognosis improves dramatically following a complete pathological response to neoadjuvant therapy. Identifying predictors of response to neoadjuvant therapy has been a challenge over the past two decades, and these factors have not been fully identified. This study aimed to analyze the clinical, biological, and therapeutic factors associated with tumor response following neoadjuvant therapy in patients with locally advanced rectal cancer, with the aim of identifying independent predictors of the absence of a complete pathological response and optimizing personalized treatment strategies. Materials and Methods: This retrospective study included a cohort of 122 patients (81 men and 41 women), with a mean age of 63.5 years, diagnosed with locally advanced rectal cancer at two centers with expertise in colorectal surgery between January 2018 and December 2023. Patients received neoadjuvant treatment in two regimens: long-course chemoradiotherapy with oral radiosensitizing chemotherapy (82 patients) and total neoadjuvant therapy consisting of chemoradiotherapy followed by consolidation chemotherapy (40 patients). A series of clinical, biological, and therapeutic variables was analyzed for their association with pathological responses. Results: According to the Ryan score, the overall complete response rate following neoadjuvant therapy was 17.2%. pCR was observed more frequently in patients treated with total neoadjuvant therapy than in those treated with standard chemoradiotherapy. Elevated pre-treatment CEA levels were independently associated with a higher risk of unfavorable tumor response. The radiation dose and interval between completion of radiotherapy and surgery were significantly associated with tumor regression. Conclusions: These results underscore the importance of personalizing neoadjuvant therapy to improve cancer prognosis. Furthermore, optimizing tumor regression could lead to the potential expansion of sphincter-preserving resection techniques, which would have a direct and significant impact on the quality of life of these patients. Full article

(This article belongs to the Special Issue Advances in Colorectal Surgery and Oncology)

24 pages, 871 KB

Open AccessSystematic Review

Hemispheric Asymmetries in Bipolar Disorder: A Systematic Review

by Efthymia Nestora, Elena Ioannidou, Panayiotis Patrikelis and Vasiliki Folia

Medicina 2026, 62(4), 792; https://doi.org/10.3390/medicina62040792 - 20 Apr 2026

Abstract

Background and Objectives: The joint study of cerebral asymmetries and bipolar disorder (BD) has long attracted the interest of researchers and clinicians. Nevertheless, despite the increasing awareness of hemispheric asymmetries in BD, the combined investigation of these two constructs constitutes a relatively [...] Read more.

Background and Objectives: The joint study of cerebral asymmetries and bipolar disorder (BD) has long attracted the interest of researchers and clinicians. Nevertheless, despite the increasing awareness of hemispheric asymmetries in BD, the combined investigation of these two constructs constitutes a relatively recent area of inquiry. The main objective of the present systematic review is to systematically examine the existing literature in order to identify, integrate and critically discuss evidence of hemispheric asymmetry in BD patients in terms of brain anatomy, physiology and neuropsychological function. The initial hypotheses support the presence of atypical cerebral asymmetry and differential hemispheric activation as a function of mood states in BD. Materials and Methods: Following the collection and analysis of numerous research papers through several databases and search engines, specific papers were identified and screened according to specified inclusion and exclusion criteria. Research papers on the adult bipolar population were included, while papers including comorbidity with other disorders, lesions, or an underage or elderly population, as well as meta-analyses and reviews, were excluded. This paper aligns with the procedures in the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020) guidelines, and was assessed for risk of bias according to the Cochrane guidelines by the Newcastle–Ottawa Scale (NOS). Results: A total of 56 papers were identified as eligible in this review. Despite inconsistent findings across the included studies, an emerging pattern suggests the presence of atypical hemispheric asymmetry in BD, both in terms of specific brain structures and functional activity. Moreover, several studies associate depressive states with increased activation of the right hemisphere, whereas manic states appear to be linked with increased activation of the left hemisphere. Conclusions: These findings support the aforementioned hypotheses and partly align with the theoretical framework of emotional laterality theories. However, although certain patterns were observed, a comprehensive understanding of functional hemispheric asymmetry in BD has not yet been achieved. The presence of contradictory findings highlights the need for further extensive and systematic research to improve understanding of this topic. Full article

(This article belongs to the Section Psychiatry)

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21 pages, 1185 KB

Open AccessArticle

Perforin and Granulysin-Mediated Cytotoxicity in Colorectal Cancer Patients

by Ludvig Letica, Ivana Šutić Lubina, Zdrinko Brekalo, Đordano Bačić, Jelena Roganović, Ana Đorđević, Ingrid Šutić Udović, Ivona Letica, Ivana Kotri and Ines Mrakovčić-Šutić

Medicina 2026, 62(4), 791; https://doi.org/10.3390/medicina62040791 - 20 Apr 2026

Abstract

Background and Objectives: The incidence of colorectal cancer (CRC) in developed Western countries is constantly growing. CRC represents the third most common cancer and the second leading cancer-related cause of death worldwide. Innate and adaptive immunity play a pivotal role in the tumor [...] Read more.

Background and Objectives: The incidence of colorectal cancer (CRC) in developed Western countries is constantly growing. CRC represents the third most common cancer and the second leading cancer-related cause of death worldwide. Innate and adaptive immunity play a pivotal role in the tumor response, but many of these interactions are still not well understood. Granulysin (GNLY) is an effector, cytolytic molecule, present in human cytotoxic granules of different lymphocyte subpopulations, mainly in cytotoxic T cells and NK cells. Pore-forming proteins GNLY, perforin and granzymes play a key role in cell-mediated immune responses against tumors and infections. Materials and Methods: We aimed to analyze perforin and GNLY-mediated cytotoxicity in the peripheral blood of patients with CRC by flow cytometry. Simultaneously, the cells were labeled with monoclonal antibodies against perforin, GNLY and different surface antigens (CD3, CD4, CD8 and CD56). Phenotypes of lymphocyte subpopulation and expression of perforin and GNLY were analyzed using intracellular and surface immunofluorescence. Results: Total perforin and GNLY expressions in peripheral blood mononuclear cells (PBMC) were significantly lower than in the control group. Statistically significant differences were observed in the distribution of perforin and GNLY expression in different stages of tumors classified according to Dukes’, indicating that the percentage of total perforin and GNLY was significantly diminished in accordance with tumor progression. Perforin and GNLY expression were significantly reduced in NK and NKT cells, accompanied by reduced cytolytic potential in patients with CRC and a consequent reduction in their ability to eliminate tumors and infected cells. Conclusions: The determination of cytotoxic potential may provide a valuable assessment of a patient’s immune status and represent a novel therapeutic target. Patients with CRC exhibit markedly impaired perforin- and GNLY-mediated cytotoxicity that correlates with disease progression. Assessment and restoration of cytolytic potential may therefore serve as indicators of immune competence and promising therapeutic strategies to improve perioperative and oncologic outcomes. Full article

(This article belongs to the Section Oncology)

12 pages, 2148 KB

Open AccessArticle

Imaging-Based Phenotyping in Bicuspid Aortic Valve and Associated Aortopathy: A Retrospective Single-Center Study

by Laurynas Šarkinas, Nomeda Rima Valevičienė, Sigita Glaveckaitė and Darius Palionis

Medicina 2026, 62(4), 790; https://doi.org/10.3390/medicina62040790 - 20 Apr 2026

Abstract

Background and Objectives: Bicuspid aortic valve (BAV) is a common congenital cardiac abnormality frequently associated with aortopathy and progressive aortic dilatation. The 2021 International consensus statement introduced standardized phenotypic definitions for BAV and BAV-associated aortopathy. The aim of this study was to [...] Read more.

Background and Objectives: Bicuspid aortic valve (BAV) is a common congenital cardiac abnormality frequently associated with aortopathy and progressive aortic dilatation. The 2021 International consensus statement introduced standardized phenotypic definitions for BAV and BAV-associated aortopathy. The aim of this study was to determine the distribution of BAV and BAV-associated aortopathy phenotypes according to the 2021 consensus statement and to assess statistical differences between imaging modalities (magnetic resonance imaging (MRI) and transthoracic echocardiography (TTE)) in aortic diameter measurements. Materials and Methods: This single-center retrospective study included 47 patients with BAV between 2014 and 2018. Aortic root and ascending aorta diameters were measured using MRI white-blood and black-blood sequences and TTE. BAV morphology and aortopathy phenotypes were classified according to the 2021 International consensus recommendations, and agreement between modalities was assessed using correlation and Bland–Altman analysis. Results: The study population had a mean age of 30 ± 11.05 years, with a male-to-female ratio of approximately 3.3:1. The fused BAV phenotype was the most prevalent (53.2%), followed by the partial-fusion (38.3%) and two-sinus (8.5%) phenotypes (p < 0.001). Aortopathy phenotypes assessed by MRI and TTE demonstrated similar distribution patterns, with the extended phenotype being the most frequent, followed by ascending and root phenotypes, with no significant difference between modalities (p = 0.74). Strong correlations were observed across all imaging techniques for both ascending aorta and aortic root measurements; however, small but statistically significant differences were identified between selected modality pairs—a mean difference of 1.59 mm between MRI black-blood and TTE ascending aorta diameters and 1.26 mm between MRI white-blood and TTE aortic root diameters. Conclusions: Multimodality imaging demonstrates strong agreement in the assessment of aortic diameters and yields comparable aortopathy phenotype distributions when applying the 2021 International Consensus Classification. Nevertheless, small systematic measurement differences between MRI and TTE may be clinically relevant in patients approaching diagnostic or therapeutic thresholds, highlighting the importance of consistent imaging methodology in longitudinal follow-up of BAV-associated aortopathy. Full article

(This article belongs to the Section Cardiology)

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15 pages, 577 KB

Open AccessArticle

Effects of a Lidocaine-Loaded Alginate/CMC/PEO Electrospun Nanofiber Film on Postoperative Pain and Peritoneal Adhesion in a Rat Model

by Ha-young Kim, Hyo-jin Kim, Geun Joo Choi and Hyun Kang

Medicina 2026, 62(4), 789; https://doi.org/10.3390/medicina62040789 - 20 Apr 2026

Abstract

Background and Objectives: Postoperative pain and intra-abdominal adhesions are common complications following surgery. Pain delays early mobilization, whereas adhesions can lead to bowel obstruction, chronic pain, or infertility. Current treatments, including systemic analgesics and physical barrier methods, are only partially effective. We [...] Read more.

Background and Objectives: Postoperative pain and intra-abdominal adhesions are common complications following surgery. Pain delays early mobilization, whereas adhesions can lead to bowel obstruction, chronic pain, or infertility. Current treatments, including systemic analgesics and physical barrier methods, are only partially effective. We hypothesized that combining these modalities would yield superior outcomes. Accordingly, we investigated whether a lidocaine-loaded alginate–carboxymethyl cellulose–polyethylene oxide (ACPE) electrospun film could more effectively reduce both postoperative pain and adhesion formation than either component alone. Materials and Methods: An electrospun nanofiber film composed of ACPE containing lidocaine was prepared. Its effects were evaluated in rats using an incisional pain and a peritoneal adhesion model. Four groups were compared: saline control, free lidocaine, drug-free ACPE film, and lidocaine-loaded ACPE film. Fifteen rats were allocated to each group. The primary outcome was the mechanical withdrawal threshold (MWT) after plantar incision, while secondary outcomes included histological changes and adhesion scores assessed by the Moreno system. Results: The lidocaine–ACPE film significantly increased MWT compared with all other groups, demonstrating a stronger and longer-lasting analgesic effect than free lidocaine. Adhesion scores were also lowest in the film group. Histological analysis confirmed a reduction in inflammatory cell infiltration and collagen deposition. Conclusions: A lidocaine-loaded ACPE nanofiber film effectively reduced both postoperative pain and adhesion formation in a rodent model. The combination of sustained local drug release and physical barrier function provides a promising strategy to address two major postoperative complications. Further preclinical studies are warranted before clinical application. Full article

(This article belongs to the Special Issue Abdominal Surgery: Innovative Techniques and Challenges)

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15 pages, 1390 KB

Open AccessArticle

Lasso-Enhanced Logistic Regression for Early Prediction of Pulmonary Infection in Critically Ill Post-Abdominal Surgery Patients

by Bin Wang, Jie Zhao and Fengxue Zhu

Medicina 2026, 62(4), 788; https://doi.org/10.3390/medicina62040788 - 20 Apr 2026

Abstract

Background and Objectives: To identify predictors of pulmonary infection in critically ill patients after abdominal surgery and to develop an early postoperative risk stratification model. Materials and Methods: Medical records of ICU patients after abdominal surgery (January 2016–June 2024) with Acute Physiology and [...] Read more.

Background and Objectives: To identify predictors of pulmonary infection in critically ill patients after abdominal surgery and to develop an early postoperative risk stratification model. Materials and Methods: Medical records of ICU patients after abdominal surgery (January 2016–June 2024) with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores ≥10 were retrospectively analyzed. Patients were categorized according to the presence or absence of pulmonary infection. Candidate variables were screened using LASSO regression, followed by multivariate logistic regression to identify independent predictors. A nomogram-based prediction model was constructed and internally validated. Results: Among 4852 patients, 390 (8.0%) developed pulmonary infections. Overall, 8 independent predictors were identified: Male sex (vs. female) (OR 1.509, 95% CI: 1.091–2.087, p = 0.013), chronic obstructive pulmonary disease (OR 4.139, 95% CI: 2.872–5.966, p < 0.001), atrial fibrillation (OR 2.320, 95% CI: 1.366–3.939, p = 0.002), hypertension (OR 1.869, 95% CI: 1.372–2.539, p < 0.001), chronic renal insufficiency (OR 2.412, 95% CI: 1.143–5.091, p = 0.021), preoperative total bilirubin (OR 1.003, 95% CI: 1.001–1.004, p = 0.002), rectal surgery (OR 0.354, 95% CI: 0.151–0.830, p = 0.017), and invasive mechanical ventilation duration > 6 h (OR 2.206, 95% CI: 1.628–2.990, p < 0.001). The nomogram demonstrated good discrimination (AUC: 0.734 95% CI: 0.698–0.770) and calibration. Conclusions: This study identified 8 independent predictors of pulmonary infection and developed an internally validated early postoperative risk stratification model with satisfactory performance. The model may assist clinicians in identifying high-risk patients and guiding timely preventive strategies in ICU practice. Full article

(This article belongs to the Section Intensive Care/ Anesthesiology)

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19 pages, 16363 KB

Open AccessArticle

Protective Role of Adenosine Triphosphate Against Tamoxifen-Induced Retinal Toxicity in a Rat Model

by Ezgi Karatas, Bulent Yavuzer, Seher Koksaldi, Mustafa Kayabasi, Esra Tuba Sezgin, Cengiz Sarigul, Ozlem Demir, Bahadir Suleyman and Halis Suleyman

Medicina 2026, 62(4), 787; https://doi.org/10.3390/medicina62040787 - 19 Apr 2026

Abstract

Background and Objectives: Tamoxifen, a cornerstone selective estrogen receptor modulator in breast cancer therapy, is increasingly recognized to be associated with retinal toxicity characterized by mitochondrial dysfunction, oxidative stress, lipid peroxidation, and oxidative DNA injury. By targeting mitochondrial bioenergetic dysfunction and redox [...] Read more.

Background and Objectives: Tamoxifen, a cornerstone selective estrogen receptor modulator in breast cancer therapy, is increasingly recognized to be associated with retinal toxicity characterized by mitochondrial dysfunction, oxidative stress, lipid peroxidation, and oxidative DNA injury. By targeting mitochondrial bioenergetic dysfunction and redox disequilibrium, adenosine triphosphate (ATP) emerges as a biologically plausible candidate for retinal cytoprotection. This study aimed to evaluate the protective effect of ATP against tamoxifen-induced retinal toxicity in a rat model. Materials and Methods: Twenty-four male albino Wistar rats were randomly assigned to four groups: healthy control (HG), ATP-alone (ATPG, 4 mg/kg, intraperitoneally), tamoxifen-alone (TAMG, 5 mg/kg, orally), and tamoxifen plus ATP-treated (ATAG; ATP, 4 mg/kg, intraperitoneally; tamoxifen, 5 mg/kg, orally). Treatments were administered once daily for 30 days. Oxidative stress markers (malondialdehyde, total glutathione), antioxidant enzyme activities (superoxide dismutase, catalase), and oxidative DNA damage (8-hydroxy-2′-deoxyguanosine) were assessed in ocular tissues. Retinal histopathological evaluation included hematoxylin–eosin staining with semiquantitative assessment of edema, vascular congestion, polymorphonuclear leukocyte infiltration, and cytoplasmic vacuolization, together with quantitative measurements of retinal layer thicknesses and ganglion cell layer (GCL) cell counts. Results: Tamoxifen administration induced marked oxidative stress, antioxidant depletion, and increased oxidative DNA damage in ocular tissues, accompanied by significant thickening of retinal layers, reduced GCL cell counts, and pronounced disruption of retinal architecture. By comparison, ATP co-administration significantly suppressed lipid peroxidation and restored antioxidant defenses, thereby reducing oxidative DNA damage and preserving retinal structural integrity, as reflected by partial normalization of retinal layer thicknesses, preservation of GCL cell counts, and the presence of only mild residual edema. Conclusions: These findings indicate that ATP attenuates tamoxifen-induced retinal toxicity by supporting mitochondrial energy balance and redox homeostasis. Accordingly, ATP administration may represent a promising protective approach for reducing retinal injury associated with long-term tamoxifen therapy. Full article

(This article belongs to the Special Issue Emerging Insights into Retinal Disease Research)

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16 pages, 697 KB

Open AccessReview

Simultaneous Bilateral Scapular Fractures: A Scoping Review

by Josip Kocur, Slavko Čičak, Dalibor Kristek, Dalibor Divković, Marko Ivanović, Dino Gregorović, David Matić, Matej Tomić, Sonja Škiljić, Ivana Haršanji Drenjančević and Gordana Kristek

Medicina 2026, 62(4), 786; https://doi.org/10.3390/medicina62040786 - 19 Apr 2026

Abstract

Background and Objectives: Simultaneous bilateral scapular fractures are exceptionally rare injuries and are most commonly associated with high-energy trauma, convulsions, or electrical injury. Their occurrence following low-energy trauma is extremely uncommon. This study aimed to conduct a scoping review of the literature [...] Read more.

Background and Objectives: Simultaneous bilateral scapular fractures are exceptionally rare injuries and are most commonly associated with high-energy trauma, convulsions, or electrical injury. Their occurrence following low-energy trauma is extremely uncommon. This study aimed to conduct a scoping review of the literature on simultaneous bilateral scapular fractures, with emphasis on demographic characteristics, mechanisms of injury, fracture patterns, treatment strategies, and clinical outcomes. To provide clinical context, the findings are illustrated by a case of a 43-year-old previously healthy recreational athlete who sustained simultaneous bilateral scapular fractures after a low-energy fall directly onto the back. Materials and Methods: A scoping review of the literature was conducted in accordance with PRISMA-ScR guidelines using the PubMed/MEDLINE and Scopus databases. Studies reporting simultaneous bilateral scapular fractures were identified and analyzed with respect to demographic characteristics, mechanisms of injury, fracture patterns, treatment modalities, and outcomes. Results: Thirty-seven studies published between 1946 and 2025 were included, comprising a total of 43 patients. Most cases resulted from high-energy trauma (41.9%), convulsions (25.6%), or electrical injury (16.3%). Low-energy trauma and spontaneous fractures were rare. The scapular body was the most commonly involved anatomical region. Conservative treatment predominated and was generally associated with favorable functional outcomes, while surgical intervention was reserved for displaced or intra-articular fractures. The illustrative case involved bilateral comminuted extra-articular fractures of the scapular bodies and spines without associated injuries and was managed conservatively, resulting in complete fracture healing and full, painless shoulder range of motion. Conclusions: The findings of this scoping review, illustrated by the representative clinical case, indicate that simultaneous bilateral scapular fractures may occur even after low-energy trauma in otherwise healthy individuals. Bilaterality alone should not be interpreted as an independent indication for surgical treatment when fractures are stable and minimally displaced. A high index of clinical suspicion and appropriate radiological evaluation are therefore warranted, particularly in emergency and trauma settings, in order to avoid missed or delayed diagnosis, even in cases with seemingly benign mechanisms of injury. Full article

(This article belongs to the Special Issue Contemporary Management and Outcomes of Orthopedic Fractures)

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17 pages, 949 KB

Open AccessArticle

Determinants of In-Stent Restenosis in ST-Elevation Myocardial Infarction: Insights from a Single-Center Retrospective Analysis

by Alice Elena Munteanu, Alexandru Andrei Badea, Silviu Marcel Stanciu, Alexandru Mihai Popescu, Florentina Cristina Pleșa and Ciprian Constantin

Medicina 2026, 62(4), 785; https://doi.org/10.3390/medicina62040785 - 19 Apr 2026

Abstract

Background and Objectives: Percutaneous coronary intervention (PCI) has markedly improved outcomes in coronary artery disease through the implantation of bare-metal stents (BMS) or drug-eluting stents (DES). However, in-stent restenosis (ISR) remains a significant complication, often necessitating repeat interventions. This study aimed to [...] Read more.

Background and Objectives: Percutaneous coronary intervention (PCI) has markedly improved outcomes in coronary artery disease through the implantation of bare-metal stents (BMS) or drug-eluting stents (DES). However, in-stent restenosis (ISR) remains a significant complication, often necessitating repeat interventions. This study aimed to identify risk factors associated with ISR in patients with ST-elevation myocardial infarction (STEMI) who underwent PCI. Materials and Methods: We conducted a retrospective, non-randomized observational study of 107 STEMI patients treated with PCI between January 2016 and December 2019 who subsequently underwent clinically indicated (predominantly symptom-driven) follow-up coronary angiography within 12 months. ISR was defined as ≥50% luminal narrowing at follow-up angiography. Time-to-event analysis was performed using Cox regression models, incorporating clinical, biochemical, and angiographic variables. Results: In this selected cohort of patients undergoing follow-up angiography, ISR of any degree was identified in 87% of patients, and 52% had restenosis >70%. Advanced age, prior cardiovascular events, diabetes mellitus, chronic kidney disease, and history of stroke significantly increased the hazard of ISR. Smoking, dyslipidemia, and hypertension were prevalent in patients with severe ISR. Women presented with more severe clinical profiles (higher Killip class and troponin levels). DES showed slightly better TIMI flow than BMS, but stent type, dimensions, and number did not significantly impact restenosis risk. Thrombolytic therapy was associated with a significantly reduced ISR hazard. Mortality was 6% in patients with severe ISR. The highest restenosis incidence occurred in the LAD and RCA territories. Conclusions: ISR is a multifactorial process influenced by demographic, clinical, and procedural factors. Despite technological advances, ISR remains a prevalent issue, particularly in high-risk groups undergoing clinically indicated follow-up angiography. Secondary prevention strategies, optimized stent deployment, and targeted therapies addressing inflammation and vascular remodeling are essential to improving long-term PCI outcomes. Full article

(This article belongs to the Special Issue Diabetes, Hypertension, and Cardiovascular Diseases: New Insights, Risk Factors, and Drug Therapies)

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18 pages, 769 KB

Open AccessReview

Exercise as a Metabolic Therapy for MASLD: Beyond Weight Loss Toward Sustainable Exercise Strategies

by Hee-Tae Roh and Ju-Yong Bae

Medicina 2026, 62(4), 784; https://doi.org/10.3390/medicina62040784 - 18 Apr 2026

Abstract

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a systemic metabolic disorder characterized by impaired metabolic flexibility involving the liver, skeletal muscle, and adipose tissue. Although weight loss has traditionally been emphasized in its management, emerging evidence suggests that exercise exerts therapeutic effects beyond [...] Read more.

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a systemic metabolic disorder characterized by impaired metabolic flexibility involving the liver, skeletal muscle, and adipose tissue. Although weight loss has traditionally been emphasized in its management, emerging evidence suggests that exercise exerts therapeutic effects beyond body weight reduction. This narrative review aims to examine exercise as a metabolic therapy for MASLD by integrating mechanistic insights and clinical evidence. Exercise improves hepatic steatosis, insulin resistance, mitochondrial function, and inflammatory signaling through interconnected pathways, including activation of AMPK-related signaling, enhanced fatty acid oxidation, and muscle–liver crosstalk mediated by myokines. Importantly, these benefits can occur independently of weight loss, supporting a shift from weight-centered to metabolism-focused treatment strategies. Both aerobic and resistance exercise demonstrate efficacy, with combined approaches providing complementary benefits. In conclusion, exercise should be considered a central therapeutic strategy for MASLD by restoring metabolic flexibility rather than solely promoting weight reduction. Future research should focus on optimizing individualized and sustainable exercise prescriptions to enhance long-term clinical outcomes. Full article

(This article belongs to the Section Sports Medicine and Sports Traumatology)

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16 pages, 731 KB

Open AccessSystematic Review

Patient Satisfaction with Anticoagulation for Venous Thromboembolic Disease: A Systematic Review of Oral and Parenteral Regiments

by Eleftheria Elmina Lefkou, Anastasia Fragkaki, Maria Mirsini Miliori, Dimitra Latsou, Kalliopi Panagiotopoulou, Paraskevi Kotsi, Grigorios Gerotziafas and Maria Geitona

Medicina 2026, 62(4), 783; https://doi.org/10.3390/medicina62040783 - 17 Apr 2026

Abstract

Background and Objectives: Venous thromboembolic disease (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity and mortality worldwide and imposes a substantial financial burden on health systems due to both the direct and indirect costs [...] Read more.

Background and Objectives: Venous thromboembolic disease (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity and mortality worldwide and imposes a substantial financial burden on health systems due to both the direct and indirect costs of acute management and long-term complications. This systematic review aimed to assess patient satisfaction with anticoagulation therapy for VTE and to highlight potential differences according to the type of anticoagulant. The review focused on factors influencing the patient experience, such as perceived efficacy, ease of use, adverse effects, and health-related quality of life. Materials and Methods: A systematic review, without quantitative meta-analysis, was conducted in accordance with PRISMA 2020 guidelines. Articles were identified through searches in major databases (PubMed, Scopus, Cochrane Library and others) using keywords including “patient satisfaction”, “anticoagulation”, “venous thromboembolic disease”, and “quality of life”. In total, 21 studies published between 2009 and 2025 met the inclusion criteria. The studies assessed patient satisfaction with different types of anticoagulation, including vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH) injections. Results: Across the included studies, patients generally reported higher levels of treatment satisfaction with DOACs compared with VKAs, mainly due to the absence of routine laboratory monitoring and fewer dietary restrictions. However, satisfaction varied according to age, sex, and clinical status. In specific patient populations, such as those with cancer-associated thrombosis, factors including fewer drug–drug interactions and perceptions of safety with LMWH appeared to influence treatment choice and satisfaction. Adverse effects, particularly bleeding, were identified as major drivers of dissatisfaction. Several studies suggested that higher treatment satisfaction was associated with better adherence, while quality of life appeared to improve in patients treated with DOACs in comparison with VKAs. Conclusions: Patient satisfaction is a critical component of successful VTE management. Overall, DOACs appear to be associated with higher treatment satisfaction than traditional therapies such as VKAs, although further high-quality research is needed to individualise anticoagulation strategies. Systematic incorporation of patient-reported satisfaction into clinical decision-making and into international guidelines may improve adherence, enhance quality of life, and ultimately increase the effectiveness of anticoagulation therapy. Full article

(This article belongs to the Special Issue Venous Thromboembolism: Diagnosis, Management, and Treatment)

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5 pages, 195 KB

Open AccessOpinion

Are Coronary Calcium-Modifying Techniques Levelling the Playfield?

by Georgiana Pintea Bentea and Pierre-Emmanuel Massart

Medicina 2026, 62(4), 782; https://doi.org/10.3390/medicina62040782 - 17 Apr 2026

Abstract

Patients with heavily calcified coronary arteries represent a challenge in percutaneous coronary intervention (PCI), as severe calcification impairs device delivery and limits optimal stent expansion, leading to higher risks of stent thrombosis, restenosis, and adverse clinical outcomes. Approximately 20% of patients undergoing PCI [...] Read more.

Patients with heavily calcified coronary arteries represent a challenge in percutaneous coronary intervention (PCI), as severe calcification impairs device delivery and limits optimal stent expansion, leading to higher risks of stent thrombosis, restenosis, and adverse clinical outcomes. Approximately 20% of patients undergoing PCI exhibit severe coronary calcification, which independently predicts incomplete revascularization, increased mortality, and higher rates of major adverse cardiovascular events over mid-term follow-up. Recent advances have focused on improving the assessment and management of calcified lesions. Intracoronary imaging modalities, including intravascular ultrasound and optical coherence tomography, allow precise detection and characterization of calcium burden, overcoming the limitations of angiography. These tools play a pivotal role in guiding procedural strategy, enabling tailored selection of calcium-modifying techniques based on lesion morphology, and optimizing stent deployment. Technological innovations have significantly expanded therapeutic options. While non-compliant balloon angioplasty alone is often insufficient, adjunctive devices such as cutting and scoring balloons improve plaque modification in focal disease. Atherectomy techniques, including rotational and orbital systems, are effective for more complex lesions but require technical expertise and carry procedural risks. Intravascular lithotripsy has emerged as a promising, less aggressive modality capable of fracturing deep calcium, while excimer laser atherectomy offers an alternative for resistant lesions. Despite these advances, current evidence supporting calcium-modifying strategies is largely based on procedural outcomes rather than definitive improvements in long-term clinical endpoints. Meta-analyses and randomized trials have not demonstrated clear superiority of any single technique, and most studies remain underpowered. Intriguingly, recent data suggest that outcomes in treated calcified lesions may approximate those of non-calcified disease, raising the hypothesis that these technologies could mitigate the adverse impact of calcification. However, this remains unproven, highlighting the urgent need for adequately powered randomized trials to determine their true clinical benefit. Full article

(This article belongs to the Special Issue Current Perspectives and Future Directions in Vascular Surgery)

17 pages, 735 KB

Open AccessArticle

Comparative Cardiovascular Outcomes of SGLT2i Plus Low-Dose of Conventional Triple Therapy Versus High-Dose of Conventional Triple Therapy for Heart Failure with Reduced Ejection Fraction (HFrEF): A Retrospective Cohort Study

by Suwat Khamboonruang, Parita Bunditboondee, Pongpun Jittham and Surarong Chinwong

Medicina 2026, 62(4), 781; https://doi.org/10.3390/medicina62040781 - 17 Apr 2026

Abstract

Background and Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular (CV) death and heart failure hospitalizations (HFH) in patients with heart failure with reduced ejection fraction (HFrEF). However, data regarding their use in combination with different doses of guideline-directed medical therapy (GDMT) [...] Read more.

Background and Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular (CV) death and heart failure hospitalizations (HFH) in patients with heart failure with reduced ejection fraction (HFrEF). However, data regarding their use in combination with different doses of guideline-directed medical therapy (GDMT) remain limited. This study aimed to evaluate whether SGLT2i combined with low-dose conventional triple therapy is non-inferior to high-dose conventional triple therapy in preventing adverse cardiovascular outcomes. Materials and Methods: This retrospective observational study included 334 patients with HFrEF treated between 31 March 2018 and 31 March 2024. Of these, 110 received SGLT2i plus low-dose conventional triple therapy, and 224 received high-dose conventional triple therapy. A non-inferiority framework was applied to compare outcomes between groups. The primary endpoint was a composite of CV death and HFH, while secondary endpoints included the individual components. Results: The composite endpoint occurred more frequently in the SGLT2i plus low-dose group. After inverse probability of treatment weighting and multivariable Cox analysis, this group demonstrated a significantly higher risk of the composite outcome (adjusted HR 4.10, 95% CI 2.07–8.13; p < 0.001). CV death was similar between groups; however, HFH was significantly more frequent in the SGLT2i plus low-dose group. Conclusions: In patients with HFrEF, SGLT2i combined with low-dose conventional triple therapy did not demonstrate comparable clinical outcomes to high-dose conventional triple therapy in reducing CV death and HFH, particularly in patients with a higher baseline burden of disease severity. These findings underscore the importance of optimizing background GDMT dosing alongside the incorporation of SGLT2i into clinical practice. Full article

(This article belongs to the Special Issue New Insights into Heart Failure Management and Treatment)

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12 pages, 508 KB

Open AccessArticle

Intra-Observer Reproducibility of Endoscopic Ultrasound Point Shear-Wave Elastography: A 120-Patient Prospective Cohort Study

by Adrian Burdan, Bogdan Miutescu, Eyad Gadour, Calin Burciu, Mirela Danila, Felix Bende, Moga Tudor, Aymen Almuhaidb, Raluca Lupusoru, Andreea Brasovan, Roxana Sirli and Alina Popescu

Medicina 2026, 62(4), 780; https://doi.org/10.3390/medicina62040780 - 17 Apr 2026

Abstract

Background and Objectives: Endoscopic ultrasound point shear-wave elastography (EUS-pSWE) bypasses subcutaneous fat and may provide weight-independent liver stiffness measurements; however, data on reproducibility and quality criteria remain limited. This study aimed to evaluate the intra-observer reproducibility and short-term variability of EUS-pSWE. Materials [...] Read more.

Background and Objectives: Endoscopic ultrasound point shear-wave elastography (EUS-pSWE) bypasses subcutaneous fat and may provide weight-independent liver stiffness measurements; however, data on reproducibility and quality criteria remain limited. This study aimed to evaluate the intra-observer reproducibility and short-term variability of EUS-pSWE. Materials and Methods: In this single-center prospective cohort study (December 2024–February 2025), 120 consecutive adults undergoing diagnostic EUS were enrolled. For each hepatic lobe, 10 consecutive measurements were obtained and grouped into two sequential blocks of five measurements without scope repositioning. Intra-observer reproducibility was assessed using intraclass correlation coefficients (ICC3,1). The agreement between acquisition runs and determinants of short-term variability was also evaluated. Same-day vibration-controlled transient elastography (VCTE) served as an external comparator. Results: Forty-six participants were obese (BMI ≥ 30 kg/m²). The mean VCTE stiffness was 6.24 kPa, while the mean EUS-pSWE stiffness was 9.40 ± 5.64 kPa. Among examinations meeting IQR/Median < 30% quality criteria, reproducibility was excellent (left ICC 0.97 [0.95–0.98]; right ICC 0.92 [0.86–0.95]) and consistent across BMI strata. EUS-pSWE correlated strongly with VCTE (r = 0.81, p < 0.001). In contrast, agreement between consecutive acquisition runs was low, indicating increased short-term variability. EUS-pSWE quality pass rates based on IQR/Median criteria were modest (left 56.7%, right 41.7%, both lobes 23.3%), although all measurements fulfilled device-specific validity criteria (VSN > 60%). Age and BMI were not significant predictors of variability. Conclusions: EUS-pSWE demonstrates excellent intra-observer reproducibility under quality-controlled conditions and shows a strong correlation with VCTE. However, short-term variability between acquisition runs and limited feasibility based on conventional quality thresholds should be considered. EUS-pSWE appears to be a promising modality for liver stiffness assessment, warranting further validation of quality criteria and clinical thresholds. Full article

(This article belongs to the Section Gastroenterology & Hepatology)

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10 pages, 694 KB

Open AccessReview

The Relationship Between Body Posture and Psychophysical Functioning in Children with Obesity: A Narrative Literature Review and Future Research Perspective Related to Preliminary Research Concept

by Kornelia Korzan, Kamila Czepczor-Bernat, Paweł Matusik and Anna Brzęk

Medicina 2026, 62(4), 779; https://doi.org/10.3390/medicina62040779 - 17 Apr 2026

Abstract

Childhood obesity is a growing global health problem with significant biomechanical and psychosocial consequences. While many studies have examined these domains separately, few integrate postural abnormalities, psychophysical functioning, and lifestyle factors within a single framework. This narrative review synthesises the literature published between [...] Read more.

Childhood obesity is a growing global health problem with significant biomechanical and psychosocial consequences. While many studies have examined these domains separately, few integrate postural abnormalities, psychophysical functioning, and lifestyle factors within a single framework. This narrative review synthesises the literature published between 2005 and 2025 to summarise current evidence and identify research gaps. The findings indicate that overweight and obesity increase the risk of musculoskeletal deviations such as genu valgum, flat feet, and increased lumbar lordosis, as well as altered gait biomechanics and reduced motor competence. Excess body weight is also associated with lower self-esteem, negative body image, depressive symptoms, and reduced health-related quality of life in children and adolescents. These outcomes appear to be influenced by modifiable lifestyle factors, including parental health behaviours, sleep patterns, and screen time, although reported associations remain inconsistent. Notably, few studies address biomechanical, psychological, and environmental factors simultaneously, which limits the understanding of their interactions. To address this gap, a prospective observational study of 250–300 children aged 7–17 years is proposed. The study will combine objective postural assessments, validated psychometric tools, and lifestyle analyses at baseline and after a 12–14-month follow-up. This integrated approach aims to identify postural compensation patterns, psychosocial risk trajectories, and modifiable behavioural predictors associated with childhood obesity, supporting the development of early preventive and interdisciplinary interventions. Full article

(This article belongs to the Special Issue The Prevention, Diagnosis, and Intervention of Childhood and Adolescent Obesity)

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