Journal of Clinical Medicine

11 pages, 246 KB

Open AccessArticle

Wise Prescriptions: Prevalence and Predictors of Polypharmacy in Patients with Type 2 Diabetes Mellitus in Primary Care: A Retrospective Cross-Sectional Study

by Mohammed M. Alsultan, Danya R. Al Thani, Sara A. Shwaiheen, Ethabah A. Al Drees, Mohammed A. Al Drees, Reem D. AlQahtani, Amnah A. Alnubi, Shuaa Y. Alali and Amani M. AlQarni

J. Clin. Med. 2026, 15(8), 3002; https://doi.org/10.3390/jcm15083002 (registering DOI) - 15 Apr 2026

Abstract

Background/Objectives: Diabetes mellitus is a common chronic disease that may lead to multimorbidity and high drug use. Therefore, this study aims to examine the prevalence of polypharmacy and hyperpolypharmacy among adult patients diagnosed with type 2 diabetes mellitus (T2DM) with its associated [...] Read more.

Background/Objectives: Diabetes mellitus is a common chronic disease that may lead to multimorbidity and high drug use. Therefore, this study aims to examine the prevalence of polypharmacy and hyperpolypharmacy among adult patients diagnosed with type 2 diabetes mellitus (T2DM) with its associated factors. Methods: This is a retrospective cross-sectional study conducted from 1 May 2023 to 31 October 2024. The outcomes in our study were polypharmacy (from five to nine drugs) and hyperpolypharmacy (≥10 drugs). Baseline and demographic characteristics, along with multinomial logistic regression, were used to analyze the data. Results: The total number of patients with T2DM was 2435. The prevalence rate of polypharmacy was 46.98%, while hyperpolypharmacy was 24.27%. Older age was significantly associated with a higher risk of polypharmacy [OR = 1.031, 95% (1.022–1.040)] and hyperpolypharmacy [OR = 1.037, 95% (1.026–1.049)]. In addition, patients with higher levels of hemoglobin A1c showed a significantly higher risk of polypharmacy and hyperpolypharmacy ([OR = 1.162, 95% (1.105–1.221)] and [OR = 1.284, 95% (1.209–1.364)], respectively). The comorbidities that increased the odds of hyperpolypharmacy were hypertension [OR = 2.136, 95% (1.449–3.148)], pulmonary disease [OR = 2.375, 95% (1.292–4.367)], mental disorders [OR = 6.269; 95% (3.284–11.964], and congestive heart failure [OR = 8.014, 95% (2.768–23.200)]. Conclusions: The prevalence of polypharmacy and hyperpolypharmacy is high in patients with T2DM. The predictors that may play a significant role in increasing the risk of hyperpolypharmacy are the poor control of HbA1c and the coexistence of comorbidities. Providing proper prescribing of patients’ therapy plans can improve individuals’ health outcomes. Therefore, this study highlights the important role of primary care physicians in coordinating care, along with clinical pharmacists, in the identification of polypharmacy. Full article

(This article belongs to the Special Issue Multimorbidity and Polypharmacy: From Clinical Complexity to Patient Safety)

16 pages, 275 KB

Open AccessArticle

Accuracy of Blood Loss Estimation and Identification of Factors Contributing to Early Postpartum Hemorrhage Following Vaginal Delivery

by Gabriela Afrykańska, Maja Kłopecka, Hanna Maciocha, Julia Wyszyńska, Zofia Włodarczyk, Szymon Paruszewski, Aleksandra Maria Śliwka, Artur Arkadiusz Ludwin and Paweł Jan Stanirowski

J. Clin. Med. 2026, 15(8), 3000; https://doi.org/10.3390/jcm15083000 (registering DOI) - 15 Apr 2026

Abstract

Objective: The study aimed to assess the accuracy of two distinct methods for estimating blood loss (EBL) and to identify potential factors contributing to early-onset postpartum hemorrhage (PPH) following a vaginal delivery (VD). Methods: Women in singleton pregnancies undergoing spontaneous/induced VD were recruited [...] Read more.

Objective: The study aimed to assess the accuracy of two distinct methods for estimating blood loss (EBL) and to identify potential factors contributing to early-onset postpartum hemorrhage (PPH) following a vaginal delivery (VD). Methods: Women in singleton pregnancies undergoing spontaneous/induced VD were recruited for this prospective observational cohort study. Methods of EBL included: (1) visual assessment by an attending obstetrician (sEBL) and (2) implementation of a mathematical formula (fEBL). Early PPH was defined as a cumulative blood loss exceeding 500 mL within the first 24 h after delivery as reflected by clinical assessment. Results: During the study period, 485 women delivered vaginally, and early PPH was diagnosed in 29 cases (5.97%). Among patients with PPH, a significant increase in the duration of the 2nd (61 min. vs. 33.5 min., p < 0.05) and 3rd (13 min. vs. 7 min., p < 0.001) stages of labor, as well as in the application of a dinoprostone insert (31% vs. 10.5%, p < 0.01) was noted. Additionally, in the same cohort, uterine atony (41.4% vs. 1.5%, p < 0.001), 3rd/4th degree perineal rupture (6.9% vs. 0%, p < 0.01), fetal macrosomia (17.2% vs. 4.8%, p < 0.05) and stillbirth (6.9% vs. 0.2%, p < 0.05) occurred significantly more frequently. In both groups visual estimation of blood loss was significantly lower compared to fEBL: (PPH sEBL: 800 mL vs. fEBL 1439.6 mL, p < 0.001; control sEBL: 250 mL vs. fEBL 621.8 mL, p < 0.001). In the multivariate analysis, factors such as third stage of delivery time ≥ 30 min. (OR 11.6; 95% CI: 4.18–32.33), FBW ≥ 4000 g (OR 6.37; 95% CI: 1.54–26.3), and dinoprostone insert application (OR 4.33; 95%CI: 1.63–11.48) were selected as independent predictors of the PPH. Conclusions: Compared to mathematical formula, visual estimation of blood loss by an attending obstetrician is significantly decreased. Prolonged third stage of delivery, fetal macrosomia, and application of a dinoprostone insert are the strongest contributors to early PPH following a VD. Full article

(This article belongs to the Special Issue High-Risk Pregnancy Management: From Prenatal Care to Postpartum Outcomes)

12 pages, 693 KB

Open AccessArticle

Impact of Malperfusion Burden on Early Outcomes After Surgery for Type A Acute Aortic Dissection: A Retrospective, Single-Center Investigation

by Matteo Marro, Gustavo Alfredo Sobrino Avellaneda, Domitilla Di Lorenzo, Andrea De Laurentis, Francesca Panvini, Andrea Costamagna, Marco Pocar, Michele William La Torre, Massimo Boffini, Antonio Loforte and Mauro Rinaldi

J. Clin. Med. 2026, 15(8), 2999; https://doi.org/10.3390/jcm15082999 (registering DOI) - 15 Apr 2026

Abstract

Objectives: Malperfusion is a major determinant of outcome in acute type A aortic dissection (ATAAD), yet its heterogeneous patterns and prognostic impact remain incompletely defined. We investigated the association between malperfusion burden, territory-specific involvement, and early outcomes after emergency ATAAD repair. Methods: We [...] Read more.

Objectives: Malperfusion is a major determinant of outcome in acute type A aortic dissection (ATAAD), yet its heterogeneous patterns and prognostic impact remain incompletely defined. We investigated the association between malperfusion burden, territory-specific involvement, and early outcomes after emergency ATAAD repair. Methods: We performed a retrospective single-center study including 483 consecutive patients undergoing emergency surgery for ATAAD (2010–2022). Malperfusion was classified by coronary, visceral, and peripheral territories and stratified as none, single-territory, or multidistrict (≥2 territories). The primary outcome was in-hospital mortality. Secondary outcomes included stroke, renal replacement therapy, peri-procedural myocardial infarction, major vascular events, and a composite endpoint of major adverse events (MAEs). Multivariable logistic regression identified independent predictors. Results: Overall, 68.5% of the population were male with a mean age of 65.4 ± 12.1 years. Malperfusion was present in 151 patients (31.3%), including 131 (27.1%) with single-territory and 20 (4.1%) with multidistrict involvement. In-hospital mortality increased stepwise with malperfusion burden (12.7%, 19.8%, and 50.0%; p < 0.001). MAEs occurred in 36.6% of patients, with a similar gradient (31.2%, 46.2%, and 65.0%, p < 0.001). In multivariable analysis, preoperative shock, neurological deficit, descending aortic involvement, and redo surgery were independent predictors of MAEs, whereas malperfusion burden showed an attenuated association after adjustment. Territory-specific analyses revealed strong associations between coronary malperfusion and peri-procedural myocardial infarction, visceral malperfusion and postoperative dialysis, and peripheral malperfusion and major vascular events. Conclusions: Malperfusion burden is associated with worse early outcomes after ATAAD repair but largely reflects underlying clinical severity. Distinct malperfusion territories confer specific postoperative risks, supporting a pattern-based approach to perioperative risk stratification. Full article

(This article belongs to the Section Cardiovascular Medicine)

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14 pages, 1027 KB

Open AccessArticle

Time-Dependent Risk of Psychiatric Disorders in Pediatric and Adolescent Patients with Microtia: A Nationwide Population-Based Cohort Study

by Jeong Yeop Ryu, Seok Gi Kim, Joon Seok Lee, Jung Dug Yang, Ho Yun Chung and Kang Young Choi

J. Clin. Med. 2026, 15(8), 2998; https://doi.org/10.3390/jcm15082998 - 15 Apr 2026

Abstract

Background/Objectives: Microtia, a congenital ear malformation ranging from mild anomalies to anotia, imposes a psychosocial burden, yet its link to pediatric psychiatric disorders in population-based settings is understudied. Methods: This study included 6048 patients with microtia and a control cohort of [...] Read more.

Background/Objectives: Microtia, a congenital ear malformation ranging from mild anomalies to anotia, imposes a psychosocial burden, yet its link to pediatric psychiatric disorders in population-based settings is understudied. Methods: This study included 6048 patients with microtia and a control cohort of 120,960 age- and sex-matched participants from the Korean National Health Insurance database. The incidence of overall psychiatric disorder events was compared between the microtia and control cohorts. Results: Compared with the control cohort, the incidence rate ratio (IRR) in patients with microtia was 1.16 (95% CI, 1.05–1.29) for overall psychiatric disorders, 5.35 (95% CI, 4.56–6.27) for hyperkinetic disorder (HKD), and 9.67 (95% CI, 5.49–17.03) for autism. After adjusting for age group, sex, and socioeconomic status, microtia was associated with an increased risk of overall psychiatric disorders, HKD, and autism. Subgroup analyses revealed an elevated risk of overall psychiatric disorders among individuals aged 5 to 14 years, males, and those with low or high socioeconomic status. Ear reconstruction surgery was associated with a lower risk of HKD among patients aged 10 to 14 years, females, and those with low socioeconomic status. The observed association between ear reconstruction surgery and lower HKD risk in these specific subgroups warrants further investigation using study designs capable of establishing causal inference. Conclusions: Microtia is associated with an increased risk of psychiatric disorders in pediatric and adolescent populations, with particularly pronounced risks for HKD and childhood autism. These findings underscore the importance of early psychiatric screening in children with microtia. Full article

(This article belongs to the Special Issue Plastic and Reconstructive Surgery: Cutting-Edge Expert Perspective)

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13 pages, 594 KB

Open AccessArticle

Assessing the Validity of the Fellow Eye as an Internal Control in Early-Phase Clinical Trials for Myopic Chorioretinal Atrophy

by Norimichi Nagano, Eisaku Kanemori, Yoshio Hirano, Takahiro Hojo, Yukinori Sakaeda, Takaaki Yuguchi, Soichiro Kuwayama, Shuntaro Ogura, Masayo Kimura, Hiroshi Morita, Kohei Uemura and Tsutomu Yasukawa

J. Clin. Med. 2026, 15(8), 2997; https://doi.org/10.3390/jcm15082997 (registering DOI) - 15 Apr 2026

Abstract

Background/Objectives: Age-related macular degeneration, particularly geographic atrophy, is a major cause of irreversible vision loss and shares pathological features with myopic chorioretinal atrophy (CRA). This study was designed as an exploratory methodological analysis to evaluate the feasibility of using the fellow eye as [...] Read more.

Background/Objectives: Age-related macular degeneration, particularly geographic atrophy, is a major cause of irreversible vision loss and shares pathological features with myopic chorioretinal atrophy (CRA). This study was designed as an exploratory methodological analysis to evaluate the feasibility of using the fellow eye as an internal control in early-phase clinical trials for myopic CRA. Methods: This exploratory and methodological retrospective study included eight patients (16 eyes) with myopic CRA who visited the Department of Ophthalmology at Nagoya City University Hospital between January 2010 and August 2023. Atrophic areas in both eyes were measured, and the longitudinal changes were analyzed. Three mixed-effects models were compared to assess the impact of inter-individual and inter-ocular variability on atrophic area progression. Subsequently, fixed-effects and mixed-effects models were compared using the Akaike Information Criterion (AIC). Finally, the square root of the variance ratio was calculated to quantify the contribution of inter-ocular variability to atrophic area progression. Results: In all eyes, the square root of the atrophic area increased over time. The model including random intercepts and slopes for each eye nested within patients had the lowest AIC of 69.4, suggesting that accounting for both inter-individual and inter-ocular variability improved model accuracy. The mixed-effects model had a lower AIC than the fixed-effects model, indicating a better fit. The square root of the variance ratio was 0.34 in the mixed-effects model, indicating that the inter-ocular variability was lower than the inter-individual variability, though it remained appreciable. Conclusions: This study quantitatively supports the feasibility and methodological validity of inter-ocular comparison designs for early-phase clinical trials in myopic CRA. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration: 3rd Edition)

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14 pages, 1186 KB

Open AccessArticle

Clinical Outcomes of Cardiac Implantable Electronic Device Infections in Octogenarians: A 20-Year Retrospective Cohort Study

by Sameer Al-Maisary, Migdat Mustafi, Gabriele Romano, Matthias Karck, Rawa Arif, Patricia Kraft and Mario Jesus Guzman-Ruvalcaba

J. Clin. Med. 2026, 15(8), 2996; https://doi.org/10.3390/jcm15082996 - 15 Apr 2026

Abstract

Background: The global demographic shift towards an aging population has driven a steady, exponential increase in the utilization of cardiac implantable electronic devices (CIEDs). Consequently, device-related infectious complications have emerged as a leading cause of morbidity and healthcare expenditure. Patients in their eighth [...] Read more.

Background: The global demographic shift towards an aging population has driven a steady, exponential increase in the utilization of cardiac implantable electronic devices (CIEDs). Consequently, device-related infectious complications have emerged as a leading cause of morbidity and healthcare expenditure. Patients in their eighth decade of life—octogenarians (aged 80–90 years)—represent an exceptionally high-risk demographic due to the compounding factors of physiological frailty, immunosenescence, and complex multi-morbidity. Despite this growing demographic, their specific clinical presentations, microbiological profiles, and procedural outcomes following infection remain poorly defined in the current literature. This study aimed to comprehensively compare the clinical characteristics, pathogen distribution, and in-hospital outcomes of CIED infections in an octogenarian cohort against a younger patient population. Methods: We conducted a robust retrospective cohort analysis of 383 consecutive patients treated for confirmed CIED infections at one major tertiary referral center (Heidelberg University Hospital) between January 2002 and December 2022. The cohort was stratified by age into octogenarians (n = 76) and a younger control group (n = 307). We systematically extracted and compared data regarding baseline clinical presentation, chronic comorbidities, detailed microbiological cultures (pocket, blood, and extracted leads), and definitive in-hospital outcomes, primarily mortality and length of stay. Results: The octogenarian cohort exhibited a significantly heavier comorbidity burden, notably higher rates of coronary artery disease (51.3% vs. 29.6%, p < 0.001), systemic hypertension (55.3% vs. 38.1%, p = 0.007), and chronic obstructive pulmonary disease (7.9% vs. 1.6%, p = 0.003). Furthermore, therapeutic systemic anticoagulant use was substantially more prevalent in the elderly group (60.5% vs. 45.0%, p = 0.015). Octogenarians presented overwhelmingly with localized generator pocket infections (73.0% vs. 30.0%, p < 0.001) but paradoxically also demonstrated higher rates of systemic bacteremia and sepsis (26.3% vs. 15.0%, p = 0.019). Microbiological analysis revealed a unique pathogen profile, with Staphylococcus capitis found with significantly higher frequency in the generator pockets of the elderly cohort. Remarkably, despite possessing a higher average lead burden (2.1 vs. 1.2 leads) and extreme comorbidity profiles, octogenarians demonstrated no statistically significant differences in in-hospital mortality (3.9% vs. 4.2%, p = 1.000) or overall length of hospital stay (14.7 vs. 17.2 days, p = 0.386) when compared to the younger cohort. Conclusions: Octogenarians suffering from CIED infections display highly distinct clinical and microbiological profiles, characterized predominantly by elevated rates of localized pocket infections, specific opportunistic pathogens, and a severe underlying comorbidity burden. Crucially, our findings indicate that with the application of modern extraction and management protocols, advanced age alone does not intrinsically correlate with increased in-hospital mortality. Future prevention and perioperative management strategies tailored to this rapidly expanding demographic must heavily prioritize the mitigation of pocket-related complications, particularly considering the high prevalence of concurrent anticoagulation therapy. Full article

(This article belongs to the Section Cardiovascular Medicine)

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11 pages, 461 KB

Open AccessArticle

Antihypertensive Therapy and Survival Outcomes in Patients with Renal Cell Carcinoma: A Retrospective Cohort Study

by Sara İleri, Mehmet Emin Yılmaz and Öztürk Ateş

J. Clin. Med. 2026, 15(8), 2995; https://doi.org/10.3390/jcm15082995 - 15 Apr 2026

Abstract

Background/Objectives: Hypertension is a recognized risk factor for renal cell carcinoma; however, the impact of antihypertensive therapy AHT on clinical outcomes in patients with established RCC remains insufficiently understood. This study aimed to evaluate the association between antihypertensive therapy use and clinical outcomes, [...] Read more.

Background/Objectives: Hypertension is a recognized risk factor for renal cell carcinoma; however, the impact of antihypertensive therapy AHT on clinical outcomes in patients with established RCC remains insufficiently understood. This study aimed to evaluate the association between antihypertensive therapy use and clinical outcomes, particularly overall survival, in patients diagnosed with renal cell carcinoma. Methods: This retrospective cohort study included 100 patients with renal cell carcinoma treated at a single center. Antihypertensive medications were evaluated according to both the presence of therapy and the number of agents used. Overall survival was defined as the time from renal cell carcinoma diagnosis to death from any cause or last follow-up. Survival outcomes were analyzed using Kaplan–Meier methods and Cox proportional hazards regression. Results: Hypertension was present in 66% of patients, all of whom were receiving antihypertensive therapy. Kaplan–Meier analysis demonstrated significantly longer overall survival among AHT users compared with non-users (log-rank p = 0.0007), with median overall survival 17.1 months in the non-AHT group and 112.2 months in the AHT group. After propensity score adjustment, antihypertensive therapy remained associated with improved survival (HR 0.35, 95% CI 0.13–0.94, p = 0.036). Antihypertensive therapy was not associated with tumor size, stage, or metastasis at diagnosis. Conclusions: Antihypertensive therapy use at diagnosis was associated with improved overall survival in patients with renal cell carcinoma. This association was not observed for tumor size, stage at diagnosis, or metastasis status, although nodal involvement was less frequent among patients receiving antihypertensive therapy. Because antihypertensive therapy exposure overlapped with hypertension status and baseline differences existed between groups, the observed survival advantage should be interpreted cautiously and considered hypothesis-generating rather than evidence of a causal relationship. Full article

(This article belongs to the Section Nephrology & Urology)

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20 pages, 2514 KB

Open AccessArticle

Clinical Profile, Risk Factors, and Microbial Dysbiosis in Periodontitis: Findings from an Adult Cohort and Microbiome-Based Predictive Models

by Sofia Jimenez de Nunzio, Jesus Pilo, Marta Bruna del Cojo, Caridad Margarita Arias-Macias, Barbara Manso de Gustin, Filipa Nunes, Eva Lago Pacheco, Clara Esteban Escobar, Francisco Tercero-Mora, Sergio Portal-Nuñez, Ana Adell Perez and Manuel Macias Gonzalez

J. Clin. Med. 2026, 15(8), 2994; https://doi.org/10.3390/jcm15082994 - 15 Apr 2026

Abstract

Background/Objective: Periodontitis is a chronic inflammatory disease influenced by clinical, behavioral, and microbial determinants. However, the contribution of these factors to disease remains a topic of debate, particularly in untreated adult populations. This study aims to characterize the clinical, epidemiological, and microbial features [...] Read more.

Background/Objective: Periodontitis is a chronic inflammatory disease influenced by clinical, behavioral, and microbial determinants. However, the contribution of these factors to disease remains a topic of debate, particularly in untreated adult populations. This study aims to characterize the clinical, epidemiological, and microbial features associated with periodontitis in an adult cohort and to compare the discriminatory performance of microbiome-based predictive models with conventional clinical–behavioral models. Methods: A cross-sectional study was conducted in 943 adults. Periodontal status was determined by experienced clinicians according to the 2017 World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions. Clinical variables, behavioral factors (smoking, bruxism, diet), intraoral conditions (caries and malocclusion), and systemic comorbidities were recorded. The oral microbiome was analyzed using targeted PCR for selected periodontal bacteria. Predictive models were constructed using logistic regression and least absolute shrinkage and selection operator (LASSO) variable selection. Results: Periodontitis was diagnosed in 47.2% of participants. Age, smoking, and bruxism were significantly associated with periodontitis. Malocclusion was the only significant intraoral predictor (OR = 2.00). Individuals with periodontitis exhibited increased levels of periodontopathogens, including P. gingivalis, T. forsythia, and E. corrodens, along with reduced levels of S. mutans. Microbiome-based models demonstrated superior discriminatory performance (AUC = 0.76, LASSO). E. corrodens and C. sputigena were independently associated with greater probing depth (p < 0.001). Conclusions: Microbiome-based predictive models, particularly at the species level, showed better discriminatory performance than conventional clinical–behavioral models. These findings support the potential utility of salivary microbial signatures as adjunctive, non-invasive biomarkers of periodontal inflammatory status. Full article

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)

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8 pages, 545 KB

Open AccessCase Report

Triple Iron Chelation in Transfusion Dependent Thalassemia: A Case Report

by Linet Njue, Emmanuel Häfliger and Alicia Rovó

J. Clin. Med. 2026, 15(8), 2993; https://doi.org/10.3390/jcm15082993 - 15 Apr 2026

Abstract

Background: Iron overload and its associated complications are major concerns in patients with transfusion-dependent β-thalassaemia (TDT). Iron chelation is an important part of TDT therapy with monotherapy or dual iron chelation being the most commonly used strategies. Evidence regarding the efficacy and [...] Read more.

Background: Iron overload and its associated complications are major concerns in patients with transfusion-dependent β-thalassaemia (TDT). Iron chelation is an important part of TDT therapy with monotherapy or dual iron chelation being the most commonly used strategies. Evidence regarding the efficacy and safety of triple iron chelation therapy remains limited. Case presentation: We present the case of a 21-year-old immigrant from the Middle East with TDT and a history of irregular transfusion management without chelation therapy, leading to clinically significant iron overload. She was successfully treated with the combination of deferoxamine, deferasirox and deferiprone over a course of 8 years. Triple chelation therapy led to sustained reductions in serum ferritin levels and improvement in hepatic and cardiac iron burden on follow-up MRI, with good tolerability. Conclusions: This case highlights the potential role of triple iron chelation therapy as a therapeutic strategy in TDT patients with severe iron overload. Further studies are needed to establish optimal dosing, eligible patients and long-term safety. Full article

(This article belongs to the Special Issue Blood Disorders: Diagnosis, Management, and Future Opportunities)

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11 pages, 447 KB

Open AccessArticle

Prognostic Role of Nutritional and Inflammatory Indices in Predicting Adverse Clinical Outcomes in Unplanned Hospitalized Oncology Patients

by Salih Karatlı, Doğan Yazılıtaş, Seher Kaya, Engin Yasin Baraklı, Selahattin Çelik and Gökşen İnanç İmamoğlu

J. Clin. Med. 2026, 15(8), 2992; https://doi.org/10.3390/jcm15082992 - 15 Apr 2026

Abstract

Background: Unplanned hospitalizations in patients with cancer are associated with adverse outcomes, including intensive care unit (ICU) transfer and in-hospital mortality. This study aimed to evaluate the predictive role of the prognostic nutritional index (PNI) and albumin-to-globulin ratio (AGR) for these outcomes [...] Read more.

Background: Unplanned hospitalizations in patients with cancer are associated with adverse outcomes, including intensive care unit (ICU) transfer and in-hospital mortality. This study aimed to evaluate the predictive role of the prognostic nutritional index (PNI) and albumin-to-globulin ratio (AGR) for these outcomes in patients with unplanned hospitalization in a medical oncology ward. Methods: This retrospective, single-center study included patients aged ≥18 years with malignancy who had unplanned hospitalization between 1 January and 30 April 2025. PNI and AGR were calculated at admission. The primary outcome was ICU transfer or in-hospital mortality. Univariable and multivariable logistic regression analyses were performed, with AGR and PNI evaluated in separate models to avoid collinearity. Predictive performance was assessed using ROC analysis. Results: A total of 418 patients were included, with adverse clinical outcomes in 26.8%. Metastatic disease was present in 73.7%, and gastrointestinal (41.6%) and lung cancers (21.5%) were most common. In univariable analysis, metastatic disease (p < 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (p < 0.001), cancer type (p = 0.030), reason for hospitalization (p = 0.001), AGR (p < 0.001), and PNI (p < 0.001) were significantly associated with adverse clinical outcomes. In multivariable analyses performed in separate models, ECOG ≥ 2 emerged as the strongest independent predictor of adverse clinical outcomes (AGR model: OR: 9.93; PNI model: OR: 11.14; both p < 0.001). Metastatic disease remained an independent risk factor, while higher AGR and PNI values were independently associated with a reduced risk (all p < 0.05). Among hospitalization reasons, only electrolyte imbalance/transfusion was associated with a lower risk, whereas most cancer type subgroups were not independently significant. Both indices showed moderate predictive performance, with PNI performing slightly better than AGR (AUC: 0.729 vs. 0.707). Conclusions: ECOG performance status, together with PNI and AGR, were identified as practical and accessible predictors of adverse clinical outcomes in patients with unplanned hospitalization in a medical oncology ward. Full article

(This article belongs to the Section Oncology)

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15 pages, 3321 KB

Open AccessArticle

A Modified Design External Fixator System for Calcaneal Fractures: Surgical Technique and an Observational Single-Center Study

by Michela Saracco, Clara De Negri, Roberta Pagano, Maria Rizzo and Massimo Mariconda

J. Clin. Med. 2026, 15(8), 2991; https://doi.org/10.3390/jcm15082991 - 15 Apr 2026

Abstract

Background: Displaced intra-articular calcaneal fractures are difficult to treat due to their complex anatomy and the high risk of soft-tissue complications. Although open reduction and internal fixation (ORIF) enables accurate anatomical reconstruction, it can be associated with substantial wound morbidity. Minimally invasive techniques [...] Read more.

Background: Displaced intra-articular calcaneal fractures are difficult to treat due to their complex anatomy and the high risk of soft-tissue complications. Although open reduction and internal fixation (ORIF) enables accurate anatomical reconstruction, it can be associated with substantial wound morbidity. Minimally invasive techniques have been developed to mitigate these risks. This study aims to describe a modified external fixation technique and report its clinical and radiographic outcomes in consecutive cases of patients with displaced intra-articular calcaneal fractures, with a minimum follow-up period of one year. Methods: The surgical technique is described in detail. The technique was evaluated by analyzing the treatment results in a case series of 17 patients. The time from injury to surgery, radiographic parameters (Böhler’s angle and time to union) and clinical outcomes were recorded and analyzed, as were complication rates. The minimum follow-up period was 12 months. Results: Surgical reconstruction was performed at a mean of three days (range 1–6 days; SD 1.5) after injury. Preoperative radiographic parameters showed significant deformity, with calcaneal morphology restored at follow-up. At 12 months, the mean Böhler angle had increased to 27.8°, and all fractures had achieved radiographic union. Functional outcomes improved progressively over time, with increases in both the AOFAS and SF-12 P scores. One complication was observed: K-wire displacement requiring conversion to ORIF in a psychiatric patient. Conclusions: The proposed technique facilitates early surgical treatment and the satisfactory restoration of calcaneal morphology with no soft-tissue complications. It appears to be safe and effective in selected patients. A longer follow-up will provide further insight into long-term outcomes, such as subtalar osteoarthritis. Full article

(This article belongs to the Special Issue Clinical Advances in Musculoskeletal Disorders: 2nd Edition)

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12 pages, 231 KB

Open AccessArticle

Clinical Profile of Outpatients Undergoing Swallowing Evaluation and Its Association with Pneumonia History: A Videofluoroscopic Study

by Ayşe Kübra Söyler, Numan Demir, Selen Serel Arslan, Inci Nur Saltik-Temizel, Ömer Faruk Yaşaroğlu, Hasan Erkan Kilinç and Aynur Ayşe Karaduman

J. Clin. Med. 2026, 15(8), 2990; https://doi.org/10.3390/jcm15082990 - 15 Apr 2026

Abstract

Background/Objectives: Dysphagia leads to severe complications, but data on patient profiles are limited in Türkiye. In this study, we present swallowing characteristics across etiologies and examine the association between a history of pneumonia and videofluoroscopic swallowing study (VFSS) findings. Methods: This [...] Read more.

Background/Objectives: Dysphagia leads to severe complications, but data on patient profiles are limited in Türkiye. In this study, we present swallowing characteristics across etiologies and examine the association between a history of pneumonia and videofluoroscopic swallowing study (VFSS) findings. Methods: This retrospective study included 1055 adults, comprising a large, heterogeneous outpatient population, referred for swallowing evaluation between 2015 and 2018. Clinical data (demographics, diagnoses, feeding status, etc.) and VFSS findings (Penetration–Aspiration Scale, PAS; pharyngeal residue) for liquid and semisolid consistencies were recorded from our electronic database. Associations were initially assessed using the chi-square test. A logistic regression analysis was performed to identify factors associated with pneumonia history. Results: Neurologic diseases (62.1%) were the most frequent diagnosis. VFSS identified liquid aspiration in 53.9% (61.8% silent) and semisolid aspiration in 20.1% (72.5% silent) of patients. Pharyngeal residue occurred in up to 10.6% of patients for liquids and 24.3% for semisolids. Diet recommendations were modified for 43.3% of patients (p < 0.05). Overall, 26.6% of patients had a history of pneumonia. In unadjusted, exploratory comparisons, pneumonia history was significantly associated with higher frequencies of aspiration and silent aspiration (p < 0.001), while pharyngeal residue was comparable between groups (p > 0.05). Multivariable logistic regression analysis showed that nonsilent aspiration (PAS 6–7) and silent aspiration (PAS 8) were associated with pneumonia history in both liquid (OR = 2.18 and 3.06) and semisolid consistencies (OR = 2.32 and 3.71), and that pharyngeal residue in semisolid consistency was also associated with pneumonia history (OR = 1.57). Conclusions: This study provides a comprehensive clinical profile of dysphagia in Türkiye, highlighting high rates of silent aspiration and the role of instrumental assessment in guiding safe feeding. While a significant association was observed between pneumonia history and impaired swallowing safety and efficiency, the retrospective nature of this study precludes causal interpretations. Full article

(This article belongs to the Section Otolaryngology)

9 pages, 703 KB

Open AccessArticle

Redirection of Urgent Geriatric Care: Diagnostics and Treatment Parallel to the Emergency Department

by Lennaert A. R. Zwart, Nikki M. F. Noorda, Chantal H. N. van Dijk, Naomi Hoekstra-Zuidema, Margreet G. Kamp-Glas, Anna C. M. Mulder and Judella O. Daal

J. Clin. Med. 2026, 15(8), 2989; https://doi.org/10.3390/jcm15082989 - 15 Apr 2026

Abstract

Objectives: Complex patients in need of an urgent medical assessment can contribute to crowding in the Emergency Department (ED). Optimising access to geriatric expertise for this patient group is known as ‘Geriatric Emergency Departments’. Methods: A parallel care pathway was designed [...] Read more.

Objectives: Complex patients in need of an urgent medical assessment can contribute to crowding in the Emergency Department (ED). Optimising access to geriatric expertise for this patient group is known as ‘Geriatric Emergency Departments’. Methods: A parallel care pathway was designed to redirect frail older patients to an Urgent Geriatric Care (UGC) service rather than the ED. The UGC has access to the diagnostic facilities of the ED. This descriptive analysis reports on delivered care, diagnostics, admissions rates, discharge policy, and 30-day and 6-month outcomes concerning hospital (re)admissions, ED visits, and mortality. Results: 269 patients were analysed. The median age was 83 years, 68% had polypharmacy, 51% cognitive disorders, and 83% a gait disturbance. A median of four conclusions was drawn per patient. Evaluation at the UGC often leads to medication regimen changes (81%), initiation or expansion of care at home (46%), and initiation of dementia care (18%). The hospital admission rate was 13%; the rate of ED visits within 30 days was 5% and, within 6 months, an additional 16%; the rate of hospital readmissions within 30 days was 7%, and 11% after 6 months. The mortality rates were 9% within 30 days and 12% within 6 months. Conclusions: Evaluation of patients at the UGC led to a high degree of medication regimen changes, initiation of care at home, and multiple conclusions or diagnoses per patient. Readmission or revisiting rates were low. A direct comparison to care delivered at the ED should be made in a future study. Full article

(This article belongs to the Section Geriatric Medicine)

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22 pages, 2105 KB

Open AccessReview

The Gracilis Muscle Reappraised: An Integrative Synthesis of Anatomy, Embryology, Imaging, and Surgical Applications

by Ingrid C. Landfald, Paloma Aragonés, Dawid Pilewski and Łukasz Olewnik

J. Clin. Med. 2026, 15(8), 2988; https://doi.org/10.3390/jcm15082988 - 15 Apr 2026

Abstract

Background and Objectives: Fragmented anatomical, imaging, and surgical accounts of the gracilis muscle hinder reproducible reporting and operative planning. We aimed to integrate prior systems into an Integrated Gracilis Framework (IGF)—an integrative synthesis, not a new classification—that harmonizes terminology, defines imaging correlates/pitfalls, and [...] Read more.

Background and Objectives: Fragmented anatomical, imaging, and surgical accounts of the gracilis muscle hinder reproducible reporting and operative planning. We aimed to integrate prior systems into an Integrated Gracilis Framework (IGF)—an integrative synthesis, not a new classification—that harmonizes terminology, defines imaging correlates/pitfalls, and links morphology to surgical decisions. Methods: Integrative narrative review (January 1900–October 2025) of PubMed/MEDLINE, Scopus, and Web of Science covering vascularization (pedicles, perforators), innervation (motor points/segments), imaging (ultrasound, MRI, MR neurography, CTA/MRA), and clinical applications (facial reanimation, elbow flexion, perineal and breast reconstruction). Two reviewers screened/extracted with consensus adjudication. Searches were restricted to English or records with reliable English-language summaries. Results: IGF consolidates morphological variants, motor-point/segmental innervation, and pedicle/perforator patterns with imaging correlates and common pitfalls. It provides a crosswalk mapping historical systems to IGF and a proposed preoperative workflow (anatomy → imaging → harvest → neurotization) for structured planning and reporting (proposed framework; not prospectively validated). We summarize considerations for free/functional gracilis in facial reanimation and elbow-flexion, and for pedicled/free myocutaneous or perforator flaps in perineal and breast reconstruction. Conclusions: IGF offers a standardized language and decision scaffold to improve study comparability and transparency in operative reporting; as a nonvalidated synthesis, it requires systematic validation through cadaver–imaging correlation and prospective surgical cohorts. Full article

(This article belongs to the Section Nuclear Medicine & Radiology)

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12 pages, 1430 KB

Open AccessArticle

Free Fat Grafts in Endoscopic Skull Base Closure: A Clinical Outcome Analysis

by Daniel Ilie Rotariu, Bogdan Florin Iliescu, Razvan Buga, Bogdan Ionut Dobrovat and Bogdan Costachescu

J. Clin. Med. 2026, 15(8), 2987; https://doi.org/10.3390/jcm15082987 - 15 Apr 2026

Abstract

Background: Autologous fat grafts are widely used for skull base reconstruction following endoscopic endonasal surgery. However, uncertainty regarding their postoperative volumetric evolution may complicate the distinction between expected postoperative changes and residual or recurrent disease on imaging. Methods: We performed a [...] Read more.

Background: Autologous fat grafts are widely used for skull base reconstruction following endoscopic endonasal surgery. However, uncertainty regarding their postoperative volumetric evolution may complicate the distinction between expected postoperative changes and residual or recurrent disease on imaging. Methods: We performed a retrospective volumetric imaging analysis of patients undergoing endoscopic endonasal skull base surgery with reconstruction using autologous fat and the 3F technique between 2013 and 2023. Fat graft volumes were measured on postoperative day 1 CT scans and on 3-, 9-, and 15-month postoperative MRI using standardized volumetric segmentation analysis (method described in detail in the main text). It should be noted that baseline measurements were derived from CT, whereas follow-up assessments were performed using MRI. Resorption rates were correlated with demographic, pathological, surgical, and postoperative variables. Results: Thirty-four patients met inclusion criteria. Mean initial fat graft volume was 3.01 ± 2.65 cm³. Overall, fat graft volume demonstrated a consistent temporal decline, with mean reductions of 56.8% at 3 months, 75.3% at 9 months, and 81.8% at 15 months. In subgroup analysis, differences in resorption were observed according to surgical approach, with higher resorption following transsellar compared with transtuberculum approaches (87.4% vs. 74.8% at 15 months, p = 0.042). These findings were closely related to graft compartment, although compartment and surgical approach showed substantial overlap in this cohort. No significant associations were detected between resorption rate and age, sex, comorbidities, postoperative CSF leak, extent of resection, or adjuvant radiotherapy. Conclusions: Autologous fat grafts used for skull base reconstruction demonstrate substantial early postoperative resorption followed by slower progressive volume loss. Recipient anatomical compartment was associated with differences in observed resorption patterns, although this relationship should be interpreted in the context of overlap with surgical approach and limited sample size. These findings may assist in improving interpretation of postoperative imaging by clarifying the expected temporal pattern of fat graft evolution after endoscopic skull base reconstruction. Full article

(This article belongs to the Section General Surgery)

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14 pages, 2814 KB

Open AccessArticle

Intraoperative Contamination of Sterile Fields and Postoperative Implications in Total Hip and Knee Arthroplasty: A Prospective Observational Study

by Nicolas Catalin Ionut Ion, Sorin Radu Fleaca, Bogdan Axente Bocea, Cosmin-Ioan Mohor, Mihai-Dan Roman, Calin-Ilie Mohor, Alexandru Florin Diconi, Alexandru Turcu, Vicentiu Vasile Veres, Iustin-Ilie Tutuianu, Mihai Faur, Vanesa-Maria Veres and Victoria Birlutiu

J. Clin. Med. 2026, 15(8), 2986; https://doi.org/10.3390/jcm15082986 - 14 Apr 2026

Abstract

Introduction: Periprosthetic joint infections (PJI) are among the most serious and costly complications in orthopedic surgery, significantly affecting patient prognosis and healthcare systems. Despite rigorous aseptic measures, intraoperative contamination of sterile fields, instruments, and air remains a persistent source of potential infection. This [...] Read more.

Introduction: Periprosthetic joint infections (PJI) are among the most serious and costly complications in orthopedic surgery, significantly affecting patient prognosis and healthcare systems. Despite rigorous aseptic measures, intraoperative contamination of sterile fields, instruments, and air remains a persistent source of potential infection. This study investigates the relationship between the microbial contamination of sterile fields during arthroplasty and postoperative inflammatory markers, with the objective of determining whether the contamination of sterile fields correlates with the presence of periprosthetic joint infection (PJI). Material and Methods: This prospective observational study included 33 patients undergoing total hip or knee arthroplasty in a university-affiliated orthopedic center. Intraoperative samples were collected from sterile fields and equipment to detect microbial contamination, while postoperative monitoring involved the C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); leukocyte count; temperature; and wound assessment on days 1, 3 and 7. All patients received 48 h of prophylactic cefuroxime. Statistical analysis was conducted using the International Business Machines (IBM) Statistical Product and Service Solutions (SPSS) software for Windows, version 30.0 (IBM Corporation, Armonk, New York, United States of America) with significance set at p ≤ 0.05. Results: Postoperative inflammatory markers showed distinct patterns depending on the isolated microorganism, with Proteus vulgaris and Staphylococcus hominis ssp. consistently associated with higher CRP and leukocyte values, indicating a more intense systemic response. Staphylococcus epidermidis was the most frequently isolated species but showed moderate inflammatory profiles, suggesting its potential role in subclinical colonization. A strong correlation between CRP on day 3 and leukocyte count (r = 0.81) confirms their combined utility in the early detection of infectious complications, while ESR appeared less dynamic and more complementary in nature. Discussion: This study highlights the significant role of intraoperative contamination and microbial virulence in shaping the postoperative inflammatory response after arthroplasty. Elevated CRP and leukocyte levels, particularly on day 3, were closely associated with pathogens known for biofilm formation and chronic infections. Despite prophylactic antibiotic use, confirmed infections still occurred, suggesting the need to reassess current protocols and enhance intraoperative contamination control. Conclusions: Pathogen presence in sterile fields during arthroplasty increases the risk of periprosthetic joint infections, often without early clinical symptoms. CRP on day 3 and leukocyte count were the most reliable early indicators of persistent inflammation. Full article

(This article belongs to the Section Orthopedics)

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11 pages, 2800 KB

Open AccessTechnical Note

A Subscapularis-Sparing Modification of the Deltopectoral Approach for Facilitated Glenoid Exposure in Reverse Shoulder Arthroplasty: A Technical Note

by Toru Ichiseki, Shusuke Ueda, Daisuke Soma, Keika Yasumoto, Ayumi Kaneuji and Norio Kawahara

J. Clin. Med. 2026, 15(8), 2985; https://doi.org/10.3390/jcm15082985 - 14 Apr 2026

Abstract

Background: In reverse shoulder arthroplasty (RSA), preservation of the subscapularis (SSC) has gained attention because of its biomechanical and functional significance. However, when SSC preservation is attempted using the conventional deltopectoral (DP) approach, glenoid visualization and instrument access may be limited. The purpose [...] Read more.

Background: In reverse shoulder arthroplasty (RSA), preservation of the subscapularis (SSC) has gained attention because of its biomechanical and functional significance. However, when SSC preservation is attempted using the conventional deltopectoral (DP) approach, glenoid visualization and instrument access may be limited. The purpose of this Technical Note is to describe a modified deltopectoral exposure technique, hereafter referred to as the Margin-Shifted, Yawing, Subscapularis-Sparing, and Transitioned Lateralized Deltopectoral (MYST–LDP) approach, and to assess its feasibility in primary RSA. Methods: The MYST–LDP approach incorporates a laterally shifted incision apex, a proximally oriented curved arc (“yawing”) toward the acromion, complete preservation of the subscapularis, and a distally transitioned limb aligned with the anterior humeral axis. We describe the surgical technique and our initial experience in three consecutive primary RSA cases performed using an inlay implant system to minimize humeral lateralization and allow focused assessment of exposure geometry. Results: In all cases, the SSC was preserved without conversion to a standard DP exposure. Adequate glenoid visualization was achieved using three retractors without excessive soft-tissue tension, allowing controlled glenoid preparation and component implantation without additional exposure or conversion. No approach-related intraoperative complications were observed. Conclusions: The MYST–LDP approach is a feasible modification of the deltopectoral exposure that preserves both SSC and the deltoid while facilitating glenoid visualization and instrument alignment. This technique represents an ergonomic and tissue-preserving option within the familiar DP framework for surgeons performing SSC-preserving RSA. Further comparative and quantitative studies are warranted to determine its clinical value. Full article

(This article belongs to the Special Issue Total Joint Arthroplasty: Clinical Advances and Innovations in Surgical Techniques and Rehabilitation)

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15 pages, 1045 KB

Open AccessReview

Tension-Type Headache: Toward an Integrative Multidimensional Framework for Clinical Stratification and Personalized Management

by Ana Bravo-Vazquez, Ernesto Anarte-Lazo, Alba Perez-Alvarez, Cleofas Rodriguez-Blanco and Carlos Bernal-Utrera

J. Clin. Med. 2026, 15(8), 2984; https://doi.org/10.3390/jcm15082984 - 14 Apr 2026

Abstract

Tension-type headache (TTH) is the most prevalent primary headache disorder worldwide, contributing substantially to individual disability and global socioeconomic burden. Despite its high prevalence, TTH remains clinically heterogeneous, with episodic and chronic forms influenced by the dynamic interplay of peripheral, central, psychosocial, and [...] Read more.

Tension-type headache (TTH) is the most prevalent primary headache disorder worldwide, contributing substantially to individual disability and global socioeconomic burden. Despite its high prevalence, TTH remains clinically heterogeneous, with episodic and chronic forms influenced by the dynamic interplay of peripheral, central, psychosocial, and lifestyle-related mechanisms. Peripheral musculoskeletal factors, including craniocervical muscle alterations and myofascial trigger points, interact with central sensitization processes, while psychosocial stressors, coping strategies, and lifestyle habits such as sleep and physical activity modulate pain perception and chronification risk. Current approaches often address these domains in isolation, limiting therapeutic effectiveness and the understanding of interindividual variability. This narrative review critically synthesizes evidence on the multifactorial determinants of TTH, providing an integrative conceptual framework. We systematically searched PubMed, Scopus, and Web of Science for articles published between 2010 and 2025, including conceptually or methodologically foundational studies outside this range. Relevant studies were selected based on predefined inclusion criteria and synthesized narratively to highlight key mechanisms and contributing factors. The proposed model emphasizes multidimensional assessment, incorporating peripheral musculoskeletal evaluation, central pain modulation, psychosocial profiling, and lifestyle factors, thereby providing a conceptual basis for future personalized management approaches. Recognizing TTH as a dynamic, multidimensional condition may inform clinical assessment and patient-centered interventions, while also highlighting key gaps for future longitudinal and multimodal research aimed at validating the framework and improving individualized therapeutic strategies. The evidence presented is primarily narrative and observational, and clinical applicability should be confirmed in future studies. Full article

(This article belongs to the Topic New Trends in Physiotherapy Care: Improvements in Functionality, Pain Management, and Quality of Life)

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15 pages, 1107 KB

Open AccessArticle

Molecularly Adapted Antitumor Therapy for Newly Diagnosed Diffuse Large B-Cell Lymphoma: Two-Year Follow-Up Results

by Marat Mingalimov, Elena Baryakh, Andrey Misyurin, Laura Kesaeva, Hasmik Mkrtchyan, Elena Misyurina, Mariia Orlova, Tatiana Tolstykh, Ekaterina Zotina, Liliia Shimanovskaia, Tatiana Chudnova, Diana Ivanova, Olga Kochneva, Kseniya Tsurkina, Dmitry Lebedev, Georgii Tyshkevich, Natalia Bekreneva, Viktoriia Basova, Mikhail Donskoy, Sergej Rodnikov, Ivan Abramov, Natalia Bodunova, Saida Gadzhieva, Tatiana Semina, Sergey Andreev, Inna Samsonova and Mariana Lysenko Show full author list Hide full author list

J. Clin. Med. 2026, 15(8), 2983; https://doi.org/10.3390/jcm15082983 - 14 Apr 2026

Abstract

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is molecularly heterogeneous, and approximately 30-50% of patients fail to achieve cure with standard R-CHOP. Genotype-directed first-line therapy may improve outcomes by targeting subtype-specific oncogenic pathways. This study evaluated the feasibility, efficacy, and safety of a molecularly [...] Read more.

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is molecularly heterogeneous, and approximately 30-50% of patients fail to achieve cure with standard R-CHOP. Genotype-directed first-line therapy may improve outcomes by targeting subtype-specific oncogenic pathways. This study evaluated the feasibility, efficacy, and safety of a molecularly adapted R-CHOP-X strategy with two-year follow-up. Methods: In this single-center, prospective, non-randomized study conducted between September 2023 and the data cut-off (16 September 2025), 43 adults with newly diagnosed DLBCL (excluding high-grade B-cell lymphoma, primary immune-privileged, and primary mediastinal large B-cell lymphomas) underwent tumor genotyping using the LymphGen classification after targeted sequencing: a 19-gene Sanger panel (Cohort 1, n = 35) or an expanded 60-gene panel (Cohort 2, n = 8; proof-of-concept). All patients received one initial cycle of R-CHOP as bridge therapy pending molecular profiling results, followed by five cycles of R-CHOP-X, with the additional agent (vorinostat, acalabrutinib, decitabine, or lenalidomide) selected according to molecular subtype. Response was assessed by PET/CT per Lugano criteria; adverse events were graded per NCI CTCAE v5.0. Results: The overall study population was predominantly high-risk: 72% had an IPI of 3–5, 58% had stage III–IV disease, and 67% exhibited a non-GCB immunophenotype. Expansion from the 19-gene to the 60-gene panel reduced unclassifiable (NOS) cases from 34% to 12%. The overall response rate was 100% (43/43); complete response among patients completing therapy was 100% (35/35). At two years, overall survival was 92% (95% CI 83–100%) and progression-free survival was 94% (95% CI 86–100%). Two early relapses occurred (NOS and N1 subtypes), both resulting in death. Grade 3–4 neutropenia, thrombocytopenia, and anemia occurred in 26%, 12%, and 7% of patients, respectively; no dose reductions or treatment discontinuations were recorded. Conclusions: Molecularly adapted R-CHOP-X is feasible and associated with high response rates and favorable two-year survival in newly diagnosed DLBCL, comparing favorably with historical R-CHOP outcomes in high-risk populations. Expanded genomic panels substantially improve molecular classifiability. These findings warrant validation in larger, multicenter, randomized clinical trials. Full article

(This article belongs to the Section Oncology)

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