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20 pages, 1511 KB  
Article
Native T1 Mapping and Clinical Risk Characterization in Non-Ischemic Dilated Cardiomyopathy: A Cardiac Magnetic Resonance Study
by Manuela Montatore, Marco Rella, Eleonora Indolfi, Federica Masino, Ruggiero Tupputi, Eluisa Muscogiuri and Giuseppe Guglielmi
J. Cardiovasc. Dev. Dis. 2026, 13(6), 279; https://doi.org/10.3390/jcdd13060279 (registering DOI) - 19 Jun 2026
Abstract
Background: Risk stratification in non-ischemic dilated cardiomyopathy (DCM) remains challenging because left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) do not fully capture the underlying myocardial substrate. Septal native T1 mapping provides a quantitative assessment of diffuse myocardial abnormalities and may [...] Read more.
Background: Risk stratification in non-ischemic dilated cardiomyopathy (DCM) remains challenging because left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) do not fully capture the underlying myocardial substrate. Septal native T1 mapping provides a quantitative assessment of diffuse myocardial abnormalities and may contribute to myocardial tissue characterization within a multiparametric CMR framework. Methods: This retrospective single-center study included 45 consecutive patients with non-ischemic DCM referred for clinically indicated CMR at Perrino Hospital, Brindisi, Italy, between November 2023 and November 2025. All examinations were performed using a standardized CMR protocol including cine imaging, LGE, and native T1 mapping on a 1.5-T Siemens Healthineers scanner. Septal native T1 was used as the primary mapping parameter because of its established reproducibility and robustness for myocardial tissue characterization. Patients were followed for a composite endpoint including all-cause mortality, major ventricular arrhythmic events, appropriate ICD therapy, and hospitalization for heart failure. Endpoint coding was verified, and all analyses were performed using the final validated dataset. Results: During a median follow-up of 15 months, 14 patients (31.1%) experienced the composite endpoint. Patients with events had lower LVEF (27.1 ± 7.8% vs. 48.3 ± 10.5%; p < 0.001), higher LVEDVi (142.6 ± 28.5 vs. 110.6 ± 23.4 mL/m2; p = 0.001), and higher septal native T1 values among patients with available T1 measurements (1047.5 ± 25.0 vs. 1031.5 ± 24.3 ms; p = 0.065). ROC analysis identified a septal native T1 threshold of 1042 ms for prediction of the composite endpoint, with an exploratory AUC of 0.70. Event-free survival was lower in patients with septal native T1 ≥ 1042 ms. Given the limited number of events, all regression and hierarchical analyses should be interpreted as exploratory and hypothesis-generating. Conclusions: Higher septal native T1 values were observed in patients experiencing adverse clinical outcomes; however, native T1 was not independently associated with the composite endpoint in exploratory Cox regression analyses. Full article
(This article belongs to the Special Issue Advanced Cardiovascular Imaging in Cardiomyopathy)
14 pages, 416 KB  
Article
Predictors of Candida auris Infection in Previously Colonized Patients: A Retrospective Cohort Study from a Large Tertiary Reference Center
by Nadide Ergün, Sevim Selen Karabulut, Melda Türken, Bengü Tatar and Süheyla Serin Senger
J. Fungi 2026, 12(6), 449; https://doi.org/10.3390/jof12060449 (registering DOI) - 19 Jun 2026
Abstract
Candida auris is a multidrug-resistant fungal pathogen associated with high mortality in healthcare settings. Although colonization is recognized as the harbinger of invasive infection, predicting which patients will develop bloodstream infection (BSI) and when this transition will occur remains a clinical challenge. In [...] Read more.
Candida auris is a multidrug-resistant fungal pathogen associated with high mortality in healthcare settings. Although colonization is recognized as the harbinger of invasive infection, predicting which patients will develop bloodstream infection (BSI) and when this transition will occur remains a clinical challenge. In this study, patients aged ≥18 years with C. auris colonization identified at İzmir City Hospital between January 2023 and June 2025 were retrospectively analyzed. Colonization was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Of 71 colonized patients (median age 65 years; 69.0% male; 93.0% intensive care unit (ICU)-admitted), 31 (43.7%) developed bloodstream infection (BSI). In-hospital mortality was 62.0%, rising to 74.2% in the BSI group, though this difference did not reach statistical significance (p = 0.105). Competing risks analysis using the Aalen–Johansen method showed a cumulative BSI incidence of 38.2% (95% confidence interval (CI): 28–50%) by day 10 and 43.0% (95% CI: 32–54%) by day 30 following colonization detection. On multivariate logistic regression, diabetes mellitus was the sole variable independently associated with a lower risk of BSI development (adjusted odds ratio (OR): 0.19; 95% CI: 0.06–0.68; p = 0.010); this finding was directionally consistent but did not reach statistical significance in the multivariable Fine–Gray competing risks model (subdistribution hazard ratio (SHR): 0.334; 95% CI: 0.108–1.040; p = 0.057). All 40 tested isolates had high fluconazole minimum inhibitory concentration (MIC) values; micafungin susceptibility was 92.5%, while anidulafungin resistance was observed in 32.5% of isolates. Our findings demonstrate that nearly half of colonized patients developed BSI, with no identifiable safe window for intervention, underscoring the necessity of sustained infection control measures and susceptibility-guided antifungal therapy. Full article
(This article belongs to the Section Fungal Pathogenesis and Disease Control)
20 pages, 4366 KB  
Article
Game Over for the Baseline: Influenza Hospitalization Patterns Before, During, and After the COVID-19 Pandemic (FluSurv-NET, 2009–2025)
by Hayden D. Hedman
Infect. Dis. Rep. 2026, 18(3), 61; https://doi.org/10.3390/idr18030061 (registering DOI) - 19 Jun 2026
Abstract
Background/Objectives: The trajectory of influenza hospitalization burden from pre-COVID-19 pandemic baseline through post-pandemic recovery remains poorly characterized at the national level. This study characterized phase-stratified burden and seasonal structure, quantified racial and ethnic disparities, and assessed whether post-pandemic seasons represent anomalous departures from [...] Read more.
Background/Objectives: The trajectory of influenza hospitalization burden from pre-COVID-19 pandemic baseline through post-pandemic recovery remains poorly characterized at the national level. This study characterized phase-stratified burden and seasonal structure, quantified racial and ethnic disparities, and assessed whether post-pandemic seasons represent anomalous departures from pre-pandemic expectations. Methods: Sixteen complete seasons of FluSurv-NET surveillance data (2009–2010 through 2024–2025; 509 observation weeks) were analyzed across pre-pandemic, disruption, and recovery phases using OLS regression with effect-size estimation, bootstrapped age-adjusted rate ratios, seasonal-trend decomposition (STL), Prophet time-series forecasting, and Isolation Forest anomaly detection. Results: Mean peak weekly hospitalization rate nearly doubled from pre-pandemic to recovery (5.1 to 11.1 per 100,000), cumulative seasonal burden increased from 46.3 to 87.0 per 100,000, and median peak timing advanced from MMWR week 9 to week 50. STL decomposition revealed a marked shift from weak pre-pandemic seasonality (Fs = 0.14) to substantially stronger annual regularity (Fs = 0.98) across three recovery seasons, with threefold amplitude increase. Non-Hispanic Black persons had rate ratios of 1.72, 2.16, and 1.99 relative to White persons across phases; American Indian and Alaska Native persons showed the highest disruption-phase ratio (2.24, 95% CI 1.90–3.53), based on two contributing seasons. A flat-growth Prophet model detected first exceedance in February 2020, outperforming a linear-growth specification on held-out validation. Isolation Forest identified 2017–2018, 2023–2024, and 2024–2025 as robust anomalies across all contamination thresholds. Conclusions: Post-COVID-19 pandemic influenza recovery is characterized by intensified and restructured seasonality, persistent racial and ethnic disparities, and anomalous burden exceeding pre-pandemic projections, identified independently by time-series forecasting and unsupervised anomaly detection. Full article
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11 pages, 759 KB  
Article
Thermal Ablation of Breast Cancer Liver Metastases Is Associated with Durable Local Control and Chemotherapy-Free Intervals in Selected Patients
by Niaz Ahmed, Alicia Okines, Sophie McGrath, Marina Parton, Emma Kipps, Nicholas Turner, Edward Johnston, Stephen Johnston and Nicos Fotiadis
Cancers 2026, 18(12), 1997; https://doi.org/10.3390/cancers18121997 - 19 Jun 2026
Abstract
Background/Objectives: In selected patients with oligometastatic breast cancer liver metastases (BCLM), liver-directed therapies may provide durable local control and may delay escalation of systemic therapy. This study reports a single-center experience of percutaneous thermal ablation (radiofrequency ablation [RFA] or microwave ablation [MWA]) [...] Read more.
Background/Objectives: In selected patients with oligometastatic breast cancer liver metastases (BCLM), liver-directed therapies may provide durable local control and may delay escalation of systemic therapy. This study reports a single-center experience of percutaneous thermal ablation (radiofrequency ablation [RFA] or microwave ablation [MWA]) for BCLM, including conventional oncologic outcomes and therapy-based endpoints. Methods: This retrospective cohort included consecutive patients treated with percutaneous ablation for BCLM following multidisciplinary team approval between 2005 and 2025. Outcomes were defined according to the Society of Interventional Oncology (SIO) and DATECAN consensus terminology. Lesion-level outcomes included primary/secondary technique efficacy and local tumor progression-free survival (LTPFS). Patient-level outcomes included progression-free survival (PFS), overall survival (OS), time to change in systemic therapy (TTCST) and chemotherapy-free survival (CFS). Kaplan–Meier and Cox regression analyses were performed. Results: Forty-six patients underwent 58 ablation sessions treating 80 metastases (median tumor size 19 mm, interquartile range [IQR] 13–27 mm). Primary and secondary technique efficacy were 95% (76/80) and 99% (79/80), respectively. Major complications occurred in 2/58 sessions (3%). Local tumor progression occurred in 16/79 tumors (20%) after a median follow-up of 28 months; LTPFS rates at 1, 3 and 5 years were 84%, 75% and 75%, respectively. Median OS was 44 months (1-, 3- and 5-year OS 94%, 58%, and 40%), and median PFS was 8.3 months. Median TTCST was 13 months, and median CFS was 16.4 months. Triple-negative disease was associated with worse LTPFS and shorter CFS. Oligopersistent disease was associated with improved PFS compared with oligoprogression. Conclusions: In this selected cohort, percutaneous thermal ablation for BCLM achieved high technique efficacy, durable local control and low major complication rates. Therapy-based endpoints suggest a clinically meaningful interval without systemic therapy escalation in appropriately selected patients, although comparative studies are needed to quantify the incremental benefit. Full article
(This article belongs to the Section Cancer Therapy)
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14 pages, 321 KB  
Article
Comparison of Health, Quality of Life, and Psychological and Cognitive Function Between Perimenopausal and Postmenopausal Women: A Cross-Sectional Study
by Jawahr Alagil and Alaa M. Albishi
Healthcare 2026, 14(12), 1770; https://doi.org/10.3390/healthcare14121770 - 19 Jun 2026
Abstract
Background: Menopause is associated with hormonal changes that may influence cognitive function, psychological health, and quality of life, but data on Middle Eastern populations remain scarce. Methods: A cross-sectional study was conducted among 220 Saudi women (110 perimenopausal, 110 postmenopausal) in Riyadh. Cognitive [...] Read more.
Background: Menopause is associated with hormonal changes that may influence cognitive function, psychological health, and quality of life, but data on Middle Eastern populations remain scarce. Methods: A cross-sectional study was conducted among 220 Saudi women (110 perimenopausal, 110 postmenopausal) in Riyadh. Cognitive function was assessed with the MMSE-2; quality of life with SF-36 and MENQOL; and psychological distress with PHQ-4 and PSS-10. Group comparisons used the Mann–Whitney U test; associations with Spearman’s correlation; and multivariable logistic regression adjusted for age, BMI, education, and anxiety. Results: In unadjusted analyses, perimenopausal women had higher MMSE-2 scores (median 30 vs. 29, p = 0.002, r = 0.211). Postmenopausal women reported greater vasomotor symptoms (p < 0.001, r = 0.090) but better emotional well-being (p = 0.038, r = 0.140). After adjustment for age, menopausal status was not a significant predictor of lower cognitive function (OR = 1.28, 95% CI: 0.56–2.92, p = 0.560). Age was the only significant predictor (OR = 1.10, 95% CI: 1.03–1.17, p = 0.003). Conclusions: The unadjusted difference in MMSE-2 scores between perimenopausal and postmenopausal women was small and not independent of age. Age, not menopausal status, was the primary factor associated with cognitive performance. Preventive strategies should target modifiable factors such as physical activity and vasomotor symptom management. Longitudinal studies with domain-specific cognitive tests are needed. Full article
(This article belongs to the Section Women’s and Children’s Health)
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14 pages, 312 KB  
Article
Association of Urea-to-Creatinine Ratio with Functional Outcomes in Patients with Traumatic Brain Injury
by Valentina Blažinčić, Anđela Grgić, Kristina Kralik, Ivica Ščurić, Ivana Klepo and Duško Cerovec
J. Clin. Med. 2026, 15(12), 4766; https://doi.org/10.3390/jcm15124766 (registering DOI) - 19 Jun 2026
Abstract
Background: In patients with traumatic brain injury (TBI), proteins are considered the main source of energy. Previous studies have suggested that an increase in the urea-to-creatinine ratio (UCR) indicates the onset of protein catabolism. Therefore, we aimed to investigate the associations of [...] Read more.
Background: In patients with traumatic brain injury (TBI), proteins are considered the main source of energy. Previous studies have suggested that an increase in the urea-to-creatinine ratio (UCR) indicates the onset of protein catabolism. Therefore, we aimed to investigate the associations of the UCR with the functional independence measure (FIM). Methods: This single-center retrospective study included 291 patients aged 17–87 years who underwent inpatient rehabilitation within the first 6 months post-TBI. Their demographic, clinical, neuroradiological, and laboratory data (eGFR, urea, creatinine, UCR) were collected. Spearman’s correlation and hierarchical multivariate regression analyses adjusted for clinical covariates were performed. Results: The strongest significant positive correlation was found between the Glasgow Coma Scale (GCS) and FIM at admission (ρ = 0.488, p < 0.001) and between GCS and FIM at discharge (ρ = 0.340, p < 0.001). A significant negative correlation was found between the discharge UCR and FIM at discharge (ρ = −0.262, p < 0.003), as well as with the change in FIM (ρ = −0.207, p < 0.02). Patients with UCRs ≥ 80 had a significantly lower discharge FIM compared to patients with UCRs < 80 (median 27 vs. 40; p = 0.02). The significant independent predictors of discharge FIM were the nutritional route (NGT/PEG), level of consciousness, and FIM at admission. The UCR did not remain independently associated with the discharge FIM (ΔR2 = 0.004, Cohen’s f2 = 0.014). Conclusions: Although UCR is associated with functional outcomes measured by FIM in TBI patients, it is not an independent predictor of these outcomes but rather a biomarker of catabolic burden. Full article
(This article belongs to the Section Brain Injury)
18 pages, 8771 KB  
Article
Real-World Outcomes of Nivolumab Plus Ipilimumab in Metastatic Melanoma: A Stratified Analysis of First- and Second-Line Treatment
by Alexandr Iurchenkov, Anastasia Danilova, Polina Shilo, Vladimir Stoliarov, Polina Rakhmanova, Ilia Kanner, Anna Basharina and Daniil Stroyakovskiy
Cancers 2026, 18(12), 1994; https://doi.org/10.3390/cancers18121994 - 18 Jun 2026
Abstract
Background: Immune checkpoint inhibitors have significantly improved survival in metastatic melanoma. Combination nivolumab plus ipilimumab demonstrated superior efficacy in randomized trials, including CheckMate 067, but data beyond the first-line setting remain limited. This study evaluated real-world outcomes and predictors of response across [...] Read more.
Background: Immune checkpoint inhibitors have significantly improved survival in metastatic melanoma. Combination nivolumab plus ipilimumab demonstrated superior efficacy in randomized trials, including CheckMate 067, but data beyond the first-line setting remain limited. This study evaluated real-world outcomes and predictors of response across different lines of therapy, with an exploratory comparison between first- and second-line use. Methods: This retrospective single-center study included patients with metastatic melanoma treated with nivolumab plus ipilimumab as first- or second-line therapy at Moscow City Oncology Hospital No. 62 between September 2015 and October 2023. Eligible patients had histologically confirmed melanoma and received at least one cycle of dual immune checkpoint blockade. Clinical and demographic data were extracted from electronic medical records. The primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included objective response rate (ORR) and safety. Survival outcomes were estimated using the Kaplan–Meier method and compared using the log-rank test. Multivariable Cox proportional hazards models adjusted for clinically relevant covariates were applied to evaluate the association between treatment line and survival outcomes. Additional prognostic analyses were performed using backward stepwise multivariable Cox regression. Results: Median follow-up was 18.2 months (IQR, 6.7–30.4). Median PFS in the overall cohort was 7.9 months (95% CI, 4.2–11.5), and median OS was not reached (NR); 5-year OS: 50%. The ORR was 45.8%, including 15.1% complete responses. Median PFS was 9.0 months (95% CI, 5.0–12.9) in first-line and 6.1 months (95% CI, 3.4–8.8) in second-line patients. Median OS was NR in the first-line cohort and was 30.5 months (95% CI: NR) in the second-line cohort. In exploratory analyses, OS did not differ significantly between patients treated in the first-line (n = 141) versus second-line setting (n = 63) (p = 0.848). After adjustment for clinical and demographic characteristics, line of therapy was not associated with OS (HR 0.93; 95% CI, 0.58–1.50; p = 0.762). Immune-related adverse events were associated with longer PFS (HR 0.66; 95% CI, 0.46–0.93), although this may reflect time-dependent bias. Conclusions: Nivolumab plus ipilimumab demonstrated clinically meaningful activity in both first- and second-line settings. Outcomes were numerically lower than in clinical trials, consistent with broader real-world populations. In exploratory analyses, OS did not differ significantly between treatment lines after adjustment for clinical and demographic characteristics. These findings should be interpreted with caution given the retrospective design and potential sources of bias. Full article
(This article belongs to the Section Cancer Therapy)
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8 pages, 240 KB  
Article
The Effects of Preoperative Bowel Function on Lower Urinary Tract Symptoms After Holmium Laser Enucleation of Prostate (HoLEP): A Prospective Study
by Kyle P. Tsai, Nabila Reem Khondakar, Amir Patel, Jenny Guo, Nathan Gill, Alyssa McDonald, Allaa Fadl-Allaa, Perry Xu and Amy E. Krambeck
Soc. Int. Urol. J. 2026, 7(3), 36; https://doi.org/10.3390/siuj7030036 (registering DOI) - 18 Jun 2026
Abstract
Background/Objectives: Variations in urinary symptom improvement after benign prostatic hyperplasia (BPH) surgery remain incompletely characterized. Preoperative factors, including bowel dysfunction, may influence postoperative recovery. We evaluated the association between baseline bowel function and urinary outcomes after holmium laser enucleation of the prostate (HoLEP), [...] Read more.
Background/Objectives: Variations in urinary symptom improvement after benign prostatic hyperplasia (BPH) surgery remain incompletely characterized. Preoperative factors, including bowel dysfunction, may influence postoperative recovery. We evaluated the association between baseline bowel function and urinary outcomes after holmium laser enucleation of the prostate (HoLEP), hypothesizing that worse baseline constipation would be associated with poorer outcomes. Methods: A prospective cohort study of patients undergoing HoLEP by a single surgeon at a high-volume center (December 2023–September 2024) was performed. Patients with neurogenic bladders, bowel disorders, or diabetes mellitus were excluded. Baseline bowel function was assessed using the Constipation Scoring System (CSS) and Vaizey Incontinence Score (VIS). The primary outcomes were 3-month changes in International Prostate Symptom Score (IPSS) and Michigan Incontinence Severity Index (MISI). Associations were evaluated using Spearman correlation and multivariable linear regression. Results: Among 102 patients (median age of 71.6 years), 81 (79.4%) completed follow-up. The median prostate size was 90.5 cc, and 50% had prior urinary retention. The baseline CSS and VIS were low. IPSS, quality of life, and MISI bother improved postoperatively, while MISI severity showed minimal change. Higher CSS correlated with higher VIS (p < 0.001). Baseline CSS and VIS were not associated with changes in IPSS, quality-of-life (QoL), or MISI bother. Baseline VIS was associated with modest improvement in MISI severity (β −1.14, p = 0.01). Conclusions: Baseline bowel function was not associated with urinary symptom improvement after HoLEP. However, preoperative fecal incontinence was associated with improvement in urinary incontinence severity. Full article
18 pages, 1553 KB  
Article
Preliminary Findings on the Predictive Value of Hematologic Inflammatory Indices for Survival in Treatment-Naïve Non-Metastatic Nasopharyngeal Carcinoma: A Retrospective Cohort Study
by Muhammed Ali Coşkuner, Gökhan Köker, Gizem Zorlu Görgülügil, Gülhan Özçelik Köker, Bilgin Bahadır Başgöz, Asım Armağan Aydın and Mustafa Yıldız
J. Clin. Med. 2026, 15(12), 4760; https://doi.org/10.3390/jcm15124760 (registering DOI) - 18 Jun 2026
Abstract
Background/Objectives: Prognostic stratification in non-metastatic nasopharyngeal carcinoma (NPC) remains challenging, particularly among patients within the same TNM stage. Readily available hematologic inflammatory indices may reflect host–tumor interactions and provide additional prognostic information beyond conventional clinicopathologic factors. This study evaluated the prognostic value [...] Read more.
Background/Objectives: Prognostic stratification in non-metastatic nasopharyngeal carcinoma (NPC) remains challenging, particularly among patients within the same TNM stage. Readily available hematologic inflammatory indices may reflect host–tumor interactions and provide additional prognostic information beyond conventional clinicopathologic factors. This study evaluated the prognostic value of pretreatment hematologic inflammatory indices for overall survival (OS) and progression-free survival (PFS) in patients with non-metastatic NPC. Methods: This single-center retrospective cohort study included adult patients with non-metastatic NPC diagnosed at a tertiary referral center between 20 February 2014 and 2 May 2023, with outcomes ascertained through 12 December 2023. Pretreatment complete blood count and biochemical parameters were used to calculate the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, pan-immune-inflammation value (PIV), and hemoglobin–albumin–lymphocyte–platelet score. Receiver operating characteristic analysis determined optimal cut-off values for mortality discrimination. Associations with OS and PFS were assessed using Cox regression models. Results: Forty-six patients were analyzed, including 37 males. Median OS and PFS were 45.90 and 37.05 months, respectively. Compared with survivors, non-survivors were older and had lower hemoglobin and albumin levels, higher PIV, NLR, PLR, and SII values, and lower HALP scores. Although NLR showed the highest conventional ROC performance for mortality discrimination, PIV retained prognostic significance in multivariable Cox models and showed stable time-dependent discrimination for PFS. Conclusions: These preliminary findings suggest that pretreatment inflammatory indices, particularly composite markers such as PIV, may provide adjunctive prognostic information in treatment-naïve non-metastatic NPC, pending larger prospective validation. Full article
(This article belongs to the Section Oncology)
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13 pages, 2439 KB  
Article
Real-World Outcomes of First-Line Pembrolizumab-Based Therapy in Advanced Non-Small-Cell Lung Cancer: A Retrospective Single-Center Study
by Einav Koren, Adar Yaacov, Jamal Zidan, Laila C. Roisman, Nir Peled and Noam Asna
J. Clin. Med. 2026, 15(12), 4757; https://doi.org/10.3390/jcm15124757 (registering DOI) - 18 Jun 2026
Abstract
Background: Pembrolizumab-based therapy is a standard first-line option for advanced non-small-cell lung cancer (NSCLC), yet pivotal clinical-trial populations may not reflect patients encountered in routine practice. Real-world cohorts enriched for Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 and high metastatic burden [...] Read more.
Background: Pembrolizumab-based therapy is a standard first-line option for advanced non-small-cell lung cancer (NSCLC), yet pivotal clinical-trial populations may not reflect patients encountered in routine practice. Real-world cohorts enriched for Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 and high metastatic burden remain underreported. We assessed real-world outcomes of first-line pembrolizumab in a heterogeneous cohort enriched for these. Methods: Retrospective cohort analysis of 45 patients with advanced NSCLC who received first-line pembrolizumab-based therapy (monotherapy or with platinum-based chemotherapy) at a single health maintenance organization in Israel between September 2017 and April 2020. Results: Mean age was 69.3 years (SD 9.0), 82.2% were male, 91.1% were current or former smokers, 37.8% had ECOG PS ≥2 (including 17.8% with ECOG ≥3), and 53.3% had three or more metastatic organ sites. PD-L1 expression was ≥50% in 46.7%, 1–49% in 13.3%, and <1% in 22.2%. After a median follow-up of 48.7 months (88.9% event rate), median overall survival (OS) was 8.87 months (95% CI, 5.88–14.32) and median progression-free survival (PFS) was 4.20 months (95% CI, 2.76–6.18), with an objective response rate of 46.7% and a disease control rate of 68.9%. On univariate Cox regression, the number of metastatic sites was most strongly associated with OS (HR 1.41 per site, 95% CI, 1.17–1.70, p = 0.0003). PD-L1 expression was significantly associated with both PFS (p < 0.0001) and OS (p = 0.0012), with the longest survival observed in patients with PD-L1 ≥50%. Conclusions: In this real-world cohort enriched for poor performance status and high metastatic burden, pembrolizumab-based therapy provided clinical benefit, but observed survival was substantially shorter than that reported in pivotal trials. Full article
(This article belongs to the Section Oncology)
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18 pages, 553 KB  
Article
Seasonal Influenza Vaccination Uptake, Illness and Economic Burden, and Vaccine Information Exposure Among Young Adults in the San Francisco Bay Area
by Taiwo Opeyemi Aremu, Carinne Brody, Shadi Doroudgar, Ikenna Chidozie Ezejiaku and Shahin Teimourtash
Pharmacy 2026, 14(3), 87; https://doi.org/10.3390/pharmacy14030087 (registering DOI) - 18 Jun 2026
Abstract
Background: Seasonal influenza prevention in young adults is influenced by access, trust, and vaccine information exposure, but local evidence linking vaccination uptake with illness and economic burden is limited. Methods: We conducted a non-probability, cross-sectional electronic survey of adults aged 18–49 years who [...] Read more.
Background: Seasonal influenza prevention in young adults is influenced by access, trust, and vaccine information exposure, but local evidence linking vaccination uptake with illness and economic burden is limited. Methods: We conducted a non-probability, cross-sectional electronic survey of adults aged 18–49 years who lived, worked, or studied in the San Francisco Bay Area during the 2025 to 2026 influenza season. Measures included vaccination uptake, influenza-like illness, recovery, functional and economic burden, vaccination sites, and vaccine information exposure. Multivariable logistic regression examined factors associated with vaccination uptake; Kaplan–Meier and Cox models examined time to recovery. Results: Of 554 responses, 463 were included. Vaccination uptake was 86.2% (n = 399; 95% confidence interval [CI], 82.7–89.2%), likely reflecting a health-engaged convenience sample. Influenza-like illness was reported by 38.4%; median recovery time was 5 days, median missed work or school was 2 days, and median direct out-of-pocket cost was US$20. Prior season vaccination (adjusted odds ratio [aOR], 2.24; 95% CI, 1.15–4.34) and greater trust in Centers for Disease Control and Prevention (CDC) or public health agencies (aOR, 1.46; 95% CI, 1.05–2.02) were associated with vaccination. Pharmacies were the second most common vaccination site and preferred future site. Conclusions: Influenza prevention for young adults may benefit from pharmacy-inclusive, multichannel access paired with trusted communication. Findings should be interpreted in light of non-probability recruitment and likely overrepresentation of health-engaged respondents. Full article
(This article belongs to the Section Pharmacy Practice and Practice-Based Research)
24 pages, 388 KB  
Article
Determinants of Carbapenem-Resistant Klebsiella pneumoniae: Clinical Outcomes and Epidemiological Risk Factors in a Single-Center Cohort Dataset
by Cristiana Ana-Maria Olguța Penea, Violeta Melinte, Claudia Simona Cambrea, Tiberiu Holban, Adelina Maria Radu, Cristina Maria Vacaroiu and Valeriu Gheorghiță
Antibiotics 2026, 15(6), 621; https://doi.org/10.3390/antibiotics15060621 (registering DOI) - 18 Jun 2026
Abstract
Background: Carbapenem-resistant K. pneumoniae (CRKP) represents a major challenge in hospitalized patients because of its association with healthcare exposure, restricted antimicrobial options, and adverse clinical outcomes. Microbiological isolation alone does not define invasive disease; therefore, clinical interpretation requires separation of colonization, localized infection, [...] Read more.
Background: Carbapenem-resistant K. pneumoniae (CRKP) represents a major challenge in hospitalized patients because of its association with healthcare exposure, restricted antimicrobial options, and adverse clinical outcomes. Microbiological isolation alone does not define invasive disease; therefore, clinical interpretation requires separation of colonization, localized infection, invasive infection, and carbapenem-resistant Enterobacterales (CRE)-associated sepsis. This study evaluated epidemiological features, resistance phenotypes, treatment adequacy, and clinical outcomes among hospitalized adults with K. pneumoniae isolates, using a clinical framework that distinguishes colonization from active infection and invasive disease. Methods: This single-center retrospective observational cohort study included 157 consecutive adults admitted between January and July 2025 to a tertiary-care hospital with at least one microbiologically confirmed K. pneumoniae isolate recovered from clinical specimens and/or CRE surveillance rectal swabs. Isolates were assigned hierarchically to four mutually exclusive phenotypic groups: carbapenem-susceptible K. pneumoniae (CSKP), extended-spectrum beta-lactamase (ESBL)-producing carbapenem-susceptible K. pneumoniae (ESBL), carbapenem-resistant non-carbapenemase-producing K. pneumoniae (CRKP), and carbapenemase-producing K. pneumoniae (CP-KP). A prespecified secondary analysis compared carbapenem-resistant isolates (CRKP + CP-KP) with non-carbapenem-resistant isolates (CSKP + ESBL). Clinical adjudication distinguished colonization-only cases, non-invasive infection, bloodstream infection, device-associated infection, and CRE-associated sepsis; ventilator-associated pneumonia (VAP) was considered when source data allowed reliable attribution. Sepsis was defined according to Sepsis-3 criteria; quick Sequential Organ Failure Assessment (qSOFA) was used only as a bedside screening tool. Statistical tests were selected according to variable type, distribution, and expected cell counts. Results: The cohort comprised 157 unique patients, with a median age of 71 years (interquartile range [IQR], 61–76). Current CRE colonization was documented in 79/154 patients with available colonization status (51.3%). Complete-case in-hospital mortality was higher in the carbapenem-resistant group (CRKP + CP-KP, n = 46) than in the non-carbapenem-resistant group (CSKP + ESBL, n = 111): 11/42 (26.2%) versus 5/108 (4.6%; Fisher exact odds ratio (OR) 7.31, 95% confidence interval (CI) 2.36–22.65; p < 0.001); overall complete-case mortality was 16/150 (10.7%). Multivariable logistic regression for carbapenem resistance (N = 150; five prespecified covariates; events per variable (EPV) = 9.0) identified age 65 years or older (adjusted odds ratio [aOR] 3.78, 95% CI 1.32–10.86), recent hospitalization within 30 days (aOR 2.56, 95% CI 1.16–5.63), and current colonization (aOR 2.96, 95% CI 1.24–7.05) as independent predictors. CRE-associated sepsis was excluded a priori because of definitional circularity with the case definition. Male sex showed a non-significant protective trend (aOR 0.50, 95% CI 0.22–1.12). CRE-associated sepsis showed a strong bivariate association with carbapenem resistance (OR 9.90, 95% CI 3.91–25.09; p < 0.001), and this association is reported descriptively because the variable was excluded from the multivariable model owing to definitional circularity. Model performance was acceptable, with area under the curve (AUC) 0.77, Hosmer–Lemeshow p = 0.95, and Nagelkerke R2 = 0.25. Of 99 molecularly characterized isolates, OXA-48-like was detected in 78 (78.8%), NDM in 71 (71.7%), KPC in 6 (6.1%), and NDM + OXA-48-like dual production in 54 (54.5%); VIM and IMP were uniformly negative. Conclusions: In this high-risk hospital cohort, carbapenem resistance in K. pneumoniae was associated with advanced age, recent healthcare exposure, current CRE colonization, and a pronounced unadjusted mortality signal. Interpretation of sepsis and mortality requires explicit separation of colonization from active infection and invasive disease. These findings support intensified CRE surveillance, source-specific clinical interpretation, rapid resistance detection, and risk-adapted empirical antimicrobial strategies in high-risk hospital settings. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
15 pages, 443 KB  
Article
Thyroid Autoimmunity in Polycystic Ovary Syndrome: Phenotype Distribution, HDL-Cholesterol, and Data-Driven Clusters in a Retrospective Cohort Study
by Raluca-Anamaria Mogoș, Alexandru Carauleanu, Ingrid-Andrada Vasilache, Simona Juliette Mogoș, Maria-Christina Ungureanu, Letitia Leustean, Iustina-Petra Condriuc, Sandra-Teodora Gavril, Ecaterina Tomaziu-Todosia Anton and Cristina Preda
Medicina 2026, 62(6), 1184; https://doi.org/10.3390/medicina62061184 - 18 Jun 2026
Abstract
Background and Objectives: Autoimmune thyroiditis (AIT) is often reported patients with PCOS, and may co-occur with altered metabolic risk markers. The aims of this study were to assess baseline differences according to thyroid autoimmunity status, evaluate adjusted associations between thyroid autoimmunity and [...] Read more.
Background and Objectives: Autoimmune thyroiditis (AIT) is often reported patients with PCOS, and may co-occur with altered metabolic risk markers. The aims of this study were to assess baseline differences according to thyroid autoimmunity status, evaluate adjusted associations between thyroid autoimmunity and metabolic parameters, examine associations with PCOS phenotype distribution, and perform k-means clustering to explore data-driven subgroups and their autoimmune enrichment. Materials and Methods: We performed a retrospective cohort study of 651 women with PCOS, comparing those without AIT (n = 506) versus with AIT (n = 145). Associations between AIT and continuous outcomes (HDL; composite metabolic score) were evaluated using robust linear regression with HC3 standard errors and age modeled with a natural cubic spline (3 knots). The association between AIT and phenotype A was assessed via logistic regression with exponentiated coefficients (odds ratios). Unsupervised phenotyping used k-means clustering with silhouette analysis across k = 2…6. Results: Patients with AIT were older (median 40 vs. 35 years; p = 0.021). Phenotype distribution differed by AIT status (overall p = 0.029), with phenotype A less frequent among AIT-positive women (27% vs. 40%). In adjusted robust regression, AIT was associated with lower HDL by β = −4.34 mg/dL (95% CI −9.18 to 0.51; p = 0.081), while obesity (−7.04 mg/dL; p < 0.001) and diabetes (−6.47 mg/dL; p = 0.004) were associated with lower HDL. AIT was not associated with the composite metabolic score (β = −0.005; 95% CI −1.22 to 1.21; p = 0.994), whereas obesity was associated with higher score (β = 1.76; p = 0.003) and urban residence with lower score (β = −0.94; p = 0.011). In logistic regression, AIT was associated with lower odds of phenotype A (OR 0.63; 95% CI 0.41–0.97; p = 0.038), and hypertension was associated with higher odds of phenotype A (OR 1.91; 95% CI 1.20–3.04; p = 0.006). Silhouette analysis supported k=3 clusters (silhouette 0.349), and AIT prevalence was highest in cluster 3 (26.4%) versus clusters 1 (19.9%) and 2 (18.3%). Conclusions: AIT was associated with lower odds of phenotype A, and showed a borderline association with lower HDL-cholesterol but not with a composite metabolic score. Data-driven clustering identified a subgroup with higher autoimmune burden. Full article
(This article belongs to the Section Endocrinology)
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21 pages, 1045 KB  
Article
Integrated Assessment of Skeletal Muscle Quantity and Quality Is Associated with Survival in Patients with Oesophagogastric Malignancies: A Retrospective Cohort Study
by Yannick Deswysen, Pierre Trefois, Etienne Danse, Alix Collard, Marc Van den Eynde and Nicolas Lanthier
Cancers 2026, 18(12), 1987; https://doi.org/10.3390/cancers18121987 - 18 Jun 2026
Abstract
Background: Oesophagogastric cancer is associated with poor survival and major alterations in body composition. This study investigated the relationship between myopenia and myosteatosis in patients with oesophagogastric cancer and evaluated their prognostic significance and association with systemic inflammation. Methods: In this retrospective single-centre [...] Read more.
Background: Oesophagogastric cancer is associated with poor survival and major alterations in body composition. This study investigated the relationship between myopenia and myosteatosis in patients with oesophagogastric cancer and evaluated their prognostic significance and association with systemic inflammation. Methods: In this retrospective single-centre study, 161 consecutive patients diagnosed with oesophagogastric cancer between 2019 and 2023 underwent computed tomography-based body-composition analysis at diagnosis. Skeletal muscle index (SMI) and skeletal muscle density (SMD) were measured at the third lumbar vertebra. Myopenia and myosteatosis were defined using Martin’s criteria. Associations with overall survival (OS) and progression-free survival (PFS), and systemic inflammation assessed using C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were analysed using Kaplan–Meier and Cox regression analyses. Results: Among the 161 patients included (67.1% male; median age 66 years), myopenia and myosteatosis were highly prevalent (62.7% and 87.6%, respectively), despite a median body mass index (BMI) within the normal range. Lowest SMI tertile was significantly associated with poorer OS and PFS, whereas lowest SMD tertile showed markedly reduced OS. On multivariate analyses, lower SMD remained independently associated with OS and with PFS, whereas SMI lost significance after adjustment for clinical and inflammatory factors. The coexistence of myopenia and myosteatosis was associated with significantly worse survival outcomes. An exploratory continuous muscle score integrating muscle quantity and muscle quality was associated with OS (hazard ratio 1.28 per SD increase) and demonstrated moderate prognostic discrimination (concordance-index 0.63). Conclusions: Muscle quantity and quality represent complementary dimensions of cancer-associated muscle impairment in oesophagogastric cancer. Collectively, these results suggest that a continuous measure integrating both muscle quantity and muscle quality provides a more clinically informative assessment of muscle impairment than traditional binary definitions of myopenia and myosteatosis. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
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8 pages, 190 KB  
Article
Incidentally Detected Basal Ganglia Calcifications Are Not Associated with Impaired Mobility and Recurrent Falls in Older Adults
by Irene M. de Graaf, Annemarieke de Jonghe, Nienke M. S. Golüke, Esther J. M. de Brouwer, Mariëlle H. Emmelot-Vonk, Pim A. de Jong, Lydia C. M. Kwekkeboom and Huiberdina L. Koek
J. Clin. Med. 2026, 15(12), 4732; https://doi.org/10.3390/jcm15124732 - 18 Jun 2026
Abstract
Background: Basal ganglia calcifications (BGCs) are frequently detected on brain CT scans in older adults, but their clinical relevance for mobility and fall risk is unclear. This study investigated the association of BGCs with impaired mobility and recurrent falls. Methods: In this cross-sectional [...] Read more.
Background: Basal ganglia calcifications (BGCs) are frequently detected on brain CT scans in older adults, but their clinical relevance for mobility and fall risk is unclear. This study investigated the association of BGCs with impaired mobility and recurrent falls. Methods: In this cross-sectional study, all consecutive patients referred to the mobility clinic of a regional teaching hospital between 2019 and 2021 were included. Mobility was assessed using the Performance-Oriented Mobility Assessment (POMA) for balance, gait and overall mobility, and the Timed Up and Go (TUG) test for functional mobility. All assessments were performed by a trained physiotherapist. Recurrent falls were defined as self-reported occurrence of more than one fall in the past 12 months. Brain CT scans were evaluated for BGCs by a trained senior radiologist and were scored by severity. Univariable and multivariable logistic regression analyses were performed, adjusting for age, sex, and history of cardiovascular events. Results: A total of 253 participants were included (median age 82 years; 58% female), of whom 31% had BGCs. Falls data were available for 246 participants, and 70% reported recurrent falls. In both univariable and multivariable analyses, there was no evidence of a statistically significant association between the presence of BGCs and impaired balance, gait, overall mobility, functional mobility, or recurrent falls. Conclusions: No evidence of a statistically significant association was found between incidentally detected BGCs and impaired mobility or recurrent falls in older adults. Further longitudinal research is needed to confirm these findings and clarify whether BGCs are clinically relevant for mobility and fall risk assessment. Full article
(This article belongs to the Section Geriatric Medicine)
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