Journal of Clinical Medicine最新文献

Background/Objectives: To analyze the financial impact of the ERAS program in two major surgical procedures (colon resection for cancer and hip replacement) in two second-level healthcare centers. Methods: A cost-benefit analysis was carried out on four hypothetical scenarios, based on the rate of compliance with the ERAS program, focusing on the additional costs and the additional benefits deriving from the decrease in hospital stay caused by the application of the ERAS protocol, with particular regard to the interventions envisaged by the National Waiting List Management Plan (PNGLA). Results: In the most optimistic scenario, with a coefficient of application of ERAS of 100% and a number of 800 days of hospitalization gained per year, the revenue-cost ratio was equal to 2.92. In the least favorable scenario, with a coefficient of application of ERAS of 50% and a number of 400 days of hospitalization gained per year, the revenue-cost ratio was equal to 1.11. Conclusions: In all the scenarios, the revenue-cost ratio was higher than 1. Implementation of the ERAS program is feasible also in second-level centers with the costs for additional healthcare professionals. Application of the ERAS program leads to a more sustainable health policy with an improvement in the number of treated patients per year and an advantage in the waiting list.

Background:Klebsiella species are a leading cause of Gram-negative bacteremia associated with nosocomial infections. They exhibit higher antimicrobial resistance compared to other Enterobacterales, emphasizing their role as a "sentinel organism". While the impact of inappropriate empiric therapy has been studied, data specific to Klebsiella bacteremia are limited due to small sample sizes. This study aims to provide high-resolution data on Klebsiella bacteremia and assess the impact of appropriate empirical therapy on clinical outcomes. Methods: We conducted a retrospective study of patients with Klebsiella bacteremia hospitalized at Beilinson Hospital between 2012 and 2022. Patients were categorized into two groups based on the appropriateness of empiric therapy. The primary outcome was 30-day all-cause mortality; subgroup analyses evaluated mortality in ESBL bacteremia treated with either carbapenems or piperacillin-tazobactam, and carbapenems versus aminoglycosides. Propensity score weighting and inverse probability treatment-weighted models were used to adjust for confounding. Results: Among 1132 patients, 79% received appropriate empirical therapy. This therapy was associated with reduced 30-day mortality (OR = 0.59, 95% CI: 0.46-0.76) and a shorter hospital stay (median 7 vs. 11 days, p < 0.001). Other significant risk factors for mortality included a higher Charlson comorbidity score (OR = 1.06), assistance with ADL (OR = 2.16), prior hospitalization (OR = 1.31), and a higher SOFA score (OR = 1.32). No significant mortality differences were observed in ESBL subgroups treated with carbapenems versus piperacillin-tazobactam (p = 0.2) or carbapenems versus aminoglycosides (p = 0.9). Conclusions: Early appropriate empirical therapy significantly reduces 30-day mortality in Klebsiella bacteremia. These findings highlight the importance of timely, appropriate empirical therapy and suggest choosing less broad-spectrum therapy. However, the lack of molecular data on resistance mechanisms limits the ability to assess strain-specific outcomes and may affect generalizability. Despite this, the study offers valuable insights for optimizing empirical therapy and advancing antimicrobial stewardship in the era of rising resistance.

Objective: To investigate the impact of proteinuria severity on obstetric and neonatal outcomes and to assess the predictive value of 24 h urinary protein excretion, both alone and within a multivariable model, for adverse pregnancy outcomes. Methods: This retrospective cohort study included 203 pregnant women with proteinuria who were classified into mild (≥0.3 g/day and <3.0 g/day, n = 50), severe (≥3.0 g/day and <5.0 g/day, n = 67), and massive (≥5.0 g/day; n = 86) groups based on 24 h urine protein levels. Maternal and neonatal outcomes were compared between these groups. Correlation analysis, receiver operating characteristic (ROC) curve analysis, and multivariable logistic regression were used to evaluate the predictive value of proteinuria for obstetric complications and identification of increased risk of early delivery. The AUC values of the proteinuria-only model and the multivariable model were compared using the DeLong test, as both models were derived from the same dataset and therefore represented correlated ROC curves. Results: The incidence of obstetric complications was significantly higher in the severe (68.7%) and massive (81.4%) proteinuria groups compared with the mild group (32.0%; p < 0.001). Increasing proteinuria severity was associated with earlier gestational age at delivery, lower birth weight, and higher rates of fetal growth restriction (all p < 0.001). The 24 h proteinuria level demonstrated moderate predictive ability for obstetric complications (AUC 0.73; 95% CI 0.66-0.80). A multivariable model including nephrotic-range proteinuria (≥3 g/day) and gestational age at diagnosis showed improved discriminatory performance compared with proteinuria alone (AUC 0.81; 95% CI 0.75-0.88). The model based on continuous 24 h proteinuria yielded an AUC of 0.73 (95% CI, 0.66-0.80) for identifying pregnancies at increased risk of obstetric complications. The multivariable model showed a numerically higher AUC of 0.81 (95% CI, 0.73-0.86); however, the difference between the two AUCs was not statistically significant according to the DeLong test (z = 0.82, p = 0.41). Conclusions: The severity of maternal proteinuria is associated with a higher likelihood of adverse maternal and neonatal outcomes, and higher proteinuria levels appear to show a graded association with increasing risk. A multivariable model integrating proteinuria with key clinical parameters demonstrated moderate discriminatory ability for obstetric complications, may support a more holistic approach to risk stratification in clinical practice.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. They can cause immune-mediated colitis (IMC), a potentially severe adverse event. Current data on severe IMC (grade 3-4) are limited, particularly regarding clinical, endoscopic, and histological features. Methods: We conducted a multicenter, retrospective observational study promoted by GETECCU, including adults with solid tumors who developed grade 3-4 IMC requiring hospitalization and systemic therapy. Clinical symptoms, endoscopic findings (Mayo and UCEIS indices), and histological features were systematically collected and analyzed. Results: A total of 196 patients were included. Diarrhea was universal (median 8 bowel movements/day), with 76% reporting abdominal pain and 39% rectal bleeding. Endoscopy (n = 139) revealed vascular pattern loss (80%), mucosal lesions (69%), and Mayo scores ≥2 in 69%. Histopathology (n = 141) showed abnormalities in 85%, including cryptitis (50%), lymphocytic infiltration (48%), and crypt abscesses (37%). Notably, 72% of patients with normal endoscopy had histological inflammation. Endoscopic severity correlated with bleeding and impaired general condition but not with stool frequency or pain intensity. Histological and endoscopic severity were modestly associated. Conclusions: Severe IMC presents with heterogeneous clinical, endoscopic, and histological features, with limited correlation between these domains. Endoscopic findings were often ulcerative and inflammatory, yet histological abnormalities were frequently present even in endoscopically inactive disease. These findings highlight the importance of biopsy in all suspected IMC cases and underscore the need for validated multidimensional assessment tools for accurate diagnosis and management of severe IMC.

Background/Objectives: Immunotherapy has improved outcomes for selected patients with advanced non-small-cell lung cancer (NSCLC), yet the predictive value of individual biomarkers such as PD-L1 remains limited. Systemic inflammatory indices derived from routine blood tests may complement molecular and immunohistochemical features, offering a broader view of host-tumor immunobiology. Methods: We conducted a retrospective study of 298 patients with stage IIIB-IV NSCLC treated with immune checkpoint inhibitors (ICIs) at a tertiary oncology center between 2022 and 2024. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) were collected alongside PD-L1 expression and molecular alterations (EGFR, KRAS, ALK, TP53). Patients were stratified into inflammatory-molecular clusters integrating these parameters. Associations with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated using Kaplan-Meier and multivariate Cox analyses. Results: Four distinct inflammatory-molecular clusters demonstrated significantly different outcomes (p < 0.001). Patients with low NLR and high PD-L1 expression (Cluster A) showed the highest ORR (41%), longest median PFS (13.0 months), and OS (22.5 months). The EGFR/ALK-driven, inflammation-dominant cluster (Cluster C) exhibited poor response (ORR 7%) and shortest survival (PFS 4.3 months). High NLR (HR 2.12), PD-L1 < 1% (HR 1.91), and EGFR mutation (HR 2.36) independently predicted shorter PFS. A combined model incorporating NLR, PD-L1, and molecular status outperformed individual biomarkers (AUC 0.82). Conclusions: Integrating systemic inflammatory indices with PD-L1 expression and molecular alterations identifies clinically meaningful NSCLC subgroups with distinct immunotherapy outcomes. This multidimensional approach improves prediction of ICI response and may enhance real-world patient stratification, particularly in settings with limited access to extended molecular profiling.

Asymptomatic aortic regurgitation (AR) has traditionally been managed conservatively until symptom onset or overt left ventricular systolic dysfunction. However, adverse myocardial remodeling-detected by myocardial strain, volumetric cardiac magnetic resonance, and fibrosis imaging-often precedes current guideline thresholds for interventions and may be irreversible. Advances in multimodal imaging now enable earlier risk stratification beyond conventional metrics. In parallel, intervention strategies are evolving, including valve repair, valve-sparing root replacement, Ross procedure, and transcatheter aortic valve replacement in selected high-risk patients. This narrative review summarizes contemporary advances in imaging and intervention for asymptomatic AR, while critically appraising current evidentiary and technical limitations that constrain earlier intervention. The review is based on a narrative synthesis of the contemporary literature, drawing from recent clinical studies, imaging advances, and guideline documents rather than a systematic evidence search.

Background: Vesicoureteral reflux (VUR) contributes significantly to recurrent childhood urinary tract infections and renal scarring, yet predicting which patients will develop adverse outcomes or benefit from specific investigations or treatments remains challenging. Numerous prognostic tools have been proposed, but none have achieved widespread adoption.

Methods: A comprehensive search of the literature available on MEDLINE, PUBMED, Embase, Emcare, CINAHL, and Google Scholar was performed to identify combinations of factors, scoring systems, ratios, models, and tools relating to VUR. This included predicting the spontaneous resolution of established vesicoureteral reflux, the risk of breakthrough urinary tract infections (UTIs), and guiding clinical decision making regarding the need for VCUG in patients with UTIs, continuous antibiotic prophylaxis (CAP), or surgical intervention in patients with confirmed VUR. Articles were included if they either described or validated a predictive tool that was designed to aid clinical decision making in patients with either suspected or confirmed VUR with regards to investigation or management strategies. All the studies included were then analysed, and the predictive tools have been summarised in a narrative format.

Results: Seventeen predictive tools developed over thirty-nine years were identified: six predicting spontaneous resolution, four predicting breakthrough urinary tract infection (BTUTI) on CAP, two determining which children benefit from CAP, and five estimating the probability of VUR or high-grade VUR after a first febrile UTI. Approaches ranged from radiological ratios to multifactorial clinical-radiological scores and machine-learning models. Only five tools had any external validation, and none demonstrated sufficient reliability for universal clinical use. Significant heterogeneity in design, imaging interpretation, inclusion criteria, and outcome definitions limited comparison and wider applicability.

Conclusions: This atlas provides the first consolidated overview of prognostic tools in paediatric VUR. Future development should prioritise multicentre, prospectively validated models that integrate established clinical and radiological predictors with transparent computational methods to create practical, generalisable risk-stratification frameworks for routine care.

Background: Weaning failure remains a major challenge in intensive care practice, often reflecting the interplay between systemic catabolism and skeletal muscle wasting. The blood urea nitrogen-to-creatinine (BUN/Cr) ratio is a routinely available biochemical index influenced by renal handling, hemodynamic status, protein metabolism, and muscle mass, and has been associated with adverse outcomes in critical illness. This study aimed to evaluate the association between BUN/Cr ratio, weaning outcomes, and ultrasound-based rectus femoris thickness. Methods: This retrospective observational study included 42 mechanically ventilated adults admitted to the medical ICU of Marmara University between December 2024 and September 2025. Rectus femoris thickness was measured via bedside ultrasonography at the time of the spontaneous breathing trial (SBT). Weaning success was defined as extubation without reintubation, death, or need for NIV/HFNO due to respiratory distress within 7 days. Laboratory and clinical variables-including BUN/Cr ratio, SOFA, APACHE II, mNUTRIC, and albumin-were recorded. Multivariable logistic regression and receiver operating characteristic (ROC) analyses were performed. Results: Weaning failure occurred in 13 patients (31.0%). These patients had higher BUN/Cr ratios (58.7 [44.6-76.9] vs. 39.7 [23.8-49.2], p = 0.007) and lower rectus femoris thickness (6.2 [5.4-7.0] vs. 7.8 [6.9-8.6] mm, p = 0.021). The BUN/Cr ratio independently predicted weaning failure (OR 1.07; 95% CI 1.01-1.14; p = 0.024). ROC analysis identified a BUN/Cr cut-off of 44.6 (AUC = 0.76) for weaning failure. An exploratory composite metabolic-muscle indicator (MMI), combining BUN/Cr ratio and rectus femoris thickness, demonstrated higher discriminative performance in this cohort (AUC = 0.81). Conclusions: An elevated BUN/Cr ratio was independently associated with weaning failure and lower rectus femoris thickness in this cohort. Given the observational design and potential confounding, these findings should be interpreted as hypothesis-generating. Combined biochemical and ultrasound-based assessment highlights the potential value of integrating metabolic and morphologic information when characterizing patients at risk for weaning failure. However, whether incorporation of such markers into clinical decision-making improves weaning outcomes requires prospective validation.

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, with ischemic and structural heart diseases being key contributors. While the 12-lead electrocardiogram (ECG) is a common low-cost diagnostic test, its interpretation is limited by human variability. Through machine learning with large diverse ECG data sets and artificial intelligence (AI) algorithms, ECG analysis can be automated for pattern recognition with higher accuracy. AI-augmented ECG algorithms have been demonstrated to be able to detect myocardial infarction with high accuracy and reduce door-to-balloon coronary intervention times. Similar models can be utilized to detect subtle ECG waveforms suggestive of current or future asymptomatic left ventricular dysfunction, aortic stenosis, and hypertrophic cardiomyopathy. Despite these promising results, there is concern for generalizability and bias or errors in training data. As AI systems evolve to multimodal integration, AI-augmented ECG has the potential to redefine cardiovascular diagnostics and enable earlier detection, risk stratification, and precision-guided interventions.

Background/Objectives: Intravenous thrombolytic therapy remains the cornerstone of managing acute ischemic stroke (AIS) patients. Given the potential adverse effects of thrombolysis, patients are admitted to an intensive care unit (ICU) for close monitoring following administration. Alternative post-thrombolytic pathways may provide safe, cost-effective care in certain populations. We aimed to determine the proportion of patients treated with thrombolytics who required ICU care for reasons other than frequent neurologic monitoring and to define their characteristics. Methods: We retrospectively (May 2020-August 2022) reviewed patients ≥ 18 years of age who received Tenecteplase (TNK) or tissue plasminogen activator (tPA) for AIS at our stroke center. Patients were classified as requiring ICU care if they required intubation within 24 h of admission, required neurosurgical intervention, had symptomatic hemorrhagic conversion or brain compression, required a continuous infusion for hemodynamic management, or were in status epilepticus. Univariate and multivariable statistical analyses were performed. The study protocol was deemed exempt by our Institutional Review Board. Results: 262 patients met inclusion criteria. A total of 54 (20.6%) required ICU care. Multivariable analysis showed that patients on antithrombotic therapies prior to arrival (AOR: 3.344, p = 0.002) or who presented with higher initial NIH stroke scale (AOR: 1.116, p < 0.001) had a significantly higher likelihood of requiring an ICU level of care. Conclusions: In our cohort, approximately 21% of patients required critical care. Antithrombotic therapy before admission and greater NIH stroke scale on arrival were associated with an increased likelihood of requiring ICU care. Further prospective studies are indicated to assess the efficacy of alternative settings for post-thrombolytic care in selected AIS patients; however, our findings suggest that a specific subset of patients with AIS can be safely and effectively cared for in a non-ICU setting. This may have implications for the provision of safe, effective care while optimizing healthcare resource utilization.