Search Results (400)

Background: We aimed to analyze radiographic sagittal balance parameters in patients who underwent a TLIF procedure for single-level degenerative spondylolisthesis with a mean follow-up of 8.6 years and to determine whether lumbar lordosis affects long-term clinical outcomes. Methods: This prospective study included 32 patients who underwent single-level TLIF surgery for degenerative spondylolisthesis. Radiographic analysis of sagittal balance parameters and clinical examination including Oswestry Disability Index (ODI) scores were performed preoperatively, postoperatively, and at the last follow-up. A minimal clinically important difference threshold of 30% was accepted as clinically relevant. Results: Mean postoperative lumbar lordosis (LL) and segmental lordosis (SL) failed to improve postoperatively; nevertheless significant improvements in short- and long-term postoperative ODI scores were demonstrated (p < 0.001). Thoracic kyphosis (TK) and global sagittal balance parameters shifted anteriorly after 8.6 years (p < 0.001), but this increase did not affect clinical outcomes. Conclusions: Adequate decompression and solid bone fusion are foremost required to achieve improved long-term clinical outcomes in single-level TLIF procedures. In our studied cohort, failure to improve lordosis did not impair clinical outcomes postoperatively. With aging, thoracic kyphosis and anterior malalignment increase, and after 8.6 years, clinical improvements are starting to become insignificant. Full article

Background: Phosphodiesterase type 5 inhibitors (PDE5i), particularly tadalafil and sildenafil, are the first-line therapies for erectile dysfunction (ED). After the patent expiration of branded tadalafil in 2017, generic formulations became available. Despite equivalent efficacy, skepticism persists regarding the effectiveness and safety of generics. The SHIFT study aimed to evaluate the non-inferiority of a generic tadalafil (Dalerpen) compared with branded and other generic tadalafil in terms of clinical efficacy and patient satisfaction. Methods: A prospective, multicenter study was conducted involving 247 patients treated with tadalafil (either 5 mg or 20 mg) for ED. Patients switched from branded or other generic tadalafil to Dalerpen. Baseline and follow-up assessments included the International Index of Erectile Function—Erectile Function Domain (IIEF-EF) (primary endpoint), Sexual Encounter Profile (SEP-2 and SEP-3), and International Prostatic Symptom Score (IPSS). A one-month follow-up was performed. Results: A total of 247 patients were included in the final analysis. After switching to Dalerpen, significant improvements were observed in both IIEF-EF (18.8 ± 5.6 vs. 16.7 ± 5.4, p < 0.001) and IPSS scores (10.4 ± 6.7 vs. 11.2 ± 6.3, p < 0.001), though the minimal clinically important difference (MCID) was not reached. SEP-3 scores also significantly increased (3 ± 1.2 vs. 2 ± 1.1, p < 0.001). Multivariate analysis identified baseline IIEF, IPSS scores, and post-treatment IPSS as predictors of IIEF-EF improvement (p < 0.001). Switching to Dalerpen was an independent predictor of both IIEF-EF and IPSS improvement. No new adverse events were reported. Conclusions: The SHIFT study demonstrates that Dalerpen is non-inferior to branded tadalafil in terms of clinical efficacy, offering a reliable and cost-effective therapeutic option. Educating patients on bioequivalence and addressing concerns regarding generic drugs are essential to facilitate therapeutic switches. Full article

Background: Stroke recovery is influenced not only by clinical but also sociodemographic factors (SDFs). However, data on how variables such as age, sex, marital status, education, and employment status affect rehabilitation outcomes remain limited, particularly in structured inpatient settings. This study aimed to analyze the impact of key SDFs on functional recovery after stroke. Methods: A retrospective cohort of 289 stroke patients undergoing structured inpatient rehabilitation was analyzed. Functional status was assessed at admission, after three weeks, and at discharge using five standardized outcomes: gait speed (primary outcome), Barthel Index, Berg Balance Scale, Action Research Arm Test, and Ashworth scale. Repeated measures ANOVA and multivariable logistic regression were used to evaluate within-subject changes and associations with SDFs. Results: The cohort consisted predominantly of middle-aged to older adults (58% female, 62% married, 60% retired, 60% with primary education or less). Most patients (88%) had ischemic strokes of moderate severity. Significant improvements were observed across all functional measures. Employed, married, younger, and male patients achieved better outcomes. Interaction models indicated that older and female patients with moderate stroke severity demonstrated greater improvement than younger and male counterparts with milder strokes. Mean gait speed increased by +0.32 m/s, exceeding the minimal clinically important difference (MCID) of 0.16 m/s. Conclusions: Age, sex, marital status, education, and employment status are relevant predictors of stroke rehabilitation outcomes. These findings emphasize the importance of incorporating sociodemographic profiles into individualized rehabilitation planning to optimize functional recovery and reduce disparities among stroke survivors. Full article

The need to improve medical diagnosis is of utmost importance in medical research, consisting of the optimization of accurate classification models able to assist clinical decisions. To minimize the errors that can be caused by using a single classifier, the voting ensemble technique can be used, combining the classification results of different classifiers to improve the final classification performance. This paper aims to compare the existing voting ensemble techniques with a new game-theory-derived approach based on Shapley values. We extended this method, originally developed for binary tasks, to the multi-class setting in order to capture complementary information provided by different classifiers. In heterogeneous clinical scenarios such as thyroid nodule diagnosis, where distinct models may be better suited to identify specific subtypes (e.g., benign, malignant, or inflammatory lesions), ensemble strategies capable of leveraging these strengths are particularly valuable. The motivating application focuses on the classification of thyroid cancer nodules whose cytopathological clinical diagnosis is typically characterized by a high number of false positive cases that may result in unnecessary thyroidectomy. We apply and compare the performance of seven individual classifiers, along with four ensemble voting techniques (including Shapley values), in a real-world study focused on classifying thyroid cancer nodules using proteomic features obtained through mass spectrometry. Our results indicate a slight improvement in the classification accuracy for ensemble systems compared to the performance of single classifiers. Although the Shapley value-based voting method remains comparable to the other voting methods, we envision this new ensemble approach could be effective in improving the performance of single classifiers in further applications, especially when complementary algorithms are considered in the ensemble. The application of these techniques can lead to the development of new tools to assist clinicians in diagnosing thyroid cancer using proteomic features derived from mass spectrometry. Full article

Background/Objectives: The tumor microenvironment (TME) plays a critical role in cancer progression by shaping immune responses and influencing patient outcomes. We hypothesized that the relative proximity of specific immune cell pairs to cancer cells within the TME could help predict their pro- or anti-tumor functions and reflect clinically relevant immune dynamics. Methods: We analyzed imaging mass cytometry (IMC) data from lung adenocarcinoma (LUAD) and triple-negative breast cancer (TNBC) cohorts. For each immune cell pair, we calculated a relative distance (RD) score, which quantifies the spatial difference in proximity to cancer cells. We assessed the prognostic and predictive significance of these RD-scores by comparing them with conventional features such as cell fractions, densities, and individual cell distances. To account for variations in cell abundance, we also derived normalized RD-scores (NRD-scores). Results: RD-scores were more strongly associated with overall patient survival than standard immunological metrics. Among all immune cell pairs, the RD-score comparing the proximity of B cells to that of intermediate monocytes showed the most significant association with improved survival. In TNBC, RD-scores also improved the distinction between responders and non-responders to immunochemotherapy and chemotherapy. Normalized RD-scores reinforced these findings by minimizing the influence of cell density and further highlighting the importance of immune cell spatial relationships. Conclusions: RD-scores offer a spatially informed biomarker that outperforms traditional metrics in predicting survival and treatment response. This approach provides a new perspective on immune cell behavior in the TME and has potential utility in guiding personalized cancer therapies and patient stratification. Full article

Circulating cell-free DNA (cfDNA) is an important biomarker for various cancer types, enabling a non-invasive testing approach. However, pre-analytical variables, including sample collection, tube type, processing conditions, and extraction methods, can significantly impact the yield, integrity, and overall quality of cfDNA. This study presents a comprehensive analytical validation of a magnetic bead-based, high-throughput cfDNA extraction system, with a focus on assessing its efficiency, reproducibility, and compatibility with downstream molecular applications. The validation was performed using a range of sample types: synthetic cfDNA spiked into DNA-free plasma, multi-analyte ctDNA plasma controls, Seraseq ctDNA reference material in a plasma-like matrix, extraction specificity controls, residual clinical specimen from patients, and samples from healthy individuals stored at room temperature or 4 °C for up to 48 h to assess stability. Extracted cfDNA was analyzed for concentration, percentage, and fragment size, using the Agilent TapeStation. Variant detection was evaluated using a next-generation sequencing (NGS) assay on the Seraseq ctDNA reference material. The results demonstrated high cfDNA recovery rates, consistent fragment size distribution (predominantly mononucleosomal and dinucleosomal), minimal genomic DNA (gDNA) contamination, and strong concordance between detected and expected variants in reference materials. The workflow also showed robust performance under different study parameters, variable sample conditions, including sample stability and integrity. Together, these findings confirm the efficiency and reliability of the evaluated cfDNA extraction system and underscore the importance of standardized pre-analytical workflows for the successful implementation of liquid biopsy for early cancer detection, therapeutic monitoring, and improved patient outcomes. Full article

Background/Objectives: Prostate cancer is the most frequent cancer in men, for which Radiotherapy (RT) is used as a radical or post-surgical treatment. Actinic proctitis is one of the most disabling side effects of RT. Intestinal microbiome studies have highlighted the importance of short-chain fatty acids, in particular butyric acid, for their beneficial effects over intestinal epithelial cells. The aim of this prospective study is to evaluate if treatment with micro-encapsulated sodium butyrate (MESB) can reduce the incidence of actinic proctitis during RT in prostate cancer patients. Methods: In total, 122 consecutive patients with prostate cancer treated in Radiotherapy Unit, Centro di Riferimento Oncologico, IRCCS Aviano, were enrolled. Patients received MESB (3 tablets/day) from one week before until four weeks after RT. They completed a diary, tracking daily bowel movements, rectal bleeding, abdominal pain, and perceived health status before, at the end, and one month after RT. Results: Although an improvement in symptoms was observed, when comparing interpatient data before RT vs. one month after the end of RT, statistically significant differences emerged only regarding abdominal pain (94.2% vs. 81.6% vs. 81.6%) (McNemar’s test p < 0.002). Conclusions: MESB appears effective in reducing radiation-induced bowel toxicity during RT, minimizing stool changes, incontinence, and abdominal pain. Although patients’ health perception declined at RT completion, it improved after one month, suggesting MESB may support clinical recovery post-treatment. Full article

Background/Objective: The objective of this study is to compare the relative effectiveness of combination therapy (exercise plus manual therapy) versus single-modality physiotherapy interventions for improving pain and function in patients with rotator cuff-related shoulder pain (RCRSP), using a network meta-analysis (NMA) approach. Methods: We systematically searched five electronic databases from inception to October 2023 for randomized controlled trials (RCTs) evaluating non-invasive physiotherapy interventions in adults with RCRSP. Primary outcomes included pain intensity and shoulder function, assessed at 12 weeks. A frequentist NMA was conducted to estimate standardized mean differences (SMDs) with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane RoB 2.0 tool. Results: Eleven RCTs (n = 548) were included. Combination therapy demonstrated the greatest improvement in function (SMD = −1.02; 95% CI: −2.59 to 0.56) and pain (SMD = −1.05; 95% CI: −2.41 to 0.30), although the wide confidence intervals crossing the null suggests statistical uncertainty. Exercise therapy alone showed moderate functional improvement (SMD = −0.41; 95% CI: −1.64 to 0.82), and Kinesio taping (KT) provided moderate pain relief (SMD = −0.53; 95% CI: −1.81 to 0.75). While these effects approached known minimal clinically important difference (MCID) thresholds (e.g., DASH: 10–15; VAS: 1.4–2.0), they did not reach statistical significance. Conclusions: Based on 11 RCTs, combination therapy (exercise plus manual therapy) appears to be the most effective non-invasive approach for improving pain and function in patients with RCRSP. However, the wide confidence intervals highlight uncertainty. Further large-scale and long-term trials are warranted to confirm its clinical utility and sustainability. Full article

Retrospective Cohort Study. Objectives: The objectives of this study are to (1) compare post-operative patient-reported outcome measures (PROMs) between non-diabetic (non-DM) and diabetic (DM) patients undergoing Anterior Cervical Discectomy and Fusion (ADCF), (2) characterize the clinical trajectory, and (3) compare the rate of post-operative complications. Methods: A total of 261 non-DM and 52 DM patients were included. Patient demographics, Neck Disability Index (NDI) and Patient-Recorded Outcomes Measurement Information System (PROMIS) scores were collected up to one year after operation. Maximum medical improvement (MMI) was defined as the timepoint where more than 90% of the cohort achieved a minimal clinically important difference (MCID) in survey scores. Post-operative complications were collected. Descriptive and inferential statistics were performed. Results: Non-DM patients achieve MMI significantly more quickly than DM patients (non-DM: 6 months; DM: 1 year, p < 0.010). No difference in ∆NDI (non-DM: 24.9; DM: 23.0; p = 0.824) or ∆PROMIS-Physical Function (non-DM: 7.1; DM: 9.1; p = 0.373) was found between the two cohorts. In diabetic patients undergoing single-level fusion ACDF, a pre-operative HbA1c of ≥7.3% demonstrates 100% sensitivity and 25% specificity in detecting failure to achieve 1-year PROMIS MCID (AUC = 0.833, p = 0.009). There was no association between diabetic status and post-operative complication rate. Conclusions: Diabetic patients may demonstrate a slower rate of achieving maximum medical improvement despite equal subjective and clinical outcomes. Pre-operative HbA1c ≥ 7.3% demonstrates a significant correlation with worse subjective outcomes following single-level ACDF. Full article

Background and Objectives: Osteoarthritis (OA) of the knee and hip is a major cause of pain and functional impairment. This study evaluated the effects of non-immersive virtual reality (NIVR) combined with conventional physical therapy (CPT) on pain intensity, mechanical hyperalgesia, and perceived recovery in older adults with OA. Materials and Methods: Sixty older adults with mild-to-moderate knee or hip OA were randomly assigned to a NIVR group (NIVR-G; n = 30) or a CPT group (CPT-G; n = 30). Both groups completed 30 sessions over 10 weeks (3 sessions/week). The NIVR-G performed 20 minutes of exergames integrated into CPT. Pain intensity was assessed using the Visual Analog Scale (VAS), and mechanical hyperalgesia was evaluated through pressure pain thresholds (PPTs). Secondary outcomes included the Global Rating of Change (GRoC) and the minimal clinically important difference (MCID) for the VAS. This study is a secondary analysis of a randomized controlled trial registered at ClinicalTrials.gov (ID: NCT05839262). Results: The NIVR-G demonstrated significant reductions in pain intensity after 30 sessions (p < 0.05, d = 1.50), with greater improvements compared to the CPT-G (p < 0.05, d = 1.17). The MCID for the VAS was established at 9.2 mm, with a higher proportion of responders in the NIVR-G (p < 0.05). The NIVR-G also reported superior recovery perception on the GRoC scale (p < 0.05). No significant changes in PPTs were observed in either group. However, the improvements in the NIVR-G diminished four weeks post-intervention. Conclusions: NIVR exergames combined with CPT significantly reduced pain intensity, improved perceived recovery, and resulted in a higher proportion of responders compared to CPT alone. These findings support the use of NIVR as an effective adjunct to CPT in older adults with OA; however, further research is needed to optimize its long-term benefits. Full article

Background/Objectives: While anterior lumbar interbody fusion (ALIF) is a well-established treatment for degenerative lumbar spine pathology, the timing and pace of postoperative recovery remain poorly defined. Understanding these temporal trends is clinically important for setting patient expectations and optimizing postoperative care. Methods: This retrospective single-institution study evaluated functional recovery in patients undergoing primary, single-level stand-alone (SA) ALIF, or with percutaneous posterior instrumentation (PI). Patient-reported outcome measures (PROMs), including the Oswestry Disability Index (ODI), the Visual Analog Scale (VAS) for back and leg pain, and the SF-12 Physical Component Score (PCS), were assessed preoperatively and at 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. Achievement of minimum clinically important difference (MCID), global rating change (GRC), and return-to-activity milestones were also analyzed. Results: A total of 143 patients were included (90 SA; 53 PI). PROMs showed significant improvement through 1 year. VAS-back improved by 2 weeks, while ODI and SF12 PCS initially worsened but improved after 6 weeks. By 6 months, over half of the cohort achieved MCID, with continued gains through 1 year. Most patients returned to driving and work, and over 90% discontinued narcotics. Recovery trajectories were comparable between groups, despite early delays in the instrumented cohort. Conclusions: These findings provide time-specific recovery benchmarks that can guide surgical decision-making, patient education, and expectations around functional milestones. Full article

Background/Introduction: Beta-lactam antibiotics are among the most frequently prescribed drugs in clinical practice, yet their therapeutic drug monitoring remains underutilized despite high interindividual pharmacokinetic variability, especially in critically ill patients. Methods: To address this, we developed and validated an ultra-high-performance liquid chromatography (UHPLC-UV/Vis) method for the simultaneous quantification of six beta-lactams (cefepime, ceftolozane, ceftazidime, meropenem, ampicillin, and ertapenem) in plasma. Results: This method uses a single gradient mobile phase and a photodiode array detector, ensuring accurate separation, minimal interference, and robust analyte identification. Validation followed EMA bioanalytical guidelines, demonstrating selectivity, precision, accuracy, and linearity within clinically relevant ranges (1.0–50.0 mg/L). Stability tests showed that the analytes were stable in plasma for up to seven days at 4 °C and one month at −20 °C. Pilot clinical implementation in 35 patients revealed significant interindividual variability, supporting the need for routine beta-lactam monitoring. Approximately 26% of trough concentrations were below the minimal inhibitory concentration, while others exceeded thresholds associated with potential toxicity. Discussion: This study represents the first UHPLC-UV/Vis method for the simultaneous determination of these six beta-lactams, overcoming limitations of prior methods that required different mobile phases or excluded clinically relevant antibiotics. The method is universally applicable and easily transferable to routine clinical practice. Conclusions: These findings underline the importance of beta-lactam monitoring in optimizing treatment outcomes and combating antibiotic resistance in vulnerable populations. Further studies to assess free drug concentrations are warranted to enhance clinical applicability. Full article

Background: Rapid molecular detection of infectious pathogen with high sensitivity and specificity has become increasingly important in clinical microbiology laboratories. The need to develop domestically produced nucleic acid extraction equipment has grown since COVID-19 pandemic in South Korea. In this study, we developed a new magnetic bead-based automated nucleic acid extraction system, T-Prep24 system, and the performance of the new system was evaluated with many clinical specimens. Methods: A total of 180 respiratory specimens were collected, and nucleic acids were extracted using three different systems, the T-Prep24 system, TANBead system, and Qiagen system. The quality and concentration of extracted nucleic acid were evaluated by spectrophotometer and Qubit fluorometer. Qualitative determination for SARS-CoV-2 was performed by PowerChek SARS-CoV-2 Real-time PCR kit. Results: The median concentration of nucleic acid extracted by T-Prep24 system and measured by a fluorescence-based method was 0.685 ng/µL (first to third interquartile range, 0.258–1.493 ng/µL), which was lower than that of nucleic acid extracted by TANBead system (median value, 0.985 ng/µL; first to third interquartile range, 0.610–1.583 ng/µL; p < 0.001), and that of nucleic acid extracted by Qiagen system (median value, 4.710 ng/µL; first to third interquartile range, 3.783–5.810 ng/µL; p < 0.001). The Cq values of PCR assays using nucleic acid extracted by T-prep24 showed minimal systematic bias (slope = 1.015) when compared with those using nucleic acid extracted by TANBead, but significant proportional constant bias (slope = 0.907) when compared with those using nucleic acid extracted by Qiagen. The results of PCR assays using nucleic acid extracted by the T-Prep24 system were identical to those of PCR assays using nucleic acid extracted by TANBead system, and two discrepant results were identified when comparing with those by the Qiagen system. Conclusions: T-Prep24 system is a reliable and effective tool for nucleic acid extraction in clinical settings. Future investigations should be carried out to widen the applicability to a range of pathogens and sample types. Full article

Background: Diode lasers are valuable in oral surgery due to their excellent hemostasis, minimum post-operative pain, and minimally invasive procedures. A dual-wavelength diode laser in dentistry combines two distinct wavelengths, typically 450 nm and 808 nm, to provide a versatile approach to soft tissue procedures. This ex vivo study investigated the quantity of thermal effects of a dual-wavelength diode laser on porcine lingual mucosa to determine the optimal laser parameters for oral soft tissue biopsies and to improve the reliability of histological evaluation. The presence of thermal damage in the prelesional margins may compromise the diagnostic accuracy, particularly in cases of suspected malignancy. Methods: Thirty-six porcine lingual mucosa samples were excised using a diode laser (Wiser 3, Doctor Smile) in continuous wave (CW) and pulsed wave (PW) modes at average powers of 2, 3, and 4 W. The samples, preserved in 5% buffered formalin, underwent histological evaluation to measure epithelial and connective tissue damage. Results: The study demonstrated variable thermal effects depending on the laser mode and power settings. Minimal epithelial damage (0.62 mm) was observed at 2 W CW, while maximum damage (3.12 mm) occurred at 4 W pulsed wave (PW). Connective tissue exhibited slightly greater damage than epithelial tissue, with minimal damage (0.53 mm) at 4 W CW and maximum damage (3.19 mm) at 4 W pulsed wave (PW). Statistical analyses were performed using t-tests and ANOVA and revealed significant differences in tissue damage between certain groups, highlighting the impact of laser parameters on thermal effects. Conclusions: The dual-wavelength diode laser seems to have good surgical properties and is suitable for managing complex clinical cases. Although the low power average showed minimal thermal damage, for the importance of the diagnosis of suspected lesions of malignancy, a 2 mm prelesional margin should be maintained. Full article

Background/Objectives: Anxiety and stress are interrelated and connected to reduced health-related quality of life. Botanicals such as Apocynum venetum L. (A. venetum) have been shown to improve health outcomes. No human studies have been conducted in a diverse large group of healthy adults in the US. The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the effects of Venetron^® Rafuma (A. venetum leaf extract) on self-reported anxiety levels and overall health outcomes compared to placebo. Methods: Healthy adults (N = 476) seeking improvement in self-reported anxiety and stress were randomly assigned to receive 50 mg of A. venetum (n = 234) or placebo (n = 242) for 6 weeks. Feelings of anxiety were assessed at baseline and weekly using Patient-Reported Outcomes Measurement Information System (PROMIS™) Anxiety 8A. Perceived stress, sleep quality, and cognitive function were evaluated at baseline and weekly using validated assessments. A linear mixed-effects regression model was used to compare the change in health outcome scores between active and placebo groups. Results: A total of 370 participants completed at least one additional assessment and were included in the analysis: 179 in the active arm and 191 in the placebo arm. There was a significant difference between the groups in the rate of improvement in perceived stress and sleep disturbance. The active group was significantly more likely to experience a Minimal Clinically Important Difference (MCID) in their perceived stress and marginally significantly more likely to experience an MCID in their feelings of anxiety. Participants who reported experiencing side effects did not significantly differ between arms. Conclusions: Venetron^® may be safe and effective therapy for stress and sleep disturbance among those suffering from feelings of anxiety. Full article