Search Results (85)

Influenza vaccines are the primary strategy to prevent severe influenza disease; however, their efficacy is often suboptimal, particularly in older adults (OAs). LiteVax Adjuvant (LVA), a novel adjuvant containing carbohydrate fatty-acid monosulphate ester (CMS) as the active ingredient, has demonstrated a favourable safety profile and enhanced immunogenicity when combined with a low-dose seasonal influenza vaccine in adults aged 18 to 50 years in a first-in-human phase 1 study. The present study investigates the reactogenicity and immunogenicity of CMS-based adjuvanted seasonal influenza vaccine in OAs, with a comparison to responses in younger adults (YAs). In this phase 1b, double-blind, active-controlled clinical trial, 36 YAs (18–50 years) and 48 OAs (≥60 years) were randomized (1:1:1) to receive either 0.5 mg or 1 mg LVA combined with VaxigripTetra, or VaxigripTetra alone. Solicited adverse events (AEs) were recorded using an electronic diary for 7 days following vaccination. Hemagglutination inhibition (HI) titers against four influenza strains were measured at baseline (pre-vaccination) and at 7-, 28-, and 180-days post-vaccination. All 24 YAs and 31 out of 32 OAs receiving CMS-based adjuvanted vaccines reported pain post-vaccination, compared to 8/12 YAs and 4/16 OAs receiving VaxigripTetra. Systemic AEs were more frequently reported among YAs receiving CMS-based adjuvanted vaccines (22/24) compared to those receiving VaxigripTetra (8/12). In OAs, the number of systemic AEs was similar regardless of CMS-based adjuvant administration. Most AEs were mild to moderate and resolved within 3 days. Both CMS-based adjuvanted formulations elicited increased HI titers at Day 7, peaking at Day 28, with a decline thereafter that remained above baseline at Day 180. In YAs, HI titers were comparable between the CMS-based adjuvanted and non-adjuvanted vaccines across all strains and timepoints. In contrast, CMS-based adjuvanted vaccination in OAs induced higher HI titers at Days 28 and 180 for all influenza strains tested. LVA shows an acceptable safety profile in both age cohorts and enhances humoral immune responses in older adults. The 1 mg dose of LVA was more immunogenic, highlighting its potential utility in this target population. Future research will focus on elucidating the mechanisms underlying the immunostimulatory effect of the CMS-based adjuvant. Full article

Introduction: Breast cancer therapy is a common cause of lymphedema. The accumulation of protein-rich fluid in the affected extremity leads to a progressive path—swelling, inflammation, and fibrosis—namely, irreversible changes. Methods: A scientific literature analysis was performed on PubMed/Medline, Scopus, Web of Science (WoS), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Physiotherapy Evidence Database (PEDro) from inception until 30 June 2024. Results: Breast cancer-related lymphedema (BCRL) is indeed an important healthcare burden both due to the significant patient-related outcomes and the overall social impact of this condition. Even though lymphedema is not life-threatening, the literature underlined harmful consequences in terms of pain, infections, distress, and functional impairment with a subsequent and relevant decrease in quality of life. Currently, since there is no cure, the therapeutic approach to BCRL aims to slow disease progression and prevent related complications. A comprehensive overview of postmastectomy lymphedema is offered. First, the pathophysiology and risk factors associated with BCRL were detailed; then, diagnosis modalities were depicted highlighting the importance of early detection. According to non-negligible changes in patients’ everyday lives, novel criteria for patients’ functioning assessment are reported. Regarding the treatment modalities, a wide array of conservative and surgical methods both physiologic and ablative were analyzed with their own outcomes and downsides. Conclusions: Combined strategies and multidisciplinary protocols for BCRL, including specialized management by reconstructive surgeons and physiatrists, along with healthy lifestyle programs and personalized nutritional counseling, should be compulsory to address patients’ demands and optimize the treatment of this harmful and non-curable condition. The Lymphedema-specific ICF Core Sets should be included more often in the overall outcome evaluation with the aim of obtaining a comprehensive appraisal of the treatment strategies that take into account the patient’s subjective score. Full article

(1) Background: Lymphedema is a common but underrecognized sequela of cancer treatment. Supermicrosurgical procedures such as lymphaticovenular anastomosis (LVA) and, more recently, lymph node-to-vein anastomosis (LNVA) have emerged as effective options for fluid-predominant disease. In 2024, we began performing robot-assisted LNVA using a next-generation microsurgical robot. This study describes our initial experience, technical insights, and the potential for robotics to extend the boundaries of supermicrosurgery. (2) Methods: Twenty-two consecutive robotic LNVAs were performed by a high-volume supermicrosurgeon at a tertiary center. Preoperative imaging with standard and ultra-high frequency ultrasound was used to identify optimal lymph nodes and veins. Robotic LNVA was performed using the Symani Surgical System, with adaptations for motion scaling, ergonomics, and console control. Intraoperative patency was confirmed by direct washout and/or indocyanine green (ICG) transit. (3) Results: All 22 procedures were technically successful, with 100% intraoperative patency. Anastomosis time improved from 37 to 18 min. Robotic assistance enhanced precision, eliminated tremors, and reduced the technical burden of operating at extreme submillimeter scales. (4) Conclusions: Robotic LNVA is safe, feasible, and efficient. It optimizes current techniques, offering the potential to extend surgical access below the 0.1 mm threshold, with implications for future treatment of lymphatic and possibly intracranial disease. Full article

Background: The patient-reported outcomes (PROs) of sacituzumab govitecan (SG) were compared with chemotherapy using two phase 3 trials (TROPiCS-02, EVER-132-002) involving patients with HR+/HER2− locally recurrent inoperable or metastatic breast cancer. Methods: A meta-analysis was performed to compare change from baseline (CFB) scores and time-to-deterioration (TTD) between SG and chemotherapy using EORTC QLQ-C30 and EQ-5D-5L VAS in the overall, prior CDK4/6i-treated, and fast-progressor populations. Results of CFB and TTD analyses were summarized using hazard ratio (HR) and mean difference measures. Results: Statistically significant improvement (p < 0.05) in CFB scores was observed with SG over chemotherapy in five EORTC QLQ-C30 domains: physical (mean difference: 2.64), role functioning (mean difference: 2.70), fatigue (mean difference: −2.51), pain (mean difference: −3.25) and dyspnea (mean difference: −3.27), and EQ-5D-5L VAS (mean difference: 1.58). In the overall population, longer TTD (p < 0.05) was observed with SG versus chemotherapy on six domains of EORTC QLQ-C30: GHS/QoL (HR: 0.76), physical (HR: 0.72), emotional functioning (HR: 0.73), fatigue (HR: 0.80), pain (HR: 0.82), and dyspnea (HR: 0.71). Results from EORTC QLQ-C30 domains were mostly consistent among the overall, prior CDK4/6i treated and fast-progressor populations. SG demonstrated longer TTD (p < 0.05) over chemotherapy for EQ-5D-5L-VAS across all studied populations (HR range: 0.63–0.69). PROs significantly worsened with SG in the domains of diarrhea and nausea and vomiting (commonly reported adverse events of SG, manageable by following established guidelines). Conclusions: SG significantly improved PROs versus chemotherapy for several subdomains of EORTC QLQ-C30 and EQ-5D-5L-VAS. The consistency of these results in the overall population and subgroups supports the generalizability of the meta-analytic evidence and reinforces the PRO benefits associated with SG versus chemotherapy. Full article

Non-maturing deposits (NMDs) are a significant source of liquidity for banks, making research into their modelling and forecasting invaluable. However, NMDs have no explicit expiration date, posing liquidity risks and complicating management. This research develops models and a framework to explain, predict, and manage variations in non-maturing deposits. Aggregate savings and transaction deposit data from an African bank were analysed to test the methodologies. The Trend-Fourier model, leveraging historical trends and Fourier analysis, forecasted 90-day deposit volumes. The model revealed prominent cyclicalities and monthly trends in deposit account volumes. Benchmarking showed high accuracy for savings deposit volumes, while transaction deposit volumes were less accurate, suggesting simpler models might be suitable. Additionally, a risk metric called LVaR (Liquidity Value at Risk) was proposed. Two approaches for calculating the LVaR were tested. An exceedance test demonstrated notable accuracy for savings deposit volumes but struggled with transaction deposits. Results indicated savings deposit volumes were more predictable than transaction deposits. These findings could enhance banks’ balance sheet management by improving non-maturing deposit forecasting. The proposed methodologies could be utilized for internal and regulatory purposes, such as calculating the liquidity coverage ratio under Basel regulations. Full article

Background and Objectives: Left ventricular aneurysm (LVA) causes geometric changes, including reduced systolic function and a more spherical shape, which is quantified by the sphericity index (SI), the ratio of the short to long axis in the apical four-chamber view. This study aimed to assess SI’s value in A-LVA and B-LVA, identify influencing factors, and evaluate its clinical relevance. Materials and Methods: This clinical study included 54 patients with post-infarction LVA and used echocardiography to determine LVA locations (A-LVA near the apex and B-LVA in the basal segments), with SI and other echocardiographic measures assessed in both systole and diastole for the entire cohort and stratified by A-LVA and B-LVA groups. Results: Among the 54 patients, 41 had A-LVA and 13 had B-LVA. The mean SI was 0.55 in diastole and 0.47 in systole for the cohort. Patients with A-LVA had a mean SI of 0.51 in diastole and 0.44 in systole, while B-LVA patients exhibited significantly higher SI values, with 0.65 in diastole and 0.57 in systole, due to lower long-axis (L) values in both phases. The mean left ventricular ejection fraction (EF) was 23.95% in A-LVA and 30.85% in B-LVA, with no significant difference. However, apical aneurysms were larger (greater LVAV and LVAA) and more significantly reduced functional myocardium. LVEDV, LVESV, LVEDA, and LVESA did not differ significantly between A-LVA and B-LVA. In cases of severe mitral regurgitation (MR), SI was notably higher (0.75 in diastole) due to a marked reduction in the L axis. Conclusions: SI is key in differentiating A-LVA and B-LVA on echocardiography. B-LVA has lower volume and area values, but similar aneurysm and left ventricular volumes and EF. Higher SI in B-LVA is due to a reduced L-axis, and is worsened by severe mitral regurgitation (MR). Surgical ventricular reconstruction (SVR) compensates for L-axis reduction, with preservation of the L axis critical for achieving a more physiological shape. SI thus serves as a marker for left ventricular geometry and surgical outcomes. Full article

The article focuses on the identification and mapping of cultural ecosystem service (CES) resources in the territory of the Local Action Group Lednice–Valtice Area (LAG LVA). The Consolidated Layer of Ecosystems (CLE) was used for mapping, and changes in the distribution and overall representation of cultural ecosystem service resources across the different CLE versions were monitored. A total of 27 ecosystem categories were identified in the region. Subsequently, the importance of cultural ecosystem services was assessed based on expert estimation. The classes of ecosystem services defined within the Common International Classification of Ecosystem Services (CICES) have been grouped into a total of four groups according to their common characteristics. Then, an expert estimation of all identified ecosystems in terms of their importance as sources of CESs was performed. It showed that ecosystems in the LAG LVA have a high potential to provide CES. As a result of the significant amount of CES resources, it is also an area that attracts a huge number of visitors annually. However, some places are more attractive and well known, causing an influx of tourists. The sustainability and protection of these resources, thus, depends on their appropriate management and integration into strategies and planning. Full article

Background/Objective: Left atrial (LA) fibrosis imaging improves the guidance of LA catheter ablation. Cardiac computed tomography (CT) may be a reasonable alternative to CMR. The aim was to evaluate late enhancement (LE) fibrosis mapping by CT, and to correlate the results with low-voltage areas on electroanatomical mapping (EAM). Methods: In patients with atrial fibrillation who underwent 128-slice dual-source CT angiography (CTA) prior to LA catheter ablation, an additional LE-CT scan was performed 7 min after CTA. (1) Left atrial wall thickness (LAWT) was measured at three sites along the LA ridge. (2) Late enhancement (LE) was quantified co-axially aligned to LAWT and compared with low-voltage areas (LVA) on EAM. Results: Of 137 patients (age: 59.8 years; 27.7% females), 108 were included. The prevalence of LE was higher in patients with LAWT > 2 mm compared with 1.5 mm, with 78 (91.7%) vs. 77 (80.2%) (p = 0.022). Of 78 patients with LE, 60 (77.1%) had focal, 13 (16.5%) had diffuse, and 5 (6.3%) had mixed LE patterns. The CT density of focal LE was not different from that of diffuse patterns (104.2 +/− 21 HU vs. 98.9 +/− 18 HU; p = 0.360). Increasing LAWT and LE-HU were weakly correlated (r = 0.229; p = 0.041). LA wall artifacts had higher CT density compared with LE (154.1 HU vs. 114.2 HU; p = 0.002). The effective radiation dose was 0.95 mSv (range, 0.52–1.2 mSv) for LE-CT. The agreement of LE-CT was 80% for LVA < 0.5 mV and 86.6% for LVA < 0.7 mV in a subset of 30 patients. Conclusions: Left atrial fibrosis mapping by LE-CT is feasible. Late enhancement was found more frequently in LAWTs of more than 2 mm, and LE was correlated with increasing LA remodeling and low-voltage areas. Full article

Lymphedema surgeries have been proven effective in treating lymphedema and are not considered experimental or unproven. The medical literature consistently supports the safe and successful use of physiologic drainage lymphedema surgeries such as lymphaticovenous anastomosis (LVA), vascularized lymph node transfer (VLNT), and reductive surgeries such as suction-assisted protein lipectomy (SAPL) when performed by an experienced lymphedema surgery team to treat properly selected patients. Proper integration of lymphedema therapy is critical to achieving successful outcomes. We review effective lymphedema surgeries, their indications, patient selection, and the proper application of surgical treatments to achieve optimal results. Full article

Background: Pulmonary vein isolation (PVI) is a foundational treatment for persistent atrial fibrillation (PeAF), but the effectiveness of adding posterior wall isolation (PWI) and selective complex fractionated atrial electrogram (CFAE) ablation in the roof and anterior wall remains debated. The potential of these additional ablation techniques to improve long-term outcomes for PeAF patients is still uncertain. Methods: This retrospective study included 151 PeAF patients who underwent first-time catheter ablation at our center. The choice of ablation strategy was based on the operator’s clinical judgment, taking into account the patient’s specific condition and anatomical features. Patients were divided into two groups: the PVI group, which received PVI alone, and the modified PWI (MPWI) group, which received PVI along with additional PWI and selective CFAEs ablation in the roof and anterior wall. The primary endpoint was the absence of atrial arrhythmia lasting more than 30 s, without antiarrhythmic drugs, at 12 months. Results: At the 12-month follow-up, 77.3% of the patients in the MPWI group and 52.1% of the patients in the PVI group remained in sinus rhythm without an atrial arrhythmia recurrence (p = 0.001). The BIC-based Cox regression analysis identified the ablation strategy and atrial fibrillation (AF) duration as independent predictors of recurrence across the cohort. It was found that MPWI significantly reduced the risk of recurrence, while a longer AF duration increased it. In the MPWI group, AF duration, left ventricular internal diameter in systole (LVIDs), and moderate or greater tricuspid regurgitation were independent predictors of recurrence. In the PVI group, only the left atrial low voltage area (LVA) index was a significant predictor. Conclusion: The addition of PWI and selective CFAE ablation to PVI significantly improves 12-month arrhythmia-free survival compared to PVI alone, demonstrating the superiority of this combined approach in improving long-term outcomes for patients with persistent AF. Full article

Background and Objectives: Left ventricular aneurysm (LVA) is associated with a decline in cardiac function, evidenced by a lower ejection fraction (EF), due to the reduction in the proportion of functional myocardium. The left ventricular end-diastolic volume (LVEDV), the left ventricular aneurysm volume (LVAV), and the LVAV/LVEDV ratio show a strong correlation with the EF. The aim of this study was to determine LVA characteristics post-myocardial infarction (basal vs. apical) and to evaluate the impact of aneurysm volume in diastole (LVAVd), aneurysm area in diastole (LVAAd), and their respective ratios with LVEDV and area (LVEDA) on the EF, in order to identify the most critical predictive factors for assessing and managing the negative impact of aneurysms on cardiac function. Materials and Methods: This observational study included post-infarction LVA patients at the “Dedinje” Cardiovascular Institute in Belgrade, Serbia, undergoing routine transthoracic echocardiography. Echocardiography assessed volumes (LVEDV, LVESV, LVAVd, LVAVs) and areas (LVAAd, LVAAs, LVEDA, LVESA) using the area–length method. The ratios (LVAVd/LVEDV, LVAVs/LVESV, LVAAd/LVEDA, LVAAs/LVESA) were derived from these measures. The left ventricular EF was calculated using Simpson’s method. Results: Basal aneurysms showed a significantly smaller LVAVd (p = 0.016), LVAAd (p = 0.003), and LVAAs (p = 0.029) compared to apical aneurysms, indicating that basal aneurysms are smaller in size. However, there was no significant difference in the EF and overall LV volumes between the groups, although the basal aneurysm group had a slightly higher EF and end-diastolic volume, with a slightly lower end-systolic volume. Furthermore, when comparing the correlation between the EF and the LVAVd, the LVEDV, and the LVAVd/LVEDV ratio, the results indicate that the LVAVd had the greatest impact on the EF (−0.695), followed by the LVAVd/LVEDV ratio (−0.637), and the lowest correlation is between the EF and LVEDV. A similar relationship is observed when comparing the EF with the LVESV, the LVAVs, and the LVAVs/LVESV ratio. Conclusions: Basal aneurysms are significantly smaller than apical ones, yet EF and LV volumes remain similar between the groups, with the EF being slightly higher in the basal group. In cases of LVA, LVAVd shows the strongest negative correlation with the EF, indicating its significant impact on systolic function, followed by the LVAVd/LVEDV ratio, with the weakest correlation seen between the EF and LVEDV. Full article

Background: The incidence of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) is high. Impaired left atrial (LA) function is a major determinant in HFpEF. However, the extent of electrical LA tissue degeneration in HFpEF is unknown. Therefore, we sought to investigate the amount of arrhythmogenic and fibrotic LA tissue degeneration in HFpEF patients presenting for AF ablation. Methods: We prospectively screened consecutive patients presenting for first time AF ablation. The HFA-PEFF score was used to identify HFpEF patients. Bipolar high-density voltage mapping was created in sinus rhythm prior to ablation to evaluate the general LA bipolar voltage and quantify areas of low voltage. LVAs were defined as areas with bipolar voltage < 0.5 mV. Results: In total, 187 patients were prospectively enrolled (age 65 ± 11 years, 45% female, 46% persistent AF, 25% HFpEF) in this study. HFpEF patients were older and had a higher CHA2DS2-VASc score (70 ± 9 vs. 63 ± 11 years and 3.2 ± 1.5 vs. 2.3 ± 1.5, each p < 0.001, respectively). Overall, low-voltage areas (LVAs) were present in 97 patients (52%), whereas 76% of the HFpEF population had LVA, as compared to 44% of patients without HFpEF (p < 0.001). HFpEF was associated with generally decreased LA bipolar voltage (1.09 ± 0.64 vs. 1.83 ± 0.91 mV; p < 0.001) and predictive of the presence of low-voltage areas (76% vs. 44% p < 0.001). The HFA-PEFF score inversely correlated with LA bipolar voltage (=−0.454; p < 0.001). Conclusions: HFpEF closely relates to generally decreased LA bipolar voltage and to the existence of fibrotic and arrhythmogenic LA tissue degeneration. Full article

We conducted a comprehensive examination of liquid mycotoxin reference standards. A total of 30 different standards were tested, each containing 10 samples of three distinct substances: Aflatoxin B1, Deoxynivalenol, and Zearalenone. The standards were sourced from 10 different global market leading manufacturers. To facilitate comparison, all the standard sets were adjusted to the same concentration level. The standards were analyzed using the techniques LC-MS/MS, HPLC-DAD, and LC-HRMS to assess their quality attributes. Regarding the validation of the reference values, it was observed that 30% of the suppliers provided reference standards that were either below the lower acceptance limit or above the higher acceptance limit, confirmed by both the LC-MS/MS and HPLC-DAD methods. Furthermore, a total of 12 impurities were found in the DON standards, 10 in the AFB₁ standards, and 8 in the ZON standards, distributed across all the suppliers. Therefore, this study suggests relevant adjustments to the ISO 17034 standard, proposing that the purity of a raw material should be uniformly based on q-NMR analysis, as most manufacturers state the purity of their certificates is determined using HPLC-UV or LC-MS/MS. Liquid standards with a shelf life of ≤1 year should not exceed an uncertainty of 3%. Standards that have a longer shelf life should not have more than 5% uncertainty. This study also emphasizes the importance of stability. The standards should undergo continuous long-term monitoring; otherwise, products may exhibit a target value of only 80%, as seen in one instance. It is also recommended to include proof of HPLC and LC-MS/MS analyses on the certificate of each released batch of a final product. Full article

Background: Primary lymphedema is a chronic condition caused by a developmental abnormality of the lymphatic system, leading to its malfunction. Various surgical options, including physiologic and excisional procedures, have been proposed. The aim of this study was to present a comprehensive algorithm for the treatment of primary lower extremity lymphedema: the Primary LYmphedema Multidisciplinary Approach (P-LYMA). Methods: Nineteen patients were treated following the P-LYMA protocol. Patients underwent pre- and postoperative complex decongestive therapy (CDT). A variety of physiologic and excisional procedures were performed, either independently or in combination. The primary outcome was to assess the circumferential reduction rate (CRR). The Lymphedema Quality of Life Score (LeQOLiS), reduction in the number of cellulitis episodes, and complications were recorded. Results: The mean CRR was 73 ± 20% at twelve months postoperatively. The frequency of cellulitis episodes per year decreased from a mean of 1.9 ± 0.8 preoperatively to 0.4 ± 0.6 during follow-up. Two patients experienced minor complications. The mean hospitalization time was 5 days. Patients’ quality of life, as measured by the LeQOLiS, significantly improved from 70.4 ± 12 preoperatively to 24 ± 14 at twelve months postoperatively. Conclusions: The P-LYMA algorithm maximizes surgical outcomes and improves the quality of life in patients with primary lymphedema. CDT is essential for optimizing results. Full article

Background: The surgical treatment of lymphedema has seen advancements in recent years, with supramicrosurgical lymphaticovenular anastomosis (sLVA) gaining global acceptance. The integration of 3D exoscopes into microsurgery offers potential ergonomic and educational benefits. However, systematic evaluation of their efficacy in sLVA remains limited. Methods: A retrospective cross-sectional study was conducted comparing the use of 3D exoscopes to conventional operating microscopes (OM) in sLVA surgeries. Patient data from January 2019 to January 2024 were reviewed, with demographic, clinical, and surgical outcome variables analyzed. Ergonomic assessments were performed using Rapid Entire Body Assessment (REBA) and Rapid Upper Limb Assessment (RULA), while surgeon satisfaction was evaluated through the Microsurgical Intraoperative Satisfaction and Comfort questionnaire (MISCq). Results: An analysis of 25 patients (OM group: n = 14; exoscope group: n = 11) revealed no significant differences in age, sex, etiology, or surgical site between the two groups. Surgical time, number of incisions, and number of anastomoses showed nonsignificant variations between the OM and exoscope groups. Ergonomic assessments indicated potential benefits with exoscope use, particularly for the assistant surgeon. Survey results demonstrated comparable levels of surgeon satisfaction with both instruments, with no significant differences in image quality, contrast, illumination, magnification, visual field, ergonomic maintenance, or stereoscopic orientation. Conclusions: The study suggests that 3D exoscopes are a valuable tool for sLVA supermicrosurgery, offering comparable outcomes to traditional microscopes with potential ergonomic advantages. Their integration into microsurgical practice may contribute to improved surgical comfort and team performance. Further research is warranted to confirm these findings and explore additional factors such as cost-effectiveness and long-term patient outcomes. Full article