Search Results (145)

The β-glucosidase CEL1B has been linked to regulating cellulase expression in Trichoderma reesei, yet its inducer-specific functions and broader regulatory roles remain poorly characterized. In this study, CRISPR-Cas9-mediated gene knockout was applied in the industrial high-producing T. reesei Rut C30 to investigate CEL1B function without the confounding effects of KU70 deletion. Unlike previous studies focused solely on cellulose or lactose induction, transcriptomic analysis of the CEL1B knockout strain revealed its regulatory roles under both lactose- and sophorose-rich conditions, with sophorose representing the most potent natural inducer of cellulase expression. Under lactose induction, CEL1B deletion resulted in a 52.4% increase in cellulase activity (p < 0.05), accompanied by transcriptome-wide upregulation of β-glucosidase genes (CEL3A: 729%, CEL3D: 666.8%, CEL3C: 110.9%), cellulose-sensing receptors (CRT1: 203.0%, CRT2: 105.8%), and key transcription factors (XYR1: 2.7-fold, ACE3: 2.8-fold, VIB1: 2.1-fold). Expression of ER proteostasis genes was significantly upregulated (BIP1: 3.3-fold, HSP70: 6.2-fold), contributing to enhanced enzyme secretion. Conversely, under sophorose induction, CEL1B deletion reduced cellulase activity by 25.7% (p < 0.05), which was associated with transcriptome profiling showing significant downregulation of β-glucosidase CEL3H (66.6%) and cellodextrin transporters (TrireC30_91594: 79.3%, TrireC30_127980: 76.3%), leading to reduced cellobiohydrolase expression (CEL7A: 57.8%, CEL6A: 67.8%). This first transcriptomic characterization of the CEL1B knockout strain reveals its dual opposing roles in modulating cellulase expression in response to lactose versus sophorose, providing new strategies for optimizing inducer-specific enzyme production in T. reesei. Full article

Breast-conserving surgery followed by external beam Radiotherapy (RT) is a standard approach for early-stage Breast Cancer (BC). This retrospective study aims to determine the risk of RT-induced lung cancer for both standard and hypofractionated treatments. Fifty-eight Sicilian women treated at Humanitas Istituto Clinico Catanese (Misterbianco, Italy) between 2015 and 2021 with standard fractionated 3D-CRT (50 Gy in 2 Gy/fraction) were included. All treatment plans were designed using a hypofractionated schedule (42.56 Gy in 2.66 Gy/fraction). An Eclipse™ plug-in script was developed using the Eclipse Scripting Application Programming Interface (ESAPI) to extract patient and treatment data from the Treatment Planning System and compute Organ At Risk (OAR) volume, Organ Equivalent Dose (OED), Excess Absolute Risk (EAR), and Lifetime Attributable Risk (LAR) using the Schneider Mechanistic Model and reference data from regional populations, A-bomb survivors, and patients with Hodgkin’s Disease (HD). The OED distributions exhibited a statistically significant shift toward higher values in standard fractionated plans (p < 0.01, one-tailed paired Student’s t-test), leading to increased EAR and LAR. These results indicate that hypofractionated treatment may lower the risk of radiation-induced lung cancer. The feasibility of a priori risk estimation was evaluated by integrating the script into the TPS, allowing rapid comparison of SF and HF plans during planning. Full article

Background/Objectives: Patients with normal sinus rhythms undergoing cardiac resynchronization therapy defibrillator (CRT-D) implantation may benefit from a novel two-lead CRT-D system (CRT-DX), which features an atrial sensing dipole integrated into the right ventricular lead. This single-arm, international, non-controlled investigation focused on the safety and clinical efficacy of CRT-DX devices in CRT-D candidates who do not require atrial pacing. Methods: Patients indicated for CRT-D implantation (resting heart rates > 40 bpm and ≥100 bpm during exercise, no second or higher-degree AV block, and no history of persistent or permanent atrial fibrillation) were enrolled across 21 sites in four European countries. The primary endpoint was the need for an additional RA lead implantation within 12 months. Secondary endpoints comprised any invasive re-intervention to the CRT-DX system or infection. Results: Among the 110 patients (mean age 62 years, 70% male), 60% had an underlying non-ischemic cardiac disease. During 12 months of follow-up, RA lead implantation was required in two patients for atrial undersensing or chronotropic incompetence (RA lead implantation-free rate: 98.2% (95% CI: 92.7–99.5%)). Atrial sensing amplitudes were stable (mean: 4.7 ± 1.7 mV), AV-synchrony was maintained at >99%, and the median percentage of biventricular pacing exceeded 98%. The left ventricular ejection fraction improved by an absolute 14.7%. Conclusions: Using simple, clinically applicable inclusion criteria, the two-lead CRT-DX system demonstrated a low rate of subsequent RA lead implantations (1.8%) and maintained adequate RA sensing amplitudes throughout the observation period. The two-lead CRT-DX concept appears to be a feasible alternative for patients with preserved chronotropic competence. Full article

Background/Objectives: Impaired kidney function significantly increases mortality in recipients of implantable cardioverter defibrillators (ICDs). However, in the landmark studies evaluating ICDs and cardiac resynchronization therapy with a defibrillator (CRT-D) for the treatment of heart failure (HF) with a reduced ejection fraction (HFrEF), patients with Chagas cardiomyopathy (CC) have been underrepresented. This study aimed to determine whether kidney dysfunction has the same negative impacts on patients with ICDs or CRT-Ds and CC. Methods: We prospectively followed patients with CC and left ventricular ejection fractions (LVEFs) of ≤40% who underwent ICD or CRT-D implantation and had at least one prior creatinine measurement. The primary outcome was the survival rate during follow-up. Variables with a p of <0.10 from the univariate analysis were selected for inclusion in the Cox regression model. Results: A total of 343 patients were enrolled, with a median follow-up duration of 777 days. The mean age was 60.2 (±11.2) years. Fifty percent of patients were observed to have a New York Heart Association (NYHA) functional class of III, and the median left ventricular ejection fraction (LVEF) was 27% (22–32). Overall mortality events occurred in 113 (32.9%) participants during follow-up. Although the estimated glomerular filtration rate (eGFR) was significantly associated with survival in the univariate analysis [HR 0.98 (CI 95% 0.98–0.99), p = 0.007], it did not retain significance in the multivariate model [HR 0.99 (0.98–1.00), p = 0.138], which was adjusted for age, gender, atrial fibrillation (AF), body mass index (BMI), and the use of digoxin, furosemide, anticoagulants, and LVEF. Conclusions: Unlike other cardiomyopathies, impaired eGFR was not an independent predictor of mortality in this cohort of CC patients undergoing ICD or CRT-D implantation, possibly due to the distinctive pathophysiological mechanisms of the disease. These findings suggest that clinicians should not be discouraged from recommending CIEDs in patients with CC and moderately impaired kidney function, although further studies are warranted to assess outcomes in those with advanced CKD. Full article

Background/Objectives: Although cardiac resynchronization therapy (CRT) plays an established role in the management of heart failure, a significant proportion of patients do not respond despite appropriate candidate selection. The optimization of CRT pacing is one strategy to enhance response. Fusion pacing algorithms aim to synchronize intrinsic right ventricular (RV) conduction with paced left ventricular (LV) activation, resulting in a more physiological ventricular depolarization pattern. This approach may improve electrical synchrony and enhance left ventricular contraction compared to conventional simultaneous biventricular pacing. The aim of this study was to compare the acute, beat-to-beat effects of standard biventricular pacing versus fusion pacing on myocardial function, using both conventional and speckle-tracking echocardiography in heart failure patients with left bundle branch block (LBBB). Methods: In total, 27 heart failure patients (21 men and 6 women) with reduced ejection fraction (EF < 35%), left bundle branch block (QRS > 150 ms), and newly implanted CRT-D systems (Abbott) underwent echocardiographic assessment immediately after device implantation. Echocardiographic parameters—including left atrial strain, left ventricular strain, TAPSE, mitral and tricuspid valve function, and cardiac output—were measured at 5 min intervals under three different pacing conditions: pacing off, simultaneous biventricular pacing, and fusion pacing using Abbott’s SyncAV^® algorithm. Results: In our study, CRT led to a significant shortening of the QRS duration from 169 ± 19 ms at baseline to 131 ± 17 ms with standard biventricular pacing, and further to 118 ± 16 ms with fusion pacing (p < 0.05). Despite the electrical improvement, no significant changes were observed in global longitudinal strain (GLS: −9.15 vs. −9.39 vs. −9.13; p = NS), left ventricular stroke volume (67.5 mL vs. 68.4 mL vs. 68.5 mL; p = NS), or left atrial parameters including strain, area, and ejection fraction. However, fusion pacing was associated with more homogeneous segmental strain patterns, improved aortic valve closure time, and enhanced right ventricular function as reflected by tissue Doppler-derived S’. Conclusions: Immediate QRS narrowing observed in CRT patients—particularly with fusion pacing optimization—is associated with a more homogeneous pattern of left ventricular contractility and improvements in selected measures of mechanical synchrony. However, these acute electrical changes do not translate into immediate improvements in stroke volume, global LV strain, or left atrial function. Longer-term follow-up is needed to determine whether the electrical benefits of CRT, especially with fusion pacing, lead to meaningful hemodynamic improvements. Full article

Currently, advanced RT techniques such as VMAT and HT are being developed to optimize tumor coverage while minimizing radiation exposure to the surrounding organs that are at risk. Despite their growing clinical use, comparative studies evaluating the dosimetric and radiobiological effects of these modalities remain limited. In this study, A549, HeLa, and HepG2 cells were exposed to a single 2 Gy dose, using three RT techniques (3D-CRT, dual arc VMAT, and HT). Treatment plans were generated using a water phantom to ensure consistent target coverage and comparable dosimetric parameters across the techniques. Multiple radiobiological endpoints were assessed to evaluate the cellular responses. Although all three techniques yielded similar dosimetric parameters without statistically significant differences, the biological responses varied among the cell lines. Notably, VMAT and HT demonstrated superior tumor cell suppression compared to 3D-CRT. This was likely due to their enhanced dose conformity and modulation precision, which potentially led to improved tumor cell killing. These findings highlight the importance of integrating radiobiological assessments with physical dose metrics to inform the clinical application of advanced RT technologies. However, this study had several limitations. The use of a single radiation dose limited its clinical relevance, and the immediate post-irradiation assessments may not have captured delayed biological responses. Additionally, the small number of replicates may have reduced the study’s statistical power. Future studies incorporating dose fractionation schemes, time course analyses, and larger sample sizes are warranted to better simulate clinical conditions and further elucidate the radiobiological effects of advanced RT techniques. Full article

Background and Objectives: Brain radionecrosis is an under-recognized but potentially life-altering late complication of radiotherapy in patients with locally advanced nasopharyngeal cancer. Temporal lobe radionecrosis and high-dose exposure to the hippocampus are strongly associated with cognitive decline and radiation-induced dementia, negatively impacting patients’ long-term quality of life (QoL). This study aimed to evaluate and compare radiation dose distributions to critical brain structures across three radiotherapy techniques—3D conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT)—in order to assess potential neurocognitive risks and support hippocampal-sparing protocols. Materials and Methods: Ten patients previously treated with 3D-CRT were retrospectively replanned using IMRT and VMAT techniques on the Eclipse v13.3 (VARIAN) planning system. Bilateral hippocampi and temporal lobes were delineated as organs at risk (OARs) according to the RTOG atlas, and dosimetric parameters including D_max, D_mean, and D_min were recorded. V7.3 values were evaluated for hippocampal avoidance regions. Results: While IMRT and VMAT provided improved target volume coverage and reduced high-dose exposure to many standard OARs, both techniques were associated with increased D_mean and D_min to the hippocampus and temporal lobes compared to 3D-CRT. The highest D_max values to the temporal lobes were observed in 3D-CRT plans, indicating a potential risk of radionecrosis. VMAT plans showed hippocampal mean doses exceeding 10 Gy in some cases, with V7.3 > 40%, breaching established neurocognitive risk thresholds. Conclusions: These findings support the routine delineation of the hippocampus and temporal lobes as OARs in radiotherapy planning for nasopharyngeal cancer. The implementation of hippocampal-sparing strategies, particularly in IMRT and VMAT, is recommended to reduce the risk of radiation-induced cognitive toxicity and preserve long-term QoL in survivors. Full article

Background: Laryngeal cancer affects quality of life (QoL), speech, and swallowing. Total laryngectomy (TL) causes severe impairments, while partial laryngectomy (PL) and chemoradiotherapy (CRT) preserve the organ but yield variable outcomes. This study assesses QoL, speech rehabilitation, swallowing, and social reintegration across these treatments. Methods: This prospective observational cohort study was conducted at the ENT Clinic, Victor Babeș University of Medicine and Pharmacy, Timișoara; recruitment was conducted between October 2019 and January 2024. Seventy-five patients diagnosed with laryngeal squamous cell carcinoma (LSCC) were initially enrolled but only 15 patients (20%) completed the 12-month follow-up, with an attrition rate of 80%. Tumor stages ranged from T1 to T4a, with TL patients having a higher proportion of advanced-stage disease (Stage III–IV: 76%) compared to PL (45%) and CRT (50%). Validated instruments, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck Cancer (EORTC QLQ-H&N35), the Voice Handicap Index-30 (VHI-30), the Hospital Anxiety and Depression Scale (HADS), and the Dysphagia Outcome and Severity Scale (DOSS), were used to assess QoL, voice function, swallowing function, and psychological impact. Results: At 12 months, the global QoL score from the EORTC QLQ-H&N35 was lowest in TL patients (49.8 ± 10.9), significantly lower than both PL (61.2 ± 9.6, p = 0.002) and CRT (64.1 ± 7.8, p < 0.001). Post hoc Bonferroni analysis confirmed significant pairwise differences between TL vs. PL (p = 0.002) and TL vs. CRT (p < 0.001), while the difference between PL and CRT was non-significant (p = 0.14). TL patients had higher speech-related disability (VHI: 88.3 ± 12.6) and dysphagia prevalence (DOSS: 4.0 ± 1.2), with 16% remaining enteral feeding-dependent. Anxiety (HADS-A: 7.5 ± 2.9) and depression (HADS-D: 9.0 ± 3.2) were highest in TL patients, with 36% meeting clinical depression criteria at 12 months. Multivariable regression identified TL (OR = 3.92, 95% CI: 2.14–5.79, p < 0.001) and advanced tumor stage (OR = 2.85, 95% CI: 1.79–4.21, p = 0.002) as strong predictors of poor QoL. Kaplan–Meier analysis showed no significant OS differences (p = 0.12), but CRT patients had lower DFS (78%) compared to TL (82%) and PL (85%) (p = 0.048). Conclusions: TL patients experience the most significant impairments in QoL, speech, and social reintegration despite rehabilitation. CRT patients show higher recurrence rates but better QoL, while PL offers the best balance of function and survival. These findings highlight the need for long-term survivorship support tailored to treatment type. Full article

Background and Objectives: The standard treatment for locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (nCRT), followed by surgery with or without adjuvant chemotherapy (CT). This study evaluated the efficacy and safety of dose-escalated radiotherapy (RT) using the volumetric modulated arc therapy–simultaneous integrated boost (VMAT–SIB) technique in patients with LARC compared to 3D conformal radiotherapy (3D-CRT). Materials and Methods: This study prospectively enrolled 75 patients with LARC. All patients received nCRT using VMAT–SIB, delivering a tumor dose (TD) of 54 Gy in 25 fractions, with concomitant CT following the 5-fluorouracil and leucovorin (5-FU–LV) protocol. To compare the treatment outcomes and toxicity associated with the increased RT dose, a retrospective cohort of 62 patients treated with the 3D-CRT technique was analyzed. The 3D-CRT group received a TD of 50.4 Gy in 28 fractions with the same CT. Outcomes, including pathological complete response (pCR), tumor regression grade (TRG), and sphincter preservation rates, were compared. Results: Among operated patients, the group treated with VMAT–SIB demonstrated improved rates of pCR (20.6% vs. 8.9%), with a statistically significant trend (p = 0.06). Sphincter-preserving surgeries were performed in 49 out of 63 operated patients (77.8%) in the VMAT–SIB group, compared to 35 out of 56 (62.5%) in the 3D-CRT group. Analysis of the definitive postoperative stage revealed a significantly higher prevalence of lower T categories (T0–2) (p < 0.01), negative N status (p < 0.05), and lower stages (I + II) (p < 0.05) in patients treated with the intensified RT approach. However, no significant differences in acute toxicity were observed. Conclusions: The implementation of intensified treatment with a higher dose using the VMAT–SIB technique demonstrated significant benefits in downsizing and downstaging compared to the standard treatment approach. These findings support its integration into clinical practice. However, further prospective, multi-center studies are needed to validate these results and assess long-term outcomes. Full article

Background: Vitamin D (VD) supplementation has increased considerably in the last decade, whether for the prevention or treatment of numerous diseases, including bone, cardiovascular, endocrine, neurologic, psychological, respiratory, infectious, or oncological. The primary objective of this scoping review was to examine and synthesize the scientific evidence on the role of VD in all-type cancer patients undergoing adjuvant and neoadjuvant therapy with chemotherapy (CT) or radiotherapy (RT), namely in improving side effects. Methods: This review was conducted by selecting papers from the CINAHL, Scopus and PubMed databases based on the descriptor terms mesh and title/abstract, taking into consideration the defined inclusion and exclusion criteria, following the PRISMA-ScR (PRISMA extension for scoping reviews) statement. Results: A total of 758 papers were identified in different databases during this review. However, using the inclusion and exclusion criteria, only five publications made up the final sample of the study. The studies included heterogeneous study methodologies, objectives, cancer diagnosis, as well as methods to assess body composition, which makes it difficult to compare them. Based on the analyzed studies, associations were found between bone density and VD in patients who underwent preoperative chemoradiotherapy (CRT). In patients with non-small-cell lung cancer receiving CT, some of the side effects associated with the treatment were attenuated and reduced. In addition, another of the studies analyzed found that VD deficiency (VDD) has been associated with increased peripheral neuropathy (PN) induced by CT in the treatment of breast cancer. VD supplementation was found to be safe and effective. Conclusions: In this scoping review, VD is highlighted as a crucial factor in preventing the side effects of neoadjuvant RT or CT, as well as treating other treatment-related health conditions, such as osteoporosis, as well as ameliorating the side effects (nausea, vomiting, fatigue) associated with aggressive CT and RT. Full article

Background: According to current guidelines, cardiac resynchronisation therapy (CRT) is recommended in patients with significantly impaired left ventricular systolic function and left bundle branch block. However, the decision between pacemaker (CRT-P) and defibrillator (CRT-D) in patients eligible for CRT remains a matter of debate. Register data have shown a higher all-cause mortality in CRT-P in comparison to patients with a CRT-D. Here, we investigated clinical determinants of the selection of CRT-P vs. CRT-D and clinical outcome in large registry data from a multi-centre ‘real-life’ registry on patients with CRT defibrillator or pacemaker therapy. Methods: The German Device Registry (DEVICE) is a nationwide, prospective registry with one-year follow-up investigating 5451 patients receiving device implantations in 50 German centres. The present analysis of DEVICE focused on all patients from the register receiving cardiac resynchronization therapy. Results: Out of 1603 patients receiving cardiac resynchronisation therapy, 1536 (95.8%) received a CRT defibrillator system and 67 (4.2%) a CRT pacemaker system. Patients in the CRT-P group had a significantly better left ventricular systolic function compared to the CRT-D group (median 35% vs. 25%), and significantly less often had a history of myocardial infarction (9.0% vs. 25.2%). A preexisting pacemaker and a history of stroke/peripheral embolism were identified as determinants for the selection of CRT-P vs. CRT-D. Overall mortality after one-year follow-up was 8.0%. Patients with ischemic cardiomyopathy receiving CRT-P therapy had a higher one-year mortality than patients receiving CRT-D (21.2% vs. 8.9%, p = 0.020). On the other hand, patients with non-ischemic cardiomyopathy did not display differences between these two treatment groups (CRT-P 8.1%, CRT-D 6.6%, p = 0.72). Conclusions: Data from the German device registry show that most patients receiving cardiac synchronization therapy have an implanted CRT-D system. In comparison to patients with CRT-D, those with CRT-P more often had a non-ischemic cardiomyopathy and a preexisting pacemaker system. The outcomes between these two treatment groups were different as regards ischemic cardiomyopathy only. Full article

Background: Myxol, a monocyclic carotenoid with β- and ψ-end groups, has been identified in only a limited number of bacteria, such as flavobacteria and cyanobacteria. Despite its biological significance, the biosynthetic pathway of myxol is not well understood, and studies on its physiological functions and biological activities are limited because of its rarity. Methods: BLAST homology searches for carotenoid biosynthesis genes in the genome of Nonlabens were performed. The carotenogenesis-related genes in the genome of the marine flavobacteria Nonlabens spongiae were individually cloned and functionally characterized using a heterologous Escherichia coli expression system. Carotenoids from N. spongiae were identified using an LC-MS analysis. Results: We identified a gene cluster involved in carotenoid biosynthesis in the genome of N. spongiae. This cluster includes genes encoding phytoene synthase (CrtB), phytoene desaturase (CrtI), lycopene cyclase (CrtY), carotenoid 1,2-hydratase (CruF), carotenoid 3,4-desaturase (ψ-end group) (CrtD), carotenoid 2-hydroxylase (ψ-end group) (CrtA-OH), and carotene hydro-xylase (CrtZ). Based on the characteristics of these enzymes, the primary products were predicted to be myxol and/or zeaxanthin. A spectroscopic analysis confirmed that myxol was the primary carotenoid. Furthermore, a plasmid containing a reconstructed gene cluster and geranylgeranyl pyrophosphate synthase (CrtE) located outside the cluster was introduced into E. coli. This system predominantly accumulated myxol, indicating that the reconstructed gene cluster enabled efficient myxol production in E. coli. Conclusions: This study highlighted the potential biotechnological applications of the carotenoid biosynthesis gene clusters for myxol production. Full article

Objectives: to evaluate the efficacy of 0.7 mg dexamethasone intravitreal implant in the treatment of patients with diabetic macular edema through mean retinal sensitivity (MRS), best corrected visual acuity (BCVA), central retinal thickness (CRT) and fixation stability. Methods: patients (n = 50) with DME, best corrected visual acuity (BCVA) of 0.1 logMAR, and central retinal thickness (CRT) of ≥300 μm determined by optical coherence tomography were treated with 0.7 mg slow-release dexamethasone, and endpoints were evaluated one and three months after the injection. Results: The best corrected visual acuity, BCVA, whose mean values at baseline were 0.42 logMAR, improved significantly post dexamethasone injection, with mean values of 0.20 logMAR at one month and 0.24 logMAR at three months. The mean central retinal thickness, CRT, was 463 µm at baseline increasing to 297 µm at one month, and 315 µm at three months. Mean retinal sensitivity (MRS) was 12.31 dB at baseline. In line with other parameters, MRS also showed significant improvement at one month after slow-release dexamethasone treatment, with a mean value of 15.35 Db and the improvement was sustained at three months after injection, with a mean value of 14.71 dB. Fixation stability was assessed using the area of the third BCEA ellipse. At baseline, patients had an ellipse area of 53.68 degrees. At one month after injection, patients showed an improvement, with a mean ellipse area of 5.23 degrees, which was maintained at three months, with a mean ellipse area of 4.13 degrees. Conclusions: The dexamethasone implant of 0.7 mg met the efficacy endpoint for improvement in MRS, BCVA, CRT and fixation stability. Full article

Background: In recent years, sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated significant cardiovascular and renal benefits in patients with heart failure (HF), in addition to their established antidiabetic effects. However, their role in arrhythmia prevention remains unclear. This study aimed to assess the effect of SGLT2 inhibitors on the incidence of supraventricular tachycardia (SVT) and ventricular tachycardia (VT) in patients with HF with reduced ejection fraction (HFrEF) during an extended follow-up period. Methods: This retrospective cohort study was conducted between January 2019 and November 2024 at the Ulm University Heart Center. All patients exhibited severely reduced left ventricular function and underwent primary prophylactic implantable cardioverter-defibrillator (ICD) implantation. Half of the cohort initiated SGLT2 inhibitor therapy alongside optimal medical HF treatment (the SGLT2 group). Patients were followed for approximately three years (846.2 ± 520.0 days) and the incidence of SVT and VT was analyzed using intracardiac Holter records of the ICD. Results: The study population consisted of 78 patients with a mean age of 66.6 ± 12.9 years. Over the follow-up period, a significant prolongation in the time to first occurrence of SVT was observed in the SGLT2 group (Log-Rank p = 0.03), suggesting a potential protective effect of SGLT2 inhibitors. However, regarding VT, additional SGLT2 inhibitor therapy did not show an additional benefit to optimal medical HF treatment. Conclusions: This study suggests that SGLT2 inhibitors may play a beneficial role in reducing the incidence of SVT in patients with HFrEF. These results highlight the importance of further investigating the antiarrhythmic potential of SGLT2 inhibitors through large-scale, prospective studies to better understand their clinical implications and mechanisms of action. Full article

At the end of the past century, the introduction of Total Mesorectal Excision (TME), preceded by either short-course radiotherapy (SCRT) or chemoradiation (CRT), established the new standard of care for locally advanced rectal cancer (LARC). Recently, significant advancements were achieved for both dMMR/MSI and pMMR/MSS LARC patients. For the 2–3% of dMMR/MSI LARCs, ablative immunotherapy emerged as a curative approach, offering the possibility of avoiding chemotherapy (CT), radiotherapy, and surgery altogether. In pMMR/MSS LARCs, the intensification of preoperative treatments with Total Neoadjuvant Treatment (TNT) afforded three outcomes: (a) a reduction of distant metastases, positively impacting on survival endpoints, (b) a significant increase of complete clinical response (cCR) rate, paving the way for non-operative management (NOM), and (c) the selective omission of radiotherapy following induction CT. The choice of the most appropriate therapeutic strategy can only be made through the shared decision-making process between physician and patient based on risk stratification and patient preferences. Full article