Unfavorable Characteristics Research Articles

High iASPP (PPP1R13L) expression is an independent predictor of adverse clinical outcome in acute myeloid leukemia (AML)

Apoptosis-stimulating proteins of p53 (ASPPs) are a family of proteins that modulate key tumor suppressor pathways via direct interaction with p53. Deregulation of these proteins promotes cancer development and impairs sensitivity to systemic (chemo)therapy and radiation. In this study, we describe that the inhibitor of ASPP (iASPP) is frequently highly expressed in acute myeloid leukemia (AML) and that overexpression correlates with a poor clinical outcome. Four independent patient cohorts comprising about 1500 patient samples were analysed and consistently confirm an association of high iASPP expression with unfavourable clinical characteristics and shorter survival. Notably, the predictive role of iASPP is independent of, and adds information to, the European LeukemiaNET (ELN) risk classification. iASPP-interference cell models were developed to investigate the underlying functional aspects of iASPP in AML biology. Attenuation of iASPP expression resulted in reduced proliferation rates of leukemic blasts and rendered cells more susceptible towards induction of apoptosis in response to cytotoxic therapy. In line, independent NSG xenograft mouse experiments demonstrate that attenuation of iASPP results in a significant delay of disease onset and tumor burden and this translates to longer overall survival of mice. In conclusion, deregulation of iASPP has direct functional consequences in AML. Determination of iASPP expression levels provides valuable additional information as a predictive marker in AML and may guide treatment decisions.

Chronic Total Occlusions in Non-Infarct-Related Coronary Arteries and Long-Term Cardiovascular Mortality in Patients Receiving Percutaneous Coronary Intervention in Acute Coronary Syndromes

Background and aim: Patients with non-infarct-related artery chronic total occlusion (non-IRA CTO) found during percutaneous coronary intervention (PCI) in acute coronary syndromes (ACSs) are not rare and have worse clinical outcomes. We aimed to analyze their long-term clinical outcomes in regard to clinical characteristics, revascularization strategies, and adherence to medical therapy. Patients and methods: The dual-center ACS registry of patients treated from Jan 2017 to May 2023 was used to identify 1950 patients with timely PCI in ACS who survived to discharge with documented adequate demographic, clinical, and angiographic characteristics, treatment strategies, and medical therapy adherence during a median follow-up time of 49 months. Results: There were 171 (9%) patients with non-IRA CTO. In comparison to patients without non-IRA CTO, they were older, with more diabetes mellitus (DM), higher Syntax scores (median 27.5 vs. 11.5), and lower left ventricular ejection fraction (LVEF) at discharge (median LVEF 50% vs. 55%). There was also a lower proportion of patients with high adherence to medical therapy (32% vs. 46%). Patients with non-IRA CTO had significantly higher cardiovascular mortality during follow-up (18% vs. 8%, RR 1.87, 95% CI 1.27–2.75). After adjusting for relevant clinical and treatment characteristics in a multivariate Cox regression analysis, only lower LVEF, worse renal function, the presence of DM, and lower adherence to medical therapy were independently associated with higher cardiovascular mortality during follow-up, with low adherence to medical therapy as the strongest predictor (RR 3.18, 95% CI 1.76–5.75). Time to cardiovascular death was significantly lower in patients who did not receive non-IRA CTO revascularization, although CTO revascularization did not show independent association with survival in the multivariate analysis. Conclusions: Patients with non-IRA CTO found during ACS treatment have more unfavorable clinical characteristics, worse adherence to medical therapy, and higher cardiovascular mortality. They need a more scrutinized approach during follow-up to increase adherence to optimal medical therapy and to receive revascularization of the non-IRA CTO whenever it is clinically indicated and reasonably achievable without excess risks.

Abstract Su906: Patient and Arrest Characteristics Associated with Rearrest and Mortality Following Out of Hospital Cardiac Arrest

Background: Cardiac rearrest post-return of spontaneous circulation (ROSC) is a critical concern in emergency care, as it is associated with worse outcomes. Patient characteristics and arrest factors associated with rearrest remain poorly understood, making predicting rearrest after out of hospital cardiac arrest (OHCA) challenging. Aim: To examine rearrest patterns, identify patient-specific risk factors for rearrest, and assess the impact of rearrest on patient outcomes. Hypothesis: Patients that experience rearrest after OHCA will have greater cardiac comorbidities, unfavorable arrest characteristics, and greater mortality. Methods: We performed an observational single-site clinical trial of consecutive adult EMS OHCA patients with ROSC (1/01/2018 to 3/31/24). EMS reports, continuous EMS ECG recordings, and electronic health records were analyzed to determine rearrest occurrence at any time during EMS and ED care. Patient demographics, comorbidities, and arrest/rearrest characteristics were determined. The primary outcome was survival at 6 months. Statistical significance was determined using Chi-square and logistic regression (LR) analyses. Results: We examined 344 patients with OHCA and ROSC, of whom 173 patients rearrested and 171 did not. Patients experiencing rearrest were older (p<0.003) and more likely to be female (p<0.013). They were also more likely to have ED resuscitation medications and interventions (epinephrine, amiodarone, lidocaine, defibrillation, all p<0.001) and a higher incidence of underlying cardiovascular comorbidities, including HTN and CAD (p<0.03). Notably, PEA and asystole were the most common rearrest rhythms, and time from arrest to ROSC was greater (30±16 vs. 25±15 min, p<0.007) in rearrest patients vs. those who did not rearrest. Patients with rearrest were less likely to receive TTM (p<0.003) and importantly, had higher rates of in-hospital and six-month mortality (both p<0.001). In a LR model, no rearrest (OR 2.4, 1.1-5.2), shockable arrest rhythm (OR 9.3, 4-22), female sex (OR 3.3, 1.6-6.5), and therapeutic hypothermia (OR 3.3, 1.7-6.4), were associated with survival (all p<0.04). Conclusions: Rearrest is independently associated with mortality. Increased age, male sex, and underlying cardiac comorbidities were associated with rearrest. Patient and arrest characteristics may predict rearrest. Improved understanding of why these factors promote rearrest will be important to prevent rearrest to enhance OHCA outcomes.

Diagnostic and prognostic significance of tetraspanin 6 and its role in facilitating glioma progression

BackgroundSeveral tetraspanin (TSPAN) proteins have been implicated in tumorigenesis and disease progression. However, the precise function of tetraspanin 6 (TSPAN6) in glioma remains unclear.MethodsIntegrated raw data from the Tumor Genome Atlas (TCGA) and Gene Expression Profiling (GEO) databases were processed using R4.2.1. Bioinformatic methods were used to analyze the gene expression levels of TSPAN6 in both glioma and normal brain tissues, correlating them with clinical characteristics. Additionally, the predictive value of TSPAN6 in relation to the immune checkpoint blockade (ICB) therapy response was assessed. In vitro experiments were conducted to investigate the effects of TSPAN6 knockdown on glioma cell proliferation, migration, cell cycle regulation, and macrophage recruitment.ResultsTSPAN6 expression was significantly upregulated in glioma tissues compared to normal tissues. Elevated TSPAN6 expression is strongly correlated with unfavorable clinical characteristics in gliomas. Bioinformatic analyses revealed a significant correlation between elevated TSPAN6 expression and reduced overall survival. Additionally, TSPAN6 was co-expressed with several immune checkpoint genes and revealed a prognostic value in the context of ICB therapy. Functional enrichment analysis revealed the involvement of TSPAN6 in cell-cycle regulation. Furthermore, TSPAN6 expression positively correlated with macrophage and neutrophil infiltration. In vitro experiments confirmed that the downregulation of TSPAN6 inhibited U251 cell proliferation, disrupted the cell cycle, diminished migratory capabilities, and reduced the recruitment of macrophages.ConclusionOur findings emphasize its potential as both a diagnostic and therapeutic target as well as a predictor of immune therapy response in gliomas.

Sociodemographic differences in low back pain: which subgroups of workers are most vulnerable?

BackgroundLow back pain (LBP) is a common health problem in workers that contributes to work disability and reduces quality of life. However, studies examining vulnerable groups in relation to sociodemographic differences in LBP remain scarce. Therefore, the current study investigates which sociodemographic groups of workers are most affected by LBP.MethodsData from the 2018 BIBB/BAuA employment survey were used (N = 16252). Age, education, occupational group, income, working hours, atypical working time, relationship status, and having children were used as sociodemographic predictors. Gender-stratified logistic regression analyses and intersectional classification tree analyses were conducted.ResultsA higher prevalence of LBP was observed for women compared to men. Significant differences in LBP emerged for age, working hours, atypical working time, occupational group and education, with some gender differences in the importance of predictors: Age was a significant predictor mostly in men as compared to women, atypical working hours had a slightly greater effect in women, whereas differences in LBP according to the occupational group were more pronounced for men. Vulnerable groups were found to be women who work in occupations other than professionals or managers, work atypical hours and have an intermediate or low educational level as well as men who work as skilled agricultural workers, craft workers, machine operators, or elementary occupations and are between 35 and 64 years old.ConclusionsThus, workers with certain occupations and lower levels of education, middle-aged men and women with unfavourable working time characteristics are most affected by low back pain. These groups should be focused on to potentially increase healthy working life and prevent work disability.

Mechanical, microstructural, and environmental performance of industrial byproducts in peat reinforcement

Peat is widely regarded as one of the most challenging soil types due to its unfavorable engineering characteristics. Traditional methods for addressing peat-related challenges often involve costly and unsustainable approaches such as soil replacement or chemical treatment with cement. This study aims to introduce novel insights into a sustainable solution for peat stabilization by utilizing industrial waste, thereby promoting sustainable development. Palm oil fuel ash (POFA) is a prevalent industrial byproduct generated in Southeast Asian countries, presenting significant disposal challenges. This research evaluates the performance of POFA as a green binder for peat stabilization through a series of mechanical, microstructural, and environmental tests. The findings demonstrate that POFA serves as an environmentally sound and effective binder, substantially improving the engineering properties of peat while also immobilizing toxic elements within the stabilized peat matrix. Consequently, this environmentally friendly and sustainable approach enhances the poor engineering properties of peat.

Engineering and physicochemical characterization of a novel, stable, symmetric bispecific antibody with dual target-binding using a common light chain.

Bispecific antibodies (BsAbs) have emerged as a major class of antibody therapeutics owing to their substantial potential in disease treatment. While several BsAbs have been successfully approved in recent years, ongoing development efforts continue to focus on optimizing various BsAbs tailored to particular antigens and action mechanisms, aiming to achieve favorable physicochemical properties. BsAbs generally encounter challenges due to their unfavorable physicochemical characteristics and poor manufacturing efficiencies, highlighting the need for optimization to achieve reliable productivity and developability. Herein, we describe the development of a novel symmetric BsAb, REGULGENT™ (N-term/C-term), comprising two Fab domains, using a common light chain. The heavy chain fragment encoded two antigen-binding determinants in one chain. The design and production of REGULGENT™ (N-term/C-term) are simple owing to the use of the same light chain, which does not induce heavy and light chain mispairing, frequently observed with the asymmetric BsAb format. REGULGENT™ (N-term/C-term) exhibited high expression and low aggregation characteristics during cell culture and stress treatment under low pH conditions. Differential scanning calorimetric data indicated that REGULGENT™ molecules had high conformational stability, similar to that of stabilized monoclonal antibodies. Surface plasmon resonance data showed that REGULGENT™ (N-term/C-term) could bind to two antigens simultaneously and exhibited a high affinity for two antigens. In summary, the symmetric BsAb format of REGULGENT™ confers its desirable IgG-like physicochemical properties, thus making it an excellent candidate for commercial development. The findings demonstrate a novel BsAb with substantial development potential for clinical applications.

Mitogen-activated protein kinase kinase kinase 1 facilitates the temozolomide resistance and migration of GBM via the MEK/ERK signalling.

Mitogen-Activated Protein Kinase Kinase Kinase 1 (MAP3K1) is overexpressed in gliomas; however, its clinical significance, biological functions, and underlying molecular mechanisms remain unclear. Abnormal overexpression of MAP3K1 in glioma is strongly associated with unfavourable clinicopathological characteristics and disease progression. MAP3K1 could potentially serve as a reliable diagnostic and prognostic biomarker for glioma. MAP3K1 silencing suppressed the migration but had no effect on the proliferation and cell death of Glioblastoma Multiforme (GBM) cells. MAP3K1 knockdown exacerbated the temozolomide (TMZ) induced inhibition of glioma cell proliferation and death of GBM cells. In addition, MAP3K1 knockdown combined with TMZ treatment significantly inhibited the growth and increased cell death in organoids derived from GBM patients. MAP3K1 knockdown reversed TMZ resistance of GBM in intracranial glioma model. In terms of molecular mechanisms, the phosphorylation level of ERK was significantly decreased by MAP3K1 silencing. No significant change in the JNK pathway was found in MAP3K1-silenced GBM cells. Inhibition of ERK phosphorylation suppressed the migration and enhanced the TMZ sensibility of GBM cells. MAP3K1 was correlated with the immune infiltration in glioma. MAP3K1 could facilitate the migration and TMZ resistance of GBM cells through MEK/ERK signalling.

Effects of irrigation and nutrients managements with plant intensification on rice under saline soil

The area of salt affected agricultural soils has grown on a global scale. The toxicity of salt and the unfavorable characteristics of the soil are two major causes of the low crop productivity on salt-affected soil. Thus, effective and economical management techniques are required for crop production which may sustainable. The experiments were conducted to identify appropriate irrigation and other management practices for higher yield of Boro rice at two locations (Horinkhola, Satkhira and Batiaghata, Khulna) of saline area during two successive years (2021 and 2022). Six treatments were used, consisting of continuous ponding of irrigation water along with recommended fertilizer (farmers practice, as control), and a range of combination of irrigation water and gypsum fertilizer and foliar spray of Urea, TSP, MOP and Zinc Sulphate. The results revealed that at both locations, the treatments showed significant difference and the highest yield (7.35 t/ha at Horinkhola and 6.75 t/ha Batiaghata) were obtained in treatment T5 [Continuous saturation (0-3cm) + 50% recommended fertilizer except MoP + K2SO4 equivalent to 50% K+ OM + no ridge, high density (15 cm x 10 cm) + Change of standing water 20 days interval + Foliar application of Urea-40 g, TSP-44 g, MOP-26 g and Zinc Sulphate 3g (4 times : 25, 35, 45, 60 DAT)]. Overall, this treatment produced 19% higher yield compared to farmer’s practice, along with maximum BCR (1.57) and net profit (52,004 Tk/ha). This technique can be adopted for higher yield in saline area. Bangladesh J. Nuclear Agric, 38(1): 53-64, 2024

Cryoablation of Primary Breast Cancer in Patients Ineligible for Clinical Trials: A Multiinstitutional Study.

BACKGROUND. Breast cancer cryoablation clinical trials have strict inclusion criteria that exclude patients with potentially treatable disease. OBJECTIVE. The purpose of this study was to evaluate the safety and outcomes of breast cancer cryoablation without surgical excision in patients ineligible for prospective cryoablation clinical trials due to unfavorable patient or tumor characteristics. METHODS. This retrospective study included women who underwent cryoablation of biopsy-proven unifocal primary breast cancer with locally curative intent, without surgical excision, despite being ineligible for (and thus excluded from) cryoablation clinical trials, across seven institutions between January 1, 2000, and August 26, 2021. Adverse events (AEs) were recorded. Cryoablation procedures were classified as technically successful if they were not prematurely terminated and achieved intended treatment parameters and if the first follow-up imaging examination showed no evidence of residual disease. The results of follow-up biopsies were recorded. Ipsilateral breast tumor recurrences (IBTRs) diagnosed during follow-up were identified and classified as true recurrence or new primary disease. A competing-risk model was used to estimate the cumulative incidence of IBTR accounting for death before IBTR as a competing risk. RESULTS. The final study sample included 112 patients (median age, 71 years). A total of seven of 112 (6.3%) patients had a minor AE; no moderate or major AEs occurred. A total of 110 of 112 cryoablation procedures (98.2%) were technically successful. During a median follow-up of 2.0 years, 22 of 110 patients (20.0%) underwent biopsy for suspicious imaging findings in the ipsilateral breast, which yielded benign concordant findings in nine of 22 patients (40.9%) and IBTR in 12 of 22 patients (54.5%). Overall, 12 of 110 patients (10.9%) experienced IBTR, including seven with true recurrence and five with new primary disease; three of 12 patients (25.0%) with IBTR had received earlier adjuvant or neoadjuvant therapy. When death was accounted for as a competing risk, the cumulative incidence of IBTR was 5.3%, 12.2%, and 18.2% at 1, 2, and 3 years, respectively. CONCLUSION. In select individuals with unfavorable patient or tumor characteristics, breast cancer cryoablation provides a safe alternative to surgery and has good outcomes. These findings may be particularly relevant in patients who are also poor surgical candidates. CLINICAL IMPACT. Breast cancer cryoablation can be safely applied in a larger patient populations than those defined by clinical trial inclusion criteria.

Sustainable urea treatment by environmental-friendly and highly hydrophilic vesicle-like iron phosphate-based carbon

Despite the versatile potential applications of urea, its unfavorable characteristics for conventional treatment methods hinder its utilization. Therefore, this study developed vesicle-like iron phosphate-based carbon (IP@C400) as a breakthrough urea removal and recovery material for a wide range of urea-containing sources. IP@C400 rapidly exhibited an exceptional capacity (2242 mg/g in 1 h) across a wide range of pH, even in synthetic hemodialysis wastewater with high urea concentrations and diverse co-existing components, compared with the 60 prominent adsorbents. The adsorption process followed dual Pseudo-kinetic, Langmuir-isotherm models with the involvement of primary robust physical (i.e., H-bonding and electrostatic interaction) and chemical mechanisms (i.e., hydrolysis). Remarkably, IP@C400 can maintain high urea removal (90 %) or recovery efficiency (95 %) even after 10 cycles with minimal leakages of Fe and P (far below WHO and EUWFD standards)—a significant improvement over disposable options. IP@C400 could also perform efficiently on batch and a new approach integrating with a naturally accessible material based on the fixed-bed column using low-range urea realistic samples, achieving 65.2 L water over 10 cycles with undetected urea, neutral pH, and well-aligned water safety standards with a minimal adsorbent dose (0.1 g.L−1) and economical cost ($0.05 L-1). Lastly, its environmentally friendly nature, which contains essential nutrients for plant growth, further enhances its recyclability after release. Thus, IP@C400 offers a solution to environmental sustainability and the urgent ultrapure water issue that industries are facing.

Lymphocyte-to-monocyte, platelet-to-albumin and platelet-to-lymphocyte ratios as prognostic biomarkers for neoadjuvant treatment response in rectal cancer patients

IntroductionSystemic inflammatory response (SIR) indicators are an emerging category of serum biomarkers with significant potential as prognostic and predictive factors in various types of cancers The primary focus of our study was to determine the prognostic value of the lymphocyte-to-monocyte ratio (LMR), platelet-to-albumin ratio (PLR) and platelet-to-albumin ratio (PAR) in evaluating the response to neoadjuvant treatment for patients with rectal cancer. Materials and methodsWe included 99 consecutive patients with rectal cancer which were admitted for surgery in our institution after completing a standard neoadjuvant radio-chemotherapy regimen. Several hematologic parameters, including LMR, PAR and PLR, were calculated by collecting and analyzing blood samples preoperatively. Cases were divided into groups using ROC curve analysis to determine optimal cutoff values for each of the investigated parameters. Treatment response was assessed through histopathological analysis of the resected specimens. ResultsPLR values over 215.2 were correlated with the presence of lymph node metastasis. A similar correlation was observed between PAR values over 41.89 and lymph node positivity. A significant correlation was observed between the presence of tumor budding on histopathological analysis and high-PAR values. A statistically significant correlation between a high PLR and a good response to neoadjuvant treatment was determined. ConclusionsHigh PLR values may be associated with a more favorable treatment response to neoadjuvant radio-chemotherapy. A high PAR may be associated with unfavorable histopathological characteristics. Further studies on these readily available biomarkers are required in order to validate their clinical utility.

Comparative characteristics of patients with a combination of obstructive sleep apnea and paroxysmal atrial fibrillation in the groups of interventional and conservative treatment of arrhythmia

Aim. To compare the clinical characteristics of two groups of patients with a combination of obstructive sleep apnea (OSA) and paroxysmal atrial fibrillation (AF), undergoing conservative treatment for arrhythmia and after pulmonary vein isolation.Material and methods. The study included 362 patients with paroxysmal AF who underwent respiratory sleep monitoring.Results. A predominance of clinically significant OSA was revealed (moderate and severe — 37% and 29%, respectively), as well as a higher drug burden and comorbidity in the group of patients receiving drug treatment for AF. The threshold value of body mass index (BMI), at which a high risk of severe OSA was predicted, corresponded to class 1 obesity (BMI ≥31 kg/m2). The results obtained demonstrated an association between an increase in the left atrium anteroposterior size and the severity of OSA (4,1 [3,8-4,4] cm, r=0,28; p<0,001), which may be due to cardiac structural remodeling in patients with a combination of paroxysmal AF and severe OSA.Conclusion. In a cohort of patients with paroxysmal AF, a high incidence of clinically significant OSA was revealed. In the group of patients with a combination of OSA and AF undergoing conservative treatment, more unfavorable cardiovascular characteristics and a more severe comorbid status were revealed compared to the group of patients undergoing surgical treatment.

How to Improve Meniscal Repair through Biological Augmentation: A Narrative Review.

Since the role of the menisci in knee stability, proprioception, and homeostasis has been well established, significant efforts have been made to repair meniscal tears, resulting in excellent clinical outcomes and a reduction in the progression of knee osteoarthritis (OA). However, varying failure rates have been reported, raising questions regarding the healing potential in cases of complex injuries, poorly vascularized and degenerated areas, and generally in the presence of unfavorable biological characteristics. Therefore, over the last few decades, different strategies have been described to increase the chances of meniscal healing. Biological augmentation of meniscal repair through various techniques represents a safe and effective strategy with proven clinical benefits. This approach could reduce the failure rate and expand the indications for meniscal repair. In the present study, we thoroughly reviewed the available evidence on meniscal repair surgery and summarized the main techniques that can be employed to enhance the biological healing potential of a meniscal lesion. Our aim was to provide an overview of the state of the art on meniscal repair and suggest the best techniques to reduce their failure rate.

The association of depression and patient and resuscitation characteristics with survival after out-of-hospital cardiac arrest: a cohort study.

Out-of-hospital cardiac arrest (OHCA) is a leading cause of death worldwide, with cardiovascular disease (CVD) being a key risk factor. This study aims to investigate disparities in patient/OHCA characteristics and survival after OHCA among patients with vs. without depression. This is a retrospective cohort study using data from the AmsteRdam REsuscitation Studies (ARREST) registry from 2008 to 2018. History of comorbidities, including depression, was obtained from the patient's general practitioner. Out-of-hospital cardiac arrest survival was defined as survival at 30 days post-OHCA or hospital discharge. Logistic regression models were used to obtain crude and adjusted odds ratios (ORs) for the association between depression and OHCA survival and possible effect modification by age, sex, and comorbidities. The potential mediating effects of initial heart rhythm and provision of bystander cardiopulmonary resuscitation were explored. Among 5594 OHCA cases, 582 individuals had pre-existing depression. Patients with depression had less favourable patient and OHCA characteristics and lower odds of survival after adjustment for age, sex, and comorbidities [OR 0.65, 95% confidence interval (CI) 0.51-0.82], with similar findings by sex and age groups. The association remained significant among the Utstein comparator group (OR 0.63, 95% CI 0.45-0.89) and patients with return of spontaneous circulation (OR 0.60, 95% CI 0.42-0.85). Initial rhythm and bystander cardiopulmonary resuscitation partially mediated the observed association (by 27 and 7%, respectively). Out-of-hospital cardiac arrest patients with depression presented more frequently with unfavourable patient and OHCA characteristics and had reduced chances of survival. Further investigation into potential pathways is warranted.

Guide catheter extension use in chronic total occlusion percutaneous coronary intervention: insights from the PROGRESS CTO registry.

There are limited data on the use of guide catheter extensions (GCE) during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We examined the frequency and temporal trends of GCE use in a large multicenter CTO-PCI registry and compared the clinical and angiographic characteristics and outcomes of cases with vs without GCE use. A GCE was used in 4106 of 14 521 CTO PCIs (28%) with increasing frequency from 18.8% in 2012 to 29.9% in 2023. The most used GCE size was 6 French (Fr) (45%), followed by 7 Fr (34%), and 8 Fr (21%). CTOs that required GCE use were more likely to have unfavorable lesion characteristics such as moderate-to-severe calcification (59% vs 40%, P < .0001), moderate-to-severe tortuosity (35% vs 28%, P < .0001), proximal cap ambiguity (39% vs 33%, P < .0001), and had higher J-CTO scores (2.78 ± 1.15 vs 2.20 ± 1.27, P < .0001). Advanced techniques like the retrograde approach (44% vs 24%, P < .0001) and antegrade dissection and re-entry (28% vs 17%, P < .0001) were more likely to be used in GCE cases. Technical success (86.6% vs 86.8%, P = .816) was similar between the 2 groups. However, major adverse cardiovascular events (MACE) (3.8% vs 2.4%, P < .0001) and procedural complications (11.2% vs 8.7%, P < .0001) were more frequent in the GCE group. In summary, GCE use in CTO PCI significantly increased between 2012 and 2023. Cases that required GCEs were more complex and had similar technical success, but higher incidence of MACE compared with cases that did not require GCEs.

UBTD1 is a potential prognostic biomarker in colorectal cancer

Colorectal cancer (CRC) is a complex malignancy with poorly understood molecular mechanisms, necessitating the identification of genetic markers. Although Ubiquitin domain-containing protein 1 (UBTD1) has received significant attention in the study of human cancers, its specific role in CRC is yet to be fully clarified. This study sought to examine how UBTD1 expression was associated with various clinical and pathological characteristics of CRC, and to determine its prognostic significance and biological function, utilizing data from clinical samples and large-scale databases. Notably, UBTD1 expression was found to be upregulated in CRC, resulting in decreased survival rates and unfavorable clinical characteristics such as advanced T, N, and pathological stages. The findings of the multivariate Cox regression analysis illustrated that UBTD1 expression upregulation is a significant independent marker of unfavorable outcomes in CRC patients. An examination of the functional enrichment of UBTD1 and the genes it co-expresses indicated that it could serve as an oncogene by modulating the expression of genes implicated in crucial tumorigenesis pathways and functions. Additionally, immune cell infiltration analysis suggested a link between UBTD1 levels and various immune cells, particularly macrophages. In conclusion, the use of UBTD1 as a biomarker for both the prognosis and diagnosis of CRC has promising prospects for further investigation and therapeutic approaches.

Adoption and Impact of Fungus-Resistant Grape Varieties within German Viticulture: A Comprehensive Mixed-Methods Study with Producers

The reduction of phytosanitary treatments in viticulture is widely demanded by policymakers and consumers. An important solution is the use of resistant grapes, which can cut plant protection applications by up to 80%. Although this is a significant improvement, viticulture is mainly carried out with traditional grapes. Therefore, the aim of this paper is to identify the factors that encourage the cultivation of fungus-resistant grape varieties (FRGV), as well as the challenges and opportunities in marketing. Our study used an exploratory sequential mixed-methods model design. In the first step, data were collected through 48 in-depth interviews and analyzed. Based on the qualitative results, a survey of 422 producers was conducted. The quantitative research results were segmented by company size and production type to provide a deeper understanding. The main drivers for cultivation are the ecological benefits resulting from the reduction of pesticide use, with organic producers particularly motivated by sustainability goals. Smaller producers are driven by the opportunity to introduce a new wine style, whereas larger producers are more cautious and focus on cost savings. The cultivation of resistant grape varieties is restricted by a large number of varieties, lack of experience, and unfavorable characteristics from initial generations of resistant grapes. A low level of grape variety prominence and customer awareness, as well as unattractive variety names, negatively affect producer acceptance. To facilitate higher market acceptance, it is important to offer attractive grape varieties, directly communicate them to consumers, and provide information about the sustainable effects.

Second-line treatment outcomes after first-line chemotherapy plus immunotherapy in Extensive-Stage small cell lung cancer (ES-SCLC) patients: A large French multicenter study

IntroductionChemotherapy combined with immunotherapy (CT-IO) is the standard treatment for patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC). This study evaluates the effectiveness of second-line (2L) following CT-IO. Patients and MethodsAll patients from 10 centers who received a 2L after a first-line CT-IO were included. They were divided into 3 groups: platinum-based, lurbinectedin or others (topotecan, CAV, taxanes). We assessed overall survival (OS) and 2L progression-free survival (2L-PFS) according to treatment and platinum free-interval (PFI) < or ≥ 90 days. ResultsAmong 82 patients included, median age was 67.0 years, 29.3 % had a Performans Status ≥ 2, 36.6 % had brain progression, 69.5 % were considered “platine-sensitive” and 30.5 % “platine-resistant” (PFI ≥ or < 90 days, respectively). As 2L, 37/82 patients (45.1 %) received platinum-doublet, 21/82 (25.6 %) lurbinectedin and 24/82 (29.3 %) others. Patients with a PFI ≥ 90 days received mainly platinum-based rechallenge (34/57, 59.6 %). With a median follow-up of 18.5 months, the median OS was 5.0 months (95 %CI, 1.5–7.9) / 6.8 months (95 %CI, 5.5–8.7) for platinum-resistant / sensitive, respectively (log rank p = 0.017). The median 2L-PFS was 1.9 months (95 %CI, 1.2–4.7) / 3.9 months (95 %CI, 2.9–6.0) for platinum-resistant / sensitive, respectively. Median OS was 8.1 (95 %CI, 6.3–12.9) / 4.9 (95 %CI, 3.7–6.8) / 5.1 months (95 %CI, 2.5–7.8) with platinum rechallenge / lurbinectedin / others, respectively (p = 0.017). Median 2L-PFS was 4.6 (95 %CI, 3.9–7.2) / 2.7 (95 %CI, 1.6–3.9) / 2.2 months (95 %CI, 1.5–4.1) with platinum rechallenge / lurbinectedin / others, respectively (p = 0.025). DiscussionPlatinum-based rechallenge after a first-line CT-IO showed promising results despite particularly unfavorable characteristics within our real-word population. Lurbinectedin when used after IO demonstrated as low efficacy as other platinum-free regimens.

Clinical Factors Associated With Mode of Death Following Cardiac Arrest

Background Death after resuscitation from cardiac arrest is common. Although associated factors have been identified, knowledge about their relationship with specific modes of death is limited. Objective To identify clinical factors associated with specific modes of death following cardiac arrest. Methods This study involved a retrospective medical record review of patients admitted to a single health care center from January 2015 to March 2020 after resuscitation from cardiac arrest who died during their index hospitalization. Mode of death was categorized as either brain death, withdrawal of life-sustaining therapies due to neurologic causes, death due to medical causes, or withdrawal of life-sustaining therapies due to patient preference. Clinical characteristics across modes of death were compared. Results The analysis included 731 patients. Death due to medical causes was the most common mode of death. Compared with the other groups of patients, those with brain death were younger, had fewer comorbidities, were more likely to have experienced unwitnessed and longer cardiac arrest, and had more severe acidosis and hyperglycemia on presentation. Patients who died owing to medical causes or withdrawal of life-sustaining therapies due to patient preference were older and had more comorbidities, fewer unfavorable cardiac arrest characteristics, and fewer days between cardiac arrest and death. Conclusions Significant associations were found between several clinical characteristics and specific mode of death following cardiac arrest. Decision-making regarding withdrawal of care after resuscitation from cardiac arrest should be based on a multimodal approach that takes account of a variety of personal and clinical factors.