Higher Survival Research Articles

Certolizumab pegol effectiveness, survival and safety in patients with psoriasis: A multicenter retrospective analysis in daily clinical practice by the Spanish Psoriasis Group.

Certolizumab is an Fc-free PEGylated tumor necrosis factor-alpha (TNFα) inhibitor recently approved for the treatment of moderate-to-severe plaque psoriasis, although there is limited real-world evidence on the effectiveness and safety in patients with plaque psoriasis treated with certolizumab. The objective of this article is to determine the effectiveness, drug survival, and safety, including pregnancy, childbirth, and lactation, of certolizumab in moderate-to-severe plaque psoriasis under real-world conditions. This is a retrospective, multicenter, observational study performed in 15 hospitals in Spain. It evaluates the effectiveness and safety of certolizumab in plaque psoriasis in the clinical practice setting. A total of 67 patients (73% female) were evaluated with a mean baseline Psoriasis Area Severity Index (PASI) of 8.9. At Week 12, the mean PASI was 2.3 (n = 67), 1.3 (n = 57) at Week 24 and 1.3 at Week 52 (n = 34). Absolute PASI < 3 was achieved in 69, 86, and 92% of patients at Weeks 12, 24, and 52, respectively, as observed. For its part, using the under-response imputation analysis, PASI < 3 at Weeks 12, 24, and 52 were achieved by 69, 73, and 49% of the patients, respectively. A total of 35 patients (52%) had concomitant psoriatic arthritis, and, in 24 of them, Disease Activity in Psoriatic Arthritis Score (DAPSA) was recorded at baseline, with a mean value of 17.9 which decreased to 8.2 at Week 12 (n = 22) and to 3.6 at Week 24 (n = 18). Certolizumab treatment was discontinued in 14 out of 67 patients (21%), due to lack/loss of cutaneous or articular effectiveness (n = 11) or patient decision (n = 2) or adverse event in only one patient who developed active tuberculosis. A lower baseline PASI [hazard ratio (HR): 1.12 (1.02-1.23); P = 0.023] and a more significant reduction in PASI at Week 12 [HR: 1.16 (1.07-1.27); P < 0.001] and Week 52 [HR: 1.47 (1.11-1.96); P = 0.007] was shown to be significantly related with better survival for the entire follow-up period. Fourteen patients were treated during pregnancy and/or lactation without reporting adverse events in either the patient or the newborn. Certolizumab consistently showed high effectiveness and drug survival rates in this real-life cohort. The safety demonstrated in clinical trials during pregnancy and lactation seems to be confirmed in clinical practice.

Overall survival in patients with acute lymphoblastic leukemia treated with protocol CALGB 9511 at a tertiary hospital in the state of Ceará.

Introduction: Acute lymphoblastic leukemia (ALL) is the most common neoplasm in childhood and has high survival rates. In adults, due to the biological characteristics of the disease and chemotherapy-related toxicity, survival is lower. CALGB 9511 is a chemotherapy protocol based on pediatric regimens with high remission rates after induction. Objectives: To evaluate the survival of patients with ALL undergoing the CALGB 9511 protocol at Walter Cantídio University Hospital (HUWC); to describe the impact of risk factors: presence of measurable residual disease, BCR-ABL fusion gene status, and allogeneic bone marrow transplant (BMT) on the survival of this group. Methodology: Retrospective evaluation of medical records of patients with ALL treated with this protocol between 2011 and 2022. Statistical analysis was performed using the Kaplan-Meier method to estimate survival probability. Results: 79 patients were eligible; 19% were BCR-ABL positive; the mean 2-year overall survival was 44%; The 2-year survival rate for patients undergoing HSCT was approximately 78%.. Conclusion: The survival curves of the study conducted at HUWC are similar to those described in the literature and corroborate the severity of the disease. Accessibility to new therapeutic modalities is a strategy that can improve the survival of these patients.

An assessment of post-capture condition and survival of Rajidae caught in fixed nets

Skates (Rajiformes: Rajidae) are commercially and ecologically-important elasmobranchs captured in targeted and mixed fisheries globally. Many species are of conservation concern and are subject to high levels of discarding. They are currently exempt from the European Union’s landing obligation due to evidence of high discard survival, although the bulk of this evidence comes from mobile gear fisheries. Improved evidence on survival after discarding from fixed gears is necessary. We assessed immediate survival rates and post-capture condition (injury, reflex impairment, and vitality) of four skate species commonly discarded from seasonal Dover sole, Solea solea and plaice, Pleuronectes platessa gillnet fisheries in the Irish Sea and Bristol Channel, UK. We also modelled the relationship between a suite of environmental and operational fishing variables to the condition of thornback skate, Raja clavata. This is the dominant skate captured as bycatch and is classified as near threatened by the IUCN due to declining populations trends. At-vessel survival on gear hauling was high for all species (R. clavata = 99.43%, R. montagui = 100%, R. microocellata = 100%, R. brachyura = 100%). Post-capture condition of R. clavata was size-dependent, with larger skates demonstrating higher levels of injury and reflex impairment and poorer vitality. Higher vitality in smaller individuals and strong negative effects of aerial exposure on skate vitality highlight the likely benefits of prioritising discarding of unwanted catch upon gear hauling. This may maximise survival and future reproductive potential and facilitate population recovery.

Overview of acute liver failure in India.

Acute liver failure (ALF) is an infrequent, but serious complication subsequent to severe acute liver injury (sALI) due to various hepatotoxic agents such as hepatotropic virus(es) and drugs such as anti-tubercular medications, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and anti-cancer and anti-epileptic therapy and due to metabolic and autoimmune disease flares. ALF after sALI presents with encephalopathy associated with prolonged international normalized ratio (INR). Mortality in ALF is high and ranges between 50% and 80%. Due to severe liver damage, multiple sequels consequent to hepatic dysfunction result in complications such as hyperammonemia that culminates in encephalopathy associated with cerebral edema; innate immune paralysis resulting in increased frequency of infections and endotoxemia causing decrease in systemic vascular resistance (SVR) and tissue hypoperfusion and damage-associated molecular patterns (DAMPs) released from damaged hepatic parenchyma inducing pro-inflammatory cytokine storm, which may cause other organ dysfunctions. Certain etiologies such as hepatitis E virus and hepatitis A virus-related ALF or paracetamol-ALF (hyper-acute presentation) have better survival than remaining causes. In addition, if etiology-specific treatment (antivirals for ALF related to hepatitis B virus (HBV) or Herpes simplex virus (HSV) or N-acetylcysteine for paracetamol) is available, then the outcome with treatment is better. About half of the patients can be salvaged with medical therapy. All patients need intensive care and organ support to provide time for the liver to regenerate. Various prognostic models to predict high probability of mortality have been described, which should be used to select patient early during the disease for liver transplantation, which is associated with high long-term survival in these sick patients. The Indian National Association for Study of the Liver (INASL) recommends the ALF-Early Dynamic (ALFED) model as a preferred prognostic model in the Indian scenario, where hepatitis viruses are a dominant etiology of ALF and occur on a naïve liver with good regenerative capacity.

Rapid Diagnosis of Pneumocystis jirovecii Pneumonia and Respiratory Tract Colonization by Next-Generation Sequencing

ObjectivesTo describe the epidemiology of Pneumocystis jirovecii pneumonia and colonization diagnosed by next-generation sequencing (NGS) and explore the usefulness of the number of P. jirovecii sequence reads for the diagnosis of P. jirovecii pneumonia.MethodsWe examined the NGS results for P. jirovecii in respiratory samples collected from patients and analysed their clinical, radiological and microbiological characteristics.ResultsAmong 285 respiratory samples collected over a 12-month period (January to December 2022), P. jirovecii sequences were detected in 56 samples from 53 patients. Fifty (94.3%) of the 53 patients were HIV-negative. Following our case definitions, 37 (69.8%) and 16 (30.2%) of the 53 patients had P. jirovecii infection and colonization respectively. P. jirovecii infection was associated with presence of underlying disease with immunosuppression (94.6% vs 18.8%, P < 0.05), positive serum 1,3-β-D-glucan (41.2% vs 0%, P < 0.01) and higher number of P. jirovecii sequence reads (P < 0.005). In contrast, P. jirovecii colonization was associated with the male sex (93.8% vs 54.1%, P < 0.01), another definitive infectious disease diagnosis of the respiratory tract (43.8% vs 2.7%, P < 0.001) and higher survival (100% vs 67.6%, P < 0.01). Although P. jirovecii pneumonia was associated with higher number of P. jirovecii reads in respiratory samples, only a sensitivity of 82.14% and a specificity of 68.75% could be achieved.ConclusionDetection of P. jirovecii sequences in respiratory samples has to be interpreted discreetly. A combination of clinical, radiological and laboratory findings is still the most crucial in determining whether a particular case is genuine P. jirovecii pneumonia.

Secondary osteoporosis prevention: three-year outcomes from a Fracture Liaison Service in elderly hip fracture patients

BackgroundHip fractures are the most serious fragility fractures due to their associated disability, higher hospitalization costs and high mortality rates. Fracture Liaison Service (FLS) programs have enhanced the management of osteoporosis-related fractures and have shown their clinical effectiveness.AimsTo analyze the effect of the implementation of a FLS model of care over the survival and mortality rates following a hip fracture.MethodsWe conducted a prospective cohort study on patients over 60 years of age who suffered a hip fracture before and after the implementation of the FLS in our center (between January 2016 and December 2019). Patients were followed for three years after the index date. Mortality, complications and refracture rates were compared between the two groups using a Multivariate Cox proportional hazard model.ResultsA total of 1366 patients were included in this study (353 before FLS implementation and 1013 after FLS implementation). Anti-osteoporotic drugs were more frequently prescribed after FLS implementation (79.3% vs 12.5%; p < 0.01) and there was an increase in adherence to treatment (51.7% vs 30.2%; p < 0.01). A total of 413 (40.8%) patients after FLS implementation and 141 (39.9%) individuals before (p = 0.47) died during the three-years follow-up period. A second fracture occurred in 101 (10.0%) patients after FLS implementation and 37 (10.5%) individuals before (p = 0.78). Patients after the implementation of the FLS protocol had a lower all cause one-year mortality [adjusted Hazard Ratio (HR) 0.74 (0.57–0.94)] and a decreased risk of suffering a second osteoporotic fracture [adjusted HR 0.54 (0.39–0.75) in males and adjusted HR 0.46 (0.30–0.71) in females].ConclusionsThe implementation of a FLS protocol was associated with a lower all-cause one-year mortality rate and a higher survivorship in elderly hip fracture patients. However, no three-year mortality rate differences were observed between the two groups. We also found a reduction in the complication and second-fracture rates.

Outcomes of Pregnancies in Women with Congenital Heart Disease: A Study in a Tertiary Care Hospital in Bangladesh

Background: Pregnancies in individuals with congenital heart disease (CHD) frequently pose complex challenges. The presence of CHD elevates the risks not only for the expectant mother but also for the well-being of the developing fetus. Additionally, careful monitoring and specialized medical care are crucial throughout the pregnancy to ensure the best possible outcomes for both. Objective: This study was aimed to assess the outcomes of pregnancies in women with congenital heart disease. Methods: This was a cross-sectional observational study that was conducted in the Combined Military Hospital (CMH), Dhaka, Bangladesh from January 2020 to December 2021. A total 30 pregnant women with congenital heart disease were enrolled through purposive sampling. All the demographic and clinical information was recorded. Data were processed, analyzed, and disseminated by using MS Office tools. Results: Among participants, Lower Segment Cesarean Section (LSCS) was the most common delivery (43.3%), followed by vaginal delivery (36.7%). Instrumental delivery, specifically through outlet forceps, was found in 6.7% of cases. Pregnancy termination occurred in 6.7% due to inevitable abortion and 3.3% for medical reasons, resulting in one maternal death (3.3%). Perinatal outcomes included 90% live births and 81.5% with Apgar scores ≥9. Neonatal Intensive Care Unit (NICU) admission was required for 33.3%, with a 3.3% perinatal death rate. Conclusions: In pregnant women with congenital heart diseases, common delivery modes are Lower Segment Cesarean Section (LSCS) and vaginal delivery. Termination and maternal fatality rates are low. Perinatal outcomes are generally positive, with most births resulting in live infants with Apgar scores ≥9 and high newborn survival rates, although some require Neonatal Intensive Care Unit (NICU) admission. J Rang Med Col. March 2024; Vol. 9, No. 1: 50-54

Indian Freshwater Elasmobranchs: Ongoing Threats along with IUCN Current Status and Conservation of Protecting Hidden Treasures: A Review

We always thought that elasmobranchs inhabit marine environments, but this is only partially true. About 5% of known elasmobranch species are the freshwater compared to 40% of teleost species. A systematic checklist is available for Indian freshwater elasmobranches with names and IUCN status. A total of 13 species belonging to 3 orders, 3 families and 10 genera were enlisted from secondary data. Euryhaline and obligate species include sharks as Carcharhinus, Glyphis (Carcharhinidae), Chiloscyllium (Hemiscylliidae), sawfishes or Pristis (Pristidae), stingrays or Himantura (whiprays) and Pastinachus (cowtailed rays) (Dasyatidae). We focus on distribution, feeding habits, threats and conservation. Freshwater excursions are relatively rare in extant elasmobranchs than other groups of fish. The low growth rate is probably due to late age at maturity and low fecundity, long gestation periods, slow growth and productivity (small, infrequent litters), high natural survivorship for all age classes and long life. Despite this, some species of freshwater elasmobranchs can tolerate and even thrive in freshwater.

Influence of TLR4 signaling on Cannabidiol’s antitumor effectiveness in lung adenocarcinoma cells

Abstract Objectives Lung cancer remains a predominant cancer type with high incidence and low survival rates. Key challenges in its treatment include impaired cellular mechanisms, notably resistance to apoptosis and altered immune responses. A critical aspect in this context is the heightened TLR4-mediated signaling, known to promote cell survival, metastasis, and resistance to cell death, particularly impacting immune microenvironment regulation. This study focuses on evaluating the impact of TLR4 signaling activation on potential therapeutic strategies. Methods Our research utilizes Cannabidiol (CBD), a compound already employed in mitigating chemotherapy side effects in lung adenocarcinoma, recognized for its antitumor properties including antiproliferative, antimetastatic, and apoptosis-inducing effects. However, the effectiveness of CBD in lung cancer cells with elevated TLR4 signaling remains uncertain. Results Our findings reveal that the combination of CBD and TLR4 agonist affects cell viability, proliferation, cell cycle progression, apoptosis, and gene expression related to immune response and extracellular matrix regulation. In lung adenocarcinoma cells with activated TLR4, CBD shows an increased IC50 value, reflecting reduced antiproliferative capacity. Furthermore, its efficacy in arresting the cell cycle and inducing apoptosis is also compromised. The influence on immune response and extracellular matrix regulation is also altered in TLR4-activated cells. Conclusions These results indicate that TLR4 activation significantly diminishes the antitumor efficacy of CBD. This highlights the importance of considering TLR4 signaling activation in future research on therapeutic agents like CBD for cancer treatment.

Social networks and start-up funding

This paper examines whether aggregate social networks influence start-up firms’ access to external funding. We find that start-ups in U.S. counties with higher social proximity to start-up funding (SPF) attract a larger investor base and secure more capital. The results are robust to several alternate specifications. We also show that start-ups in counties with higher SPF have high survival rates and successful exits. Our findings highlight the importance of aggregate social connections in facilitating access to early-stage funding.

Integrated approaches for Solenopsis invicta (Hymenoptera: Formicidae) management: insights from laboratory studies with entomopathogenic nematodes and insecticides.

In agricultural pest management, especially in combatting the invasive red imported fire ant (RIFA, Solenopsis invicta), significant challenges emerge as a consequence of the constraints of solely depending on chemical insecticides or entomopathogenic nematodes (EPNs). The utilization of chemical insecticides carries environmental and ecological hazards, whereas EPNs, when applied independently, might not offer the immediate effectiveness necessary for adequate RIFA suppression. Acknowledging these hurdles, our study investigates a synergistic method that integrates EPNs with chemical insecticides, aiming to fulfill the urgent demand for more efficient and environmentally friendly pest control solutions. Our evaluation focused on the interaction between the highly pathogenic Steinernema riobrave 7-12 EPN strain and prevalent insecticides, specifically beta-cypermethrin and a mixture of bifenthrin and clothianidin, applied at highly diluted recommended concentrations. The findings revealed a notable increase in RIFA mortality rates when EPNs and these insecticides were used together, outperforming the results achieved with each method individually. Remarkably, this enhanced efficacy was especially evident at lower concentrations of the bifenthrin-clothianidin mixture, indicating a valuable approach to minimizing reliance on chemical insecticides in agriculture. Furthermore, the high survival rates of EPNs alongside the tested insecticides indicate their compatibility and potential for sustained use in integrated pest management programs. Our research underscores the effectiveness of merging EPNs with chemical insecticides as a powerful and sustainable strategy for RIFA management. This combined approach not only meets the immediate challenges of pest control in agricultural settings, but also supports wider environmental objectives by reducing the dependency on chemical insecticides. © 2024 Society of Chemical Industry.

Long-term performance of ceramic in/-onlays vs. cast gold partial crowns – a retrospective clinical study

ObjectivesTo assess the long-term clinical performance of ceramic in-/onlays (CIOs) and cast gold partial crowns (CGPCs) in posterior teeth in terms of success, survival, complications (biological, technical) and quality.Material and methodsIn a retrospective study, a total of 325 patients were recorded after up to 24.8 years (mean 13.9 ± 3.8 years) having (pre-)molars restored with CIO (Empress I, Ivoclar Vivadent, n = 161) and CGPC (Degunorm, DeguDent, n = 164) by supervised undergraduate students. A total of 296 restorations were assessed clinically and radiologically in healthy and endodontically treated teeth using modified United States Public Health Service (USPHS) criteria. Cumulative success and survival rates of the restorations were calculated using Kaplan–Meier estimates. Biological and technical complications were recorded. Status of oral health comprising caries risk and localized periodontitis were assessed.ResultsThe cumulative success rates of CIOs were 92.1% and of CGPCs 84.2% after mean service times of 14.5 years. The annual failure rates of total service times were 0.5% in teeth restored with CIO (n = 155) and 0.7% in teeth restored with CGPC (n = 163). The cumulative survival rates of CIOs were 93.9% after a mean service time of 15.2 years and decreased to 91.7% after 23.5 years. The cumulative survival rates of CGPCs were 92.6% after a mean service time of 14.9 years and 91.8% after 23.5 years. Complications in CIOs (n = 149) were ceramic fracture (6.7%), secondary caries (4.7%), endodontic complication (2.7%) and tooth fracture (1.3%) compared to CGPCs (n = 147) with endodontic complication (8.8%), secondary caries (4.8%) and decementation (2.0%). Endodontically treated teeth restored with CIO or CGPC revealed significantly less often success compared with corresponding vital teeth (p = .02). CIOs and CGPCs revealed clinically and radiographically good and excellent qualities with 71.8% (107/149) and 68% (100/147) without any significant differences regarding type of restoration.ConclusionsBoth CIOs and CGPCs achieved high survival rates up to 24.8 years when performed by supervised undergraduate students. The longevity of the restorations may benefit from the intraoral repair of accessible defects and, in case of pulp infection or necrosis, an adequate endodontic management.Clinical relevanceCIOs and CGPCs made by supervised undergraduate students are proper restoration types in posterior teeth in the long-term. An adequate preparation design, meticulous care in the inserting technique and constant biofilm removal due to proper oral hygiene combined with professional maintenance care are substantial. The clinical long-term performance was mostly limited by ceramic fractures in CIOs and endodontic complications in CGPCs.

Abstract PO3-06-04: Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience

Abstract Background The current definition, prognosis, and optimal treatment (tx) for oligometastatic breast cancer (OMBC) are not fully known. With advances in multimodality breast cancer (BC) tx and overall improvement in patient (pt) outcomes, it is important to identify baseline pt factors that confer better prognosis in OMBC and assess the impact of local/regional tx and metastasis (mets)-directed tx on survival outcomes. Methods We reviewed 105 Mayo Clinic pts with OMBC (up to 5 mets) from 2003 to 2021. Pts were excluded from analysis if they were misidentified as having OMBC (n=6), did not have a primary breast mass (n=1), developed de novo BC during tx (n=1), or were lost to follow up (n=2). Categorical variables were summarized as counts. Continuous variables were reported as medians. Kaplan-Meier method was used to estimate survival and the time from diagnosis to next tx at 1, 3, and 5 years. Log-rank test was used to compare survival rates between baseline factors. Univariate Cox proportional hazards models were performed on both baseline and time-dependent factors. All tests were two-sided with p-value &amp;lt; 0.05 considered statistically significant. Results Total pts included were 95. Median age was 49 (range, 26-86), most (93.6%) pts were White, and 46.8% were postmenopausal. Invasive ductal carcinoma (89.5%) was the most common BC type. Median survival was 10.8 years; 1-, 3-, and 5-year survival rates were 98.9%, 87.7%, and 81%, respectively. 58 pts (61.1%) required a change in tx due to disease progression. No significant survival difference was observed in pre- vs. postmenopausal pts (p=0.71) or in groups based on hormone receptor and/or human epidermal growth factor receptor 2 status. 47 pts (49.5%) received local/regional tx; no significant difference in survival (HR 0.57, 95% CI 0.23-1.40; p=0.217) or time to next tx (HR 0.67, 95% CI 0.39-1.15; p=0.144) was seen in this subgroup. Of these pts, 36 (76.6%) received neoadjuvant chemotherapy and/or immunotherapy, 5 of whom (10.6%) also started endocrine tx preoperatively. Overall, 11/47 pts (23.4%) received neoadjuvant endocrine tx. 20 pts received systemic tx without eventual surgery, and 5 pts got palliative radiation (RT). Biopsy-confirmed mets were noted in 76 pts (80%), with bone-only mets in 50%, 30 pts (31.6%) with viscera-only mets and 7 pts (7.4%) with both bone and visceral mets. 18 pts had suspected mets on imaging but did not undergo biopsy. The hazard of death was 6.34 times higher in pts with both bone and visceral mets than those with bone-only mets (p=0.008). Pts with viscera-only mets had higher survival at 2 and 3 years than pts with bone-only or both bone and visceral mets (p=0.093). Pts with 3 mets (7/76, 7.4%) had decreased survival at 1, 2, and 3 years compared to pts with 1-2 (65/76, 85.5%) mets (p=0.6). 67 pts (70.5%) received mets-directed tx; RT alone was the most common modality (52/67, 77.6%), followed by surgery (6/67, 9%), RT plus surgery (5/67, 7.5%), and ablation alone (3/67, 4.5%). There was no significant difference in survival (HR 1.27, 95% CI (0.53, 3.07), p=0.589) or time to next tx (HR 0.95, 95% CI (0.56, 1.63), p=0.856) in pts who received mets-directed tx. Multivariate analysis was not performed because most findings were not statistically significant in univariate analysis. Conclusions We did not find any significant differences in survival based on characteristics like menopausal status or site or number of mets in pts with OMBC. There was a trend toward improved survival in pts with viscera-only mets, but this finding requires validation. Local/regional and mets-directed tx did not improve survival; however, survival at 1, 3, and 5 years was excellent in this OMBC pt population. Our study was limited by low pt numbers and heterogeneity in the pt population. Findings need validation in larger studies. Citation Format: Tanmayi Pai, Raza Zarrar, Zhongwei Peng, Zhuo Li, Lauren Cornell, Kostandinos Sideras, Rohit Rao, Alvaro Moreno-Aspitia, Saranya Chumsri, Sarah McLaughlin, James Jakub, Emmanuel gabriel, Sanjay Bagaria, Laura Vallow, Santo Maimone, Pooja Advani. Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-04.

Abstract PO5-06-07: Unravelling the role of PKC-eta in modulating the Hippo Pathway: a novel therapeutic strategy for triple-negative breast cancer metastasis

Abstract Breast cancer (BC) is the leading cause of cancer-related deaths in women, with metastasis being the primary reason for BC mortality. Triple-Negative Breast Cancer (TNBC) is aggressive and highly metastatic, having fewer treatment options than other types of breast cancer. Protein kinase C eta (PKCη), an anti-apoptotic kinase of the novel PKC subfamily, is associated with poor prognosis in invasive BC patients. In this study, we show the role of PKCη in promoting cell migration and invasion, and we demonstrate that its expression is required to maintain the mesenchymal state during EMT. Furthermore, we show that PKCη activates YAP/TAZ, tumor aggressiveness, and metastasis using in vitro and in vivo models. PKCη promotes metastasis in TNBC cells, showing that the PKCƞ-YAP signaling axis mediates this. Data analysis of BC patients with a high metastatic invasive propensity and low survival BC revealed a positive correlation between the elevated expression levels of PKCη and the expression of YAP. Knockout of PKCη (PKCηKO) in the TNBC cells 4T1 and MDA-MB-231 markedly inhibited their invasion and migration capability. We further show that PKCη enhances cell survival and anoikis prevention ability, which have crucial roles in metastasis formation, allowing cancer cells to circulate and home to distant sites in the body. Further substantiated by in vivo experiments with 4T1 xenografts in NSG mice, demonstrating that 4T1 PKCηKO cells depicted reduced primary tumor size and a significant decrease in size and number of tumor metastases in the lungs, with fewer tumor nodules. MDA-MB-231 PKCηKO xenografts also expressed reduced metastasis in the distant brain, lung, and liver organs. Mechanistically, we show that PKCη regulates epithelial-to-mesenchymal transition (EMT) markers as knockout of PKCη in TNBC cell lines increased expression of E-cadherin, EpCAM, and slug, and decreased expression of vimentin and ZEB1. Further profiling of the Hippo-YAP axis showed that PKCη is a negative regulator of the Hippo pathway that leads to YAP stabilization and is associated with phosphorylation at Ser128, which allows YAP to translocate to the nucleus and contributes to metastasis of TNBC cells. Moreover, our data support direct interaction between PKCη and YAP1 in TNBC cells. Finally, we show that treatment of TNBC cells with uPEP2 (a uORF-encoded peptide of the PKCη transcript) downregulates the PKCη expression, activates the Hippo signaling pathway and promotes YAP degradation. Our findings highlight the importance of PKCη in TNBC metastasis and provide a new avenue for therapeutic intervention in this aggressive and lethal disease. In conclusion, our studies identify a novel role of PKCη as a negative regulator of the Hippo pathway and reveal its function in promoting EMT and metastasis by modulating YAP/TAZ activity in TNBC. Results suggest that PKCη may represent a therapeutic target for this highly lethal and metastatic TNBC. Citation Format: Liju Vijaya Steltar Belsamma, Amitha Muraleedharan, Divya Ram Jayaram, Kamran Waidha, Sankar Jagadeeshan, Rose Sinay, Ekaterina Eremenko, Omer Berner, Moshe Elkabets, Etta Livneh. Unravelling the role of PKC-eta in modulating the Hippo Pathway: a novel therapeutic strategy for triple-negative breast cancer metastasis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-06-07.

Evaluation of Complications Associated with Fixed Partial Denture: A Prospective Study

ABSTRACT Objective: To assess complications, survival rates, and patient-reported outcomes associated with fixed partial dentures (FPDs). Methods: A cohort of 146 subjects, aged 18 and above, requiring FPD were recruited. Following comprehensive dental examinations, FPDs were fabricated. Complications, survival rates, and patient-reported outcomes were evaluated at 3, 6, 12, and 24 months. Results: Complications such as marginal discrepancies and framework fractures showed low frequencies over short-, mid-, and long-term intervals. Survival rates were high at 98.6%, 96.2%, 93.7%, and 91.1% at all intervals, respectively. Patient-reported outcomes indicated a mean comfort level of 8.2 with speech difficulties (8.2%) and hygiene challenges (4.8%). Overall satisfaction was high, with a mean score of 9.0. Conclusion: This study provided evidence of favorable outcomes with low complication rates, high survival rates, and positive patient-reported experiences associated with FPDs.

Abstract PO1-02-09: Efficacy of breast conserving treatment of minimal residual tumors after neoadjuvant therapy for breast cancer

Abstract Background. Determining the most effective drug therapy regimens is one of the top priorities in the individualization of the treatment of patients with breast cancer (BC). Achievement of pathological complete response (pCR) is important prognostic factor, and used as the surrogate primary end point in many clinical trials. According to the literature, the achievement of pCR after neoadjuvant systemic treatment (NST) in breast cancer varies from 30 to 70%. Patients who do not achieve pCR require post-neoadjuvant treatment, even when reaching minimal size of residual tumors. Initially, primary minimal tumors are characterized by high survival rates, which are proved by international and domestic studies. It is required to clarify the survival rates in the presence of a minimal residual tumor (ypT &amp;lt; 10mm) after neoadjuvant systemic therapy and to compare with primary minimal forms of breast cancer (pT1a-b N0M0), characterized by the most favorable prognosis. Objective. Improvement of the effectiveness of treatment of residual minimal forms (ypT1a-b) of BC after NST. Determination of the correlation between the schemes of NST and the rates of tumor response based on the results of postoperative pathological reports including RCB scale. Methods. The study included 602 patients aged 18–65 years with early and locally advanced I–IIIC stage T1-3N1-3M0 breast cancer,who underwent complex or combined treatment. This study included patients treated at the N.N. Petrov National Medical Research Center of Oncology from 2015 to 2021 Conclusion. After reaching a complete pathomorphological response of the tumor to NST (RCB 0), the 5-year disease-free (DFS) and overall (OS) survival rates (DFS – 78.5%; OS 90.4%) were inferior to the survival rates of patients with primary minimal breast cancer (pT1ab N0M0) [DFS – 86.4%; OS – 98.6%]. Neoadjuvant chemotherapy regimens that allow achieving a pathological complete response in triple-negative and HER2- positive breast cancer have been defined. An assessment of adverse factors that affect the effectiveness of breast conserving treatment and correlate with a deterioration in overall survival was performed. Results. Our data analysis revealed that the survival rates (DFS and OS) of patients with minimal residual tumor after neojuvant systemic therapy were not comparable with those in the group of patients with primary minimal breast cancer. Data analysis revealed the most effective combinations of drugs expressed in the rates of pathomorphological response according to the RCB scale. An assessment of adverse factors that affect the effectiveness of organ-preserving treatment and correlate with a deterioration in overall survival was performed. Citation Format: Roman Pesotsky, Vladimir Semiglazov, Petr Krivorotko, Tengiz Tabagua, Konstantin Zernov, Alexander Emelyanov, Viktoria Mortada, Nikolay Amirov, Daria Ulrikh, Valerii Levchenko, Yana Bondarchuk, Diana Enaldieva, Nestan Bekkeldieva, Konsantin Zirov, Sergey Yerechshenko, Vladislav Evseev, Kirill Rychagov, Sergey Novikov, Maria Kazantseva, Larisa Gigolaeva, Elena Zhiltsova, Denis Nesterov, Olga Ivanova, Tatiana Semiglazova. Efficacy of breast conserving treatment of minimal residual tumors after neoadjuvant therapy for breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-09.

Effects of small-scale outplanting fertilization on conifer seedling growth and fungal community establishment

Forestry in Sweden largely relies on planting genetically improved seedlings after clear-cutting, and high survival and early growth of planted seedlings is vital for stand establishment, economic viability, and carbon sequestration. Norway spruce (Picea abies) and Scots pine (Pinus sylvestris) are the two most important tree species in Swedish forest stands and both are associated with a variety of ectomycorrhizal fungi. While seedlings are generally not fertilized at outplanting, previous results have shown that fertilization with arginine phosphate can increase root growth and seedling survival. However, it is not clear how this affects fungal community composition on the roots of growing seedlings. In a planting experiment sampled after one and two growing seasons, we found that planting position had the largest effects both on seedling performance and on fungal community composition and provide insight into the early stages of fungal community succession on planted Norway spruce and Scots pine seedlings. Fungal taxa present on seedlings before planting persisted on seedling roots, while some degree of novel colonization by site indigenous taxa was observed. Fertilization modified the relative abundance of some fungal taxa but did not lead to significant changes in overall community composition. In terms of seedling performance, ammonium nitrate led to increased mortality while arginine phosphate improved root growth.

Should I stay or should I go? Coral bleaching from the symbionts' perspective.

Coral bleaching, the stress-induced breakdown of coral-algal symbiosis, threatens reefs globally. Paradoxically, despite adverse fitness effects, corals bleach annually, even outside of abnormal temperatures. This generally occurs shortly after the once-per-year mass coral spawning. Here, we propose a hypothesis linking annual coral bleaching and the transmission of symbionts to the next generation of coral hosts. We developed a dynamic model with two symbiont growth strategies, and found that high sexual recruitment and low adult coral survivorship and growth favour bleaching susceptibility, while the reverse promotes bleaching resilience. Otherwise, unexplained trends in the Indo-Pacific align with our hypothesis, where reefs and coral taxa exhibiting higher recruitment are more bleaching susceptible. The results from our model caution against interpreting potential shifts towards more bleaching-resistant symbionts as evidence of climate adaptation-we predict such a shift could also occur in declining systems experiencing low recruitment rates, a common scenario on today's reefs.

No Difference in 10-Year Survivorship of Total Shoulder Arthroplasty Versus Hemiarthroplasty for Avascular Necrosis of the Humeral Head

Avascular necrosis of the humeral head (AVN) is characterized by osteonecrosis secondary to disrupted blood flow to the glenohumeral joint. Following collapse of the humeral head, arthroplasty, namely total shoulder arthroplasty (TSA) or humeral head arthroplasty (hemiarthroplasty) is recommended standard of care. The literature is limited to underpowered and small sample sizes in comparing arthroplasty modalities. Therefore, the aims of this study were (1) to compare the 10-year survivorship of TSA and hemiarthroplasty in the treatment of AVN of the humeral head and (2) to identify differences in their revision etiologies. Patients who underwent primary TSA and hemiarthroplasty for AVN were identified using the PearlDiver database. TSA patients were matched by age, gender, and Charlson Comorbidity Index (CCI) to the hemiarthroplasty cohort in a 4:1 ratio since TSA patients were generally older, sicker, and more often female. The 10-year cumulative incidence rate of all-cause revision was determined using Kaplan-Meier survival analysis. Multivariable analysis was conducted using Cox Proportional Hazard modeling. Chi-squared analysis was conducted to compare the indications for revisions between matched cohorts including periprosthetic joint infection (PJI), dislocation, mechanical loosening, broken implants, periprosthetic fracture, and stiffness. In total, 4,825 patients undergoing TSA and 1,969 patients undergoing hemiarthroplasty for AVN were included in this study. The unmatched 10-year cumulative incidence of revision for patients who underwent TSA and hemiarthroplasty was 7.0% and 7.7%, respectively. The matched 10-year cumulative incidence of revision for patients who underwent TSA and hemiarthroplasty was 6.7% and 8.0%, respectively. When comparing the unmatched cohorts, TSA patients were at significantly higher risk of 10-year all-cause revision (HR: 1.39; P = 0.017) when compared to hemiarthroplasty patients. After matching, there was no significant difference in risk of 10-year all-cause revision (HR: 1.29; P = 0.148) and no difference in the observed etiologies for revision (P > 0.05 for all). After controlling for confounders, only 6.7% of TSA and 8.0% hemiarthroplasties for humeral head AVN were revised within 10-years of index surgery. The demonstrated high and comparable long-term survivorship for both modalities supports the utilization of either for the AVN induced humeral head collapse.

Long-term outcomes of a novel fully magnetically levitated ventricular assist device for the treatment of advanced heart failure in China

PurposeLeft ventricular assist devices (LVADs) are well-established for treating end-stage heart failure, but this therapy is only available to Chinese patients in recent years. The CH-VAD is the first used fully magnetically levitated pump and the most widely used device in China. This study reports the long-term outcomes of a cohort supported by the CH-VAD for the first time. MethodsFrom June 2017 to August 2023, 50 consecutive patients received CH-VAD implantation in Fuwai Hospital. Clinical data were collected during follow-up and retrospectively analyzed. ResultsBaseline characteristics included a mean age of 47.9±13.9 years, 90% male, and 26% ischemic etiology. The INTERMACS profile revealed 12% Profile 1, 56% Profile 2, 26% Profile 3 and 6% Profile 4. Mean support duration was 868 ± 630 days (range 33 days-6.4 years). Kaplan-Meier survival rate was 96% (95% confidence interval [CI], 85 to 99) at 6 months, 93% (95% CI, 79-98) at 1 year, 93% (95% CI, 79-98) at 2 years and 89% (95% CI, 71-96) at 3 years. 40 patients (80%) currently remain on support, 3 were bridged to recovery, 2 received transplant, and 5 expired during support. Major adverse events included right heart failure (10%), surgical related bleeding (8%), arrhythmia (8%) and driveline infection (16%). Major hemocompatibility-related adverse events were limited to 3 non-disabling strokes and 1 gastrointestinal bleeding. There was no major device malfunction during the follow-up period. ConclusionsThe largest single-center experience with the leading LVAD in China shows high survival with low complication rates, demonstrating the CH-VAD is safe and efficient in providing long-term support for end-stage heart failure patients.