MiRNA expression affects survival in patients with obstructive sleep apnea and metastatic colorectal cancer.

Introduction: The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs. Methods: The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients' sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs. Results: The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly. Conclusions: This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA.

Gender-Specific Long-Term Results After Elective Open Abdominal Aortic Aneurysm Repair Depending on the Site of Distal Anastomosis.

OBJECTIVE: Analysis of gender-specific differences in short- and long-term outcome after elective open abdominal aortic aneurysm repair (OAR) regarding the distal anastomosis. METHODS: In this retrospective cohort study, data from 4853 patients of a German health insurance company undergoing OAR for infrarenal abdominal aortic aneurysms (AAAs) between 2010 and 2016 were analysed. The patients were followed through 2018. RESULTS: A total of 4050 (83.5%) men and 803 (16.6%) women underwent OAR. Women were older than men (72.9 ± 8.7 vs 69.8 ± 8.5 years; P < .001). A tube graft was used in 2644 (54.5%) patients, an aorto-biiliac bifurcated graft in 1657 (34.1%) and an aorto-bifemoral bifurcated graft in 552 (11.4%). Perioperative mortality was not significantly different between men (5.7%) and women (6.5%) in the total patient population (P = .411). This was true for aorto-aortic tube grafting (P = .361), aorto-biiliac reconstructions (P = 1.000) and aorto-bifemoral reconstructions (P = .345). Kaplan-Meier estimated long-term survival of men after 9 years was better than that of women (55.0% vs 43.8%; P = .006). However, separated by the site of the distal anastomosis, this was only true for aorto-aortic reconstructions (survival men vs women 56.0% vs 42.1%; P = .005), not for aorto-biiliac and aorto-bifemoral reconstructions. In the multivariate Cox regression analysis, age over 80 years, heart failure, aorto-bifemoral reconstruction, chronic kidney disease stage 3-5, chronic obstructive pulmonary disease, peripheral artery disease, arterial hypertension, but not gender (P = .531), had a negative impact on long-term survival. CONCLUSION: If possible, an aorto-aortic tube graft should be preferred to aorto-biiliac and aorto-bifemoral reconstructions in OAR. Patients selected for aorto-bifemoral artery reconstruction exhibit higher perioperative morbidity and mortality as well as worse long-term survival compared to patients selected for an intra-abdominal reconstruction. In the multivariate regression analysis, gender was not an independent risk factor for either short- or long-term outcomes.

Method to Study the Survival Abilities of Foodborne Bacterial Pathogens Under Food Processing Conditions.

Properly using controllable atmospheric containers can facilitate investigations of the survival abilities and physiological states of key and emerging-foodborne pathogens under recreated applicable food processing environmental conditions. Notably, saturated salt solutions can efficiently control relative humidity in airtight containers. This chapter describes a practical experimental setup, with necessary prerequisites for exposing foodborne pathogens to simulated and relevant food processing environmental conditions. Subsequent analyses for studying cell physiology will also be suggested.

Encapsulation of Lactiplantibacillus plantarum with casein-gellan gum emulsions to enhance its storage, pasteurization, and gastrointestinal survival.

Probiotics serve a very important role in human health. However, probiotics have poor stability during processing, storage, and gastrointestinal digestion. The gellan gum (GG) is less susceptible to enzymatic degradation and resistant to thermal and acidic environments. This study investigated the effect of casein (CS)-GG emulsions to encapsulate Lactiplantibacillus plantarum CICC 6002 (L. plantarum CICC 6002) on its storage stability, thermal stability, and gastrointestinal digestion. L. plantarum CICC 6002 was suspended in palm oil and emulsions were prepared using CS or CS-GG complexes. We found the CS-GG emulsions improved the viability of L. plantarum CICC 6002 after storage, pasteurization, and digestion compared to the CS emulsions. In addition, we investigated the influence of the gellan gum concentration on emulsion stability, and the optimal stability was observed in the emulsion prepared by CS-0.8% GG complex. This study provided a new strategy for the protection of probiotics based on CS-GG delivery system.

Recording of Age-Related Changes on Murine and Human Brain Slices.

Preparation of brain slices for electrophysiological and imaging experiments has been developed several decades ago, and the method is still widely used due to its simplicity and advantages over other techniques. It can be easily combined with other well established and recently developed methods as immunohistochemistry and morphological analysis or opto- and chemogenetics. Several aspects of this technique are covered by a plethora of excellent and detailed review papers, in which one can gain a deep insight of variations in it. In this chapter, I briefly describe the solutions, equipment, and preparation techniques routinely used in our laboratory. I also aim to present how certain "old school" brain slice lab devices can be made in a cost-efficient way. These devices can be easily adapted for the special needs of the experiments. I also aim to present some differences in the preparatory techniques of acutely isolated human brain tissue.

The powerless extremes: Balancing altruism and individualism in environmental policy formulation / Los extremos impotentes: balance de altruismo e individualismo en la formulación de políticas ambientales

RESUMEN El objetivo es proponer un esquema conceptual que sea útil para interpretar las implicaciones económicas y ambientales que tienen las organizaciones sociales basadas en un paradigma individualista o altruista. Tras una revisión de literatura y breve recuento histórico de estos paradigmas, se concluye que son las organizaciones complejas y equilibradas las que tienen mayor propensión a desarrollar intercambios de cooperación altruistas. La implicación para las políticas ambientales contemporáneas es que, además de los mecanismos de mercado, es posible complementarlas con otros esquemas basados en mecanismos comunitarios, siempre y cuando exista un contexto propicio para implementarlo.

ABSTRACT The objective is to propose a practical conceptual scheme to interpret social organizations' economic and ecological implications based on an individualistic or altruistic paradigm. After a literature review and a brief historical analysis of these paradigms, we conclude that complex and balanced organizations have the most remarkable propensity to develop altruistic cooperation exchanges. The implication for contemporary environmental policies is the possibility of complementing market mechanisms with community-based schemes in a favorable context.

Neurotoxicity and Cardiovascular Toxicity of Zinc Oxide Nanoparticles to Oryzias melastigma.

Zinc oxide nanoparticles (ZnO NPs) are widely used in manufacturing cosmetic and pharmaceutical products. Although previous studies have reported their toxic effects on fish, the underlying mechanisms behind their toxic effects are yet to be identified. This study evaluated the impact of ZnO NPs on marine medaka's survival, heart rates (Oryzias melastigma), and the expression of genes linked to neurotoxicity and cardiovascular toxicity. Marine medaka samples were exposed to ZnO NPs at varying concentrations: 0.01, 0.1, 1, and 10 mg/L. Survival rates and heart rates were monitored on the 12th day postfertilization. Gene expression related to neurotoxicity (α-tubulin, elavl3, gap43, gfap) and cardiovascular toxicity (cdh2, atp2a1, cacna1da, crhr1, ahrra, arnt2) was assessed by performing real-time polymerase chain reaction. The survival rate of marine medaka samples was not significantly impacted by exposure to up to 1 mg/L of ZnO NPs; however, exposure to 10 mg/L of ZnO NPs resulted in a 60% reduction in survival rate. The heart rate of the samples did not significantly change across all concentrations. High ZnO NP concentrations (10 mg/L) significantly suppressed the expression of neurotoxic and cardiotoxic genes, including elavl3 and gfap. ZnO NPs exhibited dose-dependent toxic effects on the marine medaka samples by affecting the expression of genes related to neurological and cardiovascular functions. These findings underscore the potential risks of ZnO NPs to aquatic organisms. The distinct toxic actions of ZnO NPs and dissolved ions complicate the interpretation of results, as this study did not measure ion release, a critical factor in understanding NP toxicity. Moreover, ZnO NPs may cause oxidative stress and disrupt cellular pathways. Furthermore, without distinguishing between NP and ion effects, it is challenging to determine the exact cause of toxicity. These findings highlight the need for future studies to measure dissolved ions and particles separately to clarify their contributions to toxicity, where the mechanisms of action are still debated.

The role of PD-L1 in patients with non-small cell lung cancer receiving neoadjuvant immune checkpoint inhibitor plus chemotherapy: a meta-analysis.

BACKGROUND: The use of immune checkpoint inhibitors (ICIs) as neoadjuvant therapy is a promising novel approach in resectable non-small-cell lung cancer (NSCLC). This study aimed to investigate the prognostic value of PD-L1 in patients with NSCLC receiving neoadjuvant immune checkpoint inhibitor plus chemotherapy (CT). MATERIALS AND METHODS: Several databases (PubMed, Embase, and cochrane central register of controlled trials [CENTRAL]) were systematically searched. Randomized controlled trials (RCTs) investigating pathological and survival outcomes with neoadjuvant ICI + CT versus CT alone in NSCLC were analyzed. RESULTS: Overall, eight RCTs (n = 3,404) were included. The analyses showed neoadjuvant ICI + CT significantly improved complete pathological response (pCR) and event-free survival (EFS) in either tumor PD-L1 < 1%, ≥ 1%, 1-49%, or ≥ 50% population (both p < 0.0001) compared with neoadjuvant CT alone. The overall survival (OS) data are not yet mature among all included RCTs, and only three RCTs presented OS data by PD-L1 status of patients. The pooled OS favored neoadjuvant ICI + CT in the PD-L1 ≥ 1% population (hazard ratio [HR], 0.45; 95% CI, 0.31-0.65; p < 0.0001), but not in the PD-L1 < 1% population (HR, 0.89; 95% CI, 0.66-1.19; p = 0.43). CONCLUSIONS: Compared with neoadjuvant CT alone, neoadjuvant ICI + CT significantly enhanced pCR and EFS for patients with resectable NSCLC regardless of the expression of PD-L1. It seems that only patients with PD-L1 positive tumors may achieve a better OS, but it's currently inconclusive due to immature data, so future research with long-term follow-up is still needed.

Construction of a combined prognostic model for pancreatic ductal adenocarcinoma based on deep learning and digital pathology images.

BACKGROUND: Deep learning has made significant advancements in the field of digital pathology, and the integration of multiple models has further improved accuracy. In this study, we aimed to construct a combined prognostic model using deep learning-extracted features from digital pathology images of pancreatic ductal adenocarcinoma (PDAC) alongside clinical predictive indicators and to explore its prognostic value. METHODS: A retrospective analysis was conducted on 142 postoperative pathologically confirmed PDAC cases. These cases were divided into training (n = 114) and testing sets (n = 28) at an 8:2 ratio. Tumor whole-slide imaging features were extracted and screened to construct a pathological risk model based on a pre-trained deep learning model. Clinical and pathological data from the training set were used to select independent predictive factors for PDAC and establish a clinical risk model using LASSO, univariate, and multivariate Cox regression analyses. Based on the pathological and clinical risk models, a combined model was developed. The Harrell concordance index (C-index) was computed to assess the predictive performance of each model for PDAC survival prognosis. RESULTS: For the training and testing sets, the C-index values for the clinical risk model were 0.76 and 0.75, respectively; for the pathological risk model, they were 0.82 and 0.73, respectively; and for the combined model, they were 0.86 and 0.77, respectively. The combined model exhibited appropriate calibration at 1-, 3-, and 5-year time points, as well as a superior area under the curve of the receiver operating characteristic curve and clinical net benefit compared to the single models. CONCLUSIONS: Integrating the pathological and clinical risk models may provide a higher predictive value for survival prognosis.

Different surgical methods for FIGO stage IVB cervical cancer patients receiving chemotherapy: a population-based study.

OBJECTIVE: To assess survival differences between non-extensive surgery (NES) and extensive surgery (ES) in International Federation of Gynecology and Obstetrics (FIGO) stage IVB cervical cancer patients receiving chemotherapy from a population-based database, the Surveillance, Epidemiology and End Results. METHODS: Propensity matching was conducted to minimize heterogeneity. Survival analysis was performed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards model. RESULTS: A total of 154 patients met screening criteria, among whom 84 patients (84/154) underwent NES while 70 patients (70/154) underwent ES. After matching, no survival advantage was observed in ES group compared with NES group (p=0.066; hazard ratio [HR]=1.54; 95% confidence interval [CI]=0.97-2.42). Stratified analyses suggested ES prolonged overall survival in patients with histology other than squamous cell carcinoma and adenocarcinoma (p=0.028; HR=0.36; 95% CI=0.15-0.89) and American Joint Committee on Cancer (AJCC) T stage T1 (p=0.009; HR=0.18; 95% CI=0.05-0.66). Despite no survival benefit after regional lymph node surgery (p=0.629; HR=0.88; 95% CI=0.53-1.47), subgroup analyses demonstrated that patients younger than 50 (p=0.006; HR=0.21; 95% CI=0.07-0.64), with AJCC T stage T1 (p=0.002; HR=0.09; 95% CI=0.02-0.42), T3 (p=0.001; HR=0.02; 95% CI=0.00-0.21), hematogenous metastasis (p=0.036; HR=0.27; 95% CI=0.08-0.92) and without surgery of other sites (p=0.040; HR=0.01; 95% CI=0.00-0.79) might achieve longer survival after regional lymph node surgery. CONCLUSION: In conclusion, ES or regional lymph node surgery may provide survival advantage for certain subgroup of FIGO IVB cervical cancer patients receiving chemotherapy. However, it deserves large scale prospective clinical trials to confirm.

Innovations in Artificial Intelligence-Driven Breast Cancer Survival Prediction: A Narrative Review.

This narrative review explores the burgeoning field of Artificial Intelligence (AI)-driven Breast Cancer (BC) survival prediction, emphasizing the transformative impact on patient care. From machine learning to deep neural networks, diverse models demonstrate the potential to refine prognosis accuracy and tailor treatment strategies. The literature underscores the need for clinician integration and addresses challenges of model generalizability and ethical considerations. Crucially, AI's promise extends to Low- and Middle-Income Countries (LMICs), presenting an opportunity to bridge healthcare disparities. Collaborative efforts in research, technology transfer, and education are essential to empower healthcare professionals in LMICs. As we navigate this frontier, AI emerges not only as a technological advancement but as a guiding light toward personalized, accessible BC care, marking a significant stride in the global fight against this formidable disease.

Outcome of Solid Organ Transplantation in Patients With Intellectual Disability: A Systematic Literature Review.

Access to solid organ transplantation in patients with intellectual disability is associated with health inequities due to concerns about treatment adherence, survival rates, and post-transplant quality of life. This systematic literature review aims to compare outcomes after organ transplantation in patients with intellectual disability compared to patients without intellectual disability. Embase, Medline Ovid, PsycINFO, Web of Science, Cochrane Central Register of Trials, and Google Scholar databases were systematically searched for studies concerning pediatric or adult solid organ transplantation in recipients with a diagnosis of intellectual disability prior to transplantation. Primary outcomes were patient and graft survival rates. Secondary outcomes were acute rejection rate, adherence rates, and quality of life. Nine studies were included, describing kidney (n = 6), heart (n = 4) and liver (n = 1) transplantation. Reported graft survival rates were non-inferior or better compared to patients without intellectual disability, while patient survival was reportedly slightly lower in two studies reporting on kidney transplantation. Although current evidence has a potential selection bias based on including patients with a sufficient support network, intellectual disability alone should not be regarded a relative or absolute contra-indication for solid organ transplantation.

Outcomes of Dose Escalation of Imatinib in Chronic Myeloid Leukemia Patients: A Retrospective Analysis From an Indian University Teaching Hospital.

BACKGROUND: Chronic myeloid leukemia (CML) treatment in low- and middle-income countries faces significant financial and logistical constraints. In scenarios where second-line tyrosine kinase inhibitors (TKIs) are unavailable or unaffordable, dose escalation of imatinib provides an alternative. This study evaluates the efficacy, safety, and progression-free survival (PFS) outcomes of dose escalation of imatinib in CML patients who experienced suboptimal response or progression on standard doses. METHODS: A retrospective analysis of 123 CML patients treated at an Indian university teaching hospital from 2013 to 2016 was conducted. Patients who showed progression on a 400 mg dose of imatinib were escalated to 600 mg, and further to 800 mg if required. Demographic data, progression, and toxicity were analyzed. RESULTS: Out of 123 patients, 78 (63.4%) showed a complete hematologic response after dose escalation. The median PFS was 48 months, with a three-year PFS rate of 67%. Notable toxicities included Grade 3/4 neutropenia in 15% and gastrointestinal disturbances in 12%. Comparatively, studies suggest that switching to a second-line TKI in similar settings results in a higher PFS; however, our findings underscore that dose escalation of imatinib remains a viable alternative when financial constraints limit access to second-line therapies. CONCLUSION: In resource-constrained settings, dose escalation of imatinib can be an effective strategy for managing CML patients who progress on standard doses.

Successful treatment of osteosarcoma in a pregnant woman with survival of the gestational product: A case report and literature review.

Osteosarcoma (OS) is the most prevalent bone neoplasm of mesenchymal origin, accounting for 20% of all bone tumors worldwide. It mainly affects the marrow of long bones, and its diagnosis is more common among adolescents and the geriatric population. Histologically, it is characterized by high cellular variability, abundant osteoid and fibrotic material. In the early stages, it presents with only local symptoms such as pain, edema and limited joint mobility. This neoplasm, when detected promptly, is associated with a favorable prognosis and can be effectively treated through surgical removal and adjuvant therapy. The development of tumors in pregnant women is rare, and the occurrence of osteosarcoma is even more exceptional, with only 10 cases documented in the literature. Given its rarity, the present study describes the case of a female patient with OS diagnosed in the first trimester of pregnancy, where the patient responded well to treatment, resulting in no adverse effects on the pregnancy outcome.

Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy-a systematic review and meta-analysis.

Background: More and more patients with pancreatic cancer (PC) received neoadjuvant therapy (NAT) and then underwent radical pancreatectomy. However, the benefit of adjuvant chemotherapy (AC) for these patients is still controversial. This study is designed to determine the benefits of postoperative AC for patients with PC undergoing NAT and radical resection. Methods: We conducted a comprehensive search of the PubMed, Embase, Web of Science, and Cochrane Library databases, covering the period from their inception until 10 September 2023. Our analysis focused on the assessment of overall survival (OS) and recurrence-free survival (RFS) through meta-analysis. The fixed-effects model and the random-effects model were used to process the data. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were employed to determine the necessary of administering AC for patients with PC who have undergone NAT and radical resection. We retrieved 3,063 search results, of which 3,048 were excluded because of duplication or after applying our inclusion and exclusion criteria. Results: A total of 15 studies with 21,113 patients (7,794 patients in the AC group and 13,319 in the non-AC group) were included, all of which reported OS, and three studies reported disease-free survival (DFS)/tumor-specific survival (CSS)/RFS. The final results showed that AC significantly improved OS and DFS/CSS/RFS in patients with PC who underwent pancreatectomy after NAT [OS: HR = 0.80, 95% CI (0.75∼0.86), P < 0.00001, I2 = 48%; DFS/CSS/RFS: HR = 0.53, 95% CI (0.41~0.69), P < 0.00001, I2 = 0%]. Furthermore, we performed subgroup analyses and demonstrated that AC provided a significant survival benefit for patients with PC after NAT and resection regardless of the tumor size [<2-cm subgroup: HR = 0.72, 95% CI (0.5∼0.94), P = 0.01; ≥2-cm subgroup: HR = 0.79, 95% CI (0.65∼0.96), P = 0.02] and the margin status [R0 subgroup: HR = 0.83, 95% CI (0.77∼0.88), P < 0.00001; R2 subgroup: HR = 0.75, 95% CI (0.61∼0.92), P = 0.007]. AC also benefited the patients with a stage N0 [HR = 0.79, 95% CI (0.74~0.84), P < 0.00001], N1 [HR = 0.78, 95% CI (0.72∼0.85), P < 0.00001], or poorly/undifferentiated tumor [HR = 0.76, 95% CI (0.66∼0.87), P < 0.0001] in survival but not in patients with a stage N2 [HR = 0.69, 95% CI (0.43∼1.09), P = 0.11] or well/moderately differentiated tumor [HR = 0.97, 95% CI (0.66∼1.42), P = 0.87]. Conclusions: Although AC showed survival benefit for patients with PC undergoing radical pancreatectomy after NAT, we still need to consider the lymph node stage and the degree of differentiation of the tumor when we gave AC to a patient. High-quality prospective randomized controlled studies are required to well disclose the value of AC in patients with PC undergoing radical pancreatectomy after NAT. Systematic review registration: https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023461365.

Resilience of Juvenile Freshwater Pearl Mussels to Thermal Stress.

Climate change poses a significant threat to freshwater ecosystems by causing increases of average water temperatures, and more frequent and extreme heating events. Freshwater mussels are declining globally, and the distribution of the freshwater pearl mussel (Margeritifera margeritifera) has decreased dramatically over the past century. Even though it is likely that climate change is contributing to the decline of the species, little is known about the specific mechanisms involved. Here, we test how short episodes of water temperatures above the known thermotolerance range affect the survival and growth of the early post parasitic juvenile phase of freshwater pearl mussels. We also test if previous experience with elevated water temperatures can modify survival and growth responses to subsequent high-temperatures exposure. Mortality was very low in all treatments (< 5%) and not affected by the temperature treatments, while growth rate was positively affected by temperature. Our results suggest that juvenile mussels can survive short periods of heat stress when other environmental conditions are favourable. Future studies should therefore address how heat stress affects survival in combination with other stressors, such as reduced availability of dissolved oxygen.

Surgical resection and overall survival in cT4b sinonasal non-squamous cell carcinoma.

Objective: Surgical resection is associated with higher overall survival (OS) than definitive radiotherapy (RT) or chemoradiotherapy (CRT) in cT4b sinonasal squamous cell carcinoma (SCC). Our study investigates the survival benefit of surgical resection in cT4b sinonasal non-SCC. Methods: The 2004 to 2019 National Cancer Database was queried for patients with cT4b sinonasal non-SCC undergoing definitive treatment with (1) surgical resection + additional therapy (RT, chemotherapy, or both), (2) RT alone, or (3) CRT. Surgical resection + additional therapy and definitive RT/CRT were compared with Kaplan-Meier and multivariable Cox regression models. Results: Of 629 patients satisfying inclusion criteria, 513 (81.6%) underwent surgical resection + additional therapy and 116 (18.4%) underwent definitive RT/CRT. The most frequent histologic types were undifferentiated carcinoma (23.7%), adenoid cystic carcinoma (22.6%), and adenocarcinoma (20.7%). Few patients presented with clinical nodal metastasis (15.7%). There were 4 (0.8%) mortalities within 90 days of surgical resection. Patients undergoing surgical resection with positive surgical margins had higher 5-year OS than those undergoing definitive RT/CRT (56.3% vs. 39.4%, p = .039) and similar 5-year OS as those with negative margins (56.3% vs. 63.9%, p = .059). Patients undergoing neoadjuvant chemotherapy had similar 5-year OS as those undergoing definitive RT/CRT (60.9% vs. 39.5%, p = .053). Age at diagnosis, tumor diameter, and surgical resection + additional therapy (aHR 0.64, 95% CI 0.45-0.91) were associated with OS (p < .05). Conclusion: Surgical resection + additional therapy was associated with higher OS than definitive RT/CRT in cT4b sinonasal non-SCC. Surgical resection may benefit select patient with cT4b sinonasal non-SCC. Level of Evidence: 4.

A phase II study of anlotinib plus whole brain radiation therapy for patients with NSCLC with multiple brain metastases.

BACKGROUND: Whole brain radiotherapy (WBRT) is the mainstay of treatment for patients with non-small cell lung cancer (NSCLC) with multiple brain metastases (BMs); however, the BRAIN study showed that the efficacy of WBRT is unsatisfactory. This prospective phase II study aimed to evaluate the efficacy and safety of WBRT combined with anlotinib, a novel anti-angiogenic multi-target tyrosine kinase inhibitor (TKI), in patients with multiple BMs (>3) from advanced NSCLC. METHODS: Patients with advanced NSCLC with multiple BMs who had received two or more lines of treatment were eligible for enrolment into this study. All patients were treated with anlotinib (8-12 mg, QD, on days 1-14 of a 21-day cycle) combined with WBRT (DT 30 Gy/12 F), followed by maintenance therapy with anlotinib until disease progression or treatment intolerance. The primary endpoint of this study was the intracranial progression-free survival (iPFS). The secondary endpoints were intracranial objective response rate (iORR), intracranial disease control rate (iDCR), overall survival (OS) and treatment safety. RESULTS: Between May 2019 and January 2021, 28 patients were enrolled, all of whom were evaluable for efficacy and safety. The median age was 57.7 years, and 46.4% were male. Twenty-five patients had adenocarcinoma (89.3%), six had EGFR mutations (21.4%) and two had ALK mutations (7.1%). The median iPFS was 11.1 months (95% confidence interval (CI): 5.4-16.8 months) and the median OS was 13.4 months (95% CI: 5.2-21.6 months). The iORR was 71.4% (six complete responses + 14 partial responses). The most frequently observed adverse events (AEs) were hypertension (71.4%), fatigue (64.3%), anorexia (46.4%), and foot and hand skin reactions (25.0%). No patients developed ≥ grade 4 AEs. No intracranial haemorrhages occurred during treatment. Dose adjustment due to AEs occurred in 17.9% of patients. CONCLUSIONS: Anlotinib combined with WBRT is effective and well-tolerated in patients with NSCLC with multiple BMs.

MHC Class II Supertypes Affect Survival and Lifetime Reproductive Success in a Migratory Songbird.

The major histocompatibility complex (MHC) plays a critical role in the immune response against pathogens. Its high polymorphism is thought to be mainly the consequence of host-pathogen co-evolution, but elucidating the mechanism(s) driving MHC evolution remains challenging for natural populations. We investigated the diversity of MHC class II genes in a wild population of pied flycatchers Ficedula hypoleuca and tested its associations with two key components of individual fitness: lifetime reproductive success and survival. Among 180 breeding adults in our study population, we found 182 unique MHC class II exon 2 alleles. The alleles showed a strong signal of positive selection and grouped into nine functional supertypes based on physicochemical properties at the inferred antigen-binding sites. Three supertypes were found in > 98% of the sampled individuals, indicating that they are nearly fixed in the population. We found no rare supertypes in the population, as all supertypes were present in > 70% of individuals. Three supertypes were related to different components of individual fitness: two were associated with lower offspring production over time, while the third was positively associated with survival. Overall, the substantial allelic and functional diversity and the relationship between specific supertypes and fitness are in accordance with the notion that balancing selection maintains MHC class II diversity in the study population, possibly with fluctuating selection as the underlying mechanism. The absence of rare supertypes in the population suggests that the balancing selection is not driven by rare-allele advantage.

Ovarian Cancer Retrospective European (O'CaRE) study: first-line outcomes by number of risk factors for progression.

Aim: The Ovarian Cancer Retrospective European (O'CaRE) study assessed the cumulative impact of high-risk factors on progression-free survival (PFS) and overall survival (OS) following first-line treatment in patients diagnosed with advanced ovarian cancer.Patients & methods: Medical records were collected from five European countries (2014 and 2015). Patients were grouped by number of high-risk factors: stage IV diagnosis, no known BRCA mutation, interval debulking surgery or no surgery, or visible residual disease.Results: Our analysis included 405 patients grouped based on having one (20.4%); two (32.3%); three (33.7%) or four (11.9%) high-risk factors. Increasing cumulative numbers of high-risk factors were associated with numerically shorter PFS and OS.Conclusion: Risk profiles should be carefully considered when planning clinical care.

Does the number of risk factors a person with advanced ovarian cancer have affect the likely success of their cancer treatment?What is already known on this topic? Studies have found that individual factors, such as disease stage, and whether any cancer cells remain after surgery are linked to earlier disease worsening and/or shorter survival after treatment in people with advanced ovarian cancer. These are known as 'risk factors'. However, few studies have looked at whether this link is stronger if a person has several of these risk factors.What does this study add? In this study, we looked at whether outcomes after treatment worsen as the number of risk factors increases. We found that patients with more high-risk factors saw a worsening of their cancer much sooner than those with a fewer number of risk factors. Also, patients with multiple risk factors did not live as long as patients with fewer risk factors.How might this study affect research, practice or policy? When selecting therapies, healthcare providers should consider the impact of patient risk factors on how effectively that treatment will treat their cancer. The number of high-risk factors may also make an important difference in clinical trials and, therefore, should be considered when comparing results from different clinical trials.