Domestic Animal Models of Central Nervous System Tumors: Focus on Meningiomas.

Intracranial primary tumors (IPTs) are aggressive forms of malignancies that cause high mortality in both humans and domestic animals. Meningiomas are frequent adult IPTs in humans, dogs, and cats, and both benign and malignant forms cause a decrease in life quality and survival. Surgery is the primary therapeutic approach to treat meningiomas, but, in many cases, it is not resolutive. The chemotherapy and targeted therapy used to treat meningiomas also display low efficacy and many side effects. Therefore, it is essential to find novel pharmacological approaches to increase the spectrum of therapeutic options for meningiomas. This review analyzes the similarities between human and domestic animal (dogs and cats) meningiomas by evaluating the molecular and histological characteristics, diagnosis criteria, and treatment options and highlighting possible research areas to identify novel targets and pharmacological approaches, which are useful for the diagnosis and therapy of this neoplasia to be used in human and veterinary medicine.

Eculizumab as a therapeutic approach for severe crescentic recurrence of immunoglobulin A nephropathy after kidney transplantation.

Crescentic forms of immunoglobulin A nephropathy (IgAN) are rare but can be associated with rapid kidney failure and a high rate of end-stage renal disease despite immunosuppression therapy. Complement activation has emerged as a key driver of glomerular injury in IgAN. Therefore, complement inhibitors may be a rational treatment option in patients unresponsive to first-line immunosuppressive therapy. Here, we describe the case of a 24-year-old woman presenting with crescentic IgAN recurrence a few months after living kidney transplantation. Considering the dramatic graft failure accompanied by malignant hypertension and thrombotic microangiopathy features worsening after a first-line of high-dose steroids and 3 sessions of plasma exchanges, eculizumab was started as a rescue therapy. For the first time, the clinical response to eculizumab was highly successful, with a complete graft recovery without any relapse after 1 year of treatment. Further clinical studies are strongly needed to specify which patients might benefit from terminal complement blockade.

Lipid Metabolism Reprogramming and Trastuzumab Resistance in Breast Cancer Cell Lines Overexpressing the ERBB2 Membrane Receptor.

Trastuzumab (Tz), an antibody targeting ERBB2, has significantly improved the prognosis for breast cancer (BCa) patients with overexpression of the ERBB2 receptor. However, Tz resistance poses a challenge to patient outcomes. Numerous mechanisms have been suggested to contribute to Tz resistance, and this study aimed to uncover shared mechanisms in in vitro models of acquired BCa Tz resistance. Three widely used ERBB2+ BCa cell lines, adapted to grow in Tz, were examined. Despite investigating potential changes in phenotype, proliferation, and ERBB2 membrane expression in these Tz-resistant (Tz-R) cell lines compared to wild-type (wt) cells, no common alterations were discovered. Instead, high-resolution mass spectrometry analysis revealed a shared set of differentially expressed proteins (DEPs) in Tz-R versus wt cells. Bioinformatic analysis demonstrated that all three Tz-R cell models exhibited modulation of proteins associated with lipid metabolism, organophosphate biosynthesis, and macromolecule methylation. Ultrastructural examination corroborated the presence of altered lipid droplets in resistant cells. These findings strongly support the notion that intricate metabolic adaptations, including lipid metabolism, protein phosphorylation, and potentially chromatin remodeling, may contribute to Tz resistance. The detection of 10 common DEPs across all three Tz-resistant cell lines offers promising avenues for future therapeutic interventions, providing potential targets to overcome Tz resistance and potentially improve patient outcomes in ERBB2+ breast cancer.

Evaluation of the Biological Properties of an Optimized Extract of Polygonum cuspidatum Using Ultrasonic-Assisted Extraction.

Phytochemicals are natural compounds found in plants that have potential health benefits such as antioxidants, anti-inflammatory and anti-cancer properties, and immune reinforcement. Polygonum cuspidatum Sieb. et Zucc. is a source rich in resveratrol, traditionally consumed as an infusion. In this study, P. cuspidatum root extraction conditions were optimized to increase antioxidant capacity (DPPH, ABTS+), extraction yield, resveratrol concentration, and total polyphenolic compounds (TPC) via ultrasonic-assisted extraction using a Box-Behnken design (BBD). The biological activities of the optimized extract and the infusion were compared. The optimized extract was obtained using a solvent/root powder ratio of 4, 60% ethanol concentration, and 60% ultrasonic power. The optimized extract showed higher biological activities than the infusion. The optimized extract contained 16.6 mg mL-1 resveratrol, high antioxidant activities (135.1 µg TE mL-1 for DPPH, and 230.4 µg TE mL-1 for ABTS+), TPC (33.2 mg GAE mL-1), and extraction yield of 12.4%. The EC50 value (effective concentration 50) of the optimized extract was 0.194 µg mL-1, which revealed high cytotoxic activity against the Caco-2 cell line. The optimized extract could be used to develop functional beverages with high antioxidant capacity, antioxidants for edible oils, functional foods, and cosmetics.

Fraisinib: a calixpyrrole derivative reducing A549 cell-derived NSCLC tumor in vivo acts as a ligand of the glycine-tRNA synthase, a new molecular target in oncology.

Background and purpose: Lung cancer is the leading cause of death in both men and women, constituting a major public health problem worldwide. Non-small-cell lung cancer accounts for 85%-90% of all lung cancers. We propose a compound that successfully fights tumor growth in vivo by targeting the enzyme GARS1. Experimental approach: We present an in-depth investigation of the mechanism through which Fraisinib [meso-(p-acetamidophenyl)-calix(4)pyrrole] affects the human lung adenocarcinoma A549 cell line. In a xenografted model of non-small-cell lung cancer, Fraisinib was found to reduce tumor mass volume without affecting the vital parameters or body weight of mice. Through a computational approach, we uncovered that glycyl-tRNA synthetase is its molecular target. Differential proteomics analysis further confirmed that pathways regulated by Fraisinib are consistent with glycyl-tRNA synthetase inhibition. Key results: Fraisinib displays a strong anti-tumoral potential coupled with limited toxicity in mice. Glycyl-tRNA synthetase has been identified and validated as a protein target of this compound. By inhibiting GARS1, Fraisinib modulates different key biological processes involved in tumoral growth, aggressiveness, and invasiveness. Conclusion and implications: The overall results indicate that Fraisinib is a powerful inhibitor of non-small-cell lung cancer growth by exerting its action on the enzyme GARS1 while displaying marginal toxicity in animal models. Together with the proven ability of this compound to cross the blood-brain barrier, we can assess that Fraisinib can kill two birds with one stone: targeting the primary tumor and its metastases "in one shot." Taken together, we suggest that inhibiting GARS1 expression and/or GARS1 enzymatic activity may be innovative molecular targets for cancer treatment.

Two calix[4]pyrroles as potential therapeutics for castration-resistant prostate cancer.

Macrocyclic compounds meso-(p-acetamidophenyl)-calix[4]pyrrole and meso-(m-acetamidophenyl)-calix[4]pyrrole have previously been reported to exhibit cytotoxic properties towards lung cancer cells. Here, we report pre-clinical in vitro and in vivo studies showing that these calixpyrrole derivatives can inhibit cell growth in both PC3 and DU145 prostatic cancer cell lines. We explored the impact of these compounds on programmed cell death, as well as their ability to inhibit cellular invasion. In this study we have demonstrated the safety of these macrocyclic compounds by cytotoxicity tests on ex-vivo human peripheral blood mononuclear cells (PBMCs), and by in vivo subcutaneous administration. Preliminary in vivo tests demonstrated no hepato-, no nephro- and no genotoxicity in Balb/c mice compared to controls treated with cisplatin. These findings suggest these calixpyrroles might be novel therapeutic tools for the treatment of prostate cancer and of particular interest for the treatment of androgen-independent castration-resistant prostate cancer.

Metabolic changes induced by DNA damage in Ramos cells: exploring the role of mTORC1 complex.

DNA damage induces the activation of many different signals associated with repair or cell death, but it is also connected with physiological events, such as adult neurogenesis and B-cell differentiation. DNA damage induces different signaling pathways, some of them linked to important metabolic changes. The mTORC1 pathway has a central role in the regulation of growth processes and cell division in response to environmental changes and also controls protein synthesis, lipid biogenesis, nucleotide synthesis, and expression of glycolytic genes. Here, we report that double-strand breaks induced with etoposide affect the expression of genes encoding different enzymes associated with specific metabolic pathways in Ramos cells. We also analyzed the role of mTOR signaling, demonstrating that double-strand breaks induce downregulation of mTOR signaling. Specific inhibition of mTORC1 using rapamycin also induced changes in the expression of metabolic genes. Finally, we demonstrated that DNA damage and rapamycin can regulate glucose uptake. In summary, our findings show that etoposide and rapamycin affect the expression of metabolic genes as well as apoptotic and proliferation markers in Ramos cells, increasing our understanding of cancer metabolism.

Identification by MicroRNA Analysis of Environmental Risk Factors Bearing Pathogenic Relevance in Non-Smoker Lung Cancer.

MicroRNA and DNA adduct biomarkers may be used to identify the contribution of environmental pollution to some types of cancers. The aim of this study was to use integrated DNA adducts and microRNAs analyses to study retrospectively the contribution of exposures to environmental carcinogens to lung cancer in 64 non-smokers living in Sicily and Catania city near to the Etna volcano. MicroRNAs were extracted from cancer lung biopsies, and from the surrounding lung normal tissue. The expression of 2549 human microRNAs was analyzed by microarray. Benzo(a)Pyrene-DNA adducts levels were analyzed in the patients' blood by HPLC-fluorescence detection. Correlations between tetrols and environmental exposures were calculated using Pearson coefficients and regression variable plots. Compared with the healthy tissue, 273 microRNAs were downregulated in lung cancer. Tetrols levels were inversely related both with the distance from Etna and years since smoking cessation, but they were not significantly correlated to environmental exposures. The analysis of the microRNA environmental signatures indicates the contribution of environmental factors to the analyzed lung cancers in the following decreasing rank: (a) car traffic, (b) passive smoke, (c) radon, and (d) volcano ashes. These results provide evidence that microRNA analysis can be used to retrospectively investigate the contribution of environmental factors in human lung cancer occurring in non-smokers.

O uso emergente da teleodontologia durante a pandemia de Covid-19: experiência de um município do sul do Brasil / The emerging use of teleodontology during the Covid-19 pandemic: experience from a municipality in southern Brazil

Objetivo: descrever a experiência do serviço de teleodontologia no município de Palhoça, Santa Catarina, durante a pandemia da Covid-19. Métodos: trata-se de um estudo observacional, de caráter transversal. A pesquisa foi realizada com os dados de pacientes atendidos pelo serviço de teleodontologia do município Palhoça, Santa Catarina. Foram registrados dados referentes ao perfil sociodemográfico do usuário, agravos bucais e desfecho do caso. Resultados: houve 20.745 teleatendimentos e 7.666 agendamentos. A maioria dos usuários era do sexo feminino, sendo a faixa etária mais prevalente composta por jovens adultos. As principais queixas relatadas foram para monitoramento de caso e dor. Dos casos agendados, 91,23% dos usuários foram encaminhados para as unidades básicas de saúde. Conclusão: diante dos achados, a teleodontologia demonstrou ser uma excelente ferramenta, contribuindo para a diminuição no fluxo de pessoas em unidades de saúde e colaborando com os processos instituídos no atendimento, possibilitando a manutenção da assistência de casos.(AU)

Objective: to describe the experience of a Dentistry- by-phone (Teleodontologia) service in the city of Palhoça, SC, Brazil, during the Covid-19 pandemic. Methods: this is an observational, cross-sectional study. The research was carried out with data from patients assisted by the service. Data regarding the user's sociodemographic profile, oral health problems and case results were recorded. Results: there were 20745 calls and 7666 appointments. Most users were female, with the most prevalent age group being young adults. Main reported complaints were for case monitoring and pain. From the scheduled cases, 91% of users were referred to the UBSs (Health Basic Units). Conclusion: the service was considered to be an excellent tool, assisting on reducing the flow of people in health units and collaborating with the processes established in the service, allowing for health care maintenance.(AU)

MicroRNA (miRNA) Differential Expression and Exposure to Crude-Oil- Related Compounds.

This review summarizes studies on miRNA differential regulation related to exposure to crude oil and 20 different crude oil chemicals, such as hydrocarbons, sulphur, nitrogen, and metalcontaining compounds. It may be interesting to explore the possibility of using early post-transcriptional regulators as a potential novel exposure biomarker. Crude oil has been defined as a highly complex mixture of solids, liquids, and gases. Given the toxicological properties of the petroleum components, its extraction and elaboration processes represent high-risk activities for the environment and human health, especially when accidental spills occur. The effects on human health of short-term exposure to petroleum are well known, but chronic exposure effects may variate depending on the exposure type (i.e., work, clean-up activities, or nearby residence). As only two studies are focused on miRNA differential expression after crude-oil exposure, this review will also analyse the bibliography concerning different crude-oil or Petroleum-Related Compounds (PRC) exposure in Animalia L. kingdom and how it is related to differential miRNA transcript levels. Papers include in vitro, animal, and human studies across the world. A list of 10 miRNAs (miR-142-5p, miR-126-3p, miR-24-3p, miR-451a, miR-16-5p, miR-28-5p, let-7b-5p, miR-320b, miR-27a-3p and miR-346) was created based on bibliography analysis and hypothesised as a possible "footprint" for crude-oil exposure. miRNA differential regulation can be considered a Big-Data related challenge, so different statistical programs and bioinformatics tools were used to have a better understanding of the biological significate of the most interesting data.

Relationship between the miRNA Profiles and Oncogene Mutations in Non-Smoker Lung Cancer. Relevance for Lung Cancer Personalized Screenings and Treatments.

Oncogene mutations may be drivers of the carcinogenesis process. MicroRNA (miRNA) alterations may be adaptive or pathogenic and can have consequences only when mutation in the controlled oncogenes occurs. The aim of this research was to analyze the interplay between miRNA expression and oncogene mutation. A total of 2549 miRNAs were analyzed in cancer tissue-in surrounding normal lung tissue collected from 64 non-smoking patients and in blood plasma. Mutations in 92 hotspots of 22 oncogenes were tested in the lung cancer tissue. MicroRNA alterations were related to the mutations occurring in cancer patients. Conversely, the frequency of mutation occurrence was variable and spanned from the k-ras and p53 mutation detected in 30% of patients to 20% of patients in which no mutation was detected. The prediction of survival at a 3-year follow up did not occur for mutation analysis but was, conversely, well evident for miRNA analysis highlighting a pattern of miRNA distinguishing between survivors and death in patients 3 years before this clinical onset. A signature of six lung cancer specific miRNAs occurring both in the lungs and blood was identified. The obtained results provide evidence that the analysis of both miRNA and oncogene mutations was more informative than the oncogene mutation analysis currently performed in clinical practice.

Intravenous immunoglobulin as a preventive strategy against BK virus viremia and BKV-associated nephropathy in kidney transplant recipients-Results from a proof-of-concept study.

BK virus (BKV) replication occurs frequently in kidney transplant recipients (KTR), potentially leading to BKV-associated nephropathy (BKVAN) and graft loss. Patients with high titers of BKV-neutralizing antibodies (NAbs) are protected against BKV replication, and intravenous immunoglobulin (IVIg) infusion can increase NAb titers. We investigated whether early IVIg administration prevents BKV replication in patients with low NAb titers (<4 log10 against the BKV-specific genotype). Based on NAb titers on the day of transplantation, KTR followed in the Strasbourg University Hospital (n = 174) were retrospectively divided into the following 3 risk categories for BKV replication: (1) patients with low NAb titers ("high-risk") who received IVIg for the first 3 posttransplant months (n = 44), (2) patients with low NAb titers ("high-risk") who did not undergo IVIg treatment (n = 41), and (3) patients with high NAb titers ("low-risk") who did not receive IVIg (n = 89). At 12 posttransplant months, the incidence of BKV viremia in the high-risk group treated with IVIg (6.8%) was similar to that observed in the low-risk group (10.1%) and markedly lower than that of the untreated high-risk group (36.6%; P < .001). Similar results were observed with regard to BKVAN. We conclude that IVIg may be a valuable strategy for preventing BKV replication.

Biomarkers of Cytokine Release Syndrome Predict Disease Severity and Mortality From COVID-19 in Kidney Transplant Recipients.

BACKGROUND: Data on coronavirus disease 2019 (COVID-19) in immunocompromised kidney transplant recipients (KTR) remain scanty. Although markers of inflammation, cardiac injury, and coagulopathy have been previously associated with mortality in the general population of patients with COVID-19, their prognostic impact amongst KTR with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has not been specifically investigated. METHODS: We conducted a cohort study of 49 KTR who presented with COVID-19. Clinical and laboratory risk factors for severe disease and mortality were prospectively collected and analyzed with respect to outcomes. The study participants were divided into 3 groups: (1) mild disease manageable in an outpatient setting (n = 8), (2) nonsevere disease requiring hospitalization (n = 21), and (3) severe disease (n = 20). RESULTS: Gastrointestinal manifestations were common at diagnosis. The 30-day mortality rate in hospitalized patients was 19.5%. Early elevations of C-reactive protein (>100 mg/L) and interleukin-6 (>65 ng/L) followed by increases in high-sensitivity troponin I (>30 ng/L) and D-dimer (>960 ng/mL) were significantly associated with severe disease and mortality. Viral load did not have prognostic significance in our sample, suggesting that outcomes were chiefly driven by a cytokine release syndrome (CRS). CONCLUSIONS: Regular monitoring of CRS biomarkers in KTR with COVID-19 is paramount to improve clinical outcomes.

Does a Useful Test Exist to Properly Evaluate the Pathogenicity of Donor-specific Antibodies? Lessons From a Comprehensive Analysis in a Well-studied Single-center Kidney Transplant Cohort.

BACKGROUND: Donor-specific antibodies (DSA) play a major role in antibody-mediated rejection (AMR) and graft dysfunction. However, the clinical relevance of complement-binding anti-HLA antibodies remains unclear. METHODS: Here, we analyzed DSA detected in the serum (sDSA) using single antigen bead, C1q, and C3d assays combined with the study of intragraft DSA (gDSA) in 86 patients who had DSA and underwent a kidney biopsy for cause (n = 58) or without evidence of kidney dysfunction (n = 28). DSA characteristics were collected and related to the presence of AMR, graft histological features, and allograft survival. RESULTS: Forty-five patients (52%) had C1q DSA, and 42 (51%) had C3d DSA. Allograft biopsies revealed AMR in 63 cases (73%), regardless of kidney function. gDSA were identified in 74% of biopsies. We observed a strong correlation among single antigen bead mean fluorescence intensity and complement assays positivity, presence of gDSA, and AMR occurrence. CONCLUSIONS: Complement-binding DSA per se were not significantly associated with allograft survival in the entire study sample. Finally, gDSA predicted subsequent graft loss in patients who showed a stable renal function at the day of biopsy. Our data suggest that DSA mean fluorescence intensity and presence of gDSA might provide prognostic information during posttransplant monitoring.

Public health issues from crude-oil production in the Ecuadorian Amazon territories.

Crude oil production (COP) is a high-pollution industry but the vast Amazon rainforest has been an active COP zone for South America. Although COP has been associated with a variety of health effects among workers around the world, such effects have not been adequately investigated in the Amazon region, especially at the community level. Therefore, this review was conducted to provide a report about COP in the Amazon of Ecuador and about its association with health status of indigenous human populations. Some epidemiological surveys in the Amazonian Territories indicate that COP has been associated with health problems in the surrounding populations, e.g. cancers in the stomach, rectum, skin, soft tissue, kidney and cervix in adults, and leukemia in children. In addition, some biomarkers and mechanistic studies show exposure effects. However, due to limitations from these studies, contradictory associations have been reported. Our review indicates that COP in the Amazonian territories of northern Ecuador was characterised by contamination which could have affected the indigenous and non-indigenous populations. However, there have not been dedicated investigations to provide relationships between the contamination and the subsequent exposure-health effects. Since indigenous populations have different lifestyle and cultures from regular city dwellers, systematic studies on their potential health hazards need to be conducted. Due to the remote locations and sparse populations, these new studies may involve the use of novel and genomic-based biomarkers as well as using high technology in the remote regions.

Rede de apoio social à mulher com câncer de mama / Social support network of women with breast cancer / Red de apoyo social a la mujer con cáncer de mama

OBJETIVO: Conhecer a rede de apoio social à mulher com câncer de mama, participante de um grupo de apoio do Rio Grande do Sul. MÉTODOS: Estudo qualitativo, exploratório, descritivo, com mulheres de um grupo de apoio. A análise dos dados, conforme Minayo, resultou em quatro temáticas: família e amigos como provedores da rede de apoio social; grupos terapêuticos no contexto da rede de apoio; equipe de saúde como integrantes da rede de apoio; religiosidade, fé e espiritualidade integram a rede de apoio social para alivio do sofrimento. RESULTADOS: O apoio social é necessário durante o tratamento, para enfrentamento da patologia e recuperação da mulher. Revela-se que família, vizinho, amigos e grupo fazem parte da rede da mulher que vivencia o câncer. CONCLUSÃO: Prover o apoio social é parte do cuidado integral do enfermeiro e reconhecer as necessidades da mulher é importante para o planejamento de enfermagem

Objective: the study's purpose has been to know the social support network for breast cancer-bearing women, who were participating in a support group from the Rio Grande do Sul State. Method: it is a descriptiveexploratory study with a qualitative approach, which was performed by the participation of women from a support group. The data analysis carried out according to the technique of Thematic Analysis of Minayo resulted in four themes, as follows: family and friends as social support network providers; therapeutic groups in the support network framework; healthcare team as members of the support network; religiosity, faith and spirituality as part of the social support network to relieve suffering. Results: social support is needed during treatment, both for coping with the pathology and for women to recover from it. The results have shown that families, friends, neighbors and the group are all parts of the women network, who is experiencing cancer. Conclusion: providing social support is part of the comprehensive care given by nurses, so recognizing the women's needs is important to plan nursing care

Objetivo: conocer la red de apoyo social a la mujer con cáncer de mama, integrante de grupo de apoyo de Rio Grande do Sul. Método: estudio cualitativo, exploratorio, descriptivo, realizado con mujeres de un grupo de apoyo. El análisis de datos, conforme Minayo, determinó cuatro temáticas: familia y amigos como proveedores de red de apoyo social; grupos terapéuticos en el contexto de red de apoyo; equipo de salud como integrante de red de apoyo; religiosidad, fe y espiritualidad integrando red de apoyo social para mitigación del sufrimiento. Resultados: el apoyo social es necesario durante el tratamiento, para afrontar la patología y la recuperación de la mujer. La familia, vecinos, amigos y grupo forman parte de la red de la mujer que experimenta un cáncer. Conclusión: proveer apoyo social forma parte del cuidado integral del enfermero, y reconocer las necesidades de la mujer es importante para la planificación de enfermería

The Effect of Resveratrol on Cell Viability in the Burkitt's Lymphoma Cell Line Ramos.

Resveratrol is a polyphenolic natural compound produced by a variety of crops. Currently, resveratrol is considered a multi-target anti-cancer agent with pleiotropic activity, including the ability to prevent the proliferation of malignant cells by inhibiting angiogenesis and curtailing invasive and metastatic factors in many cancer models. However, the molecular mechanisms mediating resveratrol-specific effects on lymphoma cells remain unknown. To begin tackling this question, we treated the Burkitt's lymphoma cell line Ramos with resveratrol and assessed cell survival and gene expression. Our results suggest that resveratrol shows a significant anti-proliferative and pro-apoptotic activity on Ramos cells, inducing the DNA damage response, DNA repairing, and modulating the expression of several genes that regulate the apoptotic process and their proliferative activity.

Impaired P2Y12 inhibition by clopidogrel in kidney transplant recipients: results from a cohort study.

BACKGROUND: Cardiovascular complications represent a major cause of morbidity and mortality for patients who received kidney transplantation (KT). However, the impact of KT and chronic immunosuppression on platelet response to clopidogrel in patients undergoing coronary or peripheral revascularization procedures remains unclear. This cohort study compares platelet responsiveness to clopidogrel as assessed byvasodilator-stimulated phosphoprotein (VASP) phosphorylation. METHODS: The study population was divided between chronic kidney disease (CKD) patients who underwent KT (n = 36) and non-transplanted CKD patients (control group, n = 126). Patients were on maintenance antiplatelet therapy with clopidogrel 75 mg daily for at least 8 days. The mean platelet reactivity index (PRI) VASP values and the prevalence of high on-treatment platelet reactivity (HPR, defined as PRI VASP ≥61 %) were compared. RESULTS: The mean PRI VASP value was significantly higher in the transplant group (60.1 ± 3 vs 51.2 ± 1.6 %; p=0.014). HPR was significantly more common in the transplant group on clopidogrel maintenance therapy (58 vs. 31 %; p = 0.011). KT was the only independent predictor of HPR (odds ratio: 2.6; 95 % confidence interval: 1.03-6.27, p = 0.03). The effect of treatment with calcineurin inhibitors on clopidogrel response could not be analyzed separately from the kidney transplant status. CONCLUSIONS: KT is associated with an increased prevalence of HPR. Our results suggest that plateletfunction tests may be clinically useful for the management of this specific population.

Relative Contributions of Complications and Failure to Rescue on Mortality in Older Patients Undergoing Pancreatectomy.

BACKGROUND: For pancreatectomy patients, mortality increases with increasing age. Our study evaluated the relative contribution of overall postoperative complications and failure to rescue rates on the observed increased mortality in older patients undergoing pancreatic resection at specialized centers. METHODS: We identified 2694 patients who underwent pancreatic resection from the American College of Surgeons' National Surgical Quality Improvement Pancreatectomy Demonstration Project at 37 high-volume centers. Overall morbidity and in-hospital mortality were determined in patients younger than 80 years (N = 2496) and 80 years or older (N = 198). Failure to rescue was the number of deaths in patients with complications divided by the total number of patients with postoperative complications. RESULTS: No significant differences were observed between patients younger than 80 years and those 80 years or older in the rates of overall complications (41.4% vs 39.4%, P = 0.58). In-hospital mortality increased in patients 80 years or older compared to patients younger than 80 years (3.0% vs 1.1%, P = 0.02). Failures to rescue rates were higher in patients 80 years or older (7.7% vs 2.7%, P = 0.01). Across 37 high-volume centers, unadjusted complication rates ranged from 25.0% to 72.2% and failure to rescue rates ranged from 0.0% to 25.0%. Among patients with postoperative complications, comorbidities associated with failure to rescue were ascites, chronic obstructive pulmonary disease, and diabetes. Complications associated with failure to rescue included acute renal failure, septic shock, and postoperative pulmonary complications. CONCLUSIONS: In experienced hands, the rates of complications after pancreatectomy in patients 80 years or older compared to patients younger than 80 years were similar. However, when complications occurred, older patients were more likely to die. Interventions to identify and aggressively treat complications are necessary to decrease mortality in vulnerable older patients.