Efficacy and Safety of Sufentanil Infusion for Postoperative Analgesia in Cancer Surgery: A Retrospective Cohort Study.

Background Opioids have long been the cornerstone of drugs used for perioperative analgesia. Sufentanil has an advantageous pharmacological profile for its use in continuous intravenous (IV) infusion, yet remains poorly described. Our institution has implemented analgesia protocols with IV sufentanil infusions for cancer surgery with appropriate monitoring. The aim of this study was to evaluate the efficacy and safety of IV sufentanil infusion. Methods A single-center retrospective cohort study was conducted through the analysis of patients' records and the acute pain service database. Inclusion criteria were adult patients admitted for elective cancer surgery and with postoperative IV sufentanil infusion during one year period. Descriptive and inferential statistical analysis was performed by using Software SPSS Statistics (IBM Corp., Armonk USA): Kruskal-Wallis, Mann-Whitney, Chi-square and Fisher tests; Bonferroni chi-square residual analysis, binary logistic regression; p<0.05. Results The study population of 304 patients had a median age of 66 years (22-91) and 229 (75.3%) were men. 38 (12.5%) were chronic opioid users. Head and neck/otorhinolaryngology (ORL) surgery was performed in 155 (51.0%) and abdominopelvic surgery in 123 (40.5%). The median days of IV sufentanil infusion were 2 (1-13). At rest and with movement, analgesia was considered good, i.e., over 90% of patients with visual analogue scale (VAS) pain score ≤ 3. We found that patients submitted to musculoskeletal surgery had higher VAS pain scores; this group also presented older patients with higher American Society of Anesthesiologists (ASA) physical status classification and more chronic opioid users (p<0.05). 144 patients (47.4%) had at least one adverse effect related to IV sufentanil infusion, notably transient and not requiring any specific treatment. These patients were older and had longer infusion periods (p<0.05). 237 (98.3%) of the adverse effects occurred during the first 3 days and the most common were: sedation (n=104, 42.8%), hypotension (n=32, 13.2%), hypoxemia (n=31, 12.8%) and nausea/vomiting (n=25, 10.3%). The reported incidence of respiratory depression was 2.9% (n=9), with three patients (1%) requiring advanced treatment. Conclusion Multimodal analgesic protocols with IV sufentanil infusions provided good postoperative analgesia for head and neck/ORL and abdominopelvic cancer surgeries. The adverse effects associated with the IV sufentanil infusions were mild and mainly managed with opioid dose reductions. Our study showed that this approach can be a safe option for postoperative multimodal analgesia in cancer surgery with appropriate monitoring in high-dependency units.

The Influence of a Coherent Annotation and Synthetic Addition of Lung Nodules for Lung Segmentation in CT Scans.

Lung cancer is a highly prevalent pathology and a leading cause of cancer-related deaths. Most patients are diagnosed when the disease has manifested itself, which usually is a sign of lung cancer in an advanced stage and, as a consequence, the 5-year survival rates are low. To increase the chances of survival, improving the cancer early detection capacity is crucial, for which computed tomography (CT) scans represent a key role. The manual evaluation of the CTs is a time-consuming task and computer-aided diagnosis (CAD) systems can help relieve that burden. The segmentation of the lung is one of the first steps in these systems, yet it is very challenging given the heterogeneity of lung diseases usually present and associated with cancer development. In our previous work, a segmentation model based on a ResNet34 and U-Net combination was developed on a cross-cohort dataset that yielded good segmentation masks for multiple pathological conditions but misclassified some of the lung nodules. The multiple datasets used for the model development were originated from different annotation protocols, which generated inconsistencies for the learning process, and the annotations are usually not adequate for lung cancer studies since they did not comprise lung nodules. In addition, the initial datasets used for training presented a reduced number of nodules, which was showed not to be enough to allow the segmentation model to learn to include them as a lung part. In this work, an objective protocol for the lung mask's segmentation was defined and the previous annotations were carefully reviewed and corrected to create consistent and adequate ground-truth masks for the development of the segmentation model. Data augmentation with domain knowledge was used to create lung nodules in the cases used to train the model. The model developed achieved a Dice similarity coefficient (DSC) above 0.9350 for all test datasets and it showed an ability to cope, not only with a variety of lung patterns, but also with the presence of lung nodules as well. This study shows the importance of using consistent annotations for the supervised learning process, which is a very time-consuming task, but that has great importance to healthcare applications. Due to the lack of massive datasets in the medical field, which consequently brings a lack of wide representativity, data augmentation with domain knowledge could represent a promising help to overcome this limitation for learning models development.

Towards Machine Learning-Aided Lung Cancer Clinical Routines: Approaches and Open Challenges.

Advancements in the development of computer-aided decision (CAD) systems for clinical routines provide unquestionable benefits in connecting human medical expertise with machine intelligence, to achieve better quality healthcare. Considering the large number of incidences and mortality numbers associated with lung cancer, there is a need for the most accurate clinical procedures; thus, the possibility of using artificial intelligence (AI) tools for decision support is becoming a closer reality. At any stage of the lung cancer clinical pathway, specific obstacles are identified and "motivate" the application of innovative AI solutions. This work provides a comprehensive review of the most recent research dedicated toward the development of CAD tools using computed tomography images for lung cancer-related tasks. We discuss the major challenges and provide critical perspectives on future directions. Although we focus on lung cancer in this review, we also provide a more clear definition of the path used to integrate AI in healthcare, emphasizing fundamental research points that are crucial for overcoming current barriers.

Anticoagulation therapy in patients with post-operative atrial fibrillation: Systematic review with meta-analysis.

BACKGROUND: Post-operative atrial fibrillation (POAF) is a relevant complication after surgery. Several studies have shown that POAF has important consequences for long-term morbidity and mortality, by increasing the risk of thromboembolic events. However, the use of oral anticoagulation (OAC) is not well established in this context. METHODS: We searched MEDLINE, CENTRAL, PsycInfo and Web of Science for clinical trials and observational studies evaluating anticoagulation vs. no anticoagulation in patients with POAF (after cardiac or non-cardiac surgery). Data were screened and extracted by two independent reviewers. We performed a random- effects model to estimate the pooled odds ratio (OR) with 95% Confidence Intervals (CI), and heterogeneity was evaluated by I2 statistics. The outcomes of interest were all-cause mortality, thromboembolic events, and bleeding events. RESULTS: Overall, 10 observational retrospective studies were included: 5 studies with 203,946 cardiac surgery POAF patients, and 5 studies with 29,566 patients with POAF after non-cardiac surgery. In cardiac surgery POAF, the OAC use was associated with lower risk of thromboembolic events (OR 0.68; 95%CI 0.47-0.96, I2 = 31%; 4 studies) and the bleeding risk was significantly increased (OR 4.30; 95%CI 3.69 to 5.02, 1 study). In non-cardiac surgery POAF, OAC did not significantly reduce the risk of thromboembolic events (OR 0.71, 95%CI 0.33-1.15; I2 = 79%; 5 studies) but was associated with increased risk of bleeding (OR 1.20, 95%CI 1.10-1.32, I2 = 0%; 3 studies). Mortality was not significantly reduced in both cardiac and non-cardiac surgery POAF. CONCLUSION: Oral anticoagulation was associated with a lower risk of thromboembolic events in patients with POAF following cardiac surgery but not in non-cardiac surgery. Bleeding risk was increased in both settings. The confidence on pooled results is at most low, and further data, namely randomized controlled trials are necessary to derive robust conclusions.

FACT-seq: profiling histone modifications in formalin-fixed paraffin-embedded samples with low cell numbers.

The majority of biopsies in both basic research and translational cancer studies are preserved in the format of archived formalin-fixed paraffin-embedded (FFPE) samples. Profiling histone modifications in archived FFPE tissues is critically important to understand gene regulation in human disease. The required input for current genome-wide histone modification profiling studies from FFPE samples is either 10-20 tissue sections or whole tissue blocks, which prevents better resolved analyses. But it is desirable to consume a minimal amount of FFPE tissue sections in the analysis as clinical tissues of interest are limited. Here, we present FFPE tissue with antibody-guided chromatin tagmentation with sequencing (FACT-seq), the first highly sensitive method to efficiently profile histone modifications in FFPE tissues by combining a novel fusion protein of hyperactive Tn5 transposase and protein A (T7-pA-Tn5) transposition and T7 in vitro transcription. FACT-seq generates high-quality chromatin profiles from different histone modifications with low number of FFPE nuclei. We proved a very small piece of FFPE tissue section containing ∼4000 nuclei is sufficient to decode H3K27ac modifications with FACT-seq. H3K27ac FACT-seq revealed disease-specific super enhancers in the archived FFPE human colorectal and human glioblastoma cancer tissue. In summary, FACT-seq allows decoding the histone modifications in archival FFPE tissues with high sensitivity and help researchers to better understand epigenetic regulation in cancer and human disease.

Venous and Lung Thromboembolism in the Context of Lung Cancer: Clinical Manifestations, Risk Factors and Prognosis.

INTRODUCTION: The relationship between cancer and thromboembolic events has been known for a long time. Lung and venous thromboembolism are frequent complications of lung cancer and its treatment, being a great cause of morbidity and mortality. We pretend to establish the relationship between lung and venous thromboembolism and lung cancer, describe patient characteristics and analyze the impact in the survival and prognosis. MATERIAL AND METHODS: It was a retrospective study. All research subjects were selected from lung cancer patients with a newly diagnosed lung and venous thromboembolism event admitted to Hospital S. João, between January 2008 and December 2013 and were followed until December 2014. Statistical analysis was performed with SPSS. RESULTS: From the search, we obtained 113 patients. The majority was male, smokers or ex-smokers, and adenocarcinoma was the most frequent histologic type, being diagnosed mostly in advanced stages. We noticed that the median time between lung cancer diagnosis and lung venous thromboembolism was 2.9 months. In 24 patients (21.4%), the lung cancer diagnosis occurred after the lung and venous thromboembolism event and in 86 patients (76.8%), it occurred before the event. After a median follow up of 1.4 months, 107 (94.7%) patients died, 1 (0.9%) was lost to follow-up and 5 (4.4%) were still alive. The median survival rate was 1.5 months. DISCUSSION: The diagnosis of lung and venous thromboembolism in patients with lung cancer is associated with bad prognosis. It occurs most frequently in patients with advanced disease, in the first months after lung cancer diagnosis and after beginning chemotherapy. CONCLUSION: Disease progression is an independent predictor with negative impact in overall survival.

Introdução: A relação entre as neoplasias e os eventos tromboembólicos é uma realidade já conhecida. O tromboembolismo pulmonar e venoso são complicações frequentes das neoplasias e do seu tratamento. Pretende-se estabelecer a relação entre o tromboembolismo pulmonar e venoso e a neoplasia pulmonar, descrever as suas características clínicas e analisar o seu impacto na sobrevida e prognóstico. Material e Métodos: Este estudo é retrospetivo. Foram selecionados doentes com neoplasia pulmonar, diagnosticados com tromboembolismo pulmonar e venoso no Hospital de S. João entre janeiro de 2008 e dezembro de 2013, e acompanhados até dezembro de 2014. A análise estatística foi realizada utilizando o SPSS. Resultados: Da pesquisa efetuada, foram obtidos 113 doentes. A maioria eram homens, fumadores ou ex-fumadores, e o adenocarcinoma foi o tipo histológico mais frequentemente encontrado, diagnosticado maioritariamente em estádios avançados. A mediana de tempo entre o diagnóstico de neoplasia pulmonar e tromboembolismo pulmonar e venoso foi de 2,9 meses. Em 24 doentes (21,4%), o diagnóstico de neoplasia pulmonar ocorreu depois do tromboembolismo pulmonar e venoso e em 86 doentes (76,8%) antes do evento. Após uma mediana de follow-up de 1,4 meses, 107 (94,7%) dos doentes faleceram, 1 (0,9%) deixou de ser seguido e 5 (4,4%) permaneceram vivos no fim do estudo. A mediana da taxa de sobrevivência foi de 1,5 meses. Discussão: O diagnóstico de tromboembolismo pulmonar e venoso nos doentes com neoplasia pulmonar está associado a mau prognóstico. Ocorre mais frequentemente em doentes com doença avançada, nos primeiros meses depois do diagnóstico e do início da quimioterapia. Conclusão: A progressão da doença demonstrarou ser preditor independente com impacto negativo na sobrevida global.

Effect of Sleeve Gastrectomy on Angiogenesis and Adipose Tissue Health in an Obese Animal Model of Type 2 Diabetes.

INTRODUCTION: Metabolic surgery has become an accepted option for the treatment of obesity and associated metabolic diseases like hypertension and type 2 diabetes. Adipose tissue dysfunction and ectopic storage of excess lipids are thought to be involved in the underlying pathophysiological process. OBJECTIVES: The present study aims to clarify the effect of sleeve gastrectomy (SG) on adipose tissue microvasculature and health in an animal model of adipose type 2 diabetes. METHODS: After weaning, diabetic Goto-Kakizaki rats were either fed on standard rat chow or high-calorie diet. At 4 months, animals on high-calorie diet were randomized to SG, sham surgery, or control group. Non-diabetic Wistar rats served as further controls. At 6 months, glucose and lipid metabolisms were studied in vivo. After sacrifice, periepididymal adipose tissue was collected for histology and analysis of parameters of adipose tissue metabolism and insulin sensitivity. RESULTS: SG decreased body and adipose tissue weight and improved glycemic and lipid profiles. Fasting glycemia, area under the curve after intraperitoneal insulin tolerance test, and insulin resistance were decreased in operated animals. SG also reduced circulating triglycerides and cholesterol while increasing serum adiponectin and adipose tissue peroxisome proliferator-activated receptor γ (PPAR-γ) and perilipin A. Additionally, surgery improved adipose tissue vascular function and markedly increased vascular endothelial growth factor, cluster of differentiation 31, and endothelial nitric oxide synthase. CONCLUSIONS: In our obese animal model of type 2 diabetes, SG significantly improved adipose tissue health and angiogenesis while reducing insulin resistance, involving PPAR-γ and markers of sprouting angiogenesis and endothelial function.

Withdrawing and Withholding Life Support in Patients With Cancer in an ICU Setting: A 5-Year Experience at a European Cancer Center.

OBJECTIVE: This was an observational retrospective study aimed to examine the frequency and associated factors of withdrawing or withholding life support (WWLS) in the intensive care unit (ICU) of a comprehensive cancer center. METHODS: Medical records of adult patients with cancer admitted to the ICU between January 2010 and December 2014 were reviewed. Patients who died during that period were classified into 2 groups: full life support and withdrawing and withholding life support. The relative impact of demographic and clinical factors was assessed using logistic regression. RESULTS: A total of 247 patients died in our unit (mortality rate of 16.3%). Their median age was 62 (interquartile range [IQR] 51-73) years, there were 142 (57.5%) male patients, and they had predominantly solid malignancies (62.3%). The median Simplified Acute Physiology Score II and Acute Physiology and Chronic Health Evaluation scores were 67 (IQR 54-80) and 29 (IQR 23-55), respectively. Ninety-six (38.9%) patients died after WWLS with no statistically significant differences in decisions to limit therapy during the study period. Patients with advanced age, solid malignancies, nonneutropenic, and longer duration of mechanical ventilation were more likely to die after WWLS. In multivariate analysis, presenting with neutropenia was independently associated with a lower likelihood of dying after WWLS (odds ratio: 0.34, 95% confidence interval: 0.15-0.80). CONCLUSION: Limitation of therapy has been a common practice in oncologic ICUs over recent years. Neutropenia is an independent predictor of limitation of therapy.

Influence of emphysema distribution on pulmonary function parameters in COPD patients / Influência da distribuição do enfisema nos parâmetros de função pulmonar em pacientes com DPOC

ABSTRACT OBJECTIVE: To evaluate the impact that the distribution of emphysema has on clinical and functional severity in patients with COPD. METHODS: The distribution of the emphysema was analyzed in COPD patients, who were classified according to a 5-point visual classification system of lung CT findings. We assessed the influence of emphysema distribution type on the clinical and functional presentation of COPD. We also evaluated hypoxemia after the six-minute walk test (6MWT) and determined the six-minute walk distance (6MWD). RESULTS: Eighty-six patients were included. The mean age was 65.2 ± 12.2 years, 91.9% were male, and all but one were smokers (mean smoking history, 62.7 ± 38.4 pack-years). The emphysema distribution was categorized as obviously upper lung-predominant (type 1), in 36.0% of the patients; slightly upper lung-predominant (type 2), in 25.6%; homogeneous between the upper and lower lung (type 3), in 16.3%; and slightly lower lung-predominant (type 4), in 22.1%. Type 2 emphysema distribution was associated with lower FEV1, FVC, FEV1/FVC ratio, and DLCO. In comparison with the type 1 patients, the type 4 patients were more likely to have an FEV1 < 65% of the predicted value (OR = 6.91, 95% CI: 1.43-33.45; p = 0.016), a 6MWD < 350 m (OR = 6.36, 95% CI: 1.26-32.18; p = 0.025), and post-6MWT hypoxemia (OR = 32.66, 95% CI: 3.26-326.84; p = 0.003). The type 3 patients had a higher RV/TLC ratio, although the difference was not significant. CONCLUSIONS: The severity of COPD appears to be greater in type 4 patients, and type 3 patients tend to have greater hyperinflation. The distribution of emphysema could have a major impact on functional parameters and should be considered in the evaluation of COPD patients.

RESUMO OBJETIVO: Avaliar o impacto que a distribuição do enfisema tem na gravidade clínica e funcional em pacientes com DPOC. MÉTODOS: A distribuição do enfisema foi analisada em pacientes com DPOC, que foram classificados de acordo com um sistema de classificação visual de cinco pontos a partir de achados de TC de tórax. Avaliou-se a influência do tipo de distribuição do enfisema na apresentação funcional e clínica da DPOC. Hipoxemia após o teste da caminhada de seis minutos (TC6) foi também avaliada e a distância percorrida (DTC6) foi determinada. RESULTADOS: Foram incluídos 86 pacientes. A média de idade foi de 65,2 ± 12,2 anos, 91,9% eram homens, e todos menos um eram fumantes (média de carga tabágica, 62,7 ± 38,4 anos-maço). A distribuição do enfisema foi categorizada como obviamente predominante no pulmão superior (tipo 1), em 36,0% dos pacientes; levemente predominante no pulmão superior (tipo 2), em 25,6%; homogêneo entre o pulmão superior e inferior (tipo 3), em 16,3%; e levemente predominante no pulmão inferior (tipo 4), em 22,1%. A distribuição do enfisema do tipo 2 foi associada a menores valores de VEF1, CVF, relação VEF1/CVF e DLCO. Em comparação com os pacientes do tipo 1, os do tipo 4 apresentaram maior probabilidade de ter VEF1 < 65% do previsto (OR = 6,91, IC95%: 1,43-33,45; p = 0,016), DTC6 < 350 m (OR = 6,36, IC95%: 1,26-32,18; p = 0,025),e hipoxemia após o TC6 (OR = 32,66, IC95%: 3,26-326,84; p = 0,003). Os pacientes do tipo 3 tiveram uma relação VR/CPT maior, embora sem diferença significativa. CONCLUSÕES: A gravidade da DPOC parece ser maior nos pacientes do tipo 4, e os do tipo 3 tendem a apresentar maior hiperinsuflação. A distribuição do enfisema pode ter um impacto importante nos parâmetros funcionais e deve ser considerada na avaliação de pacientes com DPOC.

Influence of emphysema distribution on pulmonary function parameters in COPD patients.

OBJECTIVE: To evaluate the impact that the distribution of emphysema has on clinical and functional severity in patients with COPD. METHODS: The distribution of the emphysema was analyzed in COPD patients, who were classified according to a 5-point visual classification system of lung CT findings. We assessed the influence of emphysema distribution type on the clinical and functional presentation of COPD. We also evaluated hypoxemia after the six-minute walk test (6MWT) and determined the six-minute walk distance (6MWD). RESULTS: Eighty-six patients were included. The mean age was 65.2 ± 12.2 years, 91.9% were male, and all but one were smokers (mean smoking history, 62.7 ± 38.4 pack-years). The emphysema distribution was categorized as obviously upper lung-predominant (type 1), in 36.0% of the patients; slightly upper lung-predominant (type 2), in 25.6%; homogeneous between the upper and lower lung (type 3), in 16.3%; and slightly lower lung-predominant (type 4), in 22.1%. Type 2 emphysema distribution was associated with lower FEV1, FVC, FEV1/FVC ratio, and DLCO. In comparison with the type 1 patients, the type 4 patients were more likely to have an FEV1 < 65% of the predicted value (OR = 6.91, 95% CI: 1.43-33.45; p = 0.016), a 6MWD < 350 m (OR = 6.36, 95% CI: 1.26-32.18; p = 0.025), and post-6MWT hypoxemia (OR = 32.66, 95% CI: 3.26-326.84; p = 0.003). The type 3 patients had a higher RV/TLC ratio, although the difference was not significant. CONCLUSIONS: The severity of COPD appears to be greater in type 4 patients, and type 3 patients tend to have greater hyperinflation. The distribution of emphysema could have a major impact on functional parameters and should be considered in the evaluation of COPD patients.

[Bisphosphonate-associated osteonecrosis of the jaws in lung cancer patients]. / Osteonecrose da mandíbula associada aos bifosfonatos em doentes com cancro do pulmão.

Osteonecrosis of the jaw (ONJ) can occur as a complication of bisphosphonate therapy. This condition has been described in cancer patients and its development has been associated with prolonged exposure to high doses of bisphosphonates. Bad dental hygiene, a history of prosthesis or dental extraction, chemotherapy, corticosteroids, and radiation therapy of the head and neck are risk factors reported. In the initial stages it may be asymptomatic, but the patient subsequently develops severe pain and progressive exposed bone. The authors describe three cases of ONJ in lung cancer patients after prolonged exposure to bisphosphonates and there were known risk factors. ONJ can seriously affect the quality of life of cancer patients. An early diagnosis may reduce or avoid the consequences of progressive bone lesion.

Wegener's granulomatosis and alveolar hemorrhage - case report.

The authors present a clinical case of 55 years old female patient with limited form of Wegener's granulomatosis (WG), which first manifestation was non-erosive polyarthritis with rheumatoid factor positive that antedates one decade the pulmonary manifestations. She had acute episodes with purulent expectoration, fever and hemoptysis, with resolution in a week. The chest x-rays demonstrated migratory bilateral pulmonary infiltrates. Transthoracic lung biopsy was performed and revealed capilaritis and signs of old and recent hemorrhage. At that time, autoimmunity study was repeated and showed positive for rheumatoid factor, negative anti-cyclic citrullinated peptide antibodies (anti-CCP) and high sustained PR3 anti-neutrophil cytoplasmic antibodies. The diagnosis of WG was established and cyclophosphamide started. This patient had a less common presentation and a less common histological pattern compared to the typical necrotizing granulomatous inflammation. She was treated with immunosuppression therapy which could have contributed to a mild clinical expression and a lower diagnostic yield. In suspicious cases, repeat the autoimmunity study, when facing new findings, could confirm the correct diagnosis.

Association between EGF +61 genetic polymorphisms and non-small cell lung cancer increased risk in a Portuguese population: a case-control study.

Epidermal growth factor (EGF) and its receptor play critical roles in non-small cell lung cancer (NSCLC) carcinogenesis. A functional polymorphism in the EGF gene has been linked to increased cancer susceptibility. This study aimed to evaluate the role of the EGF +61A/G polymorphism as risk factors in NSCLC patients. For the present case-control study, we analyzed 112 NSCLC and 126 cancer-free controls from Portugal. Following DNA isolation from peripheral blood, EGF +61A/G polymorphism was assessed by polymerase chain reaction-restriction fragment length polymorphism. Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95 % confidence intervals (95 % CI). False-positive report probability was also assessed. The EGF +61 genotypes frequencies in NSCLC were AA (23.2 %), AG (51.8 %), and GG (25 %) and in controls, AA (40.5 %), AG (41.3 %), and GG (18.3 %). When compared to the reference genotype (EGF +61A/A), we found a statistically significant association between EGF +61 A/G (OR = 2.142, 95 % CI 1.170-3.924) and EGF +61G/G (OR = 2.398, 95 % CI 1.157-4.968) genotypes and susceptibility to development of NSCLC. Furthermore, stratification by sex revealed a trend to increased risk of males carrying +61A/G genotype for developing NSCLC (OR = 2.044, 95 % CI 0.998-4.188) when compared to A/A genotype. Our data suggest an increased risk to develop NSCLC in Portuguese population carrying the EGF +61A/G and +61G/G genotypes.