Gupta Perioperative Risk for Myocardial Infarction or Cardiac Arrest score is a long-term cardiovascular risk predictor after aortoiliac revascularization.

INTRODUCTION: Gupta Perioperative Risk for Myocardial Infarction or Cardiac Arrest (MICA) is a validated self-explanatory score applied in cardiac or non-cardiac surgeries. This study aims to assess the predictive value of the MICA score for cardiovascular events after aortoiliac revascularization. METHODS: This prospective cohort underwent elective aortoiliac revascularization between 2013 and 2021. Patients' demographic, clinical characteristics and outcomes were registered. The patients were divided into two groups according to the MICA score using optimal binning. Survival analysis to test for time-dependent variables and multivariate Cox regression analysis for independent predictors were performed. RESULTS: This study included 130 patients with a median follow-up of 55 months. Preoperative MICA score was ≥ 6.5 in 41 patients. MICA ≥ 6.5 presented a statistically significant association with long-term occurrence of acute heart failure (HR=1.695, 95% CI 1.208-2.379, p=0.002), major adverse cardiovascular events (HR=1.222, 95% CI 1.086-1.376, p<0.001) and all-cause mortality (HR=1.256, 95% CI 1.107-1.425, p<0.001). Multivariable Cox regression confirmed MICA as a significant independent predictor of long-term major adverse cardiovascular events (aHR=1.145 95%CI 1.010-1.298, p=0.034) and all-cause mortality (aHR=1.172 95%CI 1.026-1.339, p=0.020). CONCLUSION: The MICA score is a quick, easy-to-obtain, predictive tool in identifying patients with a higher risk of post-aortoiliac revascularization cardiovascular events, such as acute heart failure, major adverse cardiovascular events and all-cause mortality. Additional research for validation of the MICA score in the context of aortoiliac revascularization and specific interventions are necessary.

Giant hepatic hemangioma in a patient with cirrhosis: challenging to manage.

Giant hepatic hemangiomas are occasional in patients with cirrhosis. It remains a challenge to decide on the need for treatment and choose the most appropriate intervention. A 62-year-old woman was recently diagnosed with cirrhosis and complained of upper abdominal fullness, reduction in oral food intake, and weight loss of 6 kg over the last three years. Upper digestive endoscopy evidenced thin-caliber esophageal varices and significant extrinsic compression of the lesser gastric curvature. Abdominal computed tomography revealed an exophytic tumor in the left hepatic lobe, measuring 11.5 cm, which had progressive centripetal contrast enhancement from the arterial phase, compatible with hepatic hemangioma. Serum tumor markers were negative, and her liver function was unimpaired. The patient underwent surgical resection (non-anatomical hepatectomy of segments II and III) which had no immediate complications, and the histopathological evaluation confirmed cavernous hepatic hemangioma. Two weeks later, she was admitted to the emergency room with jaundice, signs of hepatic encephalopathy, and moderate ascites, and was further diagnosed with secondary bacterial peritonitis. As no perforations, abscesses, or fistulas were observed on subsequent imaging tests, clinical management was successfully carried out. This case highlights that giant hepatic hemangiomas may be symptomatic and warrant treatment. In the setting of cirrhosis and portal hypertension, physicians should be aware of the risk of hepatic decompensation following surgical resection, even in patients with Child-Pugh class A.

Giant hepatic hemangioma in a patient with cirrhosis: challenging to manage

ABSTRACT Giant hepatic hemangiomas are occasional in patients with cirrhosis. It remains a challenge to decide on the need for treatment and choose the most appropriate intervention. A 62-year-old woman was recently diagnosed with cirrhosis and complained of upper abdominal fullness, reduction in oral food intake, and weight loss of 6 kg over the last three years. Upper digestive endoscopy evidenced thin-caliber esophageal varices and significant extrinsic compression of the lesser gastric curvature. Abdominal computed tomography revealed an exophytic tumor in the left hepatic lobe, measuring 11.5 cm, which had progressive centripetal contrast enhancement from the arterial phase, compatible with hepatic hemangioma. Serum tumor markers were negative, and her liver function was unimpaired. The patient underwent surgical resection (non-anatomical hepatectomy of segments II and III) which had no immediate complications, and the histopathological evaluation confirmed cavernous hepatic hemangioma. Two weeks later, she was admitted to the emergency room with jaundice, signs of hepatic encephalopathy, and moderate ascites, and was further diagnosed with secondary bacterial peritonitis. As no perforations, abscesses, or fistulas were observed on subsequent imaging tests, clinical management was successfully carried out. This case highlights that giant hepatic hemangiomas may be symptomatic and warrant treatment. In the setting of cirrhosis and portal hypertension, physicians should be aware of the risk of hepatic decompensation following surgical resection, even in patients with Child-Pugh class A.

Comparing follow-up of patients with vitamin K antagonists in a health center: pre- and post-COVID-19 pandemic / Comparação do seguimento de doentes hipocoagulados com antagonistas da vitamina K numa unidade de saúde: pré e pós pandemia COVID-19

Introduction and objectives: During the COVID-19 pandemic, the follow-up of patients treated with vitamin K antagonists (VKAs) may have been affected. This study aims to compare how these patients were monitored pre- and post-COVID-19 pandemic and understand the impact of non-face-to-face appointments on their follow-up. Methods: We conducted a retrospective cohort study in a Portuguese Health Center. The study included patients treated with VKAs and followed at the Health Center for international normalized ratio (INR) monitoring between March 2019 and March 2021. Data collected: sex, age, type of VKA; INR; date of INR assessment, type of appointment (face-to-face or phone/e-mail). Rosendaal's method was used to calculate pre-COVID-19 and post-COVID-19 time in therapeutic range (TTR). Good TTR control was defined if values ≥ 70%. Results: 44 patients were included. The mean TTR in the pre-COVID-19 period was 64.55% (95% CI: 58.10 - 71.00%). The post-COVID-19 mean was slightly higher (+ 2.26%), 66.81% (95% CI: 59.66 - 73.97%), but the difference was not statistically significant (p = 0.576). The use of non-face-to-face appointments did not contribute to worsening post-pandemic TTR, show-ing no lower follow-up than during pre-pandemic period in which all contacts were face-to-face [CI (95%) -0.397 - 0.196 for a reference range -0.489 - 0.693]. Conclusions: The TTR value in both periods was similar and lower than the value defined for effective hypocoagulation. The use of non-face-to-face consultation in the post-COVID-19 period does not seem to have influenced the quality of hypocoagulation (AU).

Introdução e objetivos: Durante a pandemia COVID-19 o acompanhamento de doentes medicados com antagonistas da vitamina K (AVKs) pode ter sido afetado. Este estudo pretende comparar a forma como estes doentes foram monitorizados antes e depois da pandemia COVID-19 e compreender o impacto da consulta não presencial no seu seguimento. Métodos: Estudo de coorte retrospetivo num Centro de Saúde em Portugal. O estudo incluiu doentes tratados com AVKs e seguidos no Centro de Saúde para monitorização do International Normalized Ratio(INR) entre março de 2019 e março de 2021. Dados recolhidos: sexo, idade, tipo de AVK; INR; data da avaliação do INR, tipo de consulta (presencial ou por telefone/e-mail). Foi utilizado o método de interpolação linear de Rosendaal para calcular o tempo em intervalo terapêutico (TTR) pré- e pós-COVID-19. Foi definido um bom controle se valores de TTR ≥ 70%. Resultados: Foram incluídos 44 doentes. A média de TTR no período pré-COVID-19 foi de 64,55% (95% IC: 58,10 - 71,00%). A média pós-COVID-19 foi ligeiramente superior (+ 2,26%), 66,81% (95% IC: 59,66 - 73,97%), mas a diferença não foi estatisticamente significativa (p = 0,576). A utilização da consulta não presencial não contribuiu para o agravamento do TTR no período pós-pandemia, não mostrando um seguimento inferior ao do período pré-pandemia em que todos os contatos foram presenciais [IC (95%) -0,397 - 0,196 para um intervalo de referência -0,489 - 0,693]. Conclusões: O valor de TTR em ambos os períodos foi semelhante e inferior ao valor definido para hipocoagulação eficaz. A utilização da consulta não presencial no período pós-COVID-19 não parece ter influenciado a qualidade da hipocoagulação (AU).

Analytical performance of the FDA-cleared Parsortix® PC1 system.

Introduction: The Parsortix® PC1 system, Food and Drug Administration (FDA) cleared for use in metastatic breast cancer (MBC) patients, is an epitope-independent microfluidic device for the capture and harvest of circulating tumor cells from whole blood based on cell size and deformability. This report details the analytical characterization of linearity, detection limit, precision, and reproducibility for this device. Methods: System performance was determined using K2-EDTA blood samples collected from self-declared healthy female volunteers (HVs) and MBC patients spiked with prelabeled cultured breast cancer cell lines (SKBR3, MCF7, or Hs578T). Samples were processed on Parsortix® PC1 systems and captured cells were harvested and enumerated. Results: The system captured and harvested live SKBR3, MCF7, and Hs578T cells and fixed SKBR3 cells linearly between 2 and ~100 cells, with average harvest rates of 69%, 73%, 79%, and 90%, respectively. To harvest ≥1 cell ≥95% of the time, the system required 3, 5 or 4 live SKBR3, MCF7 or Hs578T cells, respectively. Average harvest rates from precision studies using 5, 10, and ~50 live cells spiked into blood for each cell line ranged from 63.5% to 76.2%, with repeatability and reproducibility percent coefficient of variation (%CV) estimates ranging from 12.3% to 32.4% and 13.3% to 34.1%, respectively. Average harvest rates using ~20 fixed SKBR3 cells spiked into HV and MBC patient blood samples were 75.0% ± 16.1% (%CV = 22.3%) and 68.4% ± 14.3% (%CV = 21.1%), respectively. Conclusions: These evaluations demonstrate the Parsortix® PC1 system linearly and reproducibly harvests tumor cells from blood over a range of 1 to ~100 cells.

FSM-DDTR: End-to-end feedback strategy for multi-objective De Novo drug design using transformers.

The design of compounds that target specific biological functions with relevant selectivity is critical in the context of drug discovery, especially due to the polypharmacological nature of most existing drug molecules. In recent years, in silico-based methods combined with deep learning have shown promising results in the de novo drug design challenge, leading to potential leads for biologically interesting targets. However, several of these methods overlook the importance of certain properties, such as validity rate and target selectivity, or simplify the generative process by neglecting the multi-objective nature of the pharmacological space. In this study, we propose a multi-objective Transformer-based architecture to generate drug candidates with desired molecular properties and increased selectivity toward a specific biological target. The framework consists of a Transformer-Decoder Generator that generates novel and valid compounds in the SMILES format notation, a Transformer-Encoder Predictor that estimates the binding affinity toward the biological target, and a feedback loop combined with a multi-objective optimization strategy to rank the generated molecules and condition the generating distribution around the targeted properties. The results demonstrate that the proposed architecture can generate novel and synthesizable small compounds with desired pharmacological properties toward a biologically relevant target. The unbiased Transformer-based Generator achieved superior performance in the novelty rate (97.38%) and comparable performance in terms of internal diversity, uniqueness, and validity against state-of-the-art baselines. The optimization of the unbiased Transformer-based Generator resulted in the generation of molecules exhibiting high binding affinity toward the Adenosine A2A Receptor (AA2AR) and possessing desirable physicochemical properties, where 99.36% of the generated molecules follow Lipinski's rule of five. Furthermore, the implementation of a feedback strategy, in conjunction with a multi-objective algorithm, effectively shifted the distribution of the generated molecules toward optimal values of molecular weight, molecular lipophilicity, topological polar surface area, synthetic accessibility score, and quantitative estimate of drug-likeness, without the necessity of prior training sets comprising molecules endowed with pharmacological properties of interest. Overall, this research study validates the applicability of a Transformer-based architecture in the context of drug design, capable of exploring the vast chemical representation space to generate novel molecules with improved pharmacological properties and target selectivity. The data and source code used in this study are available at: https://github.com/larngroup/FSM-DDTR.

Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19.

COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

The evidence base of US Food and Drug Administration approvals of novel cancer therapies from 2000 to 2020.

Concerns have been raised that regulatory programs to accelerate approval of cancer drugs in cancer may increase uncertainty about benefits and harms for survival and quality of life (QoL). We analyzed all pivotal clinical trials and all non-pivotal randomized controlled trials (RCTs) for all cancer drugs approved for the first time by the FDA between 2000 and 2020. We report regulatory and trial characteristics. Effects on overall survival (OS), progression-free survival and tumor response were summarized in meta-analyses. Effects on QoL were qualitatively summarized. Between 2000 and 2020, the FDA approved 145 novel cancer drugs for 156 indications based on 190 clinical trials. Half of indications (49%) were approved without RCT evidence; 82% had a single clinical trial only. OS was primary endpoint in 14% of trials and QoL data were available from 25%. The median OS benefit was 2.55 months (IQR, 1.33-4.28) with a mean hazard ratio for OS of 0.75 (95%CI, 0.72-0.79, I2  = 42). Improvement for QoL was reported for 7 (4%) of 156 indications. Over time, priority review was used increasingly and the mean number of trials per indication decreased from 1.45 to 1.12. More trials reported results on QoL (19% in 2000-2005; 41% in 2016-2020). For 21 years, novel cancer drugs have typically been approved based on one single, often uncontrolled, clinical trial, measuring surrogate endpoints. This leaves cancer patients without solid evidence that novel drugs improve their survival or QoL and there is no indication towards improvement.

Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19

ABSTRACT COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

Gastric bypass versus best medical treatment for diabetic kidney disease: 5 years follow up of a single-centre open label randomised controlled trial.

Background: We compared the albuminuria-lowering effects of Roux-en-Y gastric bypass (RYGB) to best medical treatment in patients with diabetic kidney disease and obesity to determine which treatment is better. Methods: A 5 year, open-label, single-centre, randomised trial studied patients with diabetic kidney disease and class I obesity after 1:1 randomization to best medical treatment (n = 49) or RYGB (n = 51). The primary outcome was the proportion of patients achieving remission of microalbuminuria after 5 years. Secondary outcomes included improvements in diabetic kidney disease, glycemic control, quality of life, and safety. For efficacy outcomes, we performed an intention-to-treat (ITT) analysis. This study was registered with ClinicalTrials.gov, NCT01821508. Findings: 88% of patients (44 per arm) completed 5-year follow-up. Remission of albuminuria occurred in 59.6% (95% CI = 45.5-73.8) after best medical treatment and 69.7% (95% CI = 59.6-79.8) after RYGB (risk difference: 10%, 95% CI, -7 to 27, P = 0.25). Patients after RYGB were twice as likely to achieve an HbA1c ≤ 6.5% (60.2% versus 25.4%, risk difference, 34.9%; 95% CI = 15.8-53.9, P < 0.001). Quality of life after five years measured by the 36-Item Short Form Survey questionnaire (standardized to a 0-to-100 scale) was higher in the RYGB group than in the best medical treatment group for several domains. The mean differences were 13.5 (95% CI, 5.5-21.6, P = 0.001) for general health, 19.7 (95% CI, 9.1-30.3, P < 0.001) for pain, 6.1 (95% CI, -4.8 to 17.0, P = 0.27) for social functioning, 8.3 (95% CI, 0.23 to 16.3, P = 0.04) for emotional well-being, 12.2 (95% CI, 3.9-20.4, P = 0.004) for vitality, 16.8 (95% CI, -0.75 to 34.4, P = 0.06) for mental health, 21.8 (95% CI, 4.8-38.7, P = 0.01) for physical health and 11.1 (95% CI, 2.24-19.9, P = 0.01) for physical functioning. Serious adverse events were experienced in 7/46 (15.2%) after best medical treatment and 11/46 patients (24%) after RYGB (P = 0.80). Interpretation: Albuminuria remission was not statistically different between best medical treatment and RYGB after 5 years in participants with diabetic kidney disease and class 1 obesity, with 6-7 in ten patients achieving remission of microalbuminuria (uACR <30 mg/g) in both groups. RYGB was superior in improving glycemia, diastolic blood pressure, lipids, body weight, and quality of life. Funding: The study was supported by research grants from Johnson & Johnson Brasil, Oswaldo Cruz German Hospital, and by grant 12/YI/B2480 from Science Foundation Ireland (Dr le Roux) and grant 2015-02733 from the Swedish Medical Research Council (Dr le Roux). Dr Pereira was funded by the Chevening Scholarship Programme (Foreign and Commonwealth Office, UK).

15-Year progression to liver cancer in the lack of treatment for lysosomal acid lipase deficiency: A case report.

RATIONALE: Lysosomal acid lipase deficiency (LAL-D) is a poorly diagnosed genetic disorder characterized by the accumulation of cholesteryl esters and triglycerides in many tissues, leading to dyslipidemia and cardiovascular complications. In the liver, deposits are found within hepatocytes and Kupffer cells, generating microvesicular steatosis, progressive fibrosis, and cirrhosis. Sebelipase alfa is the target therapy which can improve laboratory changes and reduce the progression of liver damage, but this is not yet widely available. PATIENT CONCERNS: We are reporting a 15-year follow-up of a Brazilian man who was diagnosed with cirrhosis at age 43 and with LAL-D at age 53, but he has never been treated with sebelipase alfa for economic reasons. During the coronavirus disease 2019 (COVID-19) pandemic, he lost follow-up and missed three 6-month ultrasound exams for liver cancer screening. DIAGNOSIS: At age 58, a remarkable deterioration in liver function was observed and he was diagnosed with hepatocellular carcinoma (HCC) outside the Milan Criteria (two nodules measuring 48mm and 25mm). Three other individuals with LAL-D and progression to liver cancer have been reported so far and none of them underwent enzyme replacement therapy: an 11-year-old girl with HCC, a 51-year-old male with cholangiocarcinoma, and a 21-year-old male with hepatocellular-cholangiocarcinoma. The latter had the same mutation in the gene LIPA as our patient, but a relationship between this variant and malignancies has not yet been established. LESSONS: We emphasize how important is to treat LAL-D patients after diagnosis in order to avoid worsening liver function and progression to neoplasms. Untreated individuals should be considered at a higher risk but the most appropriate liver cancer screening program for this subgroup is still unknown.

Evaluation of the Hepatocellular Carcinoma Predictive Scores PAGE-B and mPAGE-B among Brazilian Patients with Chronic Hepatitis B Virus Infection.

Hepatitis B virus (HBV) is intrinsically oncogenic and related to hepatocellular carcinoma (HCC). Predictive scores of HCC have been developed but have been poorly studied in admixed populations. Therefore, we aimed to evaluate the performance of PAGE-B and mPAGE-B scores for HCC prediction in HBV Brazilian patients and factors related to HCC occurrence. This is a retrospective study that evaluated patients followed at a tertiary university center. A total of 224 patients were included, with a median follow-up period of 9 years. The mean age at HBV diagnosis was 38.71 ± 14.19 years, predominantly males (66.1%). The cumulative incidence of HCC at 3, 5, and 7 years was 0.993%, 2.70%, and 5.25%, respectively, being related in the univariate logistic regression analysis to male sex (p = 0.0461), older age (p = 0.0001), cirrhosis at HBV diagnosis (p < 0.0001), and higher values of PAGE-B and mPAGE-B scores (p = 0.0002 and p < 0.0001, respectively). Older age, male sex, and cirrhosis at HBV diagnosis were independently associated with HCC occurrence. The AUROCs of PAGE-B and mPAGE-B were 0.7906 and 0.7904, respectively, with no differences between them (p = 0.9767). In conclusion, both PAGE-B and mPAGE-B showed a correct prediction of HCC above 70% in this cohort.

Deep generative model for therapeutic targets using transcriptomic disease-associated data-USP7 case study.

The generation of candidate hit molecules with the potential to be used in cancer treatment is a challenging task. In this context, computational methods based on deep learning have been employed to improve in silico drug design methodologies. Nonetheless, the applied strategies have focused solely on the chemical aspect of the generation of compounds, disregarding the likely biological consequences for the organism's dynamics. Herein, we propose a method to implement targeted molecular generation that employs biological information, namely, disease-associated gene expression data, to conduct the process of identifying interesting hits. When applied to the generation of USP7 putative inhibitors, the framework managed to generate promising compounds, with more than 90% of them containing drug-like properties and essential active groups for the interaction with the target. Hence, this work provides a novel and reliable method for generating new promising compounds focused on the biological context of the disease.

Validation of New York/California Score in the Preoperative Period of Liver Transplant for Hepatocellular Carcinoma at University of Campinas's Hospital.

Liver transplant is the main treatment for hepatocellular carcinoma and there is currently an important demand from patients waiting in transplant queues. Thus, it is extremely important to improve the criteria for selecting patients who will undergo transplant to mitigate graft loss and reduce cases of recurrence. Thus, it becomes necessary to use models, such as the New York/California (NYCA), that include alpha fetoprotein as a marker of recurrence and prognosis. The aim of this study was to assess whether the NYCA score correlated with the presence of tumor recurrence after transplant in patients undergoing orthotopic liver transplant at the Clinics Hospital of the University of Campinas. We had 214 patients undergoing liver transplant who met the inclusion Milan criteria. The age of the patients ranged from 34 to 77 years, with a median age of 61 years. The mean waiting time on the transplant list was 6.12 months. After calculating the NYCA score, it was possible to stratify 13 patients (6.1%) as high risk, 64 patients (29.9%) as medium risk, and 137 patients (64%) as low risk. Patients with recurrence had higher scores with a mean of 4 points in relapse and 2 points in the absence of relapse (P = .0011). Patients with recurrence had statistically higher high- and medium-risk scores (P = .0010). Therefore, the NYCA score was higher in patients with recurrence. Therefore, in this study, our findings suggest the possibility of using the NYCA score as an aid to detect patients with a higher risk of tumor recurrence.

Prevalence of Hepatocellular Carcinoma and Its Characteristics in 10 Years of Transplantation in a University Hospital in Brazil.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for up to 90% of all primary liver neoplasms. HCC treatment options depend on tumor burden, the degree of liver dysfunction, and performance status. Orthotopic liver transplant offers the best chance for cure. The selection criteria adopted for transplant are based on the Milan Criteria (MC), which depend on tumor size and number (1 lesion ≤5 cm or up to 3 lesions of ≤3 cm, without vascular invasion or extrahepatic spread). In Brazil, an expanded version of the original MC, named the Brazilian Criteria (BC), takes into consideration only tumors larger or equal to 2 cm. This retrospective cohort aims to describe the prevalence of primary liver tumors and analyze the macro and microscopic characteristics of HCC on explant pathology in a university hospital over 10 years. Of 485 transplants, 243 (50.1%) had HCC. Most patients were men (77.4%) with a mean age of 58.4 years, and the most common primary etiology of liver disease was hepatitis C infection (64.2%). The total number of tumors was 628, generally multicentric (55.6%); segment VIII was the most affected, and alpha-fetoprotein was altered in 70.7% of the cases. Most patients had tumors meeting MC at pretransplant and on explant evaluation, along with higher overall survival when compared to those exceeding MC and BC, and especially with those outside both criteria. In addition, tumors outside MC represent an independent risk factor associated with death.

Designing optimized drug candidates with Generative Adversarial Network.

Drug design is an important area of study for pharmaceutical businesses. However, low efficacy, off-target delivery, time consumption, and high cost are challenges and can create barriers that impact this process. Deep Learning models are emerging as a promising solution to perform de novo drug design, i.e., to generate drug-like molecules tailored to specific needs. However, stereochemistry was not explicitly considered in the generated molecules, which is inevitable in targeted-oriented molecules. This paper proposes a framework based on Feedback Generative Adversarial Network (GAN) that includes optimization strategy by incorporating Encoder-Decoder, GAN, and Predictor deep models interconnected with a feedback loop. The Encoder-Decoder converts the string notations of molecules into latent space vectors, effectively creating a new type of molecular representation. At the same time, the GAN can learn and replicate the training data distribution and, therefore, generate new compounds. The feedback loop is designed to incorporate and evaluate the generated molecules according to the multiobjective desired property at every epoch of training to ensure a steady shift of the generated distribution towards the space of the targeted properties. Moreover, to develop a more precise set of molecules, we also incorporate a multiobjective optimization selection technique based on a non-dominated sorting genetic algorithm. The results demonstrate that the proposed framework can generate realistic, novel molecules that span the chemical space. The proposed Encoder-Decoder model correctly reconstructs 99% of the datasets, including stereochemical information. The model's ability to find uncharted regions of the chemical space was successfully shown by optimizing the unbiased GAN to generate molecules with a high binding affinity to the Kappa Opioid and Adenosine [Formula: see text] receptor. Furthermore, the generated compounds exhibit high internal and external diversity levels 0.88 and 0.94, respectively, and uniqueness.

Refinement of the Milan Criteria: Role of α-Fetoprotein In Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary neoplasm of the liver, mainly secondary to cirrhosis caused by hepatitis C virus. Liver transplant (LT) is considered the best treatment because, in addition to removing the tumor, it also removes the underlying cirrhotic liver. The Milan criteria for LT have limitations because they do not consider the biological characteristics of the tumor. Thus, our objective was to evaluate the association of α-fetoprotein (AFP) levels before LT performed for HCC with recurrence of this tumor, and, based on the results, a new predictive model that combines the AFP values at the list entry with the usual criteria of tumor size and number of nodules was validated. In present study, the Score AFP model, we were able to correlate a greater occurrence of relapse with scores of 3 and 4 (P = .0001), indicating the usefulness of using AFP as a predictor of recurrence.

Validation of Metroticket Score in the Preoperative Period of Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer in the world, and liver transplant (LT) is a good therapeutic option in selected cases because it treats the neoplasm and the underlying disease. Recurrence after LT is usually aggressive and has low survival; thus, an adequate selection of recipients is ideal. The new models aim to assess the individual risk of HCC recurrence in patients undergoing LT and to improve post-LT survival. In this study, our aim was to assess the applicability of the "Metroticket" score, correlating it with our rates of recurrence and survival after LT. Overall survival at 5 years in our study differed from that in Metroticket 2.0 because that study did not consider only recurrence as the cause of death; our study evaluated only patients with recurrence, so we were able to validate the score as a predictor of greater tumor aggressiveness after LT.

FLUORO-CT GUIDED BIOPSY OF LUNG NODULES: A STEP BY STEP REVISION.

INTRODUCTION: Transthoracic biopsies under fluoro-computer tomography (CT) guidance play an important role on the diagnosis and management of lung nodules, permitting histological examination and differentiation between benign and malignant lesions(1). Furthermore, with recent advances in target therapy, it is increasingly necessary to obtain tumor tissue for the analysis of molecular fingerprints allowing personalized treatment(1). Although many studies report low complication rates for this procedure, they are not negligible, urging the need for a structured and reproducible guide to reduce technique-related complications(1,2).

Efficacy and costs of nanocrystalline silver dressings versus 1% silver sulfadiazine dressings to treat burns in adults in the outpatient setting: A randomized clinical trial.

BACKGROUND: Nanocrystalline silver dressings can reduce the number of changes, facilitating burn wound management. However, the evidence regarding their efficacy and cost-consequences compared to well-established treatments, such as 1% silver sulfadiazine, is still scarce. OBJECTIVE: To determine the efficacy, safety, and costs of nanocrystalline silver dressings compared to 1% silver sulfadiazine dressings to treat adult patients with burns. STUDY DESIGN AND SETTING: Randomized, single-center, single-blind trial conducted at a referral hospital in São Paulo, Brazil. METHODS: 100 adult patients were randomized 1:1 to nanocrystalline silver (n = 50) or 1% silver sulfadiazine (n = 50). The primary outcome was the proportion of participants with complete re-epithelization at day 15 after randomization. Secondary outcomes included the number of dressing changes, direct medical costs (in international dollars, I$), pain intensity, the incidence of infections, number of patients undergoing surgery, and adverse events. RESULTS: On day 15, the proportion of patients who reached the primary outcome did not differ significantly between participants treated with nanocrystalline silver dressings (24 [48%]) and those treated with 1% silver sulfadiazine dressings (26 [52%]); risk difference of -4.0 percentage points (95% confidence interval [CI], -17 to 9; P = 0.56). The number of patients undergoing surgical intervention was similar between groups (6% vs. 6%), and no local or serious adverse events were reported. The mean (standard deviation, SD) number of dressing changes in the nanocrystalline silver group was 4.1 (2.3), and the corresponding estimate in the 1% silver sulfadiazine group was 9.6 (6.7); mean difference of -5.56 (95% CI), -7.57 to -3.55, P < 0.001). Treatment with nanocrystalline silver dressing incurred significant cost reductions in medical materials, human resources, and administrative labor. However, the mean total cost with nanocrystalline silver dressing was higher compared to 1% silver sulfadiazine dressings: I$496.37 (445.90) vs. I$274.73 (182.76); mean difference = 221.63 (95% CI, 89.04 to 354.23, P = 0.001). The main driver of higher mean total costs among nanocrystalline silver-treated participants was the purchase cost of the dressings, representing 79.3% of the total cost in the nanocrystalline silver group but only 15.2% in the 1% silver sulfadiazine group. CONCLUSION: We found no evidence of a difference between nanocrystalline silver and 1% silver sulfadiazine dressings regarding efficacy and safety outcomes. Nanocrystalline silver dressings were associated with an increase in the total costs, but they could result in important savings for an institution (less changes of dressings, reducing human resources burden), especially if acquisition costs can be decreased. Additional cost-effectiveness studies are warranted. TRIAL REGISTRATION NUMBER: NCT02108535.