Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model: A cohort study.

BACKGROUND: Liver transplant (LT) patients have become older and sicker. The rate of post-LT major adverse cardiovascular events (MACE) has increased, and this in turn raises 30-d post-LT mortality. Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients. AIM: To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort. METHODS: This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center. We developed a predictive model for post-LT MACE (defined as a composite outcome of stroke, new-onset heart failure, severe arrhythmia, and myocardial infarction) using the extreme gradient boosting (XGBoost) machine learning model. We addressed missing data (below 20%) for relevant variables using the k-nearest neighbor imputation method, calculating the mean from the ten nearest neighbors for each case. The modeling dataset included 83 features, encompassing patient and laboratory data, cirrhosis complications, and pre-LT cardiac assessments. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC). We also employed Shapley additive explanations (SHAP) to interpret feature impacts. The dataset was split into training (75%) and testing (25%) sets. Calibration was evaluated using the Brier score. We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting. Scikit-learn and SHAP in Python 3 were used for all analyses. The supplementary material includes code for model development and a user-friendly online MACE prediction calculator. RESULTS: Of the 537 included patients, 23 (4.46%) developed in-hospital MACE, with a mean age at transplantation of 52.9 years. The majority, 66.1%, were male. The XGBoost model achieved an impressive AUROC of 0.89 during the training stage. This model exhibited accuracy, precision, recall, and F1-score values of 0.84, 0.85, 0.80, and 0.79, respectively. Calibration, as assessed by the Brier score, indicated excellent model calibration with a score of 0.07. Furthermore, SHAP values highlighted the significance of certain variables in predicting postoperative MACE, with negative noninvasive cardiac stress testing, use of nonselective beta-blockers, direct bilirubin levels, blood type O, and dynamic alterations on myocardial perfusion scintigraphy being the most influential factors at the cohort-wide level. These results highlight the predictive capability of our XGBoost model in assessing the risk of post-LT MACE, making it a valuable tool for clinical practice. CONCLUSION: Our study successfully assessed the feasibility and accuracy of the XGBoost machine learning model in predicting post-LT MACE, using both cardiovascular and hepatic variables. The model demonstrated impressive performance, aligning with literature findings, and exhibited excellent calibration. Notably, our cautious approach to prevent overfitting and data leakage suggests the stability of results when applied to prospective data, reinforcing the model's value as a reliable tool for predicting post-LT MACE in clinical practice.

Active Tactile Sensibility of Brånemark Protocol Prostheses: A Case-Control Clinical Study.

Few studies have assessed active tactile sensibility in patients rehabilitated with implants. Improved knowledge about functional tactile sensibility will contribute to several clinical applications, such as protocols for immediate loading, prosthesis design, occlusal improvement in implantology, and physiological integration of implant-supported prostheses. The present study evaluated active tactile sensibility in patients rehabilitated with Brånemark-type mandibular prostheses that impede the total mucosa-supported maxillary prosthesis. Thirty-five subjects participated in this study. The experimental group (n = 18) inclusion criteria were as follows: Brånemark-type prosthesis and a total mucosa-supported maxillary prosthesis. The control group (n = 17) was composed of participants with complete healthy dentition. Carbon foils with different thicknesses (12 µm, 24 µm, 40 µm, 80 µm, and 200 µm) were placed in the premolar region to evaluate the brink of active oral tactile sensibility. The researchers assessed the participants 120 times. After evaluation, we observed a statistical difference (p < 0.05) between the groups. Additionally, the degree of sensibility was found for all thicknesses, except for 12 µm, on both sides. There was a more significant increase in perception in the control group as the carbon thickness increased. The tactile sensibility threshold was 2.5 times greater for participants with prostheses. Thus, the tactile sensibility for mandibular implant-supported and maxillary mucosa-supported prostheses is significantly lower than that of dentate patients, which was detected above the thickness of 80 µm; in patients with natural dentition, different thicknesses were seen starting from 24 µm.

Analysis of Active Oral Tactile Sensitivity in Individuals with Complete Natural Dentition.

AIM: To evaluate the active tactile sensitivity in individuals with complete natural dentition, determining the smallest thickness detected by the participants, and clarifying if there is a difference between the thicknesses analyzed. MATERIALS AND METHODS: Active tactile sensitivity was evaluated in 40 research participants. Inclusion criteria included participants with complete natural dentition, without active or history of periodontal disease, absence of temporomandibular disorders, bruxism, and restorations in the evaluated area. Exclusion criteria included age below 18 years. The active tactile perception threshold was evaluated by using carbon sheets of different thicknesses (0, 12, 24, 40, 80, 100, and 200 µm), which were inserted in the participants' premolars, bilaterally. The carbon sheet was inserted so as not to come into contact with the oral soft tissues. Subsequently, the participant occluded and was asked about the perception of the intraocclusal object 20 times in each occlusal contact. The collected data were tabulated considering the amount of positive and negative responses for each carbon thickness. Values of p < 0.05 were considered significant. RESULTS: The results showed that there was linearity in perception, on both sides, besides, the natural dentition was able to perceive difference in thickness from 12 µm. CONCLUSION: We conclude that the 12 µm thickness is noticeable in occlusion and can be differentiated from other thicknesses in natural dentition and that there is no difference between the tactile sensitivity of the right and left sides. CLINICAL SIGNIFICANCE: A better understanding of active oral tactile sensitivity will contribute to numerous clinical applications in dentistry, including occlusal adjustment in dental rehabilitation, dental implants prosthesis design, and survival of prosthetic rehabilitation.

The Importance of Coordinated Actions in Preventing the Spread of Yellow Fever to Human Populations: The Experience from the 2016-2017 Yellow Fever Outbreak in the Northeastern Region of São Paulo State.

Yellow fever (YF) is a zoonotic arthropod-borne disease that is caused by the yellow fever virus (YFV) and characterized by a sylvatic and urban cycle. Its most severe presentation is manifested as a hemorrhagic disease, and it has been responsible for thousands of deaths in the last decades. This study describes the public health approaches taken to control the 2016-2017 YF outbreak in nonhuman primates (NHPs) that took place in the northeastern region of São Paulo state, Brazil. NHPs recovered from the field were necropsied, and YF diagnoses were made at the Laboratory of Molecular Virology, Ribeirão Preto Medical School and the Center of Pathology, Adolfo Lutz Institute of São Paulo. NHP samples were inoculated into Vero cells for YFV isolation. RNA extraction was performed directly from NHP tissues and tested by RT-qPCR. YFV-positive samples were confirmed by sequencing. Based on the rapid RT-qPCR results, surveillance actions were implemented in the entire region. Confirmatory histopathology and immunohistochemistry for YFV were also performed. Among nine NHPs, gross hepatic involvement was observed in six animals, five of which were YFV-RT-qPCR-positive. One YFV was isolated from the serum of an infant NHP. YFV RNA sequences diverged from the virus responsible for the last epizootic that occurred in São Paulo state, but it was similar to the current Brazilian epizootic. Public health actions included dissemination of information on YF transmission, investigation of the probable location of NHP infection, characterization of the environment, and subsequent creation of the blueprint from which prevention and control measures were implemented. The YFV sylvatic cycle occurred in the periurban areas of the northeastern region of São Paulo state, but no human cases were reported during this period, showing that integrated actions between human, animal, and environmental health professionals were critical to restrain the virus to the sylvatic cycle.

Grandes estudos clínicos que demonstraram redução de risco cardiovascular através do uso de antidiabéticos / Large clinical trials that demonstrated a decrease in cardiovascular risk through the use of antidiabetics

Nos últimos anos, os avanços nas descobertas da terapêutica para o DM2 entusiasmaram os clínicos e especialistas no que diz respeito à redução dos eventos cardiovasculares, internações e mortalidade. Outros estudos ainda estão em andamento e prometem fortalecer a expectativa de mudança nos desfechos cardiovasculares dessa população. O objetivo dessa revisão consiste em reunir os principais estudos clínicos que demonstraram a segurança e/ou redução na ocorrência de eventos cardiovasculares com uso de fármacos anti-hiperglicemiantes.

In recent years, breakthroughs in therapeutic findings for DM2 have encouraged physicians and specialists with regards to the reduction of cardiovascular events, hospitalization and mortality. Other studies are underway, and promise to strengthen the prospects of change in cardiovascular outcomes for this population. The goal of this review is to bring together the most important clinical trials that have demonstrated safety and/or a decrease in cardiovascular events with the use of antihyperglycemic drugs.

Reflexões sobre a influência do estresse crônico na transformação de células saudáveis em células cancerígenas / Reflections on the influence of chronic stress in the transformation of healthy cells in cancer cells

Objetivo: discutir, a partir de análise reflexiva, a influência do estresse crônico na transformação de células saudáveis em células cancerígenas. Método: um estudo descritivo, tipo análise reflexiva, a partir de revisão de literatura. Resultados: sabe-se que existe uma relação entre as emoções e as funções imunes. O organismo reage ao receber estímulos estressores, acionando reações do sistema nervoso, endócrino e imunológico. A partir daí, ocorre a ativação do eixo hipotálamo-hipófise-adrenal, o que faz aumentar os níveis de cortisol que, ligado a receptores nos leucócitos, causa imunossupressão. Um estresse emocional prolongado aos poucos causa no organismo diminuições químicas aptas a conceber alterações celulares funcionais. Essas células passam a ter um comportamento anormal e se multiplicam desordenadamente numa velocidade mais rápida que as células normais, podendo resultar em células cancerígenas. Conclusão: o estresse emocional crônico pode favorecer alterações no sistema imunológico e resultar na proliferação de células malignas.

An ortho-Iminoquinone Compound Reacts with Lysine Inhibiting Aggregation while Remodeling Mature Amyloid Fibrils.

Protein aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. It has been shown that lysine residues play a key role in the formation of these aggregates. Thus, the ability to disrupt aggregate formation by covalently modifying lysine residues could lead to the discovery of therapeutically relevant antiamyloidogenesis compounds. Herein, we demonstrate that an ortho-iminoquinone (IQ) can be utilized to inhibit amyloid aggregation. Using alpha-synuclein and Aß1-40 as model amyloidogenic proteins, we observed that IQ was able to react with lysine residues and reduce amyloid aggregation. We also observed that IQ reacted with free amines within the amyloid fibrils preventing their dissociation and seeding capacity.

Implantes longos inclinados com ancoragem em fossa nasal e submetidos à carga imediata: um estudo clínico retrospectivo com acompanhamento de dois a seis anos / Long, tilted dental implants anchored in the nasal floor and submitted to immediate loading: a retrospective, 2-6 year clinical follow-up

Objetivo: avaliar o índice de sobrevivência de implantes longos ancorados na fossa nasal e submetidos à carga imediata. Material e métodos: neste estudo clínico retrospectivo, pacientes das clínicas privadas dos autores foram submetidos à instalação de implantes longos inclinados na maxila, ancorados na cortical do assoalho da fossa nasal. Os implantes foram esplintados a implantes convencionais ou implantes zigomáticos, com as próteses instaladas em um período de 48 horas a sete dias após a realização da cirurgia. Alguns pacientes foram submetidos à cirurgia guiada sem retalho, e as próteses em todos os casos foram removidas após um período de seis meses. Os pacientes foram acompanhados por um período mínimo de 24 meses. Resultados: no período de setembro de 2006 a novembro de 2010, 32 implantes longos e inclinados foram instalados em maxilas totalmente edêntulas de 15 pacientes (sete homens, oito mulheres) e submetidos à carga imediata. Foram utilizados implantes longos (Conexão Sistema de Prótese – São Paulo, Brasil) com diâmetro de 3,75 mm, sistema antirrotacional interno e comprimentos de 18 mm, 21 mm e 23 mm, sendo 56,3% (n=18), 40,6% (n=13) e 3,1% (n=1), respectivamente. Todos os implantes foram ancorados com 45 Ncm no osso cortical nasal, e os pacientes foram acompanhados por um período de 24 a 72 meses. Um total de 48 implantes convencionais e quatro implantes zigomáticos foram instalados e unidos aos implantes longos inclinados em alguns pacientes. Conclusão: os implantes longos inclinados ancorados na fossa nasal, associados aos implantes convencionais ou implantes zigomáticos e submetidos à carga imediata, apresentaram bons resultados no tratamento na maxila edêntula.

Implantes curtos em diferentes condições clínicas: um estudo retrospectivo (acompanhamento de um a cinco anos) / Short dental implants in different clinical conditions: a retrospective study (1-5 year follow-up)

O objetivo deste estudo retrospectivo foi avaliar o índice de sobrevivência dos implantes curtos em diferentes situações clínicas, com um acompanhamento clínico mínimo de 12 meses. Material e Métodos: no período de setembro de 2005 a dezembro de 2011, implantes curtos (8,5 mm ou inferior) foram instalados em pacientes da clínica dos autores e da clínica da Unifeso, para substituir dentes unitários e múltiplos nas regiões anterior e posterior da maxila e da mandíbula. Todas as áreas implantadas apresentavam uma elevada reabsorção óssea. Resultados: um total de 335 implantes foi instalado, em 107 pacientes (69 mulheres e 38 homens) com idade média de 68 anos (54 a 82 anos). Os implantes instalados foram 54,6% com o comprimento de 6 mm, 40,3% com comprimento de 8,5 mm e 5,1% com comprimento de 7 mm, distribuídos na região anterior (10,4%) e região posterior (89,6%) da maxila e da mandíbula. Foram utilizadas coroas individuais em dez implantes (3,2%), e 299 implantes foram reabilitados com próteses múltiplas parciais e totais (96,8%). Dentre os 299 implantes, 13 (4,2%) foram submetidos à carga imediata. Após um acompanhamento de um a cinco anos, 309 implantes apresentavam-se em função e 26 implantes foram perdidos, atingindo um índice de sobrevivência de 92,2%. Conclusão: os resultados do presente estudo sugeriram que os implantes curtos apresentaram um bom índice de sobrevivência, devendo ser considerados como uma solução previsível para a reabilitação da maxila e da mandíbula, com elevado grau de reabsorção...

The aim of this clinical retrospective study was to assess the survival rate of short implants in different clinical situations with a minimum 12-month follow-up period. Materials and Methods: between September 2005 to December 2011, short dental implants (8.5 mm or shorter) were placed in patients of authors and Unifeso clinics to restore single and multiple teeth in the anterior and posterior jaw regions. All areas were affected by high bone resorption patterns. Results: a total of 335 implants were placed in 107 patients (69 women and 38 men) with a mean age of 68 years (range: 54–82 years). The implants placed were 6 mm (54.6%), 7 mm (5.1%), and 8.5 mm (40.3%) long, distributed in the anterior (10.4%) and posterior (89.6%) regions. Single crowns were placed in 10 implants (3.2%), and 299 implants received multiple partial and complete prostheses (96.8%). From these, 13 implants (4.2%) were submitted to immediate loading. After 1-5 year follow-up period, 309 implants are in function and 26 implants have been lost, achieving a survival rate of 92.2%. Conclusion: the results of this study suggested that short dental implants presented a good survival rate and therefore should be regarded as a predictable solution for the rehabilitation of highly resorbed jaw regions...