Local imaging to interpret tumor size in F18 fluorodeoxyglucose positron emission tomography/CT in lung cancers

SUMMARY OBJECTIVE: This study aimed to determine the thoracic and extra-thoracic extension of the disease in patients diagnosed with lung cancer and who had whole-body F18-fluorodeoxyglucose positron emission tomography/CT imaging and to investigate whether there is a relationship between tumor size and extrathoracic spread. METHODS: A total of 308 patients diagnosed with lung cancer were included in this study. These 308 patients were first classified as group 1 (SPN 30 mm>longest lesion diameter ≥10 mm) and group 2 (lung mass (longest lesion diameter ≥30 mm), and then the same patients were classified as group 3 (nodular diameter of ≤20 mm) and group 4 (nodular size of >20 mm). Group 1 was compared with group 2 in terms of extrathoracic metastases. Similarly, group 3 was compared with group 4 in terms of frequency of extrathoracic metastases. F18 fluorodeoxyglucose positron emission tomography/CT examination was used to detect liver, adrenal, bone, and supraclavicular lymph node metastasis, besides extrathoracic metastasis. RESULTS: Liver, bone, and extrathoracic metastasis in group 1 was statistically lower than in group 2 (p<0.001, p<0.01, and p=0.03, respectively). Liver, extrathoracic, adrenal, and bone metastasis in group 3 was statistically lower than that in group 4 (p<0.001, p=0.01, and p=0.04, p<0.01, respectively). The extrathoracic extension was observed in only one patient in group 3. In addition, liver, adrenal, and bone metastases were not observed in group 3 patients. CONCLUSION: Positron emission tomography/CT may be more appropriate for cases with a nodule diameter of ≤20 mm. Performing local imaging in patients with a nodule diameter of ≤20 mm could reduce radiation exposure and save radiopharmaceuticals used in positron emission tomography/CT imaging.

The association Between Sleep Quality, Fatigue and Periodontal Status: a pilot study / La asociación entre la calidad del sueño, la fatiga y el estado periodontal: un estudio piloto

Abstract Reduced sleep duration, poor sleep quality and fatigue are related to reduced immunity and increased inflammatory markers. Due to its potential to influence inflammation, poor sleep quality and fatigue could be factors for periodontitis and quality of life. Ninety-three individuals with untreated periodontitis and thirty-one individuals with healthy gingiva were included in the study. The research involved a clinical examination and a questionnaire. Demographic information, information on oral health, oral hygiene habits, the Pittsburgh Sleep Quality Index, Jenkins Sleep Scale, Multidimensional Assessment of Fatigue Scale, and Oral Health Impact Profile-14 were included in the questionnaire. Patients were diagnosed based on the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. No statistically significant difference was revealed between sleep quality, fatigue, oral health related quality of life, and stage-grade of periodontitis (p<0.05). However, periodontitis group had higher Oral Health Impact Profile-14 scores (p<0.05). A statistically significantly lower sleep duration was observed in stage IV periodontitis group than the other groups (p<0.05). A statistically significant positive correlation was observed between the Pittsburgh Sleep Quality Index and the scores of the other questionnaires (p<0.05). The stage of periodontitis may impact sleep duration.

Resumen La reducción de la duración del sueño, la mala calidad del sueño y la fatiga están relacionados con una inmunidad reducida y un aumento de los marcadores inflamatorios. Debido a su potencial para influir en la inflamación, la mala calidad del sueño y la fatiga podrían ser factores determinantes en el desarrollo de la periodontitis e incidir en la calidad de vida. Noventa y tres personas con periodontitis no tratada, además de treinta y una personas con encía sana se incluyeron en el estudio. La investigación involucró un examen clínico y un cuestionario. En el cuestionario se incluyeron información demográfica, información sobre salud bucal, hábitos de higiene bucal, el índice de calidad del sueño de Pittsburgh, la escala de sueño de Jenkins, la escala de evaluación multidimensional de la fatiga y el perfil de impacto en la salud bucal-14. Los pacientes fueron diagnosticados en base al Taller Mundial 2017 sobre la Clasificación de Enfermedades y Condiciones Periodontales y Periimplantarias. No se revelaron diferencias estadísticamente significativas entre la calidad del sueño, la fatiga, la calidad de vida relacionada con la salud bucal y el grado de etapa de la periodontitis (p<0,05). Sin embargo, el grupo de periodontitis tuvo puntajes más altos en el Perfil de Impacto en la Salud Oral-14 (p<0.05). Se observó una duración del sueño significativamente menor desde el punto de vista estadístico en el grupo de periodontitis en estadio IV que en los otros grupos (p<0,05). Se observó una correlación positiva estadísticamente significativa entre el Índice de Calidad del Sueño de Pittsburgh y las puntuaciones de los otros cuestionarios (p<0,05). La etapa de la periodontitis puede afectar la duración del sueño.

Clinicopathological and molecular analyses of uterine carcinosarcomas using next-generation sequencing: A single-center experience

Background: Uterine carcinosarcomas (UCS) constitute 3–4% of all uterine malignancies and 16% of deaths caused due to uterine neoplasms. Aim: In this study, we aimed to perform DNA-based mutation analysis in 12 genes (KRAS, NRAS, EGFR, C-KIT, BRAF, PDGFRA, ALK, ERBB2, ERBB3, ESR1, RAF1, PIK3CA) to determine the molecular subtypes of UCS using next-generation sequencing (NGS) in patients with aggressive UCS and poor prognosis. We aimed to compare the results of our analysis with clinicopathological data to contribute to the development of targeted therapy approaches related to the molecular changes of UCS. Materials and Methods: In this study, we included 12 cases diagnosed with uterine carcinosarcomas and examined the changes in oncogenes that play a role in UCS pathogenesis. For the analysis of mutation, the clinicopathological data were compared with the variations in the DNA-based gene panel consisting of 12 genes and 1237 variants in the UCS using the NGS method. Results: EGFR mutation was found in 91.7% of the cases, mutation in 41.7%, PDGFRA mutation in 25%, KRAS and PIK3CA mutation in 16.7%, and C-KIT mutation in 8.3% of the cases. Although no statistical significance was found between the detected mutation and clinicopathological data, it was concluded that PDGFRA mutation might be associated with advanced-stage disease development. Conclusion: This study's findings regarding different molecular types of UCS and information on oncogenesis of UCS can provide inferences for targeted therapies in the future by identifying targetable mutations representing early oncogenic events and thereby contribute toward further studies on this subject.

Prognostic significance of ?mmunhistochemical axl expression in pancreas ductal adenocarcinomas

Introduction and Aim: Pancreas Ductal Adenocarcinomas (PDACs) are among the leading causes of cancer-related death. Tyrosine kinase receptors (TKRs) are responsible for cell plasticity, chemoresistance, immunosuppression and metastasis potential. Axl is a receptor of the TKR family, and it has come to the fore in cancer treatment in the last decade. This study aimed to investigate the relationship of immunohistochemical Axl expression with histological features and its prognostic importance in PDACs. Materials and Methods: Fifty-three patients who were operated on for PDAC between 2006-2017 were evaluated retrospectively. Features of tumors; size, lymphovascular invasion (LVI), perineural invasion (PNI), resection margin (RM), lymph node metastasis (LNM), differentiation, tumor-infiltrating lymphocyte, stage and overall survival were recorded. Immunohistochemically, membranous and or cytoplasmic staining was considered positive for Axl. Statistically, Pearson Chi-Square, Cox regression and Kaplan Mayer tests were used in the SPSS 21.0 program. Results: Axl was positive in 28 patients (52.8%). Axl positivity was found to be associated with the presence of LVI (P = 0.009) and LNM (P = 0.002) and was an independent prognostic factor in short survival (P = 0.006). Conclusion: It was found that increased expression of Axl, which is known to increase EMT-mediated metastasis in carcinogenesis, may be an indicator of local spread and poor prognosis in PDAC patients. In this respect, it can be promising as a targeted molecule in PDAC patient's individualized treatments.

Investigation of associations between apolipoprotein A5 and C3 gene polymorphisms with plasma triglyceride and lipid levels

SUMMARY OBJECTIVE: The aim of this study was to determine frequency and associations between APOA5 c.56C>G, −1131T>C, c.553G>T, and APOC3 −482C>T and SstI gene polymorphisms with hypertriglyceridemia. METHODS: Under a case-control study model, 135 hypertriglyceridemic and 178 normotriglyceridemic control participants were recruited. Polymerase chain reaction and restriction fragment length polymorphism methods were utilized for genotyping. Statistical calculations were performed by comparing allele and genotype frequencies between groups. Clinical characteristics were compared between groups and intra-group genotypes. RESULTS: APOC3 gene −482C>T and SstI polymorphic genotypes and allele frequencies were significantly higher in hypertriglyceridemic group (genotype frequencies, p=0.035, p=0.028, respectively). Regression analysis under unadjusted model confirmed that APOC3 −482C>T and SstI polymorphisms were significantly contributing to have hypertriglyceridemia (p=0.02, odds ratio [OR]=1.831 (95% confidence interval [CI] 1.095-3.060); p=0.04, OR=1.812 (1.031-3.183), respectively). APOA5 c.56C>G was in complete linkage disequilibrium with APOA5 c.553G>T polymorphism (D'=1). CONCLUSION: For the first time in a population sample from Turkey, among the five polymorphisms of APOA5 and APOC3 genes investigated, APOC3 −482C>T and SstI polymorphisms were associated with elevated serum TG levels, while APOA5 c.56C>G, −1131T>C, and c.553G>T polymorphisms were not.

Evaluation and prognostic significance of tumor budding in pancreatic ductal adenocarcinomas

Aim: In this study, it was aimed to investigate the prognostic importance of Tumor budding (TB) in Pancreatic ductal adenocarcinomas(PDAC) and its correlation with histopathological findings according to the International Tumor Budding Consensus Conference(ITBCC) grading. Material and Methods: A total of 75 patients diagnosed with PDAC were included in this study. The demographic features of the cases (age, sex) and the macroscopic features of the tumors (localization,size) were obtained from the electronic archive system. All Hematoxylin-Eosin-stained sections were re-evaluated in terms of differentiation, presence of lymphovascular (LVI) and perineural invasion(PNI), surgical margin positivity, primary tumor(pT), lymph node metastasis(LNM) and tumor budding. Statistically, Chi-square test, cox-regression and Kaplan-Meier test were performed. Results:Thirty four of the cases were female and 41 were male. The mean age was 64.21±9.71years. The degree of TB was TB-few in 17 cases, TB-moderate in 25cases, and TB-high in 33cases. LVI, PNI, LNM and TB-high were poor prognostic factors. Moreover, TB-high was related with poor differantiation,LVI,PNI,LNM and short survival time. Tumor budding was independent negative prognostic factor in multivariable model analyzes. Conclusion: ITBCC scoring can also be used in PDACs. In addition, high tumor budding was a poor prognostic feature and might be a target for tumor-specific treatments as it could be a predictive finding for the locally invasive character of the tumor. Evaluation and grading of TB thought to represent EMT may be a histological feature that can be used in tumor selection for advanced molecular methods to identify subtypes that may be associated with poor prognosis and drug resistance.

The Effect of Perioperative Fluid Management and Operative Modifications on Mortality and Morbidity in Patients Undergoing Pulmonary Endarterectomy

ABSTRACT Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe disease treated with pulmonary endarterectomy. Our study aims to reveal the differences in liquid modalities and operation modifications, which can affect the patients' mortality and morbidity. Methods: One hundred twenty-five patients who were diagnosed with CTEPH and underwent pulmonary thromboendarterectomy (PTE) at our center between February 2011 and September 2013 were included in this retrospective study with prospective observation. They were in New York Heart Association functional class II, III, or IV, and mean pulmonary artery pressure was > 40 mmHg. There were two groups, the crystalloid (Group 1) and colloid (Group 2) liquid groups, depending on the treatment fluids. P-value < 0.05 was considered statistically significant. Results: Although the two different fluid types did not show a significant difference in mortality between groups, fluid balance sheets significantly affected the intragroup mortality rate. Negative fluid balance significantly decreased mortality in Group 1 (P<0.01). There was no difference in mortality in positive or negative fluid balance in Group 2 (P>0.05). Mean duration of stay in the intensive care unit (ICU) for Group 1 was 6.2 days and for Group 2 was 5.4 days (P>0.05). Readmission rate to the ICU for respiratory or non-respiratory reasons was 8.3% (n=4) in Group 1 and 11.7% (n=9) in Group 2 (P>0.05). Conclusion: Changes in fluid management have an etiological significance on possible complications in patient follow-up. We believe that as new approaches are reported, the number of comorbid events will decrease.

Investigation of the effectiveness of the Quick Sequential Organ Failure Assessment-Troponin scores in non- ST-elevation myocardial infarction

SUMMARY OBJECTIVE: A reliable predictor is needed for non-ST-elevation myocardial infarction patients with high mortality risk. The aim of this study was to assess the effectiveness of the Global Registry of Acute Coronary Events and Quick Sequential Organ Failure Assessment-Troponin (qSOFA-T) scores on in-hospital mortality rate in non-ST-elevation myocardial infarction patients. METHODS: This is an observational and retrospective study. Patients admitted to the emergency department with acute coronary syndrome were evaluated consecutively. A total of 914 patients with non-ST-elevation myocardial infarction who met inclusion criteria were included in the study. The Global Registry of Acute Coronary Events and qSOFA scores were calculated and investigated its contribution to prognostic accuracy by adding cardiac troponin I (cTnI) concentration to the qSOFA score. The threshold value of the investigated prognostic markers was calculated by receiver operating characteristic curve analysis. RESULTS: We found the in-hospital mortality rate to be 3.4%. The area under the receiver operating characteristic curve for Global Registry of Acute Coronary Events and qSOFA-T is 0.840 and 0.826, respectively. CONCLUSION: The qSOFA-T score, which can be calculated easily, quickly, and inexpensively and obtained by adding the cTnI level, had excellent discriminatory power for predicting in-hospital mortality. Difficulty in calculating the Global Registry of Acute Coronary Events score, which requires a computer, can be considered a limitation of this method. Thus, patients with a high qSOFA-T score are at an increased risk of short-term mortality.

Effect of echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation on the Lown classification in patients with hypertrophic obstructive cardiomyopathy / 中华超声影像学杂志

Objective:To investigate the effect of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) guided by echocardiography on the Lown classification of ventricular arrhythmias in patients with hypertrophic obstructive cardiomyopathy (HOCM).Methods:A total of 85 patients with HOCM who received PIMSRA treatment at Xijing Hospital of Air Force Military Medical University from May 2017 to October 2019 were retrospectively selected. All patients underwent 24-hour Holter examinations before and 1 year after PIMSRA to obtain parameters related to Lown classification. The changes in Lown grades after PIMSRA were analyzed. The patients were divided into improved group and unimproved group according to whether there was significant improvement in Lowen′s grades, and the difference of the parameters related were compared. The influencing factors of the changes in Lown classification were analyzed.Results:Compared with before PIMSRA, there was a significant improvement in the Lown classification after PIMSRA ( P=0.001). The patients with Lown grade Ⅰ increased significantly ( P=0.001), and the patients with grade Ⅲ decreased significantly ( P=0.005). There were no significant changes in patients with Lown grades 0, Ⅱ, and Ⅳ (all P>0.05). The proportion of patients with family history of hypertrophic cardiomyopathy (HCM), the baseline Lown classes, the reduction rate of the maximum left ventricular wall thickness and the reduction rate of the provocative left ventricular outflow tract gradient (LVOTG) were higher in the improved group than the unimproved group (all P<0.05). Multivariate Logistic regression results showed that HCM family history ( OR=3.95, 95% CI=1.34-11.64, P=0.013), baseline Lown classes ( OR=2.01, 95% CI=1.25-3.22, P=0.004) and the reduction rate of the provocative LVOTG gradient ( OR=1.02, 95% CI=1.00-1.04, P=0.041) were independent factors of postoperative Lown classification improvement. Conclusions:The Lown classes of HOCM patients after PIMSRA is significantly improved.HCM family history, the baseline Lown classes, and the reduction rate of postoperative provocative LVOTG are independent influencing factors for the improvement of Lown grade.

A follow-up study of percutaneous intramyocardial septal radiofrequency ablation in the treatment of obstructive hypertrophic cardiomyopathy with mild septal hypertrophy / 中华超声影像学杂志

Objective:To evaluate the clinical efficacy of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in the treatment of obstructive hypertrophic cardiomyopathy (HOCM) with mild septal hypertrophy.Methods:Forty-five HOCM patients with mild septal hypertrophy (the maximal left ventricular wall thickness is 15-19 mm) who were treated with PIMSRA between November 2016 to February 2021 in the Hypertrophic Cardiomyopathy Center of Xijing Hospital of Air Force Military Medical University were enrolled, and their clinical datas were collected and analyzed. The clinical symptoms and NYHA functional class before operation, 6 months and 1 year after operation were collected. Interventricular septum thickness, left ventricular outflow tract pressure gradient, left ventricular outflow tract diameter, mitral regurgitation, left ventricular systolic and diastolic function were evaluated by transthoracic echocardiography before operation, 6 months and 1 year after operation, intraoperative complications were monitored and recorded. Postoperative arrhythmias were monitored by routine 12 lead ECG and 24-hour ambulatory ECG.Results:All patients successfully completed PIMSRA procedure.No clinical adverse events such as death, bleeding and stroke occurred during and around the operation.No left bundle branch block, complete atrioventricular block and malignant arrhythmia occurred after the operation. All patients did not need permanent pacemaker implantation.NYHA functional class and clinical symptoms of patients were significantly improved after 6 months compared with values before operation (all P<0.001, respectively), it remained stable for 1 year after operation; Anterior interventricular septum, posterior interventricular septum, maximal left ventricular wall thickness all significantly decreased (all P<0.001, respectively), left ventricular outflow tract diameter widened ( P<0.001), continuous improvement 1 year after operation; left ventricular outflow tract gradient and provoked left ventricular outflow tract gradient all significantly decreased, mitral regurgitation decreased and SAM classification reduced after 6 months compared with values before operation (all P<0.001, respectively); left ventricular end-diastolic diameter widened and left atrial diameter decreased (all P<0.001, respectively), it remained stable for 1 year after operation. Left atrial volume index decreased ( P<0.001), with continuous improvement 1 year after operation; The ratio of early diastolic mitral valve velocity to early diastolic mitral annulus velocity (E/e′) decreased ( P=0.001), it remained stable for 1 year after operation. There were no significant differences in left ventricular end diastolic volume, left ventricular end systolic volume and left ventricular ejection fraction among the three groups (all P>0.05). Conclusions:PIMSRA is effective in the treatment of obstructive hypertrophic cardiomyopathy with mild ventricular septal hypertrophy.

Research progress on the effect of mitochondrial and endoplasmic reticulum stress caused by hypoxia during pregnancy on preeclampsia and intrauterine growth restriction / 生理学报

Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.

Outcome of a Simple Novel Technique to Reduce Soft Tissue Complications in Open Tendoachilles Injury: A Series of 20 Patients

@#Introduction: Open tendoachilles injuries are rare and associated with significant soft tissues complications. The objective of the present study was to assess the clinical outcome and safety of a simple and minimally invasive technique, with a goal to assess if it may help minimise flap and wound related complications in open tendoachilles injuries. Materials and methods: This prospective study of four years duration included 20 patients with open tendoachilles injuries managed with a simple minimally invasive tunnel technique. The primary outcome variable was occurrence of a major soft tissue complication. The secondary outcome variables included functional outcome measured using AOFAS Ankle hind foot score, re-rupture of tendoachilles and need for revision surgery. Results: None of the patients in the present series developed a serious soft tissue complication. Based upon the AOFAS hind foot scoring system, good to excellent outcome was achieved in 19 (95%) patients. All the patients were able to perform tip toe walking at six months post-surgery. None of the patients had a re-rupture of the tendoachilles and no patient needed a revision surgery. The complications encountered include thickening of the tendon at the repair site (15%), superficial wound infection (5%), stitch granuloma (5%) and hypertrophic scar (5%). Conclusion: This technique seems to be promising in reducing the soft tissue complications associated with the surgical management of open tendoachilles injuries. Most patients had a good final clinical outcome. The technique is safe, simple and reproducible. However, further randomised control studies with a larger sample size assessing the technique are recommended.

Benefits and Harms of COVID-19 Vaccines in Cardiovascular Disease:A Comprehensive Review

Patients with a history of cardiovascular disease (CVD) who contract coronavirus disease 2019 (COVID-19) tend to have a worse prognosis and more severe cardiovascular side effects.COVID-19 vaccines, which are intended to prevent COVID-19, may also potentially reduce the severity and complications (including cardiovascular sequelae) of COVID-19, especially in patients with a history of CVD. However, there have also been reports of cardiovascular side effects from COVID-19 vaccines of various brands and types. The purpose of this study is to review the benefits and harms of COVID-19 vaccines in relation to CVD. In this thorough review of the most current evidence on the benefits and harms of COVID-19 vaccines, we present information about the characteristics of cardiovascular complications. Most of the evidence focuses on myocarditis or pericarditis, which are most strongly associated with mRNA vaccines and predominantly occur in young males within days of receiving the second dose. Meanwhile, post-vaccination myocardial infarction is more common in older males, and the first dose of adenoviral vector vaccines appears to play a greater role in this complication. This information may guide us in formulating alternative options and implementing targeted surveillance. Gaining more knowledge about the potential benefits and harms of COVID-19 vaccines will improve our ability to make informed decisions and judgments about the balance of these factors.

Advancing Cardio-Oncology in Asia

Cardio-oncology is an emerging multi-disciplinary field, which aims to reduce morbidity and mortality of cancer patients by preventing and managing cancer treatment-related cardiovascular toxicities. With the exponential growth in cancer and cardiovascular diseases in Asia, there is an emerging need for cardio-oncology awareness among physicians and country-specific cardio-oncology initiatives. In this state-of-the-art review, we sought to describe the burden of cancer and cardiovascular disease in Asia, a region with rich cultural and socio-economic diversity. From describing the uniqueness and challenges (such as socio-economic disparity, ethnical and racial diversity, and limited training opportunities) in establishing cardio-oncology in Asia, and outlining ways to overcome any barriers, this article aims to help advance the field of cardio-oncology in Asia.

Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non–Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. @*Materials and Methods@#Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. @*Results@#At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. @*Conclusion@#Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier in vitro and in vivo / 药学学报

A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.

A Relação entre o Estado Dipping Noturno, Aumento da Pressão Arterial Matinal e Internações Hospitalares em Pacientes com a Insuficiência Cardíaca Sistólica / The Relationship between Nocturnal Dipping Status, Morning Blood Pressure Surge, and Hospital Admissions in Patients with Systolic Heart Failure

Resumo Fundamento A hipertensão é um fator de risco conhecido para o desenvolvimento de insuficiência cardíaca. No entanto, há dados limitados para investigar a associação entre pico de pressão arterial matinal (PPAM), estado dipper, parâmetros ecocardiográficos e internações hospitalares em pacientes com insuficiência cardíaca sistólica. Objetivos Avaliar a relação entre aumento matinal da pressão arterial, padrão de pressão arterial não-dipper, parâmetros ecocardiográficos e internações hospitalares em pacientes com insuficiência cardíaca sistólica. Métodos Analisamos retrospectivamente os dados de 206 pacientes consecutivos com hipertensão e fração de ejeção do ventrículo esquerdo abaixo de 40%. Dividimos os pacientes em dois grupos de acordo com os resultados da monitoramento ambulatorial da pressão arterial (MAPA) de 24 horas: dippers (n=110) e não-dippers (n=96). O aumento matinal da pressão arterial foi calculado. Achados ecocardiográficos e internações hospitalares durante o acompanhamento foram anotados. A significância estatística foi definida como p < 0,05. Resultados O grupo de estudo foi composto por 206 pacientes com predominância do sexo masculino e idade média de 63,5 ± 16,1 anos. O grupo não-dipper teve significativamente mais internações hospitalares em comparação com os dippers. Houve correlação positiva entre PPAM e índice de volume do átrio esquerdo (r=0,331, p=0,001), relação entre velocidade de influxo mitral precoce e velocidade de propagação do fluxo (r= 0,326, p=0,001) e relação entre influxo mitral precoce velocidade e velocidade diastólica inicial do anel mitral (E/Em) (r= 0,314, p=0,001). Verificou-se que a PA não-dipper, PPAM e o padrão E/Em estão independentemente associados ao aumento das admissões hospitalares. Conclusão O PPAM está associado à disfunção diastólica e pode ser um preditor sensível de internação hospitalar em pacientes com insuficiência cardíaca sistólica.

Abstract Background Hypertension is a known risk factor for developing heart failure. However, there is limited data to investigate the association between morning blood pressure surge (MBPS), dipping status, echocardiographic parameters, and hospital admissions in patients with systolic heart failure. Objectives To evaluate the relationship between morning blood pressure surge, non-dipper blood pressure pattern, echocardiographic parameters, and hospital admissions in patients with systolic heart failure. Methods We retrospectively analyzed data from 206 consecutive patients with hypertension and a left ventricular ejection fraction below 40%. We divided the patients into two groups according to 24-hour ambulatory blood pressure monitoring (ABPM) results: dippers (n=110) and non-dippers (n=96). Morning blood pressure surge was calculated. Echocardiographic findings and hospital admissions during follow-up were noted. Statistical significance was defined as p < 0.05. Results The study group comprised 206 patients with a male predominance and mean age of 63.5 ± 16.1 years. The non-dipper group had significantly more hospital admissions compared to dippers. There was a positive correlation between MBPS and left atrial volume index (r=0.331, p=0.001), the ratio between early mitral inflow velocity and flow propagation velocity (r= 0.326, p=0.001), and the ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/Em) (r= 0.314, p=0.001). Non-dipper BP, MBPS, and E/Em pattern were found to be independently associated with increased hospital admissions. Conclusion MBPS is associated with diastolic dysfunction and may be a sensitive predictor of hospital admission in patients with systolic heart failure.

The effect of Pilates on pain during pregnancy and labor: a systematic review and meta-analysis

SUMMARY OBJECTIVE: This systematic review and meta-analysis study was conducted to reveal the effect of Pilates on pain during pregnancy and labor. METHODS: The PubMed, ScienceDirect, MEDLINE, Ovid, EBSCO, CINAHL Plus, Cochrane Library databases, and Google Scholar databases were used to access the articles published in international journals, and the Dergipark, Turkish Clinics, and ULAKBİM databases were scanned to access the articles published in national journals between October 30 and November 30, 2022. The data were analyzed using Review Manager 5.4. RESULTS: This study included four articles. According to the meta-analysis results, it was elucidated that Pilates exercise during pregnancy was not statistically effective in reducing pain during pregnancy (Z=0.61, p=0.54), but it was effective in reducing pain intensity during labor (Z=11.20, p<0.00001). CONCLUSION: This study concluded that Pilates exercise was not effective in reducing pain during pregnancy but was effective in reducing labor pain. There is a need for more research on the subject. PROSPERO Registration no: CRD42023387512

Frequency And Factors Associated With Adverse Reactions After Administration of Inactivated COVID-19 Vaccine Among Health Workers

ABSTRACT Background: The 2019 coronavirus (COVID-19) has precipitated a significant public health crisis. Our study aimed to evaluate the prevalence and risk factors associated with adverse reactions to the inactivated CoronaVac vaccine. Methods: The study involved voluntary health workers who received CoronaVac vaccine. We documented the sociodemographic information of 2,019 participants who volunteered for our study. Of these, 1,964 and 1,702 participants were interviewed by phone 1 month after the first and second dose, respectively, during which they were queried about any adverse reactions. Results: Within the first week after the first dose, adverse reactions were observed in 856 (43.3%) participants, with 133 (6.7%) experiencing them during the second week, and 96 (4.9%) people at the end of the first month. For the second dose, 276 individuals (16.2%) reported adverse reactions. The prevalence of both local and systemic adverse events ranged from 9.5-11.2% overall. Fatigue was the most common adverse reaction overall, while pain at the injection site was the most frequent local adverse reaction. Conclusions: The evaluation of both systemic and local side effects revealed no significant adverse reactions to the inactivated CoronaVac vaccine (Sinovac Life Sciences, Beijing, China). Our study found that the incidence of systemic and local adverse responses to the CoronaVac vaccination was lower than the rates reported in studies involving the recombinant adenovirus type-5, BNT162b1, and ChAdOx1nCoV-19 COVID-19 vaccines, all of which underwent the World Health Organization LULUC/PQ evaluation process.

Should we reconsider high-risk features in thyroid ultrasonography?

SUMMARY OBJECTIVE: Round shape is generally considered to reduce the risk of malignancy according to recent guidelines. On the contrary, according to some reports, spherically shaped thyroid nodules are associated with a higher risk of malignancy. Thus, we aimed to evaluate the malignancy risk of solid round isoechoic nodules detected at thyroid ultrasonography and compare it with that of solid ovoid isoechoic nodules. METHODS: Between 2017 and 2022, solitary solid round isoechoic nodules with diameters ³10 and £25 mm at thyroid ultrasonography were retrospectively selected and enrolled in the study. Age, size, nodule volume, serum thyrotropin levels, thyroid antibody levels, and cytopathological and histopathological results were recorded. RESULTS: A total of 457 solitary solid isoechoechoic nodules from 457 patients (262 females and 195 males; median age, 59 [31-70] years) were selected, of which 203 were solid round isoechoic nodules, and 254 were solid ovoid isoechoic nodules. A total of 54 surgical operations were performed on 457 nodules, and 31 of them resulted in malignancy. From the 31 malignant results, 25 originated from solid round isoechoic nodules and the remaining 6 originated from solid ovoid isoechoic nodules (p<0.025). CONCLUSION: We found that round nodules have higher malignancy rates than ovoid nodules. We think that ultrasonographic risk stratification systems used to target the most suitable nodules for the necessary biopsies can be dynamically updated, and sphericity can be added as a parameter in patient-based decision-making.