Clinics最新文献

Background: To comprehensively analyze the clinical significance of Immune Checkpoint-Related Genes (ICRGs) in Pancreatic Adenocarcinoma (PAAD).

Method: PAAD tissues and normal pancreatic tissues were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, and 283 ICRGs were integrated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome datasets. Unsupervised clustering was used to obtain potential ICRGs-based PAAD subtypes. Wilcoxon test was performed to screen Differentially Expressed ICRGs (DEICRGs), while cox regression analyses were utilized to identify prognosis-related ICRGs and clinicopathological factors, and construct the corresponding models. The Tumor Immune Microenvironment (TIME) was evaluated. Moreover, the authors performed enrichment analysis, Gene Set Enrichment Analysis (GSEA), and transcription factor regulatory networks to realize underlying mechanisms.

Results: Three ICRGs-based PAAD subtypes were identified, and they were associated with three ESTIMATE scores, a Tumor Microenvironment (TMB) score, 14 therapeutic immune checkpoints, and infiltration levels of seven immune cells. On top of that, the authors constructed two signatures based on DEICRGs to predict the Overall Survival (OS) (Area Under the ROC Curve [AUC: 0.741∼0.778]) and Progression-Free Survival (PFS) (AUC: 0.746∼0.831) of patients. Two nomograms were established by combining clinical variables and signatures. In addition, the authors found higher infiltration of naïve B cells and CD8⁺ T-cells in low-risk PAAD patients, and higher infiltration of suppressive immune cells and cancer-related signaling pathways in high-risk PAAD patients.

Conclusion: The present study suggested that ICRGs were associated with TIME formation and prognosis of PAAD patients, which may serve as novel clinical biomarkers and therapeutic targets.

Objective: To explore the risk factors of Atrial Fibrillation (AF) with Cognitive Impairment (CI) and to analyze the relationship between cardiac function parameters and the degree of CI in patients.

Methods: 120 AF patients were selected, and Montreal Cognitive Assessment (MoCA) was used to distinguish between AF patients with and without CI. Univariate analysis and multivariate Logistic regression analysis were used to evaluate the impact of sociodemographic data, disease-related data, and clinical data on risk factors for AF with CI. Pearson's method was used to analyze the correlation between cardiac function parameters and cognitive function scores in AF patients.

Results: There were 89 patients with CI and 31 patients without CI, and the MoCA scores of patients with CI were lower than those in patients without CI. Age, occupational status, educational level, combined smoking history, drinking history, and heart failure, as well as systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, C-reactive protein, free thyroxine, free triiodothyronine, and D-dimer were risk factors for the patient with CI. Left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left atrial maximum volume in patients with CI were higher than those in patients without CI, and left ventricular ejection fraction and peak early diastolic velocity/peak late-diastolic mitral velocity ratio were lower.

Conclusion: The cardiac function parameters of patients are closely related to attention, orientation, memory, visuospatial, and executive ability. Cardiac function parameters were closely related to cognitive functions.

Objective: To investigate the effect of a single oral dose of 200,000 IU of vitamin D₃ on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19.

Methods: This is a post-hoc, exploratory analysis from a double-blind, placebo-controlled, randomized clinical trial performed in two centers in Sao Paulo, Brazil. Hospitalized patients with COVID-19 were randomly assigned to receive either vitamin D₃ (n = 97) or placebo (n = 97). In this post-hoc analysis, the endpoints were titers and frequency of anti-β2-Glycoprotein-I (aβ2-GP) and Anticardiolipin (aCL) antibodies [Immunoglobulin G, M and A (IgG, IgM and IgA)].

Results: Overall mean (SD) age was 55.3 (13.9) years, Body Mass Index (BMI) was 32.2 (7.1 kg/m²), and 106 participants (54.6 %) were male. There was a significant group by time interaction (p = 0.046) for frequency of aCL IgG, with increased values from baseline to discharge in the placebo group [n (%), from 13 (13.4) to 25 (25.8)] compared to the vitamin D₃ [from 25 (25.8) to 29 (29.9)]. However, the frequency of aCL IgG did not change between the groups on discharge. No significant differences between vitamin D3 and placebo groups were found for any other autoantibodies.

Conclusion: These findings do not support the use of a single oral dose of 200,000 IU of vitamin D₃ to modulate autoantibodies in hospitalized patients with moderate to severe COVID-19.

Background: The prevalence of COVID-19 as the primary diagnosis among hospitalized patients with myocardial injury has increased during the pandemic and targeting elevated oxidant stress and inflammatory biomarkers may offer a potential role for novel therapies to improve outcomes.

Methods: At a single VA Medical Center from January 1 through December 31, 2021, troponin assays from patients being evaluated in the Emergency Room for consideration of admission were analyzed and peak levels from each patient were considered abnormal if exceeding the Upper Reference Limit (URL). Among admitted patients with an elevated troponin level, ICD-10 diagnoses were categorized, biomarker elevations were recorded, and independent predictors of death in patients with COVID-19 were determined at a median of 6-months following admission.

Results: Of 998 patients, 399 (40 %) had a negative troponin and were not included in the analysis. Additional patients with an elevated troponin were also excluded, either because they were not admitted (n = 68) or had a final diagnosis of Type 1 MI (n = 117). Of the remaining 414 patients with an elevated peak troponin, COVID-19 was the primary diagnosis in 43 patients (10 %) and was the 4^th most common diagnosis of patients admitted with myocardial injury behind congestive heart failure, sepsis, and COPD or pneumonia. At a median of 6-months following admission, 18 (42 %) of the COVID-19 patients had died and independent predictors of death (Odd Ratio: Confidence Intervals) were age (1.18: 1.06‒1.37), Troponin level (Log 10 transformed) (16.54: 2.30‒266.65) and C-Reactive Protein (CRP) (1.30: 1.10‒1.65).

Conclusions: Newly diagnosed COVID-19 during the pandemic was a common cause of elevated troponin in hospitalized patients without a Type 1 MI. Age, peak troponin level and peak CRP level were independent predictors of poor outcomes and suggest a need to target these cardiac biomarkers, potentially with novel antioxidant or anti-inflammatory therapies.

Introduction: Mitotane (o,p'-DDD) is the drug of choice for Adrenocortical Carcinomas (ACC) and its measurement in plasma is essential to control drug administration.

Objective: To develop and validate a simple, reliable and straightforward method for mitotane determination in plasma samples.

Method: Drug-free plasma samples were collected in potassium-ethylenediamine tetraacetate (K-EDTA) tubes and spiked with 1.0, 2.5, 10.0, 25.0 and 50.0 µg/mL of mitotane (DDD). The p,p'-DDD was used as an Internal Standard (IS) and was added at 25.0 µg/mL concentration to all samples, standards and controls. Samples were submitted to protein precipitation with acetonitrile and then centrifuged. 50 uL of the supernatant was injected into an HPLC system coupled to a Diode Array Detector (DAD). DDD and IS were detected at 230 nm in a 12 min isocratic mode with a solvent mixture of 60 % acetonitrile and 40 % formic acid in water with 0.1 % pump mixed, at 0.6 mL/min flow rate, in a reversed-phase (C18) chromatographic column kept at 28°C. The sensitivity, selectivity, precision, presence of carry-over, recovery and matrix-effect, linearity, and method accuracy were evaluated.

Results: The present study's method resulted in a symmetrical peak shape and good baseline resolution for DDD (mitotane) and 4,4'-DDD (internal standard) with retention times of 6.0 min, 6.4 mim, respectively, with resolutions higher than 1.0. Endogenous plasma compounds did not interfere with the evaluated peaks when blank plasma and spiked plasma with standards were compared. Linearity was assessed over the range of 1.00-50.00 µg/mL for mitotane (R2 > 0.9987 and a 97.80 %‒105.50 % of extraction efficiency). Analytical sensitivity was 0.98 µg/mL. Functional sensitivity (LOQ) was 1.00 µg/L, intra-assay and inter-assay coefficient of variations were less than 9.98 %, and carry-over was not observed for this method. Recovery ranged from 98.00 % to 117.00 %, linearity ranged from 95.00 % to 119.00 %, and high accuracy of 89.40 % to 105.90 % with no matrix effects or interference was observed for mitotane measurements. Patients' sample results were compared with previous measurements by the GC-MS method with a high correlation (r = 0.88 and bias = -10.20 %).

Conclusion: DDD determination in plasma samples by the developed and validated method is simple, robust, efficient, and sensitive for therapeutic drug monitoring and dose management to achieve a therapeutic index of mitotane in patients with adrenocortical cancer.

Objective: To identify internal structure validity evidence of a dysphagia screening questionnaire for caregivers of older adults with Alzheimer's disease dementia and/or vascular dementia.

Methods: The 24-question Dysphagia Screening in Older Adults with Dementia - Caregiver Questionnaire (RaDID-QC) was administered by interviewing 170 caregivers of older people with dementia, selected by convenience at the Outpatient Reference Center for Older People. Exploratory Factor Analysis (EFA) was used to assess the internal structure validity of the questionnaire, and Cronbach's alpha was used to analyze reliability. Questions with factor loadings lower than 0.45 in magnitude were removed from the final questionnaire. Multivariate multiple linear regression was used to assess the percentage of variance explained by the remaining questions.

Results: Kayser-Meyer-Olkin (KMO) and Bartlett's tests suggested that the questionnaire was adequate for EFA. Principal Component Analysis (PCA) suggested that 12 components captured at least 75 % of the total variance. The corresponding 12-factor EFA model showed a statistically significant fit, and 15 out of the 24 questions had factor loadings greater than 0.45. Cronbach's alpha was 0.74 for the 15 questions, which explained 71 % of the total variance in the complete dataset. The questionnaire has adequate internal structure validity and good reliability. Based on EFA, RaDID-QC decreased from 24 to 15 questions. Other internal validity and reliability parameters will be obtained by administering the questionnaire to larger target populations.

Conclusion: The RaDID-QC applied to caregivers of older adults with dementia due to Alzheimer's disease and/or vascular dementia produced valid and reliable responses to screen dysphagia signs and symptoms.

Prognostic factors for local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision.

Background: The standard curative treatment for locally advanced rectal cancer of the middle and lower thirds is long-course chemoradiotherapy followed by total mesorectal excision.

Purpose: To evaluate the prognostic factors associated with local recurrence in patients with rectal cancer submitted to neoadjuvant chemoradiotherapy and total mesorectal excision.

Methods: Retrospective study including patients with rectal cancer T3-4N0M0 or T (any)N + M0 located within 10 cm from the anal border, or patients with T2N0M0 located within 5 cm, treated by long course chemoradiotherapy followed by total mesorectal excision with curative intent. Clinical, demographic, radiologic, surgical, and anatomopathological data were collected. Local recurrence was estimated using the Kaplan-Meier function, and risk was estimated according to each characteristic using univariate and multivariate analyses.

Results: 270 patients were included, 57.8% male and mean age 61.7 (30‒88) years. At initial staging, 6.7% of patients were stage I, 21.5% stage II, and 71.8% stage III. Open surgery was performed in 65.2%, with sphincter preservation in 78.1%. Mortality within 30 postoperative days was 0.7%. After 49.4 (0.5‒86.1) months of median follow-up, overall and local recurrences were 26.3% and 5.9%. On multivariate analyses, local recurrence was associated with involvement of the mesorectal fascia on restaging MRI (HR = 9.11, p = 0.001) and with pathologic involvement of radial surgical margin (HR = 8.19, p < 0.001).

Conclusion: Local recurrence of rectal cancer treated with long-course chemoradiation and total mesorectal excision is low and is associated with pathologic involvement of the radial surgical margin and can be predicted on restaging MRI.

Objective: The aim of the study was to assess the impact of the Gamma coronavirus disease 2019 (COVID-19) variant on pregnant and postpartum women with Cardiovascular Disease (CVD).

Methods: The Influenza Epidemiological Surveillance System database (SIVEP-Gripe), a compulsory notification system for cases of Severe Acute Respiratory Syndrome (SARS), was investigated for notified cases of pregnant and postpartum women with reported CVD and SARS due to COVID-19 between February 16, 2020 and May 1, 2021 (when vaccination began), was investigated. In this retrospective cohort, two groups were formed based on symptom onset date, according to the predominance of the variants: original (group 2020) and Gamma (group 2021). Cases with missing information on the presence or absence of CVD were excluded. The comparative analysis was controlled for confounding variables.

Results: Among 703 COVID-19 cases notified with CVD (406 patients in 2020 and 297 patients in 2021), compared to 2020, cases in 2021 had more respiratory symptoms (90.6 % vs. 80.1 %, p < 0.001), greater ventilatory support need (75.3 % vs. 53.9 %, p < 0.001), more ICU admission (46.6 % vs. 34.3 %, p = 0.002), longer duration (20.59 ± 14.47 vs. 16.52 ± 12.98 days, p < 0.001), higher mortality (25.6 % vs. 15.5 %, p < 0.001), with more than two-times mortality likelihood in the third trimester (adjusted OR = 2.41, 95 % CI 1.50-3.88, p < 0.001) or puerperium periods (adjusted_OR = 2.15, 95 % CI 1.34-3.44, p = 0.001).

Conclusions: In Brazil, pregnant and postpartum women with CVDs in the Gamma variant phase have higher morbidity and mortality than those affected by the original variant of Coronavirus-19.

Objective: This study aims to evaluate the role of TUSG in the postoperative period and the detection of early complications after surgical treatment, pulmonary resection, or decortication for infectious and inflammatory thoracic diseases, comparing with the standard method (Chest Radiography ‒ CXR).

Methods: Prospective non-randomized self-controlled study. Twenty-one patients over 16 years of age have undergone surgical treatment of inflammatory and infectious lung diseases. These patients were followed up with CXR and TUSG (performed on the 1^st and 3^rd postoperative days and/or after the chest tube removal).

Results: Both exams demonstrated similar results regarding their ability to safely predict the adequate moment for chest drain removal. TUSG allowed chest drain removal in 30% of cases and CXR in 34%. Statistical analysis demonstrates that both exams have similar capabilities in detecting postoperative changes in the pleural space. However, the authors report that TUSG is statistically more accurate in detecting subcutaneous emphysema than CXR (p = 0.037, Kappa [κ = 0.3068]). The analysis of other parameters showed no statistical difference.

Conclusion: The authors conclude that TUSG in trained hands is equivalent to CXR in searching for postoperative complications regarding the surgical treatment of infectious and inflammatory thoracic diseases and can be used as a complement, and not a substitute, to CXR, when CCT is not feasible, or a more urgent diagnosis is needed.