Frank's Sign and Cardiovascular Risk: An Observational Descriptive Study.

PURPOSE: This study was undertaken to analyze the relationship between the diagonal earlobe crease and the main indices of cardiovascular risk, considering the crease's anatomical variations. METHODS: The study group consisted of 1050 adults residing in Spain. Participants underwent the following determinations: age, sex, body mass index, smoking habit, blood pressure, glycemia, glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and cardiovascular events. Cardiovascular risk was calculated applying the Framingham-Anderson equation, the Systematic Coronary Risk Evaluation equation, and the Atherosclerotic Cardiovascular Disease Risk Score calculator. Both earlobes were examined, recording diagonal earlobe crease presence, length and depth, and presence of accessory creases. Results were analyzed by using chi-square test, Student's t test, analysis of variance, and Mann-Whitney or Kruskal-Wallis tests. To extract the functions of cardiovascular risk, a script in R was created (https://cran.r-project.org/). RESULTS: The estimated cardiovascular mortality risk was significantly higher in individuals who presented diagonal earlobe crease (P < .001). The number of individuals with moderate, high, or very high cardiovascular risk increased significantly as the presence of the crease increased (23.8% had no crease, 35.6% had unilateral creases, and 58% had bilateral creases; P < .001). The mean cardiovascular risk estimated was significantly higher for individuals with longest and deepest diagonal earlobe crease (P < .001 and P < .001, respectively), and with accessory creases (P < .001). CONCLUSIONS: The diagonal earlobe crease is independently associated with higher cardiovascular risk scores, especially when the crease is complete, bilateral, deep, and has accessory creases.

Atrial fibrillation as a new prognosis factor in chronic patients after hospitalization: the CHRONIBERIA index.

A collaborative project in different areas of Spain and Portugal was designed to find out the variables that influence the mortality after discharge and develop a prognostic model adapted to the current healthcare needs of chronic patients in an internal medicine ward. Inclusion criteria were being admitted to an Internal Medicine department and at least one chronic disease. Patients' physical dependence was measured through Barthel index (BI). Pfeiffer test (PT) was used to establish cognitive status. We conducted logistic regression and Cox proportional hazard models to analyze the influence of those variables on one-year mortality. We also developed an external validation once decided the variables included in the index. We enrolled 1406 patients. Mean age was 79.5 (SD = 11.5) and females were 56.5%. After the follow-up period, 514 patients (36.6%) died. Five variables were identified as significantly associated with 1 year mortality: age, being male, lower BI punctuation, neoplasia and atrial fibrillation. A model with such variables was created to estimate one-year mortality risk, leading to the CHRONIBERIA. A ROC curve was made to determine the reliability of this index when applied to the global sample. An AUC of 0.72 (0.7-0.75) was obtained. The external validation of the index was successful and showed an AUC of 0.73 (0.67-0.79). Atrial fibrillation along with an advanced age, being male, low BI score, or an active neoplasia in chronic patients could be critical to identify high risk multiple chronic conditions patients. Together, these variables constitute the new CHRONIBERIA index.

PD-L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: A retrospective study.

Anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid carcinoma (PDTC) have limited treatment options, and immune profiling may help select patients for immunotherapy. The prevalence and relevance of programmed death-1 ligand (PD-L1) expression and the presence of immune cells in ATC and PDTC has not yet been well established. The present study investigated PD-L1 expression (clone 22C3) and cells in the tumor microenvironment (TME), including tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs) and dendritic cells, in whole tissue sections of 15 cases of ATC and 13 cases of PDTC. Immunohistochemical PD-L1 expression using a tumor proportion score (TPS) with a 1% cut-off was detected in 9/15 (60%) of ATC cases and 1/13 (7.7%) of PDTC cases (P=0.006). PD-L1 expression in TILs was limited to the ATC group (73.3 vs. 0% in ATC and PDTC, respectively). In the ATC group, the TPS for tumor positive PD-L1 expression revealed a non-significant trend towards worse survival, but no difference was observed when investigating PD-L1 expression in TILs and TAMs. In addition to increased PD-L1 expression, all ATC cases exhibited significantly increased CD3+ and CD8+ T cells, CD68+ and CD163+ macrophages, and S100+ dendritic cells compared with the PDTC cases. Loss of mutL homolog 1 and PMS1 homolog 2 expression was observed in one ATC case with the highest PD-L1 expression, as well as in the only PDTC case positive for PD-L1. Notably, the latter was the only PDTC case exhibiting positivity for p53 and a cellular microenvironment similar to ATC. The current results indicated that PD-L1 expression was frequent in ATC, but rare in PDTC. In addition to PD-L1, the present study suggested that microsatellite instability may serve a role in both the TME and the identification of immunotherapy candidates among patients with PDTC.

The SCQ-SCORE: initial validation of a new scoring system for elective stone surgery prioritization in the COVID-19 era.

INTRODUCTION: Endourology waiting lists have increased during the COVID-19 pandemic and prioritization strategies are needed. Some tiered classifications have been put forward aimed at prioritizing patients by using criteria related with clinical severity or social impact of stone disease, yet no quantitative system has been published to date. The objective of this study is to present a new quantitative scoring system for elective stone surgery prioritization and show its intra- and inter-rater reliability. MATERIAL AND METHODS: A scoring system coined 'SCQ-score' was set up, which consists of 9 variables: infection (ranges 0-3), obstruction (0-3), indwelling time (0-3), admissions (0-3), symptoms (0-2), ureteral location (0-1), solitary or suboptimal kidney (0-1), chronic kidney disease (0-1) and presence of percutaneous nephrostomy (0-1).The intra- and inter-rater reliability of the SCQ-score was prospectively validated in 60 consecutive patients on the waiting list, by calculating the intraclass correlation coefficient (ICC). RESULTS: The SCQ-score demonstrated having an excellent interobserver agreement (ICC >0.75) for the final score and its different domains. After 4 weeks, a second analysis was carried out to measure its intra-rater reliability, which was also excellent. On average, 134.9 ±50 seconds were required to complete the SCQ-score. CONCLUSIONS: The SCQ-score is a new quantitative system to help prioritize elective stone surgeries, which has been shown to be user-friendly and to have an excellent intra- and inter-rater reliability. Initially developed to help during the COVID-19 pandemic, its utility will probably remain of interest in the post-COVID-19 era to ensure a fairer access to stone surgery.

Development and validation of a prognostic model based on comorbidities to predict COVID-19 severity: a population-based study.

BACKGROUND: The prognosis of patients with COVID-19 infection is uncertain. We derived and validated a new risk model for predicting progression to disease severity, hospitalization, admission to intensive care unit (ICU) and mortality in patients with COVID-19 infection (Gal-COVID-19 scores). METHODS: This is a retrospective cohort study of patients with COVID-19 infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) in Galicia, Spain. Data were extracted from electronic health records of patients, including age, sex and comorbidities according to International Classification of Primary Care codes (ICPC-2). Logistic regression models were used to estimate the probability of disease severity. Calibration and discrimination were evaluated to assess model performance. RESULTS: The incidence of infection was 0.39% (10 454 patients). A total of 2492 patients (23.8%) required hospitalization, 284 (2.7%) were admitted to the ICU and 544 (5.2%) died. The variables included in the models to predict severity included age, gender and chronic comorbidities such as cardiovascular disease, diabetes, obesity, hypertension, chronic obstructive pulmonary disease, asthma, liver disease, chronic kidney disease and haematological cancer. The models demonstrated a fair-good fit for predicting hospitalization {AUC [area under the receiver operating characteristics (ROC) curve] 0.77 [95% confidence interval (CI) 0.76, 0.78]}, admission to ICU [AUC 0.83 (95%CI 0.81, 0.85)] and death [AUC 0.89 (95%CI 0.88, 0.90)]. CONCLUSIONS: The Gal-COVID-19 scores provide risk estimates for predicting severity in COVID-19 patients. The ability to predict disease severity may help clinicians prioritize high-risk patients and facilitate the decision making of health authorities.

Thyroid Papillary Microtumor: Validation of the (Updated) Porto Proposal Assessing Sex Hormone Receptor Expression and Mutational BRAF Gene Status.

Given the high incidence and excellent prognosis of many papillary thyroid microcarcinomas, the Porto proposal uses the designation papillary microtumor (PMT) for papillary microcarcinomas (PMCs) without risk factors to minimize overtreatment and patients' stress. To validate Porto proposal criteria, we examined a series of 190 PMC series, also studying sex hormone receptors and BRAF mutation. Our updated Porto proposal (uPp) reclassifies as PMT incidental PMCs found at thyroidectomy lacking the following criteria: (a) detected under the age of 19 years; (b) with multiple tumors measuring >1 cm adding up all diameters; and (c) with aggressive morphologic features (extrathyroidal extension, angioinvasion, tall, and/or hobnail cells). PMCs not fulfilling uPp criteria were considered "true" PMCs. A total of 102 PMCs were subclassified as PMT, 88 as PMC, with no age or sex differences between subgroups. Total thyroidectomy and iodine-131 therapy were significantly more common in PMC. After a median follow-up of 9.6 years, lymph node metastases, distant metastases, and mortality were only found in the PMC subgroup. No subgroup differences were found in calcifications or desmoplasia. Expression of estrogen receptor-α and estrogen receptor-ß, progesterone receptor, and androgen receptor was higher in PMC than in nontumorous thyroid tissue. BRAF mutations were detected in 44.7% of PMC, with no differences between subgroups. In surgical specimens, the uPp is a safe pathology tool to identify those PMC with extremely low malignant potential. This terminology could reduce psychological stress associated with cancer diagnosis, avoid overtreatment, and be incorporated into daily pathologic practice.

CRONIGAL: Prognostic index for chronic patients after hospital admission.

OBJECTIVE: We have followed patients admitted to a Polypathology and Advanced Age Unit for two years in order to identify the variables that best define the mortality prognosis at medium-term (1-2years) for chronic and polypathological patients requiring admission at an Internal Medicine Department. METHODS: This is an observational, prospective study in clinical practice. Polypathological, chronic or multimorbidity patients were included. The classification of the Spanish Ministry for Health was used in order to classify patients as chronic or polypathological. The Charlson Index and Barthel Index were estimated and the Pfeiffer test was administered. The Spanish PROFUND Index was also used. Logistic regression models and Cox proportional hazard model were built in order to study the influence of prognostic factors on survival. RESULTS: A total of 567 patients were included: 333 met polypathological (PPP) criteria and 234 chronic criteria (CC). Mean age was 84.8+7.3years. A total of 469 were followed up, most patients belonged to category E (282), 174 to category A and 118 to category C. The prognosis at one year of our patients can be estimated with 7 variables: age, neoplasia, delirium, Barthel, Pfeiffer, presence of atrial fibrillation, and creatinine. The area under the curve is 0.74. CONCLUSION: The variables dementia, neoplasia, delirium at admission, Barthel Index under 60, or deceased spouse have mortality prognosis value at one or two years. An index with 7 variables applicable to chronic and polypathological patients after admission may serve as tool to better manage complex chronic patients and follow them up.

Electronic clinical records in primary care for estimating disease burden and management. An example of COPD.

Chronic obstructive pulmonary disease (COPD) is a significant health problem in developed countries. We aimed to estimate the prevalence of COPD in a single Spanish healthcare area. We also aimed to assess if there are any differences in prevalence and spirometry use among primary care services by utilizing already registered information. We designed a cross-sectional study to determine the prevalence of COPD and the performance of spirometries in each primary care service. A total of 8,444 patients were diagnosed with COPD, with a prevalence of 2.6% for individuals older than 39 years. The prevalence increased with age and was much higher in men. Significant heterogeneity was found in the prevalence of COPD and spirometry use among primary care services. COPD was underdiagnosed and there was wide variability in spirometry use in our area. Greater efforts are needed to diagnose COPD in order to improve its clinical outcomes and to refine registries so that they can be used as reliable sources of information.

A clinical model for predicting lymph node metastasis in submucosal invasive (T1) colorectal cancer.

BACKGROUND: No single histopathological feature of submucosal invasive colorectal cancer (T1-CRC) can reliably predict the risk for lymph node metastasis (LNM). AIM: The purpose of the study was to develop a prediction model of LNM in T1-CRC. METHODS: Ninety-seven surgically resected T1-CRC at our institution were retrospectively evaluated. Morphology, localization, grading, mode of growth, presence of background adenoma, lymphoid infiltration, angiolymphatic invasion, budding, and depth of invasion were assessed. Mortality and morbidity related to surgery were also evaluated. Benefit-risk balance was assessed according to the presence of severe complications and to the presence of LNM. RESULTS: Fourteen cases had LNM (14%). Eight patients (8%) presented severe surgical complications and there were two deaths (2 %). Infiltrative growth pattern (OR 31.91, 95% CI 2.37-428.36; p = 0.009) and the absence of lymphoid infiltrate (OR 28.75; 95% CI 2.13-388.37; p = 0.011) were the only variables independently associated with LNM in the multivariate analysis. Both variables were included in the prediction model together with sessile morphology (OR 4.88; 95% CI 0.81-29.3; p = 0.083) and poorly differentiated carcinoma (OR 11.77; 95% CI 0.77-179.83; p = 0.076). A 0-100 score was developed (infiltrative growth pattern: no = 0, yes = 33; lymphoid infiltrate: no = 29, yes = 0; sessile morphology: no = 0, yes = 15; poorly differentiated: no = 0, yes = 23). Cutoff point to indicate additional surgery was set in 35 points (i.e., 10% risk LNM). Discrimination of the prediction model was excellent (AUC 0.90; 95% CI 0.81-0.99). CONCLUSION: Combined evaluation of infiltrative growth pattern, lymphoid infiltration, poorly differentiated carcinoma, and sessile appearance showed good performance for discriminating T1-CRC patients with LNM. The benefit-risk balance was in favor of surgery when at least two of these criteria were present.

Risk of atrial fibrillation, stroke, and death after radiofrequency catheter ablation of typical atrial flutter.

OBJECTIVE: The purpose of this study was to assess the incidence, predictors, and prognostic clinical impact of atrial fibrillation (AF) over time after cavotricuspid isthmus (CTI) ablation of typical atrial flutter (AFL). METHODS: This was a follow-up observational study using 408 patients who underwent CTI AFL ablation between 1998 and 2010. The relationships between the different predictors and the outcomes (AF, stroke, and death) were modeled by means of multistate Cox model analyses. RESULTS: The incident rate of AF per 100 person-years during follow-up was 10.2 (95 % CI 8.7-11.8). Prior AF and chronic obstructive pulmonary disease (COPD) were the only independent variables to predict AF occurrence in the population. Their hazard ratios (HRs) were 2.55 (95 % CI 1.84-3.52) and 1.56 (95 % CI 1.08-2.27), respectively. Patients who transitioned to AF had an increased risk of death by an HR of 2.82 (95 % CI 1.88-4.70) and an increased risk of stroke by an HR of 2.93 (95 % CI 1.12-8.90). Age, COPD, and heart failure (HF) were predictive factors of death by HRs of 1.05 (95 % CI 1.00-1.08), 2.85 (95 % CI 1.39-5.83), and 2.72 (95 % CI 1.15-6.40), respectively. Age, smoking, COPD, and HF were predictive factors of death in the group of patients with AF during follow-up. HRs were 1.07 (95 % CI 1.02-1.12), 2.55 (95 % CI 1.55-4.21), 7.60 (95 % CI 3.01-19.16), and 3.07 (95 % CI 1.18-7.95), respectively. CONCLUSIONS: The transition to AF after CTI AFL ablation was high during a long-term follow-up period and maintained over time. Prior AF and COPD were the primary predictors of transition to AF after CTI AFL ablation. Patients who transitioned to AF had an increased risk of stroke and a more than twofold mortality rate. These clinical implications make it necessary to investigate AF after CTI ablation.

Method to calculate the protamine dose necessary for reversal of heparin as a function of activated clotting time in patients undergoing cardiac surgery.

Activated clotting time (ACT) has been used to monitor coagulation and guide management of anticoagulation control in patients undergoing cardiac surgery for decades. However, reversal of heparin with protamine is typically empirically based on total heparin administered. Dose-related adverse effects of protamine are well described. The aim of this study was to evaluate a heparin reversal strategy based on calculation of the protamine dose based on ACT measurements. We present a method using a mathematical formula based on the dose-response line (1). To check the formula, we performed a retrospective observational cohort study of 177 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The study group of 80 patients was administered the dose of protamine obtained using our formula, and the control group of 97 patients was administered the empirically calculated dose. The ACT returned to normal values in patients who were given doses of protamine that were calculated using our formula; all but two had a final ACT of 141. The application of the formula resulted in a significant reduction in the dose of protamine (p < .023). The formula we present is a valid method for calculating the dose of protamine necessary to neutralize heparin. This same method can be used working with a target ACT to adjust the dose of heparin. As a result of its functionality, it allows application on a daily basis standardizing the process. We believe that the formula we developed can be applied in all those procedures in which it is necessary to anticoagulate patients with heparin and later neutralization (cardiac surgery with or without CPB, vascular surgery, procedures of interventional cardiology, and extracorporeal depuration procedures).

Up to twenty-five-year survival after aortic valve replacement with size 19 mm valves.

Long-term survival was investigated in 202 patients who underwent isolated aortic valve replacement (AVR) with 19 mm valves. There were 171 women with a mean age of 69+/-9 years and 31 men with a mean age of 64+/-13 years. Patients had a mean body surface area of 1.61+/-0.13 m(2). Patient-prosthesis mismatch was moderate in 196 and severe in six patients. The mean follow-up for all patients was 78 months. There were 79 late deaths. The actuarial survival rates for all patients were 95+/-1% at 1 year, 75+/-2% at 5 years, 56+/-2% at 10 years, 41+/-2% at 15 years, 34+/-3% at 20 years and 34+/-2% at 25 years. Patients over 70 years old had a lower survival rate (P=0.0001). There were significant differences between ejection fraction (EF) >55% and EF <55% (P=0.0305). AVR with 19 mm valves appeared to provide satisfactory mid-term survival. Age and low EF were risk factors for shorter survival.

Relationships between surgical difficulty and postoperative pain in lower third molar extractions.

PURPOSE: To investigate the influence of surgical difficulty on postoperative pain after extraction of mandibular third molars. MATERIALS AND METHODS: A prospective study was performed of 139 patients who underwent a total of 157 mandibular third molar extractions. For evaluation of surgical difficulty, a 4-class scale was completed after surgery: I, extraction with forceps only; II, extraction requiring osteotomy; III, extraction requiring osteotomy and coronal section; IV, complex extraction (root section). The duration of surgery was also recorded. Postoperative pain was evaluated using a visual analog scale that each patient completed daily until day 6 postsurgery, at which time the sutures were removed. RESULTS: A statistically significant relationship was observed between surgical difficulty (as rated on the scale) and postoperative pain. Longer interventions generally produced more pain. CONCLUSIONS: Pain after extraction of a mandibular third molar increases with increased surgical difficulty and duration of the intervention.

Pederson scale fails to predict how difficult it will be to extract lower third molars.

We report a consecutive series of 105 extractions of impacted lower third molars, in each of which operative difficulty was predicted preoperatively using the Pederson scale (radiographic appearance of the anatomical position of the lower third molar), and postoperative difficulty was scored with a modified version of the Parant scale (operative manoeuvres that were needed for extraction of the third molar). Preoperative classification as "difficult" on the Pederson scale was not an accurate predictor of true difficulty (postoperative classification as "difficult" on the modified Parant scale). There was no significant association between the Pederson score and duration of operation, but high Parant scores were significantly associated with longer operations. We suggest that scales for the prediction of operative difficulty in the extraction of impacted lower third molars should take into account factors other than the anatomical position of the tooth.