Corrigendum: Evaluation of PIK3CA mutations in advanced ER+/HER2-breast cancer in Portugal - U-PIK Project.

[This corrects the article DOI: 10.3389/fmolb.2023.1082915.].

Heart rate variability and stroke or systemic embolism in patients with atrial fibrillation.

BACKGROUND: Stroke remains one of the most serious complications in atrial fibrillation (AF) patients and has been linked to disturbances of the autonomic nervous system. OBJECTIVE: We hypothesized that impaired cardiac autonomic function might be associated with an enhanced stroke risk in AF patients. METHODS: We enrolled 1922 AF patients who were either in sinus rhythm (SR-group, n=1121) or AF (AF-group, n=801) on a 5-minute resting ECG recording. HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, root mean square root of successive differences of normal-to-normal intervals, mean heart rate, 5-min total power and power in the high frequency, low frequency and very low frequency range were calculated. We constructed Cox regression models to examine the association of HRV parameters with the composite endpoint of stroke or systemic embolism. RESULTS: Mean age was 71±8 years in the SR group and 75±8 in the AF group. 37 patients in the SR group (3.4%) and 60 patients in the AF group (8.0%) experienced a stroke or systemic embolism during a follow-up time of 5 years. In patients with SR, HRVI <15 was the strongest HRV parameter to be associated with stroke or systemic embolism (hazard ratio 3.04; 95% confidence interval 1.3-7.0; p=0.009) after adjustment for multiple confounders. In the AF group, we found no HRV parameter to be associated with the composite endpoint. CONCLUSION: HRVI measured during SR on a single 5-minute ECG recording is independently associated with stroke or systemic embolism in AF patients. HRV analysis in SR may help to improve risk stratification in AF patients.

Twiddler's Syndrome Causing Lead Fracture in Sacral Neuromodulation: A Case Report.

Twiddler's syndrome is the voluntary or involuntary manipulation of an implanted device, most described in cardiac literature. Lead coiling may result in device malfunction due to lead migration or, less commonly, lead fracture. There are few but increasing reports of Twiddler's syndrome resulting in lead migration in sacral neuromodulation, but lead fracture has not yet been described. A 57-year-old Latina female presented with fecal incontinence and refractory overactive bladder. She underwent successful implantation of a sacral neuromodulation device with the resolution of symptoms. Following significant weight loss and two falls, she developed a recurrence of symptoms and was found to have lead migration on pelvic radiographs. At the time of surgical intervention, radiographs demonstrated worsened Twiddler's syndrome with complete lead fracture despite no further trauma. She subsequently underwent partial lead removal and replacement with additional measures to prevent Twiddler's syndrome and its sequelae. Twiddler's syndrome resulting in lead fracture can occur in sacral neuromodulation. Preventive techniques may be applied for patients with known risk factors for Twiddler's syndrome, especially generator anchoring and lead replacement.

Removal of Spinal Instrumentation Is Not Required to Successfully Treat Postoperative Wound Infections in Most Cases.

INTRODUCTION: Controversy exists regarding whether spinal implants need to be removed to treat postoperative deep wound infections (DWIs). This retrospective study aimed to determine whether the removal or retention of implants impacts the successful treatment of a DWI after spine surgery. METHODS: Postoperative spine surgery patients presenting with signs of infection who underwent irrigation and debridement (I&D) at Twin Cities Spine Surgeons at Abbott Northwestern Hospital, Minnesota, USA, were studied. First, the persistence of infection when implants were retained or removed was assessed. Second, we analyzed the persistence of infection with respect to the number of I&D, the use of vacuum-assisted closure (VAC) treatment, pseudoarthrosis status, and functional outcomes. RESULTS: One hundred thirty-five patients were included. Treatment of infection with retention of implants occurred in 64% (87/135); of these, 7% (6/87) had a persistent infection. Of patients with implant removal (36%, 48/135), 6% (3/48) had a persistent infection. Thus, we observed no difference between treatment with implants present compared to implants removed (p = 1.0). Fifty of the 135 patients (37%) received I&D and primary wound closure, and 85 (63%) patients received I&D and VAC treatment. There was no statistical difference between primary wound closure and VAC treatment (p = 0.15) with respect to persistence. Repeat I&D with VAC (three or more times) had a significantly lower rate of recurrence than those with two I&Ds. Pseudoarthrosis and persistent infection were unrelated. At minimum one-year follow-up, achieving a minimum clinically important difference in functional outcome was independent of persistent infection status. CONCLUSION: Persistent infection was unrelated to the retention of implants. When VAC treatment was deemed necessary, more than two I&Ds resulted in a significantly better cure for infection. Those with a persistent infection were no more likely to exhibit pseudoarthrosis than those with no persistent infection. All patients showed improvement in functional outcomes at minimum one-year follow-up.

Feature Extraction Based on Local Histogram with Unequal Bins and a Recurrent Neural Network for the Diagnosis of Kidney Diseases from CT Images.

Kidney disease remains one of the most common ailments worldwide, with cancer being one of its most common forms. Early diagnosis can significantly increase the good prognosis for the patient. The development of an artificial intelligence-based system to assist in kidney cancer diagnosis is crucial because kidney illness is a global health concern, and there are limited nephrologists qualified to evaluate kidney cancer. Diagnosing and categorising different forms of renal failure presents the biggest treatment hurdle for kidney cancer. Thus, this article presents a novel method for detecting and classifying kidney cancer subgroups in Computed Tomography (CT) images based on an asymmetric local statistical pixel distribution. In the first step, the input image is non-overlapping windowed, and a statistical distribution of its pixels in each cancer type is built. Then, the method builds the asymmetric statistical distribution of the image's gradient pixels. Finally, the cancer type is identified by applying the two built statistical distributions to a Deep Neural Network (DNN). The proposed method was evaluated using a dataset collected and authorised by the Dhaka Central International Medical Hospital in Bangladesh, which includes 12,446 CT images of the whole abdomen and urogram, acquired with and without contrast. Based on the results, it is possible to confirm that the proposed method outperformed state-of-the-art methods in terms of the usual correctness criteria. The accuracy of the proposed method for all kidney cancer subtypes presented in the dataset was 99.89%, which is promising.

Lipid-Lowering Therapy and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin low-density lipoprotein-cholesterol (LDL-C)- and triglyceride-lowering therapies. METHODS AND RESULTS: We performed a systematic review of large randomized clinical trials (≥1000 patients with ≥2 years follow-up) of LDL-C-lowering therapy (statin, ezetimibe, and PCSK-9 [proprotein convertase subtilisin/kexin type 9] inhibitor) and triglyceride-lowering therapy (omega-3 supplements and fibrate) that reported hemorrhagic stroke as an outcome. We searched MEDLINE, Embase, and Cochrane Library up to July 2, 2021 and updated a meta-analysis of cardiovascular statin trials published in 2012. Among our several subgroup analyses, we looked at difference depending on stroke status and also depending on age. We identified 37 trials for LDL-C lowering (284 301 participants) and 11 for triglyceride lowering (120 984 participants). Overall, we found a higher risk of hemorrhagic stroke for LDL-C lowering, risk ratio (RR) 1.16 (95% CI, 1.01-1.32, P=0.03). For statins (33 trials, 216 258 participants), RR=1.17 (95% CI, 1.01-1.36); for PCSK-9 inhibitors (2 trials, 46 488 participants), RR=0.86 (95% CI, 0.43-1.74); and for ezetimibe (2 trials, 21 555 participants), RR=1.14 (95% CI, 0.64-2.03). In statin trials of patients with previous stroke/transient ischemic attack, RR was 1.46 (95% CI, 1.05-2.04), and in trials with mean age ≥65 years old, RR=1.34 (95% CI, 1.04-1.73) (Pint=0.14 and Pint=0.23 respectively); for triglyceride lowering (11 trials, 120 984 participants), RR=1.05 (95% CI, 0.86-1.30). CONCLUSIONS: We found evidence for a small increased risk of hemorrhagic stroke events with LDL-C-lowering therapies but no clear evidence for triglyceride-lowering therapies. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42021275363.

Molecular crosstalk between MUC1 and STAT3 influences the anti-proliferative effect of Napabucasin in epithelial cancers.

MUC1 is a transmembrane glycoprotein that is overexpressed and aberrantly glycosylated in epithelial cancers. The cytoplasmic tail of MUC1 (MUC1 CT) aids in tumorigenesis by upregulating the expression of multiple oncogenes. Signal transducer and activator of transcription 3 (STAT3) plays a crucial role in several cellular processes and is aberrantly activated in many cancers. In this study, we focus on recent evidence suggesting that STAT3 and MUC1 regulate each other's expression in cancer cells in an auto-inductive loop and found that their interaction plays a prominent role in mediating epithelial-to-mesenchymal transition (EMT) and drug resistance. The STAT3 inhibitor Napabucasin was in clinical trials but was discontinued due to futility. We found that higher expression of MUC1 increased the sensitivity of cancer cells to Napabucasin. Therefore, high-MUC1 tumors may have a better outcome to Napabucasin therapy. We report how MUC1 regulates STAT3 activity and provide a new perspective on repurposing the STAT3-inhibitor Napabucasin to improve clinical outcome of epithelial cancer treatment.

Corrigendum: Antimicrobial resistance in the COVID-19 landscape: is there an opportunity for anti-infective antibodies and antimicrobial peptides?

[This corrects the article DOI: 10.3389/fimmu.2022.921483.].

Is there a shift from cardiovascular to cancer death in lipid-lowering trials? A systematic review and meta-analysis.

BACKGROUND: Lipid-lowering therapy (LLT) reduces cardiovascular (CV) events, but data are conflicting on all-cause mortality, especially among older adults. Though LLT does not induce cancer, some randomized clinical trials (RCTs) found a pattern of increased cancer death under LLT. Our objective was to assess a possible shift from CV to cancer death in LLT trials (i.e. an increase in cancer and decrease in CV death) and to investigate potential subgroups at risk. METHODS: We performed a systematic review and meta-analysis. We retrieved RCTs from MEDLINE, Embase, and Cochrane Central until 08/2023. We extracted the number of CV and cancer deaths in the treatment vs. in the control arm, calculated the relative risk (RR) by dividing the risk of death in the treatment over the risk of death in the control group and then pooled them using random-effect meta-analysis. We performed subgroup analyses on primary and secondary prevention, and according to different age cut-offs. RESULTS: We included 27 trials with 188'259 participants (23 statin; 4 ezetimibe trials). The trials reported 4056 cancer deaths, 2061 under LLT and 1995 in control groups. Overall, there was no increased risk of cancer mortality (RR 1.03, 95% confidence interval 0.97-1.10), with no difference between primary and secondary prevention. In the subgroup analyses for RCTs with ≥15% of participants aged ≥75 years, the RR of cancer death was 1.11 (1.00-1.23), while the RR for CV death was 0.96 (0.91-1.01). For RCTs with a mean age ≥ 70 years, the RR for cancer death was 1.21 (0.99-1.47). CONCLUSION: LLT does not lead to a shift from CV to cancer death. However, there might be a possible shift with a pattern of increased cancer deaths in trials with more older adults, particularly ≥75 years. Individual participant data from LLT trials should be made public to allow further investigations. PROSPERO REGISTRATION: CRD42021271658.

Combined 6-benzylaminopurine and H2O2 stimulate the astaxanthin biosynthesis in Xanthophyllomyces dendrorhous.

Astaxanthin is one of the most attractive carotenoids due to its high antioxidant activity and beneficial biological properties, while Xanthophyllomyces dendrorhous is one of its main microbial sources. Since astaxanthin is synthesized as a response to oxidative stress, several oxidative agents have been evaluated to increase X. dendrorhous astaxanthin yields. However, the extent of the stimulation is determined by the cellular damage caused by the applied oxidative agent. Phytohormones have also been reported as stimulants of astaxanthin biosynthesis acting directly on its metabolic pathway and indirectly promoting cellular resistance to reactive oxygen species. We reasoned that both oxidative agents and phytohormones lead to increased astaxanthin synthesis, but the latter could mitigate the drawbacks of the former. Thus, here, the stimulation on astaxanthin biosynthesis, as well as the cellular and transcriptional responses of wild type X. dendrorhous to phytohormones (6-benzylaminopurine, 6-BAP; abscisic acid, ABA; and indole-3-acetic acid, IAA), and oxidative agents (glutamate, menadione, H2O2, and/or Fe2+) were evaluated as a single or combined treatments. ABA and 6-BAP were the best individual stimulants leading to 2.24- and 2.60-fold astaxanthin biosynthesis increase, respectively. Nevertheless, the effect of combined 6-BAP and H2O2 led to a 3.69-fold astaxanthin synthesis increase (0.127 ± 0.018 mg astaxanthin/g biomass). Moreover, cell viability (> 82.75%) and mitochondrial activity (> 82.2%) remained almost intact in the combined treatment (6-BAP + H2O2) compared to control (< 52.17% cell viability; < 85.3% mitochondrial activity). On the other hand, mRNA levels of hmgR, idi, crtYB, crtR, and crtS, genes of the astaxanthin biosynthetic pathway, increased transiently along X. dendrorhous fermentation due to stimulations assayed in this study. KEY POINTS: • Combined 6-BAP and H2O2 is the best treatment to increase astaxanthin yields in X. dendrorhous. • 6-BAP preserves cell integrity under oxidative H2O2 stress conditions. • 6-BAP and H2O2 increase transcriptional responses of hmgR, idi, and crt family genes transiently.

Yeast diversity in open agave fermentations across Mexico.

Yeasts are a diverse group of fungal microorganisms that are widely used to produce fermented foods and beverages. In Mexico, open fermentations are used to obtain spirits from agave plants. Despite the prevalence of this traditional practice throughout the country, yeasts have only been isolated and studied from a limited number of distilleries. To systematically describe the diversity of yeast species from open agave fermentations, here we generate the YMX-1.0 culture collection by isolating 4524 strains from 68 sites with diverse climatic, geographical, and biological contexts. We used MALDI-TOF mass spectrometry for taxonomic classification and validated a subset of the strains by ITS and D1/D2 sequencing, which also revealed two potential novel species of Saccharomycetales. Overall, the composition of yeast communities was weakly associated with local variables and types of climate, yet a core set of six species was consistently isolated from most producing regions. To explore the intraspecific variation of the yeasts from agave fermentations, we sequenced the genomes of four isolates of the nonconventional yeast Kazachstania humilis. The genomes of these four strains were substantially distinct from a European isolate of the same species, suggesting that they may belong to different populations. Our work contributes to the understanding and conservation of an open fermentation system of great cultural and economic importance, providing a valuable resource to study the biology and genetic diversity of microorganisms living at the interface of natural and human-associated environments.

Dairy Intake and Risk of Cognitive Decline and Dementia: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis has been conducted yet. Therefore, we performed a systematic review with a dose-response meta-analysis about the association between dairy intake and cognitive decline or incidence of dementia. We investigated prospective studies with a follow-up ≥6 mo on cognitive decline or dementia incidence in adults without known chronic conditions through a systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar from inception to 11 July 2023. We evaluated the dose-response association using a random-effects model. We identified 15 eligible cohort studies with >300,000 participants and a median follow-up of 11.4 y. We observed a negative nonlinear association between cognitive decline/dementia incidence and dairy intake as assessed through the quantity of consumption, with the nadir at ∼150 g/d (risk ratio: 0.88; 95% confidence interval: 0.78, 0.99). Conversely, we found an almost linear negative association when we considered the frequency of consumption (risk ratio for linear trend: 0.84; 95% confidence interval: 0.77, 0.92 for 1 time/d increase of dairy products). Stratified analysis by dairy products showed different shapes of the association with linear inverse relationship for milk intake, whereas possibly nonlinear for cheese. The inverse association was limited to Asian populations characterized by generally lower intake of dairy products, compared with the null association reported by European studies. In conclusion, our study suggests a nonlinear inverse association between dairy intake and cognitive decline or dementia, also depending on dairy types and population characteristics, although the heterogeneity was still high in overall and several subgroup analyses. Additional studies should be performed on this topic, including a wider range of intake and types of dairy products, to confirm a potential preventing role of dairy intake on cognitive decline and identify ideal intake doses. This review was registered at PROSPERO as CRD42020192395.

Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults.

CONTEXT: With age, the prevalence of subclinical hypothyroidism rises. However, incidence and determinants of spontaneous normalization remain largely unknown. OBJECTIVE: To investigate incidence and determinants of spontaneous normalization of TSH levels in older adults with subclinical hypothyroidism. DESIGN: Pooled data were used from the (1) pretrial population and (2) in-trial placebo group from 2 randomized, double-blind, placebo-controlled trials (Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism Trial and Institute for Evidence-Based Medicine in Old Age thyroid 80-plus thyroid trial). SETTING: Community-dwelling 65+ adults with subclinical hypothyroidism from the Netherlands, Switzerland, Ireland, and the United Kingdom. PARTICIPANTS: The pretrial population (N = 2335) consisted of older adults with biochemical subclinical hypothyroidism, defined as ≥1 elevated TSH measurement (≥4.60 mIU/L) and a free T4 within the laboratory-specific reference range. Individuals with persistent subclinical hypothyroidism, defined as ≥2 elevated TSH measurements ≥3 months apart, were randomized to levothyroxine/placebo, of which the in-trial placebo group (N = 361) was included. MAIN OUTCOME MEASURES: Incidence of spontaneous normalization of TSH levels and associations between participant characteristics and normalization. RESULTS: In the pretrial phase, TSH levels normalized in 60.8% of participants in a median follow-up of 1 year. In the in-trial phase, levels normalized in 39.9% of participants after 1 year of follow-up. Younger age, female sex, lower initial TSH level, higher initial free T4 level, absence of thyroid peroxidase antibodies, and a follow-up measurement in summer were independent determinants for normalization. CONCLUSION: Because TSH levels spontaneously normalized in a large proportion of older adults with subclinical hypothyroidism (also after confirmation by repeat measurement), a third measurement may be recommended before considering treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01660126 and Netherlands Trial Register, NTR3851.

Multiple TP53 p.R337H haplotypes and implications for tumor susceptibility.

The germline TP53 p.R337H mutation is reported as the most common germline TP53 variant. It exists at a remarkably high frequency in the population of southeast Brazil as founder mutation in two distinct haplotypes with the most frequent co-segregating with the p.E134∗ variant of the XAF1 tumor suppressor and an increased cancer risk. Founder mutations demonstrate linkage disequilibrium with neighboring genetic polymorphic markers that can be used to identify the founder variant in different geographic regions and diverse populations. We report here a shared haplotype among Brazilian, Portuguese, and Spanish families and the existence of three additional distinct TP53 p.R337H alleles. Mitochondrial DNA sequencing and Y-STR profiling of Brazilian carriers of the founder TP53 p.R337H allele reveal an excess of Native American haplogroups in maternal lineages and exclusively European haplogroups in paternal lineages, consistent with communities established through male European settlers with extensive intermarriage with Indigenous women. The identification of founder and independent TP53 p.R337H alleles underlines the importance for considering the haplotype as a functional unit and the additive effects of constitutive polymorphisms and associated variants in modifier genes that can influence the cancer phenotype.

Overall Survival and Exploratory Biomarker Analyses of Abemaciclib plus Trastuzumab with or without Fulvestrant versus Trastuzumab plus Chemotherapy in HR+, HER2+ Metastatic Breast Cancer Patients.

PURPOSE: The monarcHER trial has shown that abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, combined with fulvestrant and trastuzumab, improves progression-free survival (PFS) in hormone receptor-positive (HR+), HER2-positive (HER2+) advanced breast cancer (ABC) compared with standard-of-care (SOC) chemotherapy combined with trastuzumab. We report the final overall survival (OS) analysis, updated safety and efficacy data, and exploratory biomarker results from monarcHER. PATIENTS AND METHODS: monarcHER (NCT02675231), a randomized, multicenter, open-label, phase II trial, enrolled 237 patients across Arm A (abemaciclib, trastuzumab, fulvestrant), Arm B (abemaciclib, trastuzumab), and Arm C (SOC chemotherapy, trastuzumab). Following the statistical plan, OS and PFS were estimated in all arms. RNA sequencing (RNA-seq) was performed on archival tissue. RESULTS: Median OS was 31.1 months in Arm A, 29.2 months in Arm B, and 20.7 months in Arm C [A vs. C: HR, 0.71; 95% confidence interval (CI), 0.48-1.05; nominal two-sided P value 0.086; B vs. C: HR 0.83 (95% CI, 0.57-1.23); nominal two-sided P value 0.365]. Updated PFS and safety findings were consistent with previous results. The most frequently reported treatment-emergent adverse events included diarrhea, fatigue, nausea, neutrophil count decrease, and anemia. In exploratory RNA-seq analyses, Luminal subtypes were associated with longer PFS [8.6 vs. 5.4 months (HR, 0.54; 95% CI, 0.38-0.79)] and OS [31.7 vs. 19.7 months (HR, 0.68; 95% CI, 0.46-1.00)] compared with non-Luminal. CONCLUSIONS: In this phase II trial, abemaciclib + trastuzumab ± fulvestrant numerically improved median OS in women with HR+, HER2+ ABC compared with SOC chemotherapy + trastuzumab.

Adjunct prednisone in community-acquired pneumonia: 180-day outcome of a multicentre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Several trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia). METHODS: This predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence. RESULTS: From the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension. CONCLUSIONS: In patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP. TRIAL REGISTRATION: This trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015.

Factors Associated with Cancer Prevention/Risk Reduction Behaviors among Latinos.

Improving understanding of behaviors that increase or reduce cancer risk for different Hispanic groups is a public health priority; such knowledge is sparse in new gateway immigration locations such as Indiana. The aims of this study were to: 1) describe cancer beliefs and cancer preventive/risk reduction behaviors (physical activity, tobacco, and alcohol use) among Hispanic adults; 2) examine differences in cancer beliefs and preventive behaviors by country/territory of birth, socioeconomic status, and area of residence (urban vs. rural); and 3) determine predictors of engagement in cancer prevention and risk reduction behaviors in this population. A cross-sectional online survey targeted adult Indiana residents who identified as Latino, Hispanic, or Spanish recruited using Facebook-targeted advertising. Complete survey data from 1520 respondents were analyzed using descriptive, unadjusted, and adjusted models. The majority of respondents believed they were unlikely to get cancer but held many other fatalistic beliefs about cancer. Only 35.6% of respondents had received the HPV vaccine, 37.6% reported they were currently smoking cigarettes, and 64% reported occasional or frequent drinking of alcohol. Respondents spent an average of 3.55 days per week engaged in moderate exercise. Differences were observed by country/territory of birth, income, and education but not by rural residence status. Predictors of cancer risk/risk reduction behaviors were identified. The Hispanic population in Indiana is diverse and effective interventions for cancer prevention should be culturally targeted based on country/territory of birth and individually tailored based on cancer-related beliefs.

Achilles tendon ultrasonography in the clinical screening of familial hypercholesterolaemia - a cross-sectional analysis.

BACKGROUND AND AIMS: People with familial hypercholesterolaemia are 13 times more likely to develop cardiovascular disease than the general population. However, familial hypercholesterolaemia remains largely underdiagnosed. Tendon xanthoma is a specific clinical feature of familial hypercholesterolaemia and its presence alone implies a probable diagnosis of familial hypercholesterolaemia according to the Dutch Lipid Clinic Network Score (DLCNS). The aim of the study was to determine whether ultrasound detects more Achilles tendon xanthomas (ATX) than clinical examination. METHODS: We recruited 100 consecutive patients with LDL-C ≥4 mmol/l. Achilles tendons were evaluated through clinical examination by trained physicians and sonographic examination by another physician blind to the results of clinical examination. Blind second readings of ultrasound images were performed by an expert in musculoskeletal ultrasound. We compared the proportion of patients with ATX detected by either clinical examination or ultrasound and the proportion of patients with a probable/definite familial hypercholesterolaemia diagnosis on the DLCNS before and after ultrasound. RESULTS: Mean (SD) age was 47 (12) years; mean highest LDL-C was 6.57 mmol/l (2.2). ATX were detected in 23% of patients by clinical examination and in 60% by ultrasound. In consequence, 43% had a probable/definite diagnosis of familial hypercholesterolaemia on the DLCNS using clinical examination compared with 72% when ultrasound was used. CONCLUSION: Compared to clinical examination, ultrasound examination of the Achilles tendon substantially improves the detection of ATX and may help to better identify patients with familial hypercholesterolaemia who are at high risk for premature cardiovascular disease.