Analytical validation of HER2DX genomic test for early-stage HER2-positive breast cancer.

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

Clinical and histological predictive factors of reclassification of prostate cancer patients on active surveillance.

INTRODUCTION AND OBJECTIVE: Active surveillance (AS) has been established as a therapeutic strategy in patients with low-risk prostate cancer. Demographic and anatomopathological factors that increase the probability of reclassifying patients have been identified. MATERIALS AND METHODS: Laboratory and histopathological data were collected from 116 patients included on AS since 2014. Univariate analysis was performed with Chi-square, t-student and Kendall's Tau, multivariate analysis according to logistic regression and Kaplan-Meier curves were calculated. RESULTS: Of the 116 patients in AS, the median age at diagnosis was 66 years and the median follow-up was 13 months (2-72). Of these, 61 (52.6%) are still on surveillance, while 55 (47.4%) have left the program, mostly due to histological progression (52 patients (45.2%)); radical prostatectomy was performed in 27 (49.1%). Prostate volume (PV)≤60cc and the number of positive cylinders >1 in diagnostic biopsy (P=.05) were associated with higher reclassification rate in univariate analysis (P<.05). Multivariate analysis showed that these two variables significantly correlated with higher reclassification rate (PV 60 cc: OR 4.39, P=.04; >1 positive cylinder at diagnostic biopsy: OR 2.48, P=.03). CONCLUSIONS: It has been shown that initial ultrasound volume and the number of positive cylinders in the diagnostic biopsy are independent risk factors for reclassification. Initial PSA, laterality of the affected cylinders and PSA density were not predictive factors of progression in our series.

TB treatment using family members, treatment supporters and self-administered therapies in rural Papua New Guinea.

SETTING: Papua New Guinea (PNG) has one of the world's highest TB incidence rates. It is difficult for patients to access TB care in remote provinces due to insufficient infrastructure and challenging terrain, making varied, targeted delivery models for treating TB necessary. OBJECTIVE: To assess treatment outcomes using self-administered treatment (SAT), family-supported treatment and community-based directly observed therapy (DOT) via treatment supporter (TS) in the PNG context. DESIGN: A retrospective, descriptive analysis of routinely collected data from 360 patients at two sites in 2019-2020. All patients were assigned a treatment model based on risk factors (adherence or default) and offered patient education and counselling (PEC), family counselling and transportation fees. End-of-treatment outcomes were assessed for each model. RESULTS: Treatment success rates among drug-susceptible TB (DS-TB) were good overall: 91.1% for SAT, 81.4% for family-supported treatment and 77% for DOT patients. SAT was strongly associated with favourable outcomes (OR 5.7, 95% CI 1.7-19.3), as were PEC sessions (OR 4.3, 95% CI 2.5-7.2). CONCLUSION: By considering risk factors when determining their treatment delivery model, strong outcomes were seen in all three groups. Multiple modes of treatment administration, tailored to individuals' needs and risk factors, is a feasible, effective, patient-centred care model for hard-to-reach, resource-limited settings.

LIEU: La Papouasie-Nouvelle-Guinée (PNG) présente l'un des taux d'incidence de TB les plus élevés au monde. Il est difficile pour les patients d'accéder aux soins contre la TB dans les provinces éloignées en raison d'une infrastructure insuffisante et d'un terrain difficile, rendant nécessaire l'utilisation de modèles de prestation variés et ciblés pour le traitement de la tuberculose. OBJECTIF: Évaluer les résultats du traitement en utilisant l'autotraitement, le traitement soutenu par la famille et la thérapie directement observée (DOT) basée sur la communauté avec un accompagnateur de traitement, dans le contexte de la PNG. MÉTHODES: Une analyse rétrospective et descriptive des données collectées de manière routinière auprès de 360 patients dans deux sites entre 2019 et 2020. Tous les patients ont été assignés à un modèle de traitement en fonction des facteurs de risque (adhésion ou abandon) et ont bénéficié d'une éducation et d'un accompagnement des patients, de conseils aux familles et de frais de transport. Les résultats en fin de traitement ont été évalués pour chaque modèle. RÉSULTATS: Les taux de réussite du traitement de la TB sensible aux médicaments (DS-TB) étaient globalement bons: 91,1% pour l'autotraitement, 81,4% pour le traitement soutenu par la famille et 77% pour les patients en DOT. L'autotraitement était fortement associé à des résultats favorables (OR 5,7; IC 95% 1,7­19,3), tout comme les séances d'éducation et d'accompagnement des patients (OR 4,3; IC 95% 2,5­7,2). CONCLUSION: En tenant compte des facteurs de risque lors de la détermination du modèle de prestation de traitement, de bons résultats ont été observés dans les trois groupes. Plusieurs modes d'administration du traitement, adaptés aux besoins et aux facteurs de risque individuels, constituent un modèle de soins réalisable, efficace et centré sur le patient pour les contextes difficiles d'accès et aux ressources limitées.

Development and implementation of an immunotherapy unit in a urology department.

INTRODUCTION: Immunotherapy is revolutionizing cancer treatment, with monoclonal antibodies directed against checkpoint regulatory molecules currently being the most widely used therapy. A total of six immune checkpoint inhibitor (CPI) drugs have been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in various solid tumors of the genitourinary tract. MATERIAL AND METHODS: The literature is reviewed and the methodology, as well as our own experience, are analyzed to establish treatment with CPIs in a urology department. RESULTS: The requirements recommended in terms of training, logistics and procedure are described in order to safely offer expert treatment with CPIs to patients with genitourinary tumors. CONCLUSIONS: Compliance with the proposed program ensures safe administration of immune checkpoint inhibitors in a hospital setting.

New Biomarkers in Anaphylaxis (Beyond Tryptase).

Purpose of Review: The purpose of this review is to provide a better understanding of anaphylaxis pathophysiology and describe the underlying mechanisms, effector cells, and the potential biomarkers involved depending on the anaphylaxis endotypes. Recent Findings: New insight into the potential relevance of pathways others than IgE-dependent anaphylaxis has been unraveled, as well as other biomarkers than tryptase, such as the role of platelet activation factor, basogranulin, dipeptidyl peptidase I, CCL-2, and other cytokines. Summary: Gaining knowledge of all the mediators and cellular activation/communication pathways involved in each endotype of anaphylaxis will allow the application of precision medicine in patients with anaphylactic reactions, providing insights to the most appropriate approach in each case and helping to stratify severity and risk prediction.

Biometry data and prevalence of corneal astigmatism in caucasian spanish candidates for cataract surgery.

PURPOSE: To describe ocular biometric parameters and the prevalence of corneal astigmatism as well as age and gender correlations in a population of cataract surgery candidates and to estimate the number of eyes that would be candidates for a toric intraocular lens (IOL). METHODS: In consecutive patients requiring cataract surgery over a one-year period (June 2016 to June 2017), the following optical biometry measurements were performed on an IOLMaster 700 or Lenstar 900: axial length (AL), anterior chamber depth (ACD), lens thickness (LT), mean keratometry (K), flat keratometry (K1), steep keratometry (K2), corneal astigmatism (Cyl) and white-to-white diameter (WTW). Descriptive statistics for the demographic and biometric data were analyzed. RESULTS: The study sample included 6111 eyes of 3332 patients (59.3% women), with a mean age of 74.78±9.7years. The means of the compiled data are as follows: AL 23.58±1.55mm, ACD 3.08±0.41mm, LT 4.55±0.52mm,K 44.15±1.54 diopters (D), K1 43.64±1.57 D, K2 44.69±1.61 D, Cyl 1.0±0.81. D and WTW 11.88±0.46mm. The male patients had significantly larger eyes (higher AL, ACD and WTW) and flatter corneas (lower flat and steep K). Older patients had significantly lower AL, ACD and WTW, while their LT values were higher. Corneas became significantly steeper with age. 60.5% of eyes had less than 1 D of corneal astigmatism, while 3.1% had ≥3.0 D. CONCLUSIONS: Less than 1 D of corneal astigmatism was present in the majority of cataract surgery candidates. 3.1% of eyes were candidates for a toric IOL. This study provides useful information on inventory requirements for planning hospital resources.

Clinical and histological characterization of vesicular COVID-19 rashes: a prospective study in a tertiary care hospital.

COVID-19 is an infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). Vesicular skin rashes have been reported as associated with COVID-19, but there is little information about this cutaneous manifestation. We designed a prospective observational study of patients diagnosed with COVID-19 who had vesicular lesions. Clinical characterization of skin findings was conducted by dermatologists. When possible, histological analysis and detection of SARS-CoV-2 in the content of the vesicles was performed. In total, 24 patients were included. A disseminated pattern was found in 18 patients (75%), and a localized pattern was found in 6 (25%). Median duration of the skin rash was 10 days. Of the 24 patients, 19 (79.2%) developed the skin rash after the onset of COVID-19 symptoms. Histological examination in two patients was consistent with viral infection, SARS-CoV-2 was not detected in four patients. This single-centre study shows the clinical characteristics of vesicular skin rashes in patients with COVID-19.

Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases.

BACKGROUND: The cutaneous manifestations of COVID-19 disease are poorly characterized. OBJECTIVES: To describe the cutaneous manifestations of COVID-19 disease and to relate them to other clinical findings. METHODS: We carried out a nationwide case collection survey of images and clinical data. Using a consensus we described five clinical patterns. We later described the association of these patterns with patient demographics, the timing in relation to symptoms of the disease, the severity and the prognosis. RESULTS: The lesions may be classified as acral areas of erythema with vesicles or pustules (pseudo-chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo-chilblain pattern frequently appears late in the evolution of the COVID-19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID-19. The severity of COVID-19 shows a gradient from less severe disease in acral lesions to more severe in the latter groups. The results are similar for confirmed and suspected cases, in terms of both clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo-chilblain and vesicular). CONCLUSIONS: We provide a description of the cutaneous manifestations associated with COVID-19 infection. These may help clinicians approach patients with the disease and recognize cases presenting with few symptoms. What is already known about this topic? Previous descriptions of cutaneous manifestations of COVID-19 were case reports and mostly lacked illustrations. What does this study add? We describe a large, representative sample of patients with unexplained skin manifestations and a diagnosis of COVID-19, using a consensus method to define morphological patterns associated with COVID-19. We describe five clinical patterns associated with different patient demographics, timing and prognosis, and provide illustrations of these patterns to allow for easy recognition.

Prognostic utility of electrocardiograms in patients with hypertension older than 65 years. The PAFRES study. / Utilidad pronóstica del electrocardiograma en pacientes hipertensos mayores de 65 años. Estudio FAPRES.

OBJECTIVE: Left ventricular hypertrophy is the most common marker of target organ damage in arterial hypertension. Electrocardiograms are typically performed to identify left ventricular hypertrophy. The aim of this study was to analyse the prognostic utility of other electrocardiographic abnormalities in patients with arterial hypertension, beyond ventricular hypertrophy. MATERIALS AND METHODS: The study included 1003 patients older than 65years with arterial hypertension. We recorded risk factors, previous cardiovascular history and medical treatment and analysed various electrocardiographic abnormalities including the Sokolow-Lyon index, the Cornell index, ventricular overload and branch blocks. The study conducted a 2-year follow-up, recording the major cardiovascular events (mortality, myocardial infarction, stroke and hospitalisation for heart failure). RESULTS: The study population's mean age was 72.9±5.8years, 47.5% of whom were men. During the follow-up, 13.9% of the patients experienced a major cardiovascular event. These patients were older, more often smokers and engaged in less physical exercise, without presenting differences in the antihypertensive therapy or blood pressure control. The ventricular overload pattern (HR: 1.93; 95%CI: 1.160-3.196; P=.011) and the complete left bundle branch block (HR: 2.27; 95%CI: 1.040-4.956; P=.040) behaved as independent electrocardiographic predictors of major cardiovascular events; however, left ventricular hypertrophy using the Sokolow and/or Cornell index did not behave as such. CONCLUSIONS: For patients with hypertension, the presence in the baseline electrocardiogram of complete left bundle branch block or a pattern of ventricular overload identifies a population at increased cardiovascular risk.

Have the Government's prescription algorithm and the 2013 American College of Cardiology/American Heart Association guidelines for managing dyslipidaemia influenced the management of dyslipidaemia? The MEJORALO-CV Project. / ¿Han influido el algoritmo de prescripción de la Administración y las guías de manejo de la dislipemia de la ACC/AHA 2013 en el manejo de la dislipemia? Proyecto MEJORA-LO CV.

OBJECTIVE: To determine the management of dyslipidaemia in primary care after the publication of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 guidelines and Valencian government's algorithm. METHOD: We conducted a cross-sectional descriptive study that employed a survey of primary care physicians of the Community of Valencia between January and October 2016. RESULTS: A total of 199 physicians (mean age, 48.9±11.0 years; experience, 21.3±11.1 years) participated in the survey. The most followed guidelines were those of the European Society of Cardiology (37.5% of respondents) and Valencian government (23.4% of respondents). Some 6.3% of the respondents followed the 2013 ACC/AHA guidelines, and 88.0% established objectives based on LDL cholesterol and cardiovascular risk. The choice of lipid-lowering drug was based on its LDL cholesterol lowering capacity (28.6% of respondents), on the Valencian government's algorithm (23.4%) and on the drug's safety (20.4%). Statins, ezetimibe and fibrates were the preferred hypolipemiant agents, and their combination (51% of respondents) and dosage increases (35%) were the strategies employed for poor control. Lipid profile and transaminase and creatine kinase levels were measured every 6 (59.5%, 52.3% and 54.3% of respondents, respectively) or 12 months (25.1%, 29.2% and 30.3%, respectively). Forty-one percent of the respondents were aware of the controversy surrounding the 2013 ACC/AHA guidelines. Although 60% of the respondents acknowledged its relevance, only 21% changed their daily practices accordingly. CONCLUSIONS: The Valencian government's algorithm had a greater impact than the 2013 ACC/AHA guidelines in primary care in Valencia. Areas for improvement included the low use of validated guidelines and risk tables and the streamlining of laboratory test periodicity.

Application of the STOPP criteria in hospitalised elderly patients to detect and optimise inappropriate psychopharmaceutical prescriptions.

BACKGROUND: Psychotropic drugs are frequently used in the elderly population, but their inappropriate prescription can cause numerous adverse effects and interactions. OBJECTIVE: To evaluate the impact of a multidisciplinary intervention to detect and optimise inappropriate prescriptions of psychotropic drugs in patients aged over 75 years in a hospital setting. DESIGN, SETTING, SUBJECTS AND METHODS: A prospective study which included every patient aged over 75 years admitted to the Consorcio Hospital General in Valencia, Spain, and who had been prescribed psychotropic drugs inappropriately, carried out over 1 year. The intervention was to detect inappropriate prescriptions of psychotropic drugs using the STOPP criteria, treatment optimisation by a team of psychiatrists, readjustment of the electronic prescription register, and communication to the primary care physician. The impact of the intervention was assessed by measuring the persistence of the changes made 3 months after discharge and by quarterly assessment of inappropriate prescriptions. RESULTS: Of 4571 admissions, 378 inappropriate prescriptions were detected in 346 patients. The drugs most frequently used were long half-life benzodiazepines (70%), which were substituted in 62% of the cases, withdrawn in 32%, and maintained in 6%. At 3 months follow-up, the changes had been maintained by the patients' primary care physician in 67%. Evaluation of the prescriptions during the subsequent quarters of the year showed a significant decrease in the inappropriate prescriptions, especially benzodiazepines. CONCLUSIONS: Coordinated intervention by pharmacologists and psychiatrists in hospital settings, and communication between these professionals and primary care teams, can reduce psychotropic drugs inappropriately prescribed to the elderly.

Additive value of diabetes and peripheral arterial disease in the risk stratification of patients admitted after an acute coronary syndrome: a subanalysis of the PAMISCA Study.

BACKGROUND: There is an increasing interest in the use of non-invasive methods for the detection of subclinical atherosclerosis to better identify patients with high risk of cardiovascular events The presence of diabetes mellitus (DM) and peripheral arterial disease (PAD) is associated with increased risk of events but their value in the acute coronary syndrome (ACS) patient has not been ascertained. METHODS: We performed a subanalysis of the PAMISCA study, designed to investigate the prevalence of PAD in patients admitted to Spanish hospitals with a diagnosis of an ACS. RESULTS: A total of 1410 patients were analysed (71.4% men, age 66 +/- 11.9 years, 35% DM). The prevalence of PAD was higher in DM vs. no-DM (41.5% vs. 30.6% respectively, p < 0.001). Patients with PAD and DM had more in-hospital cardiac complications such as atrial fibrillation/flutter, recurrent myocardial ischaemia and heart failure and a trend towards higher in-hospital mortality (p = 0.08). Non-DM patients with PAD and DM without PAD shared similar cardiac complications and the group without neither PAD nor DM had the best prognosis. In patients without PAD, DM was an independent predictor of three-vessel coronary disease (OR 1.6; 95% CI: 1.1-2.5, p < 0.05) after adjustment by age, sex, low density lipoproteins (LDL), smoking and the previous myocardial infarction. However, in PAD patients, DM failed to be an independent risk factor in the multivariate analysis (OR 1.0; 95% CI 0.6-1.6, p < 0.05). CONCLUSIONS: The concurrence of DM and PAD helps identify patients with an adverse risk profile.

[Spinal cord compression by tumor with onset following epidural catheterization]. / Compresión medular neoplásica iniciada tras cateterización peridural.

We report the case of a 16-year-old boy with a pelvic tumor who developed signs of spinal cord compression following placement of a lumbar epidural catheter to obtain a percutaneous biopsy. The fact that a catheter had been inserted led us to suspect epidural hematoma as a complication, but surgery revealed that the pelvic tumor had spread to the lumbar epidural space and was causing motor blockade of both legs.