Few-shot genes selection: subset of PAM50 genes for breast cancer subtypes classification.

BACKGROUND: In recent years, researchers have made significant strides in understanding the heterogeneity of breast cancer and its various subtypes. However, the wealth of genomic and proteomic data available today necessitates efficient frameworks, instruments, and computational tools for meaningful analysis. Despite its success as a prognostic tool, the PAM50 gene signature's reliance on many genes presents challenges in terms of cost and complexity. Consequently, there is a need for more efficient methods to classify breast cancer subtypes using a reduced gene set accurately. RESULTS: This study explores the potential of achieving precise breast cancer subtype categorization using a reduced gene set derived from the PAM50 gene signature. By employing a "Few-Shot Genes Selection" method, we randomly select smaller subsets from PAM50 and evaluate their performance using metrics and a linear model, specifically the Support Vector Machine (SVM) classifier. In addition, we aim to assess whether a more compact gene set can maintain performance while simplifying the classification process. Our findings demonstrate that certain reduced gene subsets can perform comparable or superior to the full PAM50 gene signature. CONCLUSIONS: The identified gene subsets, with 36 genes, have the potential to contribute to the development of more cost-effective and streamlined diagnostic tools in breast cancer research and clinical settings.

APOLLO-B, a study of patisiran in patients with transthyretin cardiac amyloidosis: primary long-term results from the open-label extension period

INTRODUCTION: The Phase 3 APOLLO-B study evaluates patisiran in patients (pts) with transthyretin (ATTR) cardiac amyloidosis over a 12-month (M) double-blind (DB) period, followed by an open-label extension (OLE) period when all pts receive patisiran (NCT03997383). Hypothesis: Patisiran provides long-term benefit in pts with ATTR cardiac amyloidosis. Aims: Describe safety and efficacy of patisiran during the APOLLO-B OLE (18M+). METHODS: Pts (18-85 yrs) with ATTR cardiac amyloidosis and heart failure history were randomized 1:1 to patisiran or placebo (pbo). Pts completing DB period were eligible to receive patisiran in the OLE for ≤36M. Results summarized based on DB treatment arm. Exploratory assessments include change from study baseline (CFB) in 6-minute walk test (6MWT), KCCQ-OS, NT-proBNP, and troponin I. RESULTS: In the DB period, 359 pts (pbo n=178; patisiran n=181) received study drug (median [range] age, 76.0 [41, 85] yrs; male, 89%; wtATTR, 80%; tafamidis at baseline, 25%); 334 (93%) entered the OLE. In patisiran arm, M12 and M18 results, respectively, were similar for each endpoint: 6MWT and KCCQ-OS (mean [SEM] CFB) −8.09 [5.73] vs −9.21 [6.04] meters (m) and 0.60 [1.36] vs 0.22 [1.48]; NT-proBNP and troponin I (geometric mean fold-CFB [95%CI]) 1.10 [1.03, 1.17] vs 1.17 [1.07, 1.27] and 1.11 [1.05, 1.18] vs 1.09 [1.01, 1.17]). In pbo arm, patisiran initiation in OLE was associated with a slower rate of worsening or relative stability across endpoints; CFB at M12 vs M18, respectively: 6MWT, −25.43 [5.61] vs −31.08 [5.45] m; KCCQ-OS, −3.41 [1.33] vs −4.02 [1.49]; NT-proBNP, 1.39 [1.28, 1.51] vs 1.53 [1.38, 1.71]; and troponin I, 1.29 [1.21, 1.38] vs 1.21 [1.13, 1.30]. Patisiran had an acceptable safety profile; no new concerns. OLE analyses are ongoing; updated data to be presented. CONCLUSIONS: The M18 results provide evidence that beneficial effects observed in DB period on functional capacity, health status, and quality of life were maintained by continued treatment with patisiran during the OLE. Pbo-treated pts initiating patisiran at M12 showed slowed worsening or stabilization in most endpoints at M18. Early treatment initiation is important: pbo-treated pts did not recover functional capacity or health lost prior to initiating OLE patisiran.

A machine learning method integrating ECG and gated SPECT for cardiac resynchronization therapy decision support.

PURPOSE: Cardiac resynchronization therapy (CRT) has been established as an important therapy for heart failure. Mechanical dyssynchrony has the potential to predict responders to CRT. The aim of this study was to report the development and the validation of machine learning models which integrate ECG, gated SPECT MPI (GMPS), and clinical variables to predict patients' response to CRT. METHODS: This analysis included 153 patients who met criteria for CRT from a prospective cohort study. The variables were used to model predictive methods for CRT. Patients were classified as "responders" for an increase of LVEF ≥ 5% at follow-up. In a second analysis, patients were classified as "super-responders" for an increase of LVEF ≥ 15%. For ML, variable selection was applied, and Prediction Analysis of Microarrays (PAM) approach was used to model response while Naïve Bayes (NB) was used to model super-response. These ML models were compared to models obtained with guideline variables. RESULTS: PAM had AUC of 0.80 against 0.72 of partial least squares-discriminant analysis with guideline variables (p = 0.52). The sensitivity (0.86) and specificity (0.75) were better than for guideline alone, sensitivity (0.75) and specificity (0.24). Neural network with guideline variables was better than NB (AUC = 0.93 vs. 0.87) however without statistical significance (p = 0.48). Its sensitivity and specificity (1.0 and 0.75, respectively) were better than guideline alone (0.78 and 0.25, respectively). CONCLUSIONS: Compared to guideline criteria, ML methods trended toward improved CRT response and super-response prediction. GMPS was central in the acquisition of most parameters. Further studies are needed to validate the models.

Development and validation of a prognostic model for the early identification of COVID-19 patients at risk of developing common long COVID symptoms.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic demands reliable prognostic models for estimating the risk of long COVID. We developed and validated a prediction model to estimate the probability of known common long COVID symptoms at least 60 days after acute COVID-19. METHODS: The prognostic model was built based on data from a multicentre prospective Swiss cohort study. Included were adult patients diagnosed with COVID-19 between February and December 2020 and treated as outpatients, at ward or intensive/intermediate care unit. Perceived long-term health impairments, including reduced exercise tolerance/reduced resilience, shortness of breath and/or tiredness (REST), were assessed after a follow-up time between 60 and 425 days. The data set was split into a derivation and a geographical validation cohort. Predictors were selected out of twelve candidate predictors based on three methods, namely the augmented backward elimination (ABE) method, the adaptive best-subset selection (ABESS) method and model-based recursive partitioning (MBRP) approach. Model performance was assessed with the scaled Brier score, concordance c statistic and calibration plot. The final prognostic model was determined based on best model performance. RESULTS: In total, 2799 patients were included in the analysis, of which 1588 patients were in the derivation cohort and 1211 patients in the validation cohort. The REST prevalence was similar between the cohorts with 21.6% (n = 343) in the derivation cohort and 22.1% (n = 268) in the validation cohort. The same predictors were selected with the ABE and ABESS approach. The final prognostic model was based on the ABE and ABESS selected predictors. The corresponding scaled Brier score in the validation cohort was 18.74%, model discrimination was 0.78 (95% CI: 0.75 to 0.81), calibration slope was 0.92 (95% CI: 0.78 to 1.06) and calibration intercept was -0.06 (95% CI: -0.22 to 0.09). CONCLUSION: The proposed model was validated to identify COVID-19-infected patients at high risk for REST symptoms. Before implementing the prognostic model in daily clinical practice, the conduct of an impact study is recommended.

Current status of nuclear cardiology practice in Latin America and the Caribbean, in the era of multimodality cardiac imaging approach: 2022 update.

Cardiovascular diseases (CVDs) are the leading cause of mortality in Latin America and the Caribbean (LAC), with the risk in men being slightly higher than in women. The coronavirus disease 2019 (COVID-19) pandemic caused a significant reduction in the number of cardiac diagnostic procedures globally and in particular in LAC. Nuclear cardiology is available in the region, but there is variability in terms of existing technology, radiopharmaceuticals, and human resources. In the region, there are 2385 single photon emission computed tomography (SPECT) and 315 PET scanners, Argentina and Brazil have the largest number. There is an increasing number of new technologies such as cadmium-zinc-telluride (CZT) cardiac-dedicated gamma cameras, SPECT/computed tomography (CT), and PET/CT. All countries performed myocardial perfusion imaging studies, mainly gated-SPECT; the rest are multi-gated acquisition, mainly for cardiac toxicity; detection of viability; rest gated SPECT in patients with dilated cardiomyopathy, and bone-avid tracer cardiac scintigraphy for transthyretin cardiac amyloidosis diagnosis. Regarding other non-nuclear cardiac imaging modalities, Argentina, Colombia, and Chile have the highest ratio of CT scanners, while Brazil, Argentina, and Chile show the highest ratio of MRI scanners. The development of nuclear cardiology and other advanced imaging modalities is challenged by the high cost of equipment, lack of equipment maintenance and service, insufficient-specific training both for imaging specialists and referring clinicians, and lack of awareness of cardiologists or other referring physicians on the clinical applications of nuclear cardiology. Another important aspect to consider is the necessity of implementing cardiac imaging multimodality training. A joint work of nuclear medicine specialists, radiologists, cardiologists, and clinicians, in general, is mandatory to achieve this goal. National, regional, and international cooperation including support from scientific professional societies such as the American Society of Nuclear Cardiology and Latin American Association of Biology and Nuclear Medicine Societies, cardiological societies, and organizations such as the International Atomic Energy Agency, and Pan American Health Organization, as well as government commitment are key factors in the overall efforts to tackle the burden of cardiovascular diseases in the region.

Reproducibility of global LV function and dyssynchrony parameters derived from phase analysis of gated myocardial perfusion SPECT: A multicenter comparison with core laboratory setting.

BACKGROUND: Gated myocardial perfusion scintigraphy (GMPS) phase analysis is an important tool to investigate the physiology of left ventricular (LV) dyssynchrony. We aimed to test the performance of GMPS LV function and phase analysis in different clinical settings and on a diverse population. METHODS: This is a post hoc analysis of a prospective, non-randomized, multinational, multicenter cohort study. Clinical evaluation and GMPS prior to cardiac resynchronization therapy (CRT)(baseline) and 6-month post CRT (follow-up) were done. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), LV phase standard deviation (LVPSD), and percentage of left ventricle non-viable (PLVNV) were obtained by 10 centers and compared to the core lab. RESULTS: 276 GMPS studies had all data available from individual sites and from core lab. There were no statistically significant differences between all variables except for LVPSD. When subjects with no mechanical dyssynchrony were excluded, LVPSD difference became non-significant. LVESV, LVEF, LVPSD and PLVNV had strong correlation in site against core lab comparison. Bland-Altman plots demonstrated good agreement. CONCLUSIONS: The presented correlation and agreement of LV function and dyssynchrony analysis over different sites with a diverse sample corroborate the strength of GMPS in the management of heart failure in clinical practice.

A Gene Selection Method Based on Outliers for Breast Cancer Subtype Classification.

Breast cancer is the second most common cancer type and is the leading cause of cancer-related deaths worldwide. Since it is a heterogeneous disease, subtyping breast cancer plays an important role in performing a specific treatment. Gene expression data is a viable alternative to be employed on cancer subtype classification, as they represent the state of a cell at the molecular level, but generally has a relatively small number of samples compared to a large number of genes. Gene selection is a promising approach that addresses this uneven high-dimensional matrix of genes versus samples and plays an important role in the development of efficient cancer subtype classification. In this work, an innovative outlier-based gene selection (OGS) method is proposed to select relevant genes for efficiently and effectively classify breast cancer subtypes. Experiments show that our strategy presents an F1 score of 1.0 for basal and 0.86 for her 2, the two subtypes with the worst prognoses, respectively. Compared to other methods, our proposed method outperforms in the F1 score using 80% less genes. In general, our method selects only a few highly relevant genes, speeding up the classification, and significantly improving the classifier's performance.

SUBPLEX: A Visual Analytics Approach to Understand Local Model Explanations at the Subpopulation Level.

Understanding the interpretation of machine learning (ML) models has been of paramount importance when making decisions with societal impacts, such as transport control, financial activities, and medical diagnosis. While local explanation techniques are popular methods to interpret ML models on a single instance, they do not scale to the understanding of a model's behavior on the whole dataset. In this article, we outline the challenges and needs of visually analyzing local explanations and propose SUBPLEX, a visual analytics approach to help users understand local explanations with subpopulation visual analysis. SUBPLEX provides steerable clustering and projection visualization techniques that allow users to derive interpretable subpopulations of local explanations with users' expertise. We evaluate our approach through two use cases and experts' feedback.

Clinical and gated SPECT MPI parameters associated with super-response to cardiac resynchronization therapy.

PURPOSE: We sought to evaluate the behavior of cardiac mechanical synchrony as measured by phase SD (PSD) derived from gated MPI SPECT (gSPECT) in patients with super-response after CRT and to evaluate the clinical and imaging characteristics associated with super-response. METHODS: 158 subjects were evaluated with gSPECT before and 6 months after CRT. Patients with an improvement of LVEF > 15% and NYHA class I/II or reduction in LV end-systolic volume > 30% and NYHA class I/II were labeled as super-responders (SR). RESULTS: 34 patients were classified as super-responders (22%) and had lower PSD (32° ± 17°) at 6 months after CRT compared to responders (45° ± 24°) and non-responders 46° ± 28° (P = .02 for both comparisons). Regression analysis identified predictors independently associated with super-response to CRT: absence of previous history of CAD (odds ratio 18.7; P = .002), absence of diabetes mellitus (odds ratio 13; P = .03), and history of hypertension (odds ratio .2; P = .01). CONCLUSION: LV dyssynchrony after CRT implantation, but not at baseline, was significantly better among super-responders compared to non-super-responders. The absence of diabetes, absence of CAD, and history of hypertension were independently associated with super-response after CRT.

Incremental value of left ventricular shape parameters measured by gated SPECT MPI in predicting the super-response to CRT.

BACKGROUND: The purpose of this study was to evaluate the predictive value of left ventricular (LV) shape parameters measured by gated SPECT myocardial perfusion imaging (MPI) in super-responders enrolled in the VISION-CRT trial. METHODS: One hundred and ninety-nine patients who met standard criteria for CRT from multiple centers were enrolled in this study. End-systolic eccentricity (ESE) and end-diastolic eccentricity (EDE) were measures of LV shape. Super-responders were the patients who had a relative increase in left ventricular ejection fraction (LVEF) ≥ 15%. RESULTS: Complete data were obtained in 165 patients, and 43.6% of them were classified as super-responders. ESE was an independent predictor of CRT super-responders in univariate (OR 12.59, 95% CI 1.56-101.35, P = .017) and multivariate analysis (OR 35.71, 95% CI 1.66-766.03, P = .006). ESE had an incremental value over significant clinical and SPECT imaging variables, including angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker, coronary artery disease, myocardial infarction, LVEF, end-diastolic volume index, and scar burden (AUC 0.82 vs. 0.80, sensitivity 0.68 vs. 0.65, specificity 0.82 vs. 0.78). CONCLUSIONS: LV shape parameters derived from gated SPECT MPI have the promise to improve the prediction of the super-response to CRT. Moreover, ESE provides incremental value over existing clinical and nuclear imaging variables.

Assessing Antibiotic Tolerance of Staphylococcus aureus Derived Directly from Patients by the Replica Plating Tolerance Isolation System (REPTIS).

Antibiotic-tolerant Staphylococcus aureus poses a great challenge to clinicians as well as to microbiological laboratories and is one reason for treatment failure. Antibiotic-tolerant strains survive transient antibiotic exposure despite being fully susceptible in vitro. Thus, fast and reliable methods to detect tolerance in the routine microbiology laboratory are urgently required. We therefore evaluated the feasibility of the replica plating tolerance isolation system (REPTIS) to detect antibiotic tolerance in Staphylococcus aureus isolates derived directly from patients suffering from different types of infections and investigated possible connections to clinical presentations and patient characteristics. One hundred twenty-five S. aureus isolates were included. Replica plating of the original resistance testing plate was used to assess regrowth in the zones of inhibition, indicating antibiotic tolerance. Bacterial regrowth was assessed after 24 and 48 h of incubation, and an overall regrowth score (ORS) was assigned. Regrowth scores were compared to the clinical presentation. Bacterial regrowth was high for most antibiotics targeting protein synthesis and relatively low for antibiotics targeting other cellular functions such as DNA replication, transcription, and cell wall synthesis, with the exception of rifampin. Isolates with a blaZ penicillinase had lower regrowth in penicillin and ampicillin. Low ORSs were more prevalent among isolates recovered from patients with immunosuppression or methicillin-resistant S. aureus (MRSA) isolates. In conclusion, REPTIS is useful to detect antibiotic tolerance in clinical microbiological routine diagnostics. Further studies should evaluate the impact of rapid detection of antibiotic tolerance as a clinical decision-making tool for tailored antibiotic treatments.

CriPAV: Street-Level Crime Patterns Analysis and Visualization.

Extracting and analyzing crime patterns in big cities is a challenging spatiotemporal problem. The hardness of the problem is linked to two main factors, the sparse nature of the crime activity and its spread in large spatial areas. Sparseness hampers most time series (crime time series) comparison methods from working properly, while the handling of large urban areas tends to render the computational costs of such methods impractical. Visualizing different patterns hidden in crime time series data is another issue in this context, mainly due to the number of patterns that can show up in the time series analysis. In this article, we present a new methodology to deal with the issues above, enabling the analysis of spatiotemporal crime patterns in a street-level of detail. Our approach is made up of two main components designed to handle the spatial sparsity and spreading of crimes in large areas of the city. The first component relies on a stochastic mechanism from which one can visually analyze probable×intensive crime hotspots. Such analysis reveals important patterns that can not be observed in the typical intensity-based hotspot visualization. The second component builds upon a deep learning mechanism to embed crime time series in Cartesian space. From the embedding, one can identify spatial locations where the crime time series have similar behavior. The two components have been integrated into a web-based analytical tool called CriPAV (Crime Pattern Analysis and Visualization), which enables global as well as a street-level view of crime patterns. Developed in close collaboration with domain experts, CriPAV has been validated through a set of case studies with real crime data in São Paulo - Brazil. The provided experiments and case studies reveal the effectiveness of CriPAV in identifying patterns such as locations where crimes are not intense but highly probable to occur as well as locations that are far apart from each other but bear similar crime patterns.

Motion Analytics of Trapezius Muscle Activity in an 18-Year-Old Female with Extended Upper Brachial Plexus Birth Palsy.

Background The trapezius muscle is often utilized as a muscle or nerve donor for repairing shoulder function in those with brachial plexus birth palsy (BPBP). To evaluate the native role of the trapezius in the affected limb, we demonstrate use of the Motion Browser, a novel visual analytics system to assess an adolescent with BPBP. Method An 18-year-old female with extended upper trunk (C5-6-7) BPBP underwent bilateral upper extremity three-dimensional motion analysis with Motion Browser. Surface electromyography (EMG) from eight muscles in each limb which was recorded during six upper extremity movements, distinguishing between upper trapezius (UT) and lower trapezius (LT). The Motion Browser calculated active range of motion (AROM), compiled the EMG data into measures of muscle activity, and displayed the results in charts. Results All movements, excluding shoulder abduction, had similar AROM in affected and unaffected limbs. In the unaffected limb, LT was more active in proximal movements of shoulder abduction, and shoulder external and internal rotations. In the affected limb, LT was more active in distal movements of forearm pronation and supination; UT was more active in shoulder abduction. Conclusion In this female with BPBP, Motion Browser demonstrated that the native LT in the affected limb contributed to distal movements. Her results suggest that sacrificing her trapezius as a muscle or nerve donor may affect her distal functionality. Clinicians should exercise caution when considering nerve transfers in children with BPBP and consider individualized assessment of functionality before pursuing surgery.

Closed-Loop Versus Conventional Mechanical Ventilation in COVID-19 ARDS.

BACKGROUND: Lung-protective ventilation is key in bridging patients suffering from COVID-19 acute respiratory distress syndrome (ARDS) to recovery. However, resource and personnel limitations during pandemics complicate the implementation of lung-protective protocols. Automated ventilation modes may prove decisive in these settings enabling higher degrees of lung-protective ventilation than conventional modes. METHOD: Prospective study at a Swiss university hospital. Critically ill, mechanically ventilated COVID-19 ARDS patients were allocated, by study-blinded coordinating staff, to either closed-loop or conventional mechanical ventilation, based on mechanical ventilator availability. Primary outcome was the overall achieved percentage of lung-protective ventilation in closed-loop versus conventional mechanical ventilation, assessed minute-by-minute, during the initial 7 days and overall mechanical ventilation time. Lung-protective ventilation was defined as the combined target of tidal volume <8 ml per kg of ideal body weight, dynamic driving pressure <15 cmH2O, peak pressure <30 cmH2O, peripheral oxygen saturation ≥88% and dynamic mechanical power <17 J/min. RESULTS: Forty COVID-19 ARDS patients, accounting for 1,048,630 minutes (728 days) of cumulative mechanical ventilation, allocated to either closed-loop (n = 23) or conventional ventilation (n = 17), presenting with a median paO2/ FiO2 ratio of 92 [72-147] mmHg and a static compliance of 18 [11-25] ml/cmH2O, were mechanically ventilated for 11 [4-25] days and had a 28-day mortality rate of 20%. During the initial 7 days of mechanical ventilation, patients in the closed-loop group were ventilated lung-protectively for 65% of the time versus 38% in the conventional group (Odds Ratio, 1.79; 95% CI, 1.76-1.82; P < 0.001) and for 45% versus 33% of overall mechanical ventilation time (Odds Ratio, 1.22; 95% CI, 1.21-1.23; P < 0.001). CONCLUSION: Among critically ill, mechanically ventilated COVID-19 ARDS patients during an early highpoint of the pandemic, mechanical ventilation using a closed-loop mode was associated with a higher degree of lung-protective ventilation than was conventional mechanical ventilation.

Bacterial pulmonary superinfections are associated with longer duration of ventilation in critically ill COVID-19 patients.

The impact of secondary bacterial infections (superinfections) in coronavirus disease 2019 (COVID-19) is not well understood. In this prospective, monocentric cohort study, we aim to investigate the impact of superinfections in COVID-19 patients with acute respiratory distress syndrome. Patients are assessed for concomitant microbial infections by longitudinal analysis of tracheobronchial secretions, bronchoalveolar lavages, and blood cultures. In 45 critically ill patients, we identify 19 patients with superinfections (42.2%). Superinfections are detected on day 10 after intensive care admission. The proportion of participants alive and off invasive mechanical ventilation at study day 28 (ventilator-free days [VFDs] at 28 days) is substantially lower in patients with superinfection (subhazard ratio 0.37; 95% confidence interval [CI] 0.15-0.90; p = 0.028). Patients with pulmonary superinfections have a higher incidence of bacteremia, virus reactivations, yeast colonization, and required intensive care treatment for a longer time. Superinfections are frequent and associated with reduced VFDs at 28 days despite a high rate of empirical antibiotic therapy.

Capillary Leukocytes, Microaggregates, and the Response to Hypoxemia in the Microcirculation of Coronavirus Disease 2019 Patients.

OBJECTIVES: In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia. DESIGN: Multicenter case-controlled study. SETTING: Two ICUs in The Netherlands and one in Switzerland. PATIENTS: Thirty-four critically ill coronavirus disease 2019 patients were compared with 33 healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The microcirculatory parameters quantified included total vessel density (mm × mm-2), functional capillary density (mm × mm-2), proportion of perfused vessels (%), capillary hematocrit (%), the ratio of capillary hematocrit to systemic hematocrit, and capillary RBC velocity (µm × s-1). The number of leukocytes in capillary-postcapillary venule units per 4-second image sequence (4 s-1) and capillary RBC microaggregates (4 s-1) was measured. In comparison with healthy volunteers, the microcirculation of coronavirus disease 2019 patients showed increases in total vessel density (22.8 ± sd 5.1 vs 19.9 ± 3.3; p < 0.0001) and functional capillary density (22.2 ± 4.8 vs 18.8 ± 3.1; p < 0.002), proportion of perfused vessel (97.6 ± 2.1 vs 94.6 ± 6.5; p < 0.01), RBC velocity (362 ± 48 vs 306 ± 53; p < 0.0001), capillary hematocrit (5.3 ± 1.3 vs 4.7 ± 0.8; p < 0.01), and capillary-hematocrit-to-systemic-hematocrit ratio (0.18 ± 0.0 vs 0.11 ± 0.0; p < 0.0001). These effects were present in coronavirus disease 2019 patients with Sequential Organ Failure Assessment scores less than 10 but not in patients with Sequential Organ Failure Assessment scores greater than or equal to 10. The numbers of leukocytes (17.6 ± 6.7 vs 5.2 ± 2.3; p < 0.0001) and RBC microaggregates (0.90 ± 1.12 vs 0.06 ± 0.24; p < 0.0001) was higher in the microcirculation of the coronavirus disease 2019 patients. Receiver-operating-characteristics analysis of the microcirculatory parameters identified the number of microcirculatory leukocytes and the capillary-hematocrit-to-systemic-hematocrit ratio as the most sensitive parameters distinguishing coronavirus disease 2019 patients from healthy volunteers. CONCLUSIONS: The response of the microcirculation to coronavirus disease 2019-induced hypoxemia seems to be to increase its oxygen-extraction capacity by increasing RBC availability. Inflammation and hypercoagulation are apparent in the microcirculation by increased numbers of leukocytes and RBC microaggregates.

Emergence of MDR invasive Neisseria meningitidis in El Salvador, 2017-19.

BACKGROUND: Invasive meningococcal disease (IMD) is an acute, highly transmissible and potentially fatal disease caused by Neisseria meningitidis. Prompt antimicrobial therapy and prophylaxis are recommended, where penicillin or ciprofloxacin are the available choices. However, the emergence of resistant isolates of N. meningitidis poses a challenge for antimicrobial therapy. OBJECTIVES: To describe the clinical, epidemiological and biological characteristics of six penicillin- and ciprofloxacin-resistant, culture-confirmed IMD cases reported in El Salvador, Central America, between 2017 and 2019. METHODS: Following the detection of six patients presenting with IMD in El Salvador, clinical data were collected and epidemiological action plans conducted. Isolates were subjected to antimicrobial susceptibility testing by broth microdilution and WGS for genotyping and molecular characterization analysis, including phylogeny comparison with global sequences available from public databases. RESULTS: A total of six IMD cases caused by N. meningitidis serogroup Y, resistant to both penicillin (MIC >8.0 mg/L) and ciprofloxacin (MIC 0.125 mg/L), were detected from 2017 to 2019. Genomic analysis showed that penicillin resistance was mediated by the production of ß-lactamase ROB-1. Ciprofloxacin resistance was attributed to an amino acid substitution in DNA gyrase (T91I). All isolates were classified as ST3587, clonal complex 23, and were genetically highly similar, based on core-genome SNP analysis. CONCLUSIONS: To the best of our knowledge, we report the first cases of MDR N. meningitidis causing IMD in Latin America. Our findings highlight the emergence of this potential public health threat, with a profound impact on the efficacy of IMD treatment and prophylaxis protocols.

Value of intraventricular dyssynchrony assessment by gated-SPECT myocardial perfusion imaging in the management of heart failure patients undergoing cardiac resynchronization therapy (VISION-CRT).

BACKGROUND: Placing the left ventricular (LV) lead in a viable segment with the latest mechanical activation (vSOLA) may be associated with optimal cardiac resynchronization therapy (CRT) response. We assessed the role of gated SPECT myocardial perfusion imaging (gSPECT MPI) in predicting clinical outcomes at 6 months in patients submitted to CRT. METHODS: Ten centers from 8 countries enrolled 195 consecutive patients. All underwent gSPECT MPI before and 6 months after CRT. The procedure was performed as per current guidelines, the operators being unaware of gSPECT MPI results. Regional LV dyssynchrony (Phase SD) and vSOLA were automatically determined using a 17 segment model. The lead was considered on-target if placed in vSOLA. The primary outcome was improvement in ≥1 of the following: ≥1 NYHA class, left ventricular ejection fraction (LVEF) by ≥5%, reduction in end-systolic volume by ≥15%, and ≥5 points in Minnesota Living With Heart Failure Questionnaire (MLHFQ). RESULTS: Sixteen patients died before the follow-up gSPECT MPI. The primary outcome occurred in 152 out of 179 (84.9%) cases. Mean change in LV phase standard deviation (PSD) at 6 months was 10.5°. Baseline dyssynchrony was not associated with the primary outcome. However, change in LV PSD from baseline was associated with the primary outcome (OR 1.04, 95% CI 1.01-1.07, P = .007). Change in LV PSD had an AUC of 0.78 (0.66-0.90) for the primary outcome. Improvement in LV PSD of 4° resulted in the highest positive likelihood ratio of 7.4 for a favorable outcome. In 23% of the patients, the CRT lead was placed in the vSOLA, and in 42% in either this segment or in a segment within 10° of it. On-target lead placement was not significantly associated with the primary outcome (OR 1.53, 95% CI 0.71-3.28). CONCLUSION: LV dyssynchrony improvement by gSPECT MPI, but not on-target lead placement, predicts clinical outcomes in patients undergoing CRT.

CrimAnalyzer: Understanding Crime Patterns in São Paulo.

São Paulo is the largest city in South America, with crime rates that reflect its size. The number and type of crimes vary considerably around the city, assuming different patterns depending on urban and social characteristics of each particular location. Previous works have mostly focused on the analysis of crimes with the intent of uncovering patterns associated to social factors, seasonality, and urban routine activities. Therefore, those studies and tools are more global in the sense that they are not designed to investigate specific regions of the city such as particular neighborhoods, avenues, or public areas. Tools able to explore specific locations of the city are essential for domain experts to accomplish their analysis in a bottom-up fashion, revealing how urban features related to mobility, passersby behavior, and presence of public infrastructures (e.g., terminals of public transportation and schools) can influence the quantity and type of crimes. In this paper, we present CrimAnalyzer, a visual analytic tool that allows users to study the behavior of crimes in specific regions of a city. The system allows users to identify local hotspots and the pattern of crimes associated to them, while still showing how hotspots and corresponding crime patterns change over time. CrimAnalyzer has been developed from the needs of a team of experts in criminology and deals with three major challenges: i) flexibility to explore local regions and understand their crime patterns, ii) identification of spatial crime hotspots that might not be the most prevalent ones in terms of the number of crimes but that are important enough to be investigated, and iii) understand the dynamic of crime patterns over time. The effectiveness and usefulness of the proposed system are demonstrated by qualitative and quantitative comparisons as well as by case studies run by domain experts involving real data. The experiments show the capability of CrimAnalyzer in identifying crime-related phenomena.

Diastolic dyssynchrony assessment by gated myocardial perfusion-SPECT in subjects who underwent cardiac resynchronization therapy.

BACKGROUND: Left ventricular diastolic dyssynchrony (LVDD) can be assessed by gated myocardial perfusion single-photon emission computed tomography (GMP-SPECT). LVDD is an area of interest in subjects who underwent cardiac resynchronization therapy (CRT). The aim of this post hoc analysis was to assess the role of LVDD in subjects with CRT who were followed up at 6-month period. MATERIAL & METHODS: Left ventricular diastolic dyssynchrony was assessed by GMP-SPECT at baseline and after CRT procedure in 160 subjects from 10 different cardiological centers. CRT procedure was performed as per current guidelines. Outcomes were defined as improvement in ≥1 New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF) by 5%, and reduction in end-systolic volume (ESV) by 15% and 5% points in Minnesota Living with Heart Failure Questionnaire. LVDD was defined as diastolic phase standard deviation ≥40 ± 14°. RESULTS: Improvement in NYHA functional class occurred in 105 (65.6%), LVEF in 74 (46.3%), decrease in ESV in 86 (53.8%), and Minnesota score in 85 (53.1%) cases. Baseline LV diastolic standard deviation was 53.53° ± 20.85 and at follow-up 40.44° ± 26.1283; (P < 0.001). LVDD was not associated with improvement in clinical outcomes at follow-up. CONCLUSION: CRT improves both systolic and diastolic dyssynchrony values at 6-month follow-up. LVDD at baseline is correlated with cardiac functionality at follow-up, but not with overall favorable clinical outcomes.