Vitamin B12 status in hospitalised cancer patients: Prevalence and clinical implications of depletion and hypervitaminosis.

BACKGROUND & AIMS: The prevalence and clinical significance of vitamin B12 alterations in patients with cancer are poorly understood. We aimed to assess the prevalence and risk factors of vitamin B12 depletion or hypervitaminosis in patients with cancer. METHODS: We retrospectively included hospitalised patients with cancer in 2017-2022. Plasma B12 levels were stratified as very low (VL, <200 pg/ml), low (L, 200-299 pg/ml), normal (N, 300-812 pg/ml), or high (H, ≥813 pg/ml). We collected demographic and several clinical data (e.g., comorbidities, nutritional status, ECOG-PS, cancer site and stage). Univariate and multivariate analyses for factors associated to the vitamin B12 status were fitted. RESULTS: 788 patients (F/M ratio 1.05, median age 72 years, [25th, 75th percentiles 62, 78 years]) were included. Vitamin B12 was VL in 14.1%, L in 19.4%, N in 49.4%, and H in 17.1% cases. Vitamin B12 distribution increased significantly as function of ECOG-PS levels. Patients with breast cancer were characterized by the highest median B12 value, while colorectal cancer patients by the lowest. Vitamin B12 was also significantly higher in advanced compared to early-stage patients as well as in those who had liver failure. Multivariate analysis showed that the probability of H vs. VL B12 levels was significantly increased in patients with hypoproteinemia, hypo-prealbuminemia, and ECOG-PS≥2, and decreased in those with colorectal and gastric cancer. CONCLUSION: Vitamin B12 impairment is common in cancer patients. Increased vitamin B12 is associated with an impaired clinical status, while vitamin B12 depletion is more common in early-stage cancer and in elderly patients.

Clinical outcome predictors for metastatic renal cell carcinoma: a retrospective multicenter real-life case series.

Over the last decades, the therapeutic armamentarium of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of tyrosin-kinase inhibitors (TKI), immune-checkpoint inhibitors (ICI), and immune-combinations. RCC is heterogeneous, and even the most used validated prognostic systems, fail to describe its evolution in real-life scenarios. Our aim is to identify potential easily-accessible clinical factors and design a disease course prediction system. Medical records of 453 patients with mRCC receiving sequential systemic therapy in two high-volume oncological centres were reviewed. The Kaplan-Meier method and Cox proportional hazard model were used to estimate and compare survival between groups. As first-line treatment 366 patients received TKI monotherapy and 64 patients received ICI, alone or in combination. The mean number of therapy lines was 2.5. A high Systemic Inflammation Index, a BMI under 25 Kg/m2, the presence of bone metastases before systemic therapy start, age over 65 years at the first diagnosis, non-clear-cell histology and sarcomatoid component were correlated with a worse OS. No significant OS difference was observed between patients receiving combination therapies and those receiving exclusively monotherapies in the treatment sequence. Our relapse prediction system based on pathological stage and histological grade was effective in predicting the time between nephrectomy and systemic treatment. Our multicentric retrospective analysis reveals additional potential prognostic factors for mRCC, not included in current validated prognostic systems, suggests a model for disease course prediction and describes the outcomes of the most common therapeutic strategies currently available.

Neurological diagnoses in hospitalized COVID-19 patients associated with adverse outcomes: A multinational cohort study.

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients <18 years, January 2020-October 2021), 15,101 (14%) had at least one CNS diagnosis, while 2,788 (3%) had at least one PNS diagnosis. After controlling for demographics and pre-existing conditions, adults with CNS involvement had longer hospital stay (11 versus 6 days) and greater risk of (Hazard Ratio = 1.78) and faster time to death (12 versus 24 days) than patients with no neurological condition (NNC) during acute COVID-19 hospitalization. Adults with PNS involvement also had longer hospital stay but lower risk of mortality than the NNC group. Although children had a low frequency of neurological involvement during COVID-19 hospitalization, a substantially higher proportion of children with CNS involvement died compared to those with NNC (6% vs 1%). Overall, patients with concurrent CNS manifestation during acute COVID-19 hospitalization faced greater risks for adverse clinical outcomes than patients without any neurological diagnosis. Our global informatics framework using a federated approach (versus a centralized data collection approach) has utility for clinical discovery beyond COVID-19.

An eHealth App (CAPABLE) Providing Symptom Monitoring, Well-Being Interventions, and Educational Material for Patients With Melanoma Treated With Immune Checkpoint Inhibitors: Protocol for an Exploratory Intervention Trial.

BACKGROUND: Since treatment with immune checkpoint inhibitors (ICIs) is becoming standard therapy for patients with high-risk and advanced melanoma, an increasing number of patients experience treatment-related adverse events such as fatigue. Until now, studies have demonstrated the benefits of using eHealth tools to provide either symptom monitoring or interventions to reduce treatment-related symptoms such as fatigue. However, an eHealth tool that facilitates the combination of both symptom monitoring and symptom management in patients with melanoma treated with ICIs is still needed. OBJECTIVE: In this pilot study, we will explore the use of the CAPABLE (Cancer Patients Better Life Experience) app in providing symptom monitoring, education, and well-being interventions on health-related quality of life (HRQoL) outcomes such as fatigue and physical functioning, as well as patients' acceptance and usability of using CAPABLE. METHODS: This prospective, exploratory pilot study will examine changes in fatigue over time in 36 patients with stage III or IV melanoma during treatment with ICI using CAPABLE (a smartphone app and multisensory smartwatch). This cohort will be compared to a prospectively collected cohort of patients with melanoma treated with standard ICI therapy. CAPABLE will be used for a minimum of 3 and a maximum of 6 months. The primary endpoint in this study is the change in fatigue between baseline and 3 and 6 months after the start of treatment. Secondary end points include HRQoL outcomes, usability, and feasibility parameters. RESULTS: Study inclusion started in April 2023 and is currently ongoing. CONCLUSIONS: This pilot study will explore the effect, usability, and feasibility of CAPABLE in patients with melanoma during treatment with ICI. Adding the CAPABLE system to active treatment is hypothesized to decrease fatigue in patients with high-risk and advanced melanoma during treatment with ICIs compared to a control group receiving standard care. The Medical Ethics Committee NedMec (Amsterdam, The Netherlands) granted ethical approval for this study (reference number 22-981/NL81970.000.22). TRIAL REGISTRATION: ClinicalTrials.gov NCT05827289; https://clinicaltrials.gov/study/NCT05827289. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49252.

Artificial intelligence-based prediction of overall survival in metastatic renal cell carcinoma.

Background and objectives: Investigations of the prognosis are vital for better patient management and decision-making in patients with advanced metastatic renal cell carcinoma (mRCC). The purpose of this study is to evaluate the capacity of emerging Artificial Intelligence (AI) technologies to predict three- and five-year overall survival (OS) for mRCC patients starting their first-line of systemic treatment. Patients and methods: The retrospective study included 322 Italian patients with mRCC who underwent systemic treatment between 2004 and 2019. Statistical analysis included the univariate and multivariate Cox proportional-hazard model and the Kaplan-Meier analysis for the prognostic factors' investigation. The patients were split into a training cohort to establish the predictive models and a hold-out cohort to validate the results. The models were evaluated by the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. We assessed the clinical benefit of the models using decision curve analysis (DCA). Then, the proposed AI models were compared with well-known pre-existing prognostic systems. Results: The median age of patients in the study was 56.7 years at RCC diagnosis and 78% of participants were male. The median survival time from the start of systemic treatment was 29.2 months; 95% of the patients died during the follow-up that finished by the end of 2019. The proposed predictive model, which was constructed as an ensemble of three individual predictive models, outperformed all well-known prognostic models to which it was compared. It also demonstrated better usability in supporting clinical decisions for 3- and 5-year OS. The model achieved (0.786 and 0.771) AUC and (0.675 and 0.558) specificity at sensitivity 0.90 for 3 and 5 years, respectively. We also applied explainability methods to identify the important clinical features that were found to be partially matched with the prognostic factors identified in the Kaplan-Meier and Cox analyses. Conclusions: Our AI models provide best predictive accuracy and clinical net benefits over well-known prognostic models. As a result, they can potentially be used in clinical practice for providing better management for mRCC patients starting their first-line of systemic treatment. Larger studies would be needed to validate the developed model.

Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study.

Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1-365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53-3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03-4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55-5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14-1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37-0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17-1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20-1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45-1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80-13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10-1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32-1.67) and 365 days (RR 1.54, 95%CI 1.21-1.96) compared to COVID-19 patients with no AKI. Interpretation: COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery. Funding: Authors are supported by various funders, with full details stated in the acknowledgement section.

Prognostic Potential of Immune Inflammatory Biomarkers in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy.

Immune inflammatory biomarkers are easily obtained and inexpensive blood-based parameters that recently showed prognostic and predictive value in many solid tumors. In this study, we aimed to investigate the role of these biomarkers in predicting distant relapse in breast cancer patients treated with neoadjuvant chemotherapy (NACT). All breast cancer patients who referred to our Breast Unit and underwent NACT were retrospectively reviewed. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) were calculated from complete blood counts. The primary outcome was 5-year distant-metastasis-free survival (DMFS). In receiver operating characteristic analyses, the optimal cutoff values for the NLR, PLR, MLR, and PIV were determined at 2.25, 152.46, 0.25, and 438.68, respectively. High levels of the MLR, but not the NLR, PLR, or PIV, were associated with improved 5-year DMSF in the study population using both univariate (HR 0.52, p = 0.03) and multivariate analyses (HR, 0.44; p = 0.02). Our study showed that the MLR was a significant independent parameter affecting DMFS in breast cancer patients undergoing NACT. Prospective studies are required to confirm this finding and to define reliable cutoff values, thus leading the way for the clinical application of this biomarker.

SurvMaximin: Robust federated approach to transporting survival risk prediction models.

OBJECTIVE: For multi-center heterogeneous Real-World Data (RWD) with time-to-event outcomes and high-dimensional features, we propose the SurvMaximin algorithm to estimate Cox model feature coefficients for a target population by borrowing summary information from a set of health care centers without sharing patient-level information. MATERIALS AND METHODS: For each of the centers from which we want to borrow information to improve the prediction performance for the target population, a penalized Cox model is fitted to estimate feature coefficients for the center. Using estimated feature coefficients and the covariance matrix of the target population, we then obtain a SurvMaximin estimated set of feature coefficients for the target population. The target population can be an entire cohort comprised of all centers, corresponding to federated learning, or a single center, corresponding to transfer learning. RESULTS: Simulation studies and a real-world international electronic health records application study, with 15 participating health care centers across three countries (France, Germany, and the U.S.), show that the proposed SurvMaximin algorithm achieves comparable or higher accuracy compared with the estimator using only the information of the target site and other existing methods. The SurvMaximin estimator is robust to variations in sample sizes and estimated feature coefficients between centers, which amounts to significantly improved estimates for target sites with fewer observations. CONCLUSIONS: The SurvMaximin method is well suited for both federated and transfer learning in the high-dimensional survival analysis setting. SurvMaximin only requires a one-time summary information exchange from participating centers. Estimated regression vectors can be very heterogeneous. SurvMaximin provides robust Cox feature coefficient estimates without outcome information in the target population and is privacy-preserving.

Changes in laboratory value improvement and mortality rates over the course of the pandemic: an international retrospective cohort study of hospitalised patients infected with SARS-CoV-2.

OBJECTIVE: To assess changes in international mortality rates and laboratory recovery rates during hospitalisation for patients hospitalised with SARS-CoV-2 between the first wave (1 March to 30 June 2020) and the second wave (1 July 2020 to 31 January 2021) of the COVID-19 pandemic. DESIGN, SETTING AND PARTICIPANTS: This is a retrospective cohort study of 83 178 hospitalised patients admitted between 7 days before or 14 days after PCR-confirmed SARS-CoV-2 infection within the Consortium for Clinical Characterization of COVID-19 by Electronic Health Record, an international multihealthcare system collaborative of 288 hospitals in the USA and Europe. The laboratory recovery rates and mortality rates over time were compared between the two waves of the pandemic. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was all-cause mortality rate within 28 days after hospitalisation stratified by predicted low, medium and high mortality risk at baseline. The secondary outcome was the average rate of change in laboratory values during the first week of hospitalisation. RESULTS: Baseline Charlson Comorbidity Index and laboratory values at admission were not significantly different between the first and second waves. The improvement in laboratory values over time was faster in the second wave compared with the first. The average C reactive protein rate of change was -4.72 mg/dL vs -4.14 mg/dL per day (p=0.05). The mortality rates within each risk category significantly decreased over time, with the most substantial decrease in the high-risk group (42.3% in March-April 2020 vs 30.8% in November 2020 to January 2021, p<0.001) and a moderate decrease in the intermediate-risk group (21.5% in March-April 2020 vs 14.3% in November 2020 to January 2021, p<0.001). CONCLUSIONS: Admission profiles of patients hospitalised with SARS-CoV-2 infection did not differ greatly between the first and second waves of the pandemic, but there were notable differences in laboratory improvement rates during hospitalisation. Mortality risks among patients with similar risk profiles decreased over the course of the pandemic. The improvement in laboratory values and mortality risk was consistent across multiple countries.

International electronic health record-derived post-acute sequelae profiles of COVID-19 patients.

The risk profiles of post-acute sequelae of COVID-19 (PASC) have not been well characterized in multi-national settings with appropriate controls. We leveraged electronic health record (EHR) data from 277 international hospitals representing 414,602 patients with COVID-19, 2.3 million control patients without COVID-19 in the inpatient and outpatient settings, and over 221 million diagnosis codes to systematically identify new-onset conditions enriched among patients with COVID-19 during the post-acute period. Compared to inpatient controls, inpatient COVID-19 cases were at significant risk for angina pectoris (RR 1.30, 95% CI 1.09-1.55), heart failure (RR 1.22, 95% CI 1.10-1.35), cognitive dysfunctions (RR 1.18, 95% CI 1.07-1.31), and fatigue (RR 1.18, 95% CI 1.07-1.30). Relative to outpatient controls, outpatient COVID-19 cases were at risk for pulmonary embolism (RR 2.10, 95% CI 1.58-2.76), venous embolism (RR 1.34, 95% CI 1.17-1.54), atrial fibrillation (RR 1.30, 95% CI 1.13-1.50), type 2 diabetes (RR 1.26, 95% CI 1.16-1.36) and vitamin D deficiency (RR 1.19, 95% CI 1.09-1.30). Outpatient COVID-19 cases were also at risk for loss of smell and taste (RR 2.42, 95% CI 1.90-3.06), inflammatory neuropathy (RR 1.66, 95% CI 1.21-2.27), and cognitive dysfunction (RR 1.18, 95% CI 1.04-1.33). The incidence of post-acute cardiovascular and pulmonary conditions decreased across time among inpatient cases while the incidence of cardiovascular, digestive, and metabolic conditions increased among outpatient cases. Our study, based on a federated international network, systematically identified robust conditions associated with PASC compared to control groups, underscoring the multifaceted cardiovascular and neurological phenotype profiles of PASC.

A Process Mining Pipeline to Characterize COVID-19 Patients' Trajectories and Identify Relevant Temporal Phenotypes From EHR Data.

The impact of the COVID-19 pandemic involved the disruption of the processes of care and the need for immediately effective re-organizational procedures. In the context of digital health, it is of paramount importance to determine how a specific patients' population reflects into the healthcare dynamics of the hospital, to investigate how patients' sub-group/strata respond to the different care processes, in order to generate novel hypotheses regarding the most effective healthcare strategies. We present an analysis pipeline based on the heterogeneous collected data aimed at identifying the most frequent healthcare processes patterns, jointly analyzing them with demographic and physiological disease trajectories, and stratify the observed cohort on the basis of the mined patterns. This is a process-oriented pipeline which integrates process mining algorithms, and trajectory mining by topological data analyses and pseudo time approaches. Data was collected for 1,179 COVID-19 positive patients, hospitalized at the Italian Hospital "Istituti Clinici Salvatore Maugeri" in Lombardy, integrating different sources including text admission letters, EHR and hospital infrastructure data. We identified five temporal phenotypes, from laboratory values trajectories, which are characterized by statistically significant different death risk estimates. The process mining algorithms allowed splitting the data in sub-cohorts as function of the pandemic waves and of the temporal trajectories showing statistically significant differences in terms of events characteristics.

Obstructive Sleep Apnea Home-Monitoring Using a Commercial Wearable Device.

Obstructive sleep apnea (OSA) is a common sleep disorder and polysomnography (PSG) is the gold standard for its diagnosis and treatment monitoring. There are nowadays several activity trackers measuring sleep quality through the detection of sleep stages. To allow an easier monitoring of the treatment efficacy at home, this work explores the possibility of using one of those commercial smart-bands. To this aim, we studied the signals provided by PSG and a Fitbit smart-band on 26 consecutive patients, admitted to the hospital after the diagnosis of OSA, and submitted to ventilation or positional treatment. They underwent monitoring for three nights (basal, titration, and control). We developed both a visualization software allowing doctors to visually compare the two hypnograms, and a set of statistics for assessing the concordance of the two methods. Results indicate that Fitbit can detect normal sleep patterns, while it is less able to detect the abnormal ones.

Personalising Symptoms Reporting in Telemonitoring Applications for Cancer Patients.

Patient reported outcomes have been shown to be predictive of cancer patients' prognosis, and their monitoring through electronic applications have been shown to positively impact survival. On the other hand, patient apps in general show a number of criticalities that often lead patients to abandon their use. One of them is usability. A scarce attention to usability during app development leads to unsatisfactory user experience. In this work, we present an algorithm to facilitate patient symptoms reporting, by personalising the list of symptoms according to their probability of occurrence in the specific patient. This avoids searching long lists of items, thus decreasing the patients' burden in symptom reporting.

Association of improvement in functional capacity after rehabilitation with long-term survival in heart failure.

BACKGROUND: The prognostic value of change in six-minute walking distance (6MWD) after treatment to predict mortality in heart failure (HF) remains a controversial issue. We assessed the prognostic value of rehabilitation-induced improvement in 6MWD in predicting mortality in patients with HF. METHODS: We studied 2257 patients admitted to six inpatient rehabilitation facilities after a hospitalization for HF (N. 912) or because of worsening functional capacity and/or deteriorating clinical status (N. 1345). A six-minute walking test was performed at admission and discharge. The primary outcome was 3-year all-cause mortality after discharge from cardiac rehabilitation. We used multivariable Cox proportional hazard modeling to assess the association of increase in 6MWD with 3-year mortality, adjusting for established predictors of mortality. RESULTS: 6MWD significantly increased by 61 m (p < .001) from admission to discharge and 969 patients (42.9%) achieved an increase in 6MWD >50 m. After full adjustment, an increase in 6MWD >50 m was associated with a 22% decreased risk for 3-year mortality (HR 0.78 [95% CI 0.68-0.91]; p = .002). When modeled as a continuous variable, improvement in 6MWD remained independently associated with decreased risk for 3-year mortality (HR per each 50 m increase: 0.92 [95% CI 0.88-0.96]). CONCLUSIONS: Rehabilitation-induced improvement in 6MWD was associated with a significantly reduced risk for 3-year mortality. Our data also suggest that an improvement in 6MWD of more than 50 m could represent a clinically meaningful endpoint of cardiac rehabilitation for patients with heart failure.

Preoperative Systemic Inflammatory Biomarkers Are Independent Predictors of Disease Recurrence in ER+ HER2- Early Breast Cancer.

The host's immune system plays a crucial role in determining the clinical outcome of many cancers, including breast cancer. Peripheral blood neutrophils and lymphocytes counts may be surrogate markers of systemic inflammation and potentially reflect survival outcomes. The aim of the present study is to assess the role of preoperative systemic inflammatory biomarkers to predict local or distant relapse in breast cancer. In particular we investigated ER+ HER2- early breast cancer, considering its challenging risk stratification. A total of 1,763 breast cancer patients treated at tertiary referral Breast Unit were reviewed. Neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte (LMR) ratios were assessed from the preoperative blood counts. Multivariate analyses for 5-years locoregional recurrence-free (LRRFS), distant metastases-free (DMFS) and disease-free survivals (DFS) were performed, taking into account both blood inflammatory biomarkers and clinical-pathological variables. Low NLR and high LMR were independent predictors of longer LRRFS, DMFS and DFS, and low PLR was predictive of better LRRFS and DMFS in the study population. In 999 ER+ HER2- early breast cancers, high PLR was predictive of worse LRRFS (HR 0.42, p=0.009), while high LMR was predictive of improved LRRFS (HR 2.20, p=0.02) and DFS (HR 2.10, p=0.01). NLR was not an independent factor of 5-years survival in this patients' subset. Inflammatory blood biomarkers and current clinical assessment of the disease were not in agreement in terms of estimate of relapse risk (K-Cohen from -0.03 to 0.02). In conclusion, preoperative lymphocyte ratios, in particular PLR and LMR, showed prognostic relevance in ER+ HER2- early breast cancer. Therefore, they may be used in risk stratification and therapy escalation/de-escalation in patients with this type of tumor.

Exploring the inter-subject variability in the relationship between glucose monitoring metrics and glycated hemoglobin for pediatric patients with type 1 diabetes.

OBJECTIVES: Despite the widespread diffusion of continuous glucose monitoring (CGM) systems, which includes both real-time CGM (rtCGM) and intermittently scanned CGM (isCGM), an effective application of CGM technology in clinical practice is still limited. The study aimed to investigate the relationship between isCGM-derived glycemic metrics and glycated hemoglobin (HbA1c), identifying overall CGM targets and exploring the inter-subject variability. METHODS: A group of 27 children and adolescents with type 1 diabetes under multiple daily injection insulin-therapy was enrolled. All participants used the isCGM Abbott's FreeStyle Libre system on average for eight months, and clinical data were collected from the Advanced Intelligent Distant-Glucose Monitoring platform. Starting from each HbA1c exam date, windows of past 30, 60, and 90 days were considered to compute several CGM metrics. The relationships between HbA1c and each metric were explored through linear mixed models, adopting an HbA1c target of 7%. RESULTS: Time in Range and Time in Target Range show a negative relationship with HbA1c (R2>0.88) whereas Time Above Range and Time Severely Above Range show a positive relationship (R2>0.75). Focusing on Time in Range in 30-day windows, random effect represented by the patient's specific intercept reveals a high variability compared to the overall population intercept. CONCLUSIONS: This study confirms the relationship between several CGM metrics and HbA1c; it also highlights the importance of an individualized interpretation of the CGM data.

Validation of an internationally derived patient severity phenotype to support COVID-19 analytics from electronic health record data.

OBJECTIVE: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) is an international collaboration addressing coronavirus disease 2019 (COVID-19) with federated analyses of electronic health record (EHR) data. We sought to develop and validate a computable phenotype for COVID-19 severity. MATERIALS AND METHODS: Twelve 4CE sites participated. First, we developed an EHR-based severity phenotype consisting of 6 code classes, and we validated it on patient hospitalization data from the 12 4CE clinical sites against the outcomes of intensive care unit (ICU) admission and/or death. We also piloted an alternative machine learning approach and compared selected predictors of severity with the 4CE phenotype at 1 site. RESULTS: The full 4CE severity phenotype had pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of individual code categories for acuity had high variability-up to 0.65 across sites. At one pilot site, the expert-derived phenotype had mean area under the curve of 0.903 (95% confidence interval, 0.886-0.921), compared with an area under the curve of 0.956 (95% confidence interval, 0.952-0.959) for the machine learning approach. Billing codes were poor proxies of ICU admission, with as low as 49% precision and recall compared with chart review. DISCUSSION: We developed a severity phenotype using 6 code classes that proved resilient to coding variability across international institutions. In contrast, machine learning approaches may overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold-standard outcomes, possibly owing to heterogeneous pandemic conditions. CONCLUSIONS: We developed an EHR-based severity phenotype for COVID-19 in hospitalized patients and validated it at 12 international sites.

Evolving determinants of carotid atherosclerosis vulnerability in asymptomatic patients from the MAGNETIC observational study.

MRI can assess plaque composition and has demonstrated an association between some atherosclerotic risk factors (RF) and markers of plaque vulnerability in naive patients. We aimed at investigating this association in medically treated asymptomatic patients. This is a cross-sectional interim analysis (August 2013-September 2016) of a single center prospective study on carotid plaque vulnerability (MAGNETIC study). We recruited patients with asymptomatic carotid atherosclerosis (US stenosis > 30%, ECST criteria), receiving medical treatments at a tertiary cardiac rehabilitation. Atherosclerotic burden and plaque composition were quantified with 3.0 T MRI. The association between baseline characteristics and extent of lipid-rich necrotic core (LRNC), fibrous cap (CAP) and intraplaque hemorrhage (IPH) was studied with multiple regression analysis. We enrolled 260 patients (198 male, 76%) with median age of 71-y (interquartile range: 65-76). Patients were on antiplatelet therapy, ACE-inhibitors/angiotensin receptor blockers and statins (196-229, 75-88%). Median LDL-cholesterol was 78 mg/dl (59-106), blood pressure 130/70 mmHg (111-140/65-80), glycosylated hemoglobin 46 mmol/mol (39-51) and BMI 25 kg/m2 (23-28); moreover, 125 out of 187 (67%) patients were ex-smokers. Multivariate analysis of a data-set of 487 (94%) carotid arteries showed that a history of hypercholesterolemia, diabetes, hypertension or smoking did not correlate with LRNC, CAP or IPH. Conversely, maximum stenosis was the strongest independent predictor of LRNC, CAP and IPH (p < 0.001). MRI assessment of plaque composition in patients on treatment for asymptomatic carotid atherosclerosis shows no correlation between plaque vulnerability and the most well-controlled modifiable RF. Conversely, maximum stenosis exhibits a strong correlation with vulnerable features despite treatment.

Health informatics and EHR to support clinical research in the COVID-19 pandemic: an overview.

The coronavirus disease 2019 (COVID-19) pandemic has clearly shown that major challenges and threats for humankind need to be addressed with global answers and shared decisions. Data and their analytics are crucial components of such decision-making activities. Rather interestingly, one of the most difficult aspects is reusing and sharing of accurate and detailed clinical data collected by Electronic Health Records (EHR), even if these data have a paramount importance. EHR data, in fact, are not only essential for supporting day-by-day activities, but also they can leverage research and support critical decisions about effectiveness of drugs and therapeutic strategies. In this paper, we will concentrate our attention on collaborative data infrastructures to support COVID-19 research and on the open issues of data sharing and data governance that COVID-19 had made emerge. Data interoperability, healthcare processes modelling and representation, shared procedures to deal with different data privacy regulations, and data stewardship and governance are seen as the most important aspects to boost collaborative research. Lessons learned from COVID-19 pandemic can be a strong element to improve international research and our future capability of dealing with fast developing emergencies and needs, which are likely to be more frequent in the future in our connected and intertwined world.

Impact of COVID-19 Outbreak on Cancer Patient Care and Treatment: Data from an Outpatient Oncology Clinic in Lombardy (Italy).

Lombardy was the first area in Italy to have an outbreak of coronavirus disease 19 (COVID-19) at the beginning of 2020. In this context, cancer has been reported as a major risk factor for adverse outcomes and death, so oncology societies have quickly released guidelines on cancer care during the pandemic. The aim of this study was to investigate the management of cancer patients and oncological treatments during the COVID-19 pandemic and to describe the containment measures performed in our outpatient clinic at Pavia (Lombardy). A comparison with the same period of the four previous years (2019, 2018, 2017, and 2016) was also performed. Using our electronic databases, we evaluated the number and characteristics of patients accessing the hospital for anticancer drug infusion from 24 February, 2020 to 30 April, 2020 and the number of radiological exams performed. Although a significant reduction in access for therapy was seen when compared with 2019 (2590 versus 2974, access rate ratio (ARR) = 0.85, p < 0.001), no significant differences in access numbers and ARR was evident between 2020 and 2018, 2017, or 2016 (2590 versus 2626 (ARR = 0.07), 2660 (ARR = 0.99), and 2694 (ARR = 0.96), respectively, p > 0.05). In 2020, 63 patients delayed treatment: 38% for "pandemic fear", 18% for travel restrictions, 13% for quarantine, 18% for flu syndrome other than COVID-19, and 13% for worsening of clinical conditions and death. Only 7/469 patients developed COVID-19. A significant reduction in radiological exams was found in 2020 versus all the other years considered (211 versus 360, 355, 385, 390 for the years 2020, 2019, 2018, 2017, and 2016, respectively, p < 0.001). The low incidence of COVID-19 among our cancer patients, along with the hospital policy to control infection, enabled safe cancer treatment and a continuum of care in most patients, while a small fraction of patients experienced a therapeutic delay due to patient-related reasons.