Non-Invasive Ventilation Support during Hospitalization for SARS-CoV-2 and the Risk of Venous Thromboembolism.

Background/Objectives: Although SARS-CoV-2 infection is a significant risk factor for venous thromboembolism (VTE), data on the impact of the use of non-invasive ventilation support (NIVS) to mitigate the risk of VTE during hospitalization are scarce. Methods: Data for 1471 SARS-CoV-2 patients, hospitalized in a single hub during the first pandemic wave, were collected from clinical records, including symptom duration and type, information on lung abnormalities on chest computed tomography (CT), laboratory parameters and the use of NIVS. Determining VTE occurrence during hospital stays was the main endpoint. Results: Patients with VTE (1.8%) had an increased prevalence of obesity (26% vs. 11%), diabetes (41% vs. 21%), higher CHA2DS2VASC score (4, IQR 2-5 vs. 3, IQR 1-4, age- and sex-adjusted, p = 0.021) and cough (65% vs. 44%) and experienced significantly higher rates of NIVS (44% vs. 8%). Using a stepwise multivariate logistic regression model, the prevalence of electrocardiogram abnormalities (odds ratio (OR) 2.722, 95% confidence interval (CI) 1.039-7.133, p = 0.042), cough (OR 3.019, 95% CI 1.265-7.202, p = 0.013), CHA2DS2-VASC score > 3 (OR 3.404, 95% CI 1.362-8.513, p = 0.009) and the use of NIVS (OR 15.530, 95% CI 6.244-38.627, p < 0.001) were independently associated with a risk of VTE during hospitalization. NIVS remained an independent risk factor for VTE even after adjustment for the period of admission within the pandemic wave. Conclusions: Our study suggests that NIVS is a risk factor for VTE during hospitalization in SARS-CoV-2 patients. Future studies should assess the optimal prophylactic strategy against VTE in patients with a SARS-CoV-2 infection candidate to non-invasive ventilatory support.

The Multidisciplinary Mobile Unit (MMU) Program Bringing Hospital Specialist Geriatric Competencies at Home: A Feasible Alternative to Admission in Older Patients with Urgent Complaints.

Background/Objectives: Older patients are subject to a high number of Emergency Department (ED) visits and hospitalizations. Innovative strategies to manage geriatric urgencies in the community are thus needed. Methods: In this prospective observational study, we examined the case mix of a hospital-based domiciliary urgent care service tailored to older patients, called Multidisciplinary Mobile Unit (MMU), from January to September 2023. The service, activated by general practitioners or territorial specialists during workdays, provided domiciliary geriatric assessment, point-of-care diagnostics, including multi-site ultrasound and lab tests, and therapeutical measures, including intravenous treatment and insertion of invasive devices, with the goal of reaching on-site stabilization and avoiding ED referral. We collected data regarding multimorbidity, polypharmacy, and frailty according to the Clinical Frailty Scale (CFS), reasons for MMU activation, and diagnostic and therapeutical services provided. The assessed outcomes were immediate hospitalization after a visit, 30-day admission, and 30-day mortality. Results: Participants (n = 205, 102 M) were mostly aged (median age 83 years old), with multimorbidity and frailty (CFS median 6). The most frequent reasons for MMU activation were dyspnea (49%), cough (34%), and musculoskeletal pain (17%), while the commonest diagnostic test provided was thoracic ultrasound (81%). Only five patients (2.4%) were hospitalized immediately after MMU visit. The 30-day rate of hospitalization was 10.2%, with age, cancer, and abdominal pain as independent predictors on a stepwise binary logistic regression model. 30-day mortality was 4.9%. Conclusions: The MMU model is a feasible strategy to manage geriatric urgencies, especially involving the cardiorespiratory system, is associated with good outcomes and may prevent ED visits.

Factors associated with delirium in a real-world acute-care setting: analysis considering the interdependence of clinical variables with the frailty syndrome.

PURPOSE: Delirium risk assessment in the acute-care setting generally does not account for frailty. The objective of this retrospective study was to identify factors associated with delirium, considering the interdependency of clinical variables with frailty syndrome in complex older patients. METHODS: The clinical records of 587 participants (248 M, median age 84) were reviewed, collecting clinical, anamnestic and pharmacological data. Frailty syndrome was assessed with the Clinical Frailty Scale (CFS). Delirium was the main study endpoint. The correlations of the considered anamnestic and clinical variables with delirium and its subtypes were investigated selecting only those variables not showing a high overlap with frailty. Correlations associated with a 25% excess of frequency of delirium in comparison with the average of the population were considered as statistically significant. RESULTS: Delirium was detected in 117 (20%) participants. The presence of one among age > 85 years old, CFS > 4 and invasive devices explained 95% of delirium cases. The main factors maximizing delirium incidence at the individual level were dementia, other psychiatric illness, chronic antipsychotic treatment, and invasive devices. The coexistence of three of these parameters was associated with a peak frequency of delirium, ranging from 57 to 61%, mostly hypoactive forms. CONCLUSIONS: In acute-care wards, frailty exhibited a strong association with delirium during hospitalization, while at the individual level, dementia and the use of antipsychotics remained important risk factors. Modern clinical prediction tools for delirium should account for frailty syndrome.

Disentangling the Complexity of Nutrition, Frailty and Gut Microbial Pathways during Aging: A Focus on Hippuric Acid.

Hippuric acid (HA) is a metabolite resulting from the hepatic glycine conjugation of benzoic acid (BA) or from the gut bacterial metabolism of phenylalanine. BA is generally produced by gut microbial metabolic pathways after the ingestion of foods of vegetal origin rich in polyphenolic compounds, namely, chlorogenic acids or epicatechins. It can also be present in foods, either naturally or artificially added as a preservative. The plasma and urine HA levels have been used in nutritional research for estimating the habitual fruit and vegetable intake, especially in children and in patients with metabolic diseases. HA has also been proposed as a biomarker of aging, since its levels in the plasma and urine can be influenced by the presence of several age-related conditions, including frailty, sarcopenia and cognitive impairment. Subjects with physical frailty generally exhibit reduced plasma and urine levels of HA, despite the fact that HA excretion tends to increase with aging. Conversely, subjects with chronic kidney disease exhibit reduced HA clearance, with HA retention that may exert toxic effects on the circulation, brain and kidneys. With regard to older patients with frailty and multimorbidity, interpreting the HA levels in the plasma and urine may result particularly challenging because HA is at the crossroads between diet, gut microbiota, liver and kidney function. Although these considerations may not make HA the ideal biomarker of aging trajectories, the study of its metabolism and clearance in older subjects may provide valuable information for disentangling the complex interaction between diet, gut microbiota, frailty and multimorbidity.

Insights from comparison of the clinical presentation and outcomes of patients hospitalized with COVID-19 in an Italian internal medicine ward during first and third wave.

Background: The reasons of variability of clinical presentation of coronavirus disease-19 (COVID-19) across different pandemic waves are not fully understood, and may include individual risk profile, SARS-CoV-2 lineage and seasonal variations of viral spread. The objective of this retrospective study was to compare the characteristics and outcomes of patients admitted with confirmed coronavirus disease-19 (COVID-19) in the same season during the first (March 2020) and the third pandemic wave (March 2021, dominance of SARS-CoV-2 B.1.1.7 lineage) in an internal medicine ward of a large teaching hospital in Italy. Materials and methods: Data of 769 unvaccinated patients (399 from the first and 370 from the third wave) were collected from clinical records, including symptom type and duration, extension of lung abnormalities on chest computed tomography (CT) and PaO2/FiO2 ratio on admission arterial blood gas analysis. Results: Third wave patients were in average younger (median 65, interquartile range [IQR] 55-75, vs. 72, IQR 61-81 years old, p < 0.001), with less comorbidities and better pulmonary (CT visual score median 25, IQR 15-40, vs. 30, IQR 15-50, age- and sex-adjusted p = 0.017) and respiratory involvement (PaO2/FiO2 median 288, IQR 237-338, vs. 233, IQR 121-326 mmHg, age- and sex-adjusted p < 0.001) than first wave patients. Hospital mortality was lower (19% vs. 36%, p < 0.001), but not for subjects over 75 years old (46 vs. 49%). Age, number of chronic illnesses, PCT levels, CT visual score [Odds Ratio (OR) 1.022, 95% confidence interval (CI) 1.009-1.036, p < 0.001] and PaO2/FiO2 (OR 0.991, 95% CI 0.988-0.994, p < 0.001), but not the pandemic wave, were associated with mortality on stepwise multivariate logistic regression analysis. Conclusion: Despite the higher virulence of B.1.1.7 lineage, we detected milder clinical presentation and improved mortality in patients hospitalized during the third COVID-19 wave, with involvement of younger subjects. The reasons of this discrepancy are unclear, but could involve the population effect of vaccination campaigns, that were being conducted primarily in older frail subjects during the third wave.

Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018.

BACKGROUND: Resistance to anti-malarial drugs is associated with polymorphisms in target genes and surveillance for these molecular markers is important to detect the emergence of mutations associated with drug resistance and signal recovering sensitivity to anti-malarials previously used. METHODS: The presence of polymorphisms in genes associated with Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated by Sanger sequencing, in 85 P. falciparum day of enrollment samples from a therapeutic efficacy study of artemether-lumefantrine conducted in 2018-2019 in Quibdo, Colombia. Samples were genotyped to assess mutations in pfcrt (codons 72-76), pfdhfr (codons 51, 59, 108, and 164), and pfdhps genes (codons 436, 437, 540, and 581). Further, the genetic diversity of infections using seven neutral microsatellites (NMSs) (C2M34, C3M69, Poly α, TA1, TA109, 2490, and PfPK2) was assessed. RESULTS: All isolates carried mutant alleles for pfcrt (K76T and N75E), and for pfdhfr (N51I and S108N), while for pfdhps, mutations were observed only for codon A437G (32/73, 43.8%). Fifty samples (58.8%) showed a complete neutral microsatellites (NMS) profile. The low mean number of alleles (2 ± 0.57) per locus and mean expected heterozygosity (0.17 ± 0.03) showed a reduced genetic diversity. NMS multilocus genotypes (MMG) were built and nine MMG were identified. CONCLUSIONS: Overall, these findings confirm the fixation of chloroquine and pyrimethamine-resistant alleles already described in the literature, implying that these drugs are not currently appropriate for use in Colombia. In contrast, mutations in the pfdhps gene were only observed at codon 437, an indication that full resistance to sulfadoxine has not been achieved in Choco. MMGs found matched the clonal lineage E variant 1 previously reported in northwestern Colombia.

Multimorbidity and Frailty Are the Key Characteristics of Patients Hospitalized with COVID-19 Breakthrough Infection during Delta Variant Predominance in Italy: A Retrospective Study.

The aims of this study were to describe the characteristics of patients hospitalized with delta SARS-CoV-2 breakthrough infection, and to identify factors associated with pneumonia on chest Computed Tomography (CT) and mortality. The clinical records of 229 patients (105 F), with a median age of 81 (interquartile range, IQR, 73−88) years old, hospitalized between June and December 2021 after completion of the primary vaccination cycle, were retrospectively analyzed, retrieving data on comorbidities, Clinical Frailty Scale (CFS), clinical presentation and outcomes. Multimorbidity (91.7% with ≥2 chronic illnesses) and frailty (61.6% with CFS ≥ 5) were highly prevalent. CFS (OR 0.678, 95% CI 0.573−0.803, p < 0.001) and hypertension were independently associated with interstitial pneumonia. Mortality was 25.1% and unrelated with age. PaO2/FiO2 on blood gas analysis performed upon admission (OR 0.986, 95% CI 0.977−0.996, p = 0.005), and CFS (OR 1.723, 95% CI 1.152−2.576, p = 0.008) were independently associated with mortality only in subjects < 85 years old. Conversely, serum PCT levels were associated with mortality in subjects ≥ 85 years old (OR 3.088, 95% CI 1.389−6.8628, p = 0.006). In conclusion, hospitalization for COVID-19 breakthrough infection mainly involved geriatric patients, with those aged ≥ 85 more characterized by decompensation of baseline comorbidities rather than typical COVID-19 respiratory symptoms.

Co-Administration of Remdesivir and Azithromycin May Protect against Intensive Care Unit Admission in COVID-19 Pneumonia Requiring Hospitalization: A Real-Life Observational Study.

The benefits of remdesivir treatment, with or without co-administration of antibiotics such as azithromycin, are uncertain in COVID-19 pneumonia. The aim of this retrospective single-center study was to assess the effects of remdesivir, with or without azithromycin, on hospital mortality, intensive care unit (ICU) admission, and need of non-invasive ventilation. The clinical records of the COVID-19 patients hospitalized in an Italian ward in March 2021 were analyzed, and data on comorbidities and clinical, radiological, and laboratory presentation of the disease were collected. Among 394 participants (234 M), 173 received remdesivir (43.9%), including 81 with azithromycin (20.5%). Remdesivir recipients were younger, with less comorbidities, and had better PaO2/FiO2 and clinical outcomes, including reduced mortality, but the differences were not independent of covariates. Rates of ICU transferal were 17%, 9%, and 1% in the no remdesivir, remdesivir without azithromycin, and remdesivir/azithromycin groups, respectively. In a stepwise multivariate logistic regression model, remdesivir/azithromycin co-treatment was independently associated with reduced ICU admission (vs remdesivir alone, OR 0.081, 95% CI 0.008-0.789, p = 0.031; vs no remdesivir, OR 0.060, 95% CI 0.007-0.508, p = 0.010). These data suggest that the therapeutical effect of remdesivir in COVID-19 pneumonia may be potentiated by azithromycin. The association between the two drugs should be further investigated.

Pediatric appendicitis in the time of the COVID-19 pandemic: A retrospective chart review.

Aim: Conduct a time trend analysis that describes 2 groups of patients admitted to a large tertiary children's hospital that presented with appendicitis and determine if there was an increase in complicated appendicitis when compared between 2 time periods before and during the early coronavirus disease 2019 (COVID-19) pandemic of 2020. Methods: We conducted a retrospective analysis of all children presenting to a single-center site with appendicitis between March 23 and August 31, 2020, in the Central Texas region. We compared 507 patients presenting with appendicitis from the non-COVID-19 era in 2019 with n = 249 to patients presenting during the COVID time period with n = 258. All patients with appendicitis within those time periods were reviewed with analysis of various characteristics in regard to presentation, diagnosis of uncomplicated versus complicated appendicitis, and management outcomes. Results: There were no significant demographic differences or change in the number of appendicitis cases noted between the 2 time periods of comparison. There was no significant difference in rates of complicated appendicitis or presentation time following symptom onset between the 2 eras. There was no significant difference in intraoperative or postoperative complications. There was a statistically significant increase in the use of computed tomography (CT) scans (P-value = 0.004) with patients 1.81 times more likely to have a CT scan in the pandemic era after adjusting for patient-level factors. The effect of severe acute respiratory syndrome coronavirus 2 status on outcomes was not part of the data analysis. Conclusion: Our study is the largest to date examining appendicitis complications in the era of COVID. In the time of the COVID-19 pandemic, we found no delay in presentation in children presenting to the emergency department and no increase in complicated appendicitis. We did identify an increase in the use of CT scans for definitive diagnosis of appendicitis noted in the pandemic era. Although COVID-19 status was not studied, the finding of increased CT use for a definitive diagnosis of appendicitis was a distinctive finding of this study showing a change in practice in pediatric emergency medicine.

Implementing a multidisciplinary rapid geriatric observation unit for non-critical older patients referred to hospital: observational study on real-world data.

BACKGROUND: Geriatric rapid observation units may represent an alternative to hospitalization in older patients with non-critical acute illness. AIMS: To describe the characteristics and outcomes of patients admitted to a geriatric observation unit called URGe (Unità Geriatrica Rapida), implemented in an Italian hospital and characterized by multidisciplinary medical staff with geriatric expertise, fast-track access to diagnostic resources, regular use of point-of-care ultrasound and predicted length of stay (LOS) < 72 h. METHODS: The medical records of patients admitted to URGe during a 3-month period (452 subjects, 247 F and 205 M, median age 82 years, IQR 77-87) were retrospectively examined. The primary study endpoint was transferral from URGe to regular wards. Baseline covariates included demographics, comprehensive geriatric assessment, acute illnesses, comorbidities, vital signs and routine laboratory tests. RESULTS: Despite elevated burden of multimorbidity (median number of chronic diseases 4, IQR 2-5) and frailty (median Rockwood Clinical Frailty Scale score 4, IQR 3-6), only 137 patients (30.3%) required transferral from URGe to regular wards. The main factors positively associated with this outcome were Rockwood score, fever, cancer and red cell distribution width (P < 0.05 on multivariate logistic regression model). The rate of complications (mortality, delirium, and falls) during URGe stay was low (0.5%, 7% and 2%, respectively). Overall duration of hospital stay was lower than that of a group of historical controls matched by age, sex, main diagnosis, multimorbidity and frailty. CONCLUSIONS: The URGe model of acute geriatric care is feasible, safe and has the potential of reducing unnecessary hospitalizations of older patients.

Accounting for frailty and multimorbidity when interpreting high-sensitivity troponin I tests in oldest old.

BACKGROUND: Older patients evaluated in Emergency Departments (ED) for suspect Myocardial Infarction (MI) frequently exhibit unspecific elevations of serum high-sensitivity troponin I (hs-TnI), making interpretation particularly challenging for emergency physicians. The aim of this longitudinal study was to identify the interaction of multimorbidity and frailty with hs-TnI levels in older patients seeking emergency care. METHODS: A group of patients aged≥75 with suspected MI was enrolled in our acute geriatric ward immediately after ED visit. Multimorbidity and frailty were measured with Cumulative Illness Rating Scale (CIRS) and Clinical Frailty Scale (CFS), respectively. The association of hs-TnI with MI (main endpoint) was assessed by calculation of the Area Under the Receiver-Operating Characteristic Curve (AUROC), deriving population-specific cut-offs with Youden test. The factors associated with hs-TnI categories, including MI, CFS and CIRS, were determined with stepwise multinomial logistic regression. The association of hs-TnI with 3-month mortality (secondary endpoint) was also investigated with stepwise logistic regression. RESULTS: Among 268 participants (147 F, median age 85, IQR 80-89), hs-TnI elevation was found in 191 cases (71%, median 23 ng/L, IQR 11-65), but MI was present in only 12 cases (4.5%). hs-TnI was significantly associated with MI (AUROC 0.751, 95% CI 0.580-0.922, p = 0.003), with an optimal cut-off of 141 ng/L. hs-TnI levels ≥141 ng/L were significantly associated with CFS (OR 1.58, 95% CI 1.15-2.18, p = 0.005), while levels <141 ng/L were associated with the cardiac subscore of CIRS (OR 1.36, 95% CI 1.07-1.71, p = 0.011). CFS, but not hs-TnI levels, predicted 3-month mortality. CONCLUSIONS: In geriatric patients with suspected MI, frailty and cardiovascular multimorbidity should be carefully considered when interpreting emergency hs-TnI testing.

The Clinical Significance of Procalcitonin Elevation in Patients over 75 Years Old Admitted for COVID-19 Pneumonia.

AIM: To investigate the clinical significance of procalcitonin (PCT) elevation on hospital admission for coronavirus disease-19 (COVID-19) and its association with mortality in oldest old patients (age > 75 years). METHODS: The clinical records of 1074 patients with chest high-resolution computed-tomography (HRCT) positive for interstitial pneumonia and symptoms compatible for COVID-19, hospitalized in medical wards during the first pandemic wave in a single academic center in Northern Italy, were retrospectively analyzed. All patients had serum PCT testing performed within six hours from admission. Information on COVID-19-related symptoms, comorbidities, drugs, autonomy in daily activities, respiratory exchanges, other routine lab tests, and outcomes were collected. Clinical characteristics were compared across different admission PCT levels and ages. The association of admission PCT with mortality was tested separately in participants aged > 75 and ≤75 years old by stepwise multivariate Cox regression model with forward selection. RESULTS: With increasing classes of PCT levels (<0.05, 0.05-0.49, 0.5-1.99, and ≥2 ng/ml), there was a significant trend (P < 0.0001) towards older age, male gender, wider extension of lung involvement on HRCT, worse respiratory exchanges, and several other laboratory abnormalities. Each incremental PCT class was associated with increased risk of hospital death at multivariate models in subjects older than 75 (hazard ratio for PCT ≥ 2 vs. <0.05 ng/ml: 30.629, 95% confidence interval 4.176-224.645, P = 0.001), but not in subjects aged 75 or younger. CONCLUSIONS: In patients admitted for COVID-19, PCT elevation was associated with several clinical, radiological, and laboratory characteristics of disease severity. However, PCT elevation was strongly associated with hospital mortality only in oldest old subjects (age > 75).

Trends of COVID-19 Admissions in an Italian Hub during the Pandemic Peak: Large Retrospective Study Focused on Older Subjects.

Older multimorbid frail subjects have been severely involved in the coronavirus disease-19 (COVID-19) pandemic. The aim of this retrospective study is to compare the clinical features and outcomes of patients admitted in different phases of the outbreak in a COVID-19 hospital hub, with a particular focus on age, multimorbidity, and functional dependency. The clinical records of 1264 patients with clinical and radiological features compatible with COVID-19 pneumonia admitted in February-June, 2020, were analyzed, retrieving demographical, clinical, laboratory data, and outcomes. All variables were compared after stratification by the period of admission (first phase: rising slope of pandemic wave; second phase: plateau and falling slope), age, results of the first reverse transcriptase-polymerase chain reaction (RT-PCR) test for detection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), multimorbidity (≥2 chronic diseases), and presence of disability. Factors independently associated with hospital mortality were determined by multivariate forward-selection logistic regression. Patients admitted during the second phase were older, more frequently multimorbid, disabled, and of female gender. However, on admission they exhibited milder respiratory impairment (PaO2/FiO2 268, IQR 174-361, vs. 238, IQR 126-327 mmHg, p < 0.001) and lower mortality (22% vs. 27%, p < 0.001). Age, respiratory exchanges, positive RT-PCR test, number of chronic diseases (odds ratio (OR) 1.166, 95% confidence interval (CI) 1.036-1.313, p = 0.011), and disability (OR 1.927, 95% CI 1.027-3.618, p = 0.022) were positively associated with mortality, while admission during the second phase exhibited an inverse association (OR 0.427, 95% CI 0.260-0.700, p = 0.001). In conclusion, older multimorbid patients were mainly hospitalized during the second phase of the pandemic wave. The prognosis was strongly influenced by the COVID-19 phenotype and period of admission, not just by age, multimorbidity, and disability.

Metabolic Effects of a Eucalyptus Bark Lipophilic Extract on Triple Negative Breast Cancer and Nontumor Breast Epithelial Cells.

In this work, untargeted metabolomics was used to unveil the impact of a Eucalyptus (Eucalyptus nitens) outer bark lipophilic extract on the metabolism of triple negative breast cancer (TNBC) and nontumor breast cells. Integrative analysis of culture medium, intracellular polar metabolites, and cellular lipids provided a comprehensive picture of cell metabolic adaptations, which enabled several hypotheses about the metabolic targets and pathways affected to be proposed. One of the most marked effects in MDA-MB-231 breast cancer cells, upon 48 h incubation with the E. nitens extract (15 µg/mL), was the enhancement of the NAD+/NADH ratio, likely reflecting a shift to mitochondrial respiration, which appeared to be fueled by amino acids and fatty acids resulting from hydrolysis of neutral lipids (triglycerides and cholesteryl esters). Contrastingly, in MCF-10A breast epithelial cells, the E. nitens extract appeared to intensify glycolysis and the tricarboxylic acid cycle (resulting in a decreased NAD+/NADH ratio), while having no effect on the cell lipid composition. This knowledge improves the current understanding of the biological activity of E. nitens bark extracts and is potentially useful to promote their development in the field of TNBC anticancer therapy.

Delirium in COVID-19: epidemiology and clinical correlations in a large group of patients admitted to an academic hospital.

BACKGROUND: Delirium incidence and clinical correlates in coronavirus disease-19 (COVID-19) pneumonia are still poorly investigated. AIM: To describe the epidemiology of delirium in patients hospitalized for suspect COVID-19 pneumonia during the pandemic peak in an academic hospital of Northern Italy, identify its clinical correlations and evaluate the association with mortality. METHODS: The clinical records of 852 patients admitted for suspect COVID-19 pneumonia, defined as respiratory symptoms or fever or certain history of contact with COVID-19 patients, plus chest CT imaging compatible with alveolar-interstitial pneumonia, were retrospectively analyzed. Delirium was defined after careful revision of daily clinical reports in accordance with the Confusion Assessment Method criteria. Data on age, clinical presentation, comorbidities, drugs, baseline lab tests and outcome were collected. The factors associated with delirium, and the association of delirium with mortality, were evaluated through binary logistic regression models. RESULTS: Ninety-four patients (11%) developed delirium during stay. They were older (median age 82, interquartile range, IQR 78-89, vs 75, IQR 63-84, p < 0.001), had more neuropsychiatric comorbidities and worse respiratory exchanges at baseline. At multivariate models, delirium was independently and positively associated with age [odds ratio (OR) 1.093, 95% confidence interval (CI) 1.046-1.143, p < 0.001], use of antipsychotic drugs (OR 4.529, 95% CI 1.204-17.027, p = 0.025), serum urea and lactate-dehydrogenase at admission. Despite a higher mortality in patients with delirium (57% vs 30%), this association was not independent of age and respiratory parameters. CONCLUSIONS: Delirium represents a common complication of COVID-19 and a marker of severe disease course, especially in older patients with neuropsychiatric comorbidity.

Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids.

Plant-derived pentacyclic triterpenic acids (TAs) have gained increasing attention due to their multiple biological activities. Betulinic acid (BA) and ursolic acid (UA) modulate diverse pathways in carcinogenesis, offering increased changes of success in refractory cancers, such as triple negative breast cancer (TNBC). The present work aimed to assess the metabolic effects of BA and UA in MDA-MB-231 breast cancer cells (TNBC model), as well as in MCF-10A non-cancer breast epithelial cells, with a view to unveiling the involvement of metabolic reprogramming in cellular responses to these TAs. Cell viability and cell cycle analyses were followed by assessment of changes in the cells exo- and endometabolome through 1H NMR analysis of cell culture medium supernatants, aqueous and organic cell extracts. In MDA-MB-231 cells, BA was suggested to induce a transient upregulation of glucose consumption and glycolytic conversion, tricarboxylic acid (TCA) cycle intensification, and hydrolysis of neutral lipids, while UA effects were much less pronounced. In MCF-10A cells, boosting of glucose metabolism by the two TAs was accompanied by diversion of glycolytic intermediates to the hexosamine biosynthetic pathway (HBP) and the synthesis of neutral lipids, possibly stored in detoxifying lipid droplets. Additionally, breast epithelial cells intensified pyruvate consumption and TCA cycle activity, possibly to compensate for oxidative impairment of pyruvate glycolytic production. This study provided novel insights into the metabolic effects of BA and UA in cancer and non-cancer breast cells, thus improving current understanding of the action of these compounds at the molecular level.

Concordance analysis of three diagnostic tests for malaria in the symptomatic population of Colombian endemic municipalities / [Análisis de concordancia de tres pruebas para el diagnóstico de malaria en la población sintomática de los municipios endémicos de Colombia].

Introduction: Taking into account the difficulty of performing malaria microscopic diagnosis in rural areas, rapid diagnostic tests (RDT) are a good alternative, but it is important to verify their diagnostic performance. Objective: To evaluate the diagnostic performance of the RDTs used in five Colombian departments by comparing them with the microscopic diagnosis and using PCR as the reference standard. Materials and methods: Thick blood film and RDTs were used to diagnose symptomatic individuals; additionally, the filter paper was impregnated with blood for the molecular test. Results: We included 314 samples whose percentage of positivity for malaria was 49% by PCR, 48% by microscopy and 46% by RDT; parasitemia ranged between 180 and 23,800 p/µL of blood. The concordance of the results from the microscopy units and those of the PCR (National Laboratory of Reference) was as follows: Cohen's kappa coefficient, 0.975 (95% CI: 0.950-0.999); sensitivity, 97% (95% CI 95-100); specificity 100% (95% CI: 100-100), and kappa index of species, 0.958 (IC95%: 0.912-1.00). The concordance between the Pf/Pv RDT (at the microscopy units) and the PCR (National Laboratory of Reference) was as follows: kappa coefficient, 0.878 (95% CI: 0.784-0.973); sensitivity, 94% (95% CI: 87-100); specificity, 95% (95% CI: 90-100), and kappa index of species, 1.0 (95% CI: 1.00-1.00). The concordance between the Pf/Pan RDT versus PCR was: Cohen's kappa coefficient, 0.920 (95 % CI: 0.865- 0.974); sensitivity, 94% (95% CI: 90-98); specificity, 99% (95% CI 95-100), and kappa index of species, 0.750 (IC95% 0,637-0,863). Conclusion: The results of this study support the use of RDTs in Colombia; however, more training of the personnel is required to accurately differentiate Plasmodium species.

Introducción. Dadas las dificultades del diagnóstico microscópico de la malaria o paludismo en las áreas rurales, las pruebas de diagnóstico rápido constituyen una buena alternativa, por lo que es importante conocer su desempeño. Objetivo. Evaluar el desempeño de las pruebas de diagnóstico rápido utilizadas en cinco departamentos para al diagnóstico microscópico de la malaria usando la reacción en cadena de la polimerasa (PCR) como estándar de referencia. Materiales y métodos. Se usaron la prueba de gota gruesa y las pruebas de diagnóstico rápido y, además, se impregnó papel de filtro con sangre para la prueba molecular (PCR), en individuos sintomáticos. Resultados. Se incluyeron 314 muestras cuyo porcentaje de positividad para malaria fue de 49 % con la PCR, de 48 % con microscopía y de 46 % con las pruebas de diagnóstico rápido; la parasitemia fluctuó entre 180 y 23.800 parásitos/µl de sangre. La concordancia de los resultados de los puestos de microscopía comparados con la PCR (Laboratorio Nacional de Referencia) fueron los siguientes: coeficiente kappa de Cohen de 0,975 (IC95% 0,950-0,999), sensibilidad de 97 % (IC95% 95-100) y especificidad de 100 % (IC95% 100-100), e índice kappa de especie de 0,958 (IC95% 0,912-1,00). La concordancia de los resultados de la prueba de diagnóstico rápido Pf/Pv en los puestos de microscopía y los de la PCR (Laboratorio Nacional de Referencia), fue la siguiente: coeficiente kappa de 0,878 (IC95% 0,784-0,973), sensibilidad de 94 % (IC95% 87-100), especificidad de 95 % (IC95% 90-100), e índice kappa de especie de 1,0 (IC95% 1,00-1,00). La concordancia entre la prueba de diagnóstico rápido Pf/Pan y la PCR fue la siguiente: coeficiente kappa de Cohen de 0,920 (IC95% 0,865-0,974), sensibilidad de 94 % (IC95% 90-98), especificidad de 99 % (IC95% 95-100), e índice kappa de especie de 0,750 (IC95% 0,637-0,863). Conclusión. Los resultados de este estudio respaldan el uso de las pruebas de diagnóstico rápido en Colombia, aunque se requiere un mejor entrenamiento del personal para diferenciar eficientemente las especies de Plasmodium.

Análisis de concordancia de tres pruebas para el diagnóstico de malaria en la población sintomática de los municipios endémicos de Colombia / Concordance analysis of three diagnostic tests for malaria in the symptomatic population of Colombian endemic municipalities

Introducción. Dadas las dificultades del diagnóstico microscópico de la malaria o paludismo en las áreas rurales, las pruebas de diagnóstico rápido constituyen una buena alternativa, por lo que es importante conocer su desempeño. Objetivo. Evaluar el desempeño de las pruebas de diagnóstico rápido utilizadas en cinco departamentos para al diagnóstico microscópico de la malaria usando la reacción en cadena de la polimerasa (PCR) como estándar de referencia. Materiales y métodos. Se usaron la prueba de gota gruesa y las pruebas de diagnóstico rápido y, además, se impregnó papel de filtro con sangre para la prueba molecular (PCR), en individuos sintomáticos. Resultados. Se incluyeron 314 muestras cuyo porcentaje de positividad para malaria fue de 49 % con la PCR, de 48 % con microscopía y de 46 % con las pruebas de diagnóstico rápido; la parasitemia fluctuó entre 180 y 23.800 parásitos/pl de sangre. La concordancia de los resultados de los puestos de microscopía comparados con la PCR (Laboratorio Nacional de Referencia) fueron los siguientes: coeficiente kappa de Cohen de 0,975 (IC95% 0,950-0,999), sensibilidad de 97 % (IC95% 95-100) y especificidad de 100 % (IC95% 100-100), e índice kappa de especie de 0,958 (IC95% 0,912-1,00). La concordancia de los resultados de la prueba de diagnóstico rápido Pf/Pv en los puestos de microscopía y los de la PCR (Laboratorio Nacional de Referencia), fue la siguiente: coeficiente kappa de 0,878 (IC95% 0,784-0,973), sensibilidad de 94 % (IC95% 87-100), especificidad de 95 % (IC95% 90-100), e índice kappa de especie de 1,0 (IC95% 1,00-1,00). La concordancia entre la prueba de diagnóstico rápido Pf/Pan y la PCR fue la siguiente: coeficiente kappa de Cohen de 0,920 (IC95% 0,865-0,974), sensibilidad de 94 % (IC95% 90-98), especificidad de 99 % (IC95% 95-100), e índice kappa de especie de 0,750 (IC95% 0,637-0,863). Conclusión. Los resultados de este estudio respaldan el uso de las pruebas de diagnóstico rápido en Colombia, aunque se requiere un mejor entrenamiento del personal para diferenciar eficientemente las especies de Plasmodium.

Introduction: Taking into account the difficulty of performing malaria microscopic diagnosis in rural areas, rapid diagnostic tests (RDT) are a good alternative, but it is important to verify their diagnostic performance. Objective: To evaluate the diagnostic performance of the RDTs used in five Colombian departments by comparing them with the microscopic diagnosis and using PCR as the reference standard. Materials and methods: Thick blood film and RDTs were used to diagnose symptomatic individuals; additionally, the filter paper was impregnated with blood for the molecular test. Results: We included 314 samples whose percentage of positivity for malaria was 49% by PCR, 48% by microscopy and 46% by RDT; parasitemia ranged between 180 and 23,800 p/µl of blood. The concordance of the results from the microscopy units and those of the PCR (National Laboratory of Reference) was as follows: Cohen's kappa coefficient, 0.975 (95% CI: 0.9500.999); sensitivity, 97% (95% CI 95-100); specificity 100% (95% CI: 100-100), and kappa index of species, 0.958 (IC95%: 0.912-1.00). The concordance between the Pf/Pv RDT (at the microscopy units) and the PCR (National Laboratory of Reference) was as follows: kappa coefficient, 0.878 (95% CI: 0.784-0.973); sensitivity, 94% (95% CI: 87-100); specificity, 95% (95% CI: 90-100), and kappa index of species, 1.0 (95% CI: 1.00-1.00). The concordance between the Pf/Pan RDT versus PCR was: Cohen's kappa coefficient, 0.920 (95 % CI: 0.865- 0.974); sensitivity, 94% (95% CI: 90-98); specificity, 99% (95% CI 95-100), and kappa index of species, 0.750 (IC95% 0,637-0,863). Conclusion: The results of this study support the use of RDTs in Colombia; however, more training of the personnel is required to accurately differentiate Plasmodium species.

Artemether-Lumefantrine Efficacy for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Choco, Colombia after 8 Years as First-Line Treatment.

Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated Plasmodium falciparum infection in Colombia. To assess AL efficacy for uncomplicated falciparum malaria in Quibdo, Choco, Colombia, we conducted a 28-day therapeutic efficacy study (TES) following the WHO guidelines. From July 2018 to February 2019, febrile patients aged 5-65 years with microscopy-confirmed P. falciparum mono-infection and asexual parasite density of 250-100,000 parasites/µL were enrolled and treated with a supervised 3-day course of AL. The primary endpoint was adequate clinical and parasitological response (ACPR) on day 28. We attempted to use polymerase chain reaction (PCR) genotyping to differentiate reinfection and recrudescence, and conducted genetic testing for antimalarial resistance-associated genes. Eighty-eight patients consented and were enrolled; four were lost to follow-up or missed treatment doses. Therefore, 84 (95.5%) participants reached a valid endpoint: treatment failure or ACPR. No patient remained microscopy positive for malaria on day 3, evidence of delayed parasite clearance and artemisinin resistance. One patient had recurrent infection (12 parasites/µL) on day 28. Uncorrected ACPR rate was 98.8% (83/84) (95% CI: 93.5-100%). The recurrent infection sample did not amplify during molecular testing, giving a PCR-corrected ACPR of 100% (83/83) (95% CI: 95.7-100%). No P. falciparum kelch 13 polymorphisms associated with artemisinin resistance were identified. Our results support high AL efficacy for falciparum malaria in Choco. Because of the time required to conduct TESs in low-endemic settings, it is important to consider complementary alternatives to monitor antimalarial efficacy and resistance.