Navigating the waves in Colombia: a cohort study of inpatient care during four COVID-19 waves.

INTRODUCTION: Understanding the intricate dynamics between different waves of the COVID-19 pandemic and the corresponding variations in clinical outcomes is essential for informed public health decision-making. Comprehensive insights into these fluctuations can guide resource allocation, healthcare policies, and the development of effective interventions. This study aimed to compare the characteristics and clinical outcomes of COVID-19 at peak transmission points by including all patients attended during the first four pandemic waves in a referral center in Colombia. MATERIAL AND METHODS: In a prospective observational study of 2733 patients, clinical and demographic data were extracted from the Fundacion Valle de Lili's COVID-19 Registry, focusing on ICU admission, Invasive Mechanical Ventilation (IMV), length of hospital stay, and mortality. RESULTS: Our analysis unveiled substantial shifts in patient care patterns. Notably, the proportion of patients receiving glucocorticoid therapy and experiencing secondary infections exhibited a pronounced decrease across waves (p < 0.001). Remarkably, there was a significant reduction in ICU admissions (62.83% vs. 51.23% vs. 58.23% vs. 46.70 %, p < 0.001), Invasive Mechanical Ventilation (IMV) usage (39.25% vs. 32.22% vs. 31.22% vs. 21.55 %, p < 0.001), and Length of Hospital Stay (LOS) (9 vs. 8 vs. 8 vs. 8 days, p < 0.001) over the successive waves. Surprisingly, hospital mortality remained stable at approximately 18‒20 % (p > 0.05). Notably, vaccination coverage with one or more doses surged from 0 % during the initial waves to 66.71 % in the fourth wave. CONCLUSIONS: Our findings emphasize the critical importance of adapting healthcare strategies to the evolving dynamics of the pandemic. The reduction in ICU admissions, IMV utilization, and LOS, coupled with the rise in vaccination rates, underscores the adaptability of healthcare systems. Hospital mortality's persistence may warrant further exploration of treatment strategies. These insights can inform public health responses, helping policymakers allocate resources effectively and tailor interventions to specific phases of the pandemic.

Consolidation of a Molecular Signature of Healing in Cutaneous Leishmaniasis Is Achieved during the First 10 Days of Treatment.

The immune response is central to the pathogenesis of cutaneous leishmaniasis (CL). However, most of our current understanding of the immune response in human CL derives from the analysis of systemic responses, which only partially reflect what occurs in the skin. In this study, we characterized the transcriptional dynamics of skin lesions during the course of treatment of CL patients and identified gene signatures and pathways associated with healing and nonhealing responses. We performed a comparative transcriptome profiling of serial skin lesion biopsies obtained before, in the middle, and at the end of treatment of CL patients (eight who were cured and eight with treatment failure). Lesion transcriptomes from patients who healed revealed recovery of the stratum corneum, suppression of the T cell-mediated inflammatory response, and damping of neutrophil activation, as early as 10 d after initiation of treatment. These transcriptional programs of healing were consolidated before lesion re-epithelization. In stark contrast, downregulation of genes involved in keratinization was observed throughout treatment in patients who did not heal, indicating that in addition to uncontrolled inflammation, treatment failure of CL is mediated by impaired mechanisms of wound healing. This work provides insights into the factors that contribute to the effective resolution of skin lesions caused by Leishmania (Viannia) species, sheds light on the consolidation of transcriptional programs of healing and nonhealing responses before the clinically apparent resolution of skin lesions, and identifies inflammatory and wound healing targets for host-directed therapies for CL.

Single B cell transcriptomics identifies multiple isotypes of broadly neutralizing antibodies against flaviviruses.

Sequential dengue virus (DENV) infections often generate neutralizing antibodies against all four DENV serotypes and sometimes, Zika virus. Characterizing cross-flavivirus broadly neutralizing antibody (bnAb) responses can inform countermeasures that avoid enhancement of infection associated with non-neutralizing antibodies. Here, we used single cell transcriptomics to mine the bnAb repertoire following repeated DENV infections. We identified several new bnAbs with comparable or superior breadth and potency to known bnAbs, and with distinct recognition determinants. Unlike all known flavivirus bnAbs, which are IgG1, one newly identified cross-flavivirus bnAb (F25.S02) was derived from IgA1. Both IgG1 and IgA1 versions of F25.S02 and known bnAbs displayed neutralizing activity, but only IgG1 enhanced infection in monocytes expressing IgG and IgA Fc receptors. Moreover, IgG-mediated enhancement of infection was inhibited by IgA1 versions of bnAbs. We demonstrate a role for IgA in flavivirus infection and immunity with implications for vaccine and therapeutic strategies.

Clinical and microbiological characterization of Salmonella spp. isolates from patients treated in a university hospital in South America between 2012-2021: a cohort study.

BACKGROUND: Salmonellosis is a major cause of morbidity and mortality and one of the most frequent etiologies of diarrhea in the world. Mortality due to Salmonellosis in Latin America still poorly understood, and there is a lack of studies that evaluate resistance and clinical manifestations. The aims of this study were to characterize patients infected with Salmonella spp. seen in a university hospital in Colombia between 2012 and 2021, to evaluate trends in antibiotic resistance and to determine the proportion of overall mortality and related factors. METHODS: Retrospective observational study. All patients with microbiological diagnosis of Salmonella spp. were included. The sociodemographic, clinical and microbiological characteristics were described, and the proportion of antibiotic resistant isolates per year was estimated. The prevalence of mortality according to age groups was calculated. Log binomial regression models were used to establish factors associated with mortality. RESULTS: Five hundred twenty-two patients were analyzed. Salmonellosis accounted for 0.01% of all medical consultations. The median age was 16 years old. The most common clinical presentation was gastroenteric syndrome (77.1%) and symptoms included diarrhea (79.1%), fever (66.7%), abdominal pain (39.6%) and vomiting (35.2%). Of the Salmonella spp. isolates, 78.2% were not classified, 19.1% corresponded to non-typhoidal Salmonella and 2.7% to Salmonella typhi. Mortality occurs in 4.02% of the patients and was higher in patients with hematologic malignancy (11.6%). When analyzing by age group, the proportion of deaths was 2.8% in patients aged 15 years or younger, while in those older than 15 years it was 5.4%. Factors associated to mortality where bacteremia (aPR = 3.41 CI95%: 1.08-10.76) and to require treatment in the ICU (aPR = 8.13 CI95%: 1.82-37.76). In the last 10 years there has been a steady increase in resistance rates to ciprofloxacin, ampicillin, ampicillin/sulbactam and ceftriaxone, reaching rates above 60% in recent years. CONCLUSIONS: Despite improved availability of antibiotics for the treatment of salmonellosis in the past decades, mortality due to salmonellosis continues occurring in children and adults, mainly in patients with hematological malignancies and bacteremia. Antibiotic resistance rates have increased significantly over the last 10 years. Public health strategies for the control of this disease should be strengthened, especially in vulnerable populations.

Postoperative Outcomes of Analgesic Management with Erector Spine Plane Block at T5 Level in Pediatric Patients Undergoing Cardiac Surgery with Sternotomy: A Cohort Study.

Introduction: There is limited evidence on the impact of erector spinae plane block (ESPB) as part of multimodal analgesia in pediatric population undergoing cardiac surgery. Methods: A retrospective cohort study was conducted in patients under 18 years of age, who underwent cardiac surgery Risk Adjusted classification for Congenital Heart Surgery (RACHS-1) ≤3 by sternotomy. The study aims to evaluate the effect of ESPB as part of multimodal analgesia in pediatric patients undergoing cardiac surgery compared to conventional analgesia (CA) on relevant clinical outcomes: length of hospital stay, length of ICU stay, opioid consumption, time to extubation, mortality, and postoperative complications. The participants included were treated in a reference hospital in Colombia from July 2019 to June 2022. Results: Eighty participants were included, 40 in the ESPB group and 40 in the CA group. There was a significant decrease (Log rank test p = 0.007) in days to length of hospital stay in ESPB group (median 6.5 days (IQR: 4-11)) compared to the CA group (median 10.5 days (IQR: 6-25)). Likewise, there was a higher probability of discharge from the ICU in the ESPB group (HR 1.71 (95% CI: 1.05-2.79)). The ESPB group had lower opioid consumption (p < 0.05). There were no differences in time to extubation, mortality, and postoperative complications. Conclusion: ESPB as part of multimodal analgesia in pediatric patients undergoing cardiac surgery is feasible and associated with shorter hospital length of stay, faster ICU discharge and lower opioid consumption.

Inductively coupled plasma mass spectrometry method for plasma and intracellular antimony quantification applied to pharmacokinetics of meglumine antimoniate.

Background: A high-throughput method using inductively coupled plasma mass spectrometry (ICP-MS) was developed and validated for the quantitative analysis of antimony in human plasma and peripheral blood mononuclear cells from patients with cutaneous leishmaniasis undergoing treatment with meglumine antimoniate. Materials & methods: Antimony was digested in clinical samples with 1% tetramethylammonium hydroxide/1% EDTA and indium was used as internal standard. Accuracy, precision and stability were evaluated. Conclusion: Taking the lower limit of quantitation to be the lowest validation concentration with precision and accuracy within 20%, the current assay was successfully validated from 25 to 10000 ng/ml for antimony in human plasma and peripheral blood mononuclear cells. This protocol will serve as a baseline for future analytical designs, aiming to provide a reference method to allow inter-study comparisons.

Lay abstract Cutaneous leishmaniasis is a disease caused by single-cell parasites in the genus Leishmania which results in painful skin ulcers and is spread by insect bites. Drugs containing antimony are the mainstay therapy for cutaneous leishmaniasis, but if and how the amount of these compounds in the cells can affect the success of the treatment, remains unknown. Validated methods to reliably measure these amounts in human cells are limited. Here we have developed a validated method that allows quantifying antimony in human plasma and peripheral blood cells from patients undergoing antileishmanial treatment. This protocol will serve as a baseline for future studies aiming to understand how antimonials work to treat leishmaniasis infections and how this therapy can be improved.

Effective Reproductive Number estimation for initial stage of COVID-19 pandemic in Latin American Countries.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) has become pandemic and turn in a challenge for Latin America. Understanding the dynamics of the epidemic is essential for decision making, and to reduce the health, economic, and social impacts of the pandemic. The present study aimed to estimate the effective reproductive number (Rt) of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov2) infection during the first 10 days of the outbreak in seven Latin American countries with the highest incidence of cases as of March 23, 2020. Furthermore, we chose to compare the seven countries with Spain and Italy given their history with the virus. METHODS: Incidence data retrieved from the COVID-19 data repository by Johns Hopkins University were analyzed. The Rt was calculated for the first 10 days of the epidemic in Brazil, Ecuador, Chile, Colombia, Panama, Mexico, and Peru. Rt estimations were compared with Spain and Italy values for the same interval. RESULTS: The median Rt for the first 10 days of the COVID-19 epidemic were 2.90 (2.67-3.14) for Spain and 2.83 (2.7-2.96) for Italy. Latin American Rt estimations were higher in Ecuador (3.95(3.7-4.21)), Panama (3.95(3.7-4.21)), and Brazil (3.95(3.7-4.21)). The smallest one was observed in Peru (2.36(2.11-2.63)). All Latin American countries had Rt greater than 2. CONCLUSIONS: The initial stages of the COVID-19 epidemic in Latin America suggested a high Rt. Interventions such as domestic and international travel restrictions, educational institutions closure, social distancing, and intensified case surveillance should be adopted to prevent the collapse of the health systems.