Ocular involvement in highly treatment-experienced patients with HIV.

Introduction: Ocular involvement in human immunodeficiency virus (HIV) infected and treatment-experienced patients is a significant concern, despite the advancements in antiretroviral therapy (ART) medication. The extended life expectancy of HIV patients has altered the spectrum of HIV-associated ocular diseases, ranging from minor issues to severe vision impairment or blindness. Therefore, understanding these complications becomes crucial in providing comprehensive medical care and quality of life improvement. HIV patients on multiple ARTs can experience various ocular disorders due to the complexity of their treatment regimens, drug toxicities, immune reconstitution, and opportunistic infections. Most worthy to consider are: cytomegalovirus (CMV) retinitis, immune recovery uveitis (IRU), keratoconjunctivitis sicca (dry eye syndrome), and HIV-associated neuroretinal disorders. Materials and methods: A retrospective clinical investigation was conducted on HIV/AIDS-infected patients from January 1, 2013, to December 31, 2023. The study included 62 patients over 18 years, who tested HIV-positive via enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot (WB), with assessments of HIV plasma viral load (VL) and CD4+ T cell counts (CD4). Data collected included demographics, pathological histories, clinical characteristics, blood tests, assessments for opportunistic infections, patient staging, antiretroviral therapy initiation, and disease prognosis. Results: The study found that of most patients, 37 were aged 30-39 (59.7%), with 59.7% males and 40.3% females. Most had been living with HIV for 10-19 years (35.5%). Initial CD4 counts were < 200 cells/mm3 in 46.8% of patients, which improved to 19.3% when the study was done. CMV retinitis prevalence decreased from 46.8% initially to 35.5% despite ART. Other conditions included ocular toxoplasmosis (3.22%), tuberculosis-related uveitis (1,6%), keratoconjunctivitis sicca (19.3%), and HIV retinopathy (29%). Notably, 62.1% of CMV retinitis patients experienced significant visual acuity reduction. Oral valganciclovir was beneficial for patients with CMV disease affecting multiple sites and effective for both induction and maintenance therapy of CMV retinitis. Conclusions: Managing ocular complications in HIV-experienced patients requires a multidisciplinary approach with regular ophthalmologic evaluations, prompt treatment of infections, and continuous monitoring of ART effectiveness. Early detection and intervention are crucial for preserving vision and improving outcomes. The study highlighted the importance of constant monitoring even after viral suppression. Abbreviations: HIV = Human immunodeficiency virus, ART = antiretroviral therapy, CMV = cytomegalovirus, IRU = immune recovery uveitis, ELISA = enzyme-linked immunosorbent assay, WB = Western Blot, VL = viral load, CD4 = CD4+ T cells.

Age, comorbidity burden and late presentation are significant predictors of hospitalization length and acute respiratory failure in patients with influenza.

Influenza viruses are responsible for a high number of infections and hospitalizations every year. In this study, we aimed to identify clinical and host-specific factors that influence the duration of hospitalization and the progression to acute respiratory failure (ARF) in influenza. We performed an analysis of data from a prospective active influenza surveillance study that was conducted over five seasons (2018/19 to 2022/23). A total of 1402 patients with influenza were included in the analysis, the majority of which (64.5%) were children (under 18 years), and 9.1% were elderly. At least one chronic condition was present in 29.2% of patients, and 9.9% of patients developed ARF. The median hospital stay was 4 days (IQR: 3, 6 days). The most important predictors of prolonged hospital stay and development of ARF were extremes of age (infants and elderly), presence of chronic diseases, particularly the cumulus of at least 3 chronic diseases, and late presentation to hospital. Among the chronic diseases, chronic obstructive pulmonary disease, cardiovascular disease, cancer, diabetes, obesity, and chronic kidney disease were strongly associated with a longer duration of hospitalization and occurrence of ARF. In this context, interventions aimed at chronic disease management, promoting influenza vaccination, and improving awareness and access to health services may contribute to reducing the impact of influenza not only in Romania but globally. In addition, continued monitoring of the circulation of influenza viruses is essential to limit their spread among vulnerable populations.

Miscellaneous ophthalmic conditions related to low CD4 cell count in HIV-positive patients.

Introduction: Management of patients living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (AIDS) (PLWHA) still represents a challenge for doctors in various medical fields. The presence of co-infections, with different degrees of immune system impairment, raises the need for a multi-disciplinary approach to the PLWHA. Methods: In this paper, we present three cases of PLWHA with various ophthalmological conditions, who were admitted to "Prof. Dr. Matei Balș" National Institute for Infectious Diseases (INBIMB). Three of them were late presenters, recently diagnosed with AIDS. All three were in immuno-virological failure. The ophthalmic conditions were either related to the HIV infection, or the result of other complications. Discussion: The diversity and complexity of ocular involvement in PLWHA were deeply linked to the patient's immunological status at the ophthalmological evaluation moment. Thus, antiretroviral therapy (ART) played an important immune status recovery role. Encountered ocular conditions vary, some being directly caused by the presence of the virus, and the others were the result of opportunistic infections (cytomegalovirus, Varicella virus) or other co-infections (Treponema pallidum). Neurological conditions disturbing the natural defense mechanism, prolonged hospital stay, and exposure to multiple antibiotic regimens are risk factors for difficult-to-treat eye infections with multidrug-resistant bacteria. Some ocular conditions can be the reason that leads to HIV infection diagnosis, while others can appear during the time, especially in patients with low ART adherence. The prognostic is conditioned by the early recognition and correct management of the disease and the immunological status recovery under ART. Conclusions: Correct and early diagnosis of HIV-related eye conditions is mandatory to establish the most appropriate medical management to obtain an increase in the quality of life of the patient. Abbreviations: HIV = Human Immunodeficiency Virus, AIDS = Acquired Immunodeficiency Syndrome, ART = Antiretroviral Therapy.

Zika virus non-coding RNAs antagonize antiviral responses by PKR-mediated translational arrest.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that causes severe outbreaks in human populations. ZIKV infection leads to the accumulation of small non-coding viral RNAs (known as sfRNAs) that are crucial for evasion of antiviral responses and for viral pathogenesis. However, the mechanistic understanding of how sfRNAs function remains incomplete. Here, we use recombinant ZIKVs and ribosome profiling of infected human cells to show that sfRNAs block translation of antiviral genes. Mechanistically, we demonstrate that specific RNA structures present in sfRNAs trigger PKR activation, which instead of limiting viral replication, enhances viral particle production. Although ZIKV infection induces mRNA expression of antiviral genes, translation efficiency of type I interferon and interferon stimulated genes were significantly downregulated by PKR activation. Our results reveal a novel viral adaptation mechanism mediated by sfRNAs, where ZIKV increases its fitness by repurposing the antiviral role of PKR into a proviral factor.

Hospitalizations for Acute Otitis and Sinusitis in Patients Living with HIV: A Retrospective Analysis of a Tertiary Center in Romania.

Background/Objectives: Acute or chronic ear, nose and throat (ENT) conditions in people living with HIV can lead to hospitalization and affect their quality of life. The aim of our study was to determine the frequency and characteristics of hospitalizations for acute sinusitis (AS) and acute otitis (AO) in people living with HIV. Methods: We performed a retrospective analysis over the course of six years (from January 2018 to December 2023), assessing all hospitalizations for AS and/or AO occurring in patients living with HIV, at the largest infectious diseases hospital in Romania. Results: We identified a total of 179 cases, among which 149 cases (83.2%) were attributed to AS and 41 cases (22.9%) were due to AO. Among cases of AS, maxillary sinuses were most frequently involved (n = 140/149, 94.0%), and among cases of AO, acute congestive otitis media (n = 14, 34.1%) and acute purulent otitis media (n = 13, 31.7%) were the most common forms. The underlying HIV infection was classified as stage C3 in 57.5% of cases. In 19.6% of cases, it was possible to identify either the trigger or the etiological agent, and the most frequent bacterial pathogens were Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. Conclusions: In conclusion, this study highlights that hospitalizations due to acute sinus and ear involvement are not isolated events in people living with HIV. A prospective follow-up is needed to gain a deeper and more dynamic understanding of how ENT health is affected in people with HIV infection. Furthermore, promoting prevention through vaccination may reduce to a certain extent the burden of ENT infections in this population.

Bioinformatics Analysis Reveals E6 and E7 of HPV 16 Regulate Metabolic Reprogramming in Cervical Cancer, Head and Neck Cancer, and Colorectal Cancer through the PHD2-VHL-CUL2-ELOC-HIF-1α Axis.

Human papillomavirus 16 (HPV 16) infection is associated with several types of cancer, such as head and neck, cervical, anal, and penile cancer. Its oncogenic potential is due to the ability of the E6 and E7 oncoproteins to promote alterations associated with cell transformation. HPV 16 E6 and E7 oncoproteins increase metabolic reprogramming, one of the hallmarks of cancer, by increasing the stability of hypoxia-induced factor 1 α (HIF-1α) and consequently increasing the expression levels of their target genes. In this report, by bioinformatic analysis, we show the possible effect of HPV 16 oncoproteins E6 and E7 on metabolic reprogramming in cancer through the E6-E7-PHD2-VHL-CUL2-ELOC-HIF-1α axis. We proposed that E6 and E7 interact with VHL, CUL2, and ELOC in forming the E3 ubiquitin ligase complex that ubiquitinates HIF-1α for degradation via the proteasome. Based on the information found in the databases, it is proposed that E6 interacts with VHL by blocking its interaction with HIF-1α. On the other hand, E7 interacts with CUL2 and ELOC, preventing their binding to VHL and RBX1, respectively. Consequently, HIF-1α is stabilized and binds with HIF-1ß to form the active HIF1 complex that binds to hypoxia response elements (HREs), allowing the expression of genes related to energy metabolism. In addition, we suggest an effect of E6 and E7 at the level of PHD2, VHL, CUL2, and ELOC gene expression. Here, we propose some miRNAs targeting PHD2, VHL, CUL2, and ELOC mRNAs. The effect of E6 and E7 may be the non-hydroxylation and non-ubiquitination of HIF-1α, which may regulate metabolic processes involved in metabolic reprogramming in cancer upon stabilization, non-degradation, and translocation to the nucleus.

International Nosocomial Infection Control Consortium (INICC) report of health care-associated infections, data summary of 25 countries for 2014 to 2023, Surgical Site Infections Module.

BACKGROUND: Surgical site infection (SSI) rates are higher in low-resource countries (LRC) than in high-income counterparts. METHODS: Prospective cohort study using the INICC Surveillance Online System, from 116 hospitals in 75 cities across 25 Latin-American, Asian, Eastern-European, and Middle-Eastern countries: Argentina, Bahrain, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Egypt, Honduras, India, Kosovo, Kuwait, Lebanon, Mexico, Mongolia, Pakistan, Papua New Guinea, Philippines, Poland, Romania, Saudi Arabia, Thailand, Turkey, Venezuela, Vietnam. CDC/NHSN definitions were applied. Surgical procedures (SPs) were categorized according to the International Classification of Diseases criteria. RESULTS: From 2014 to 2023, we collected data on 1,251 SSIs associated with 56,617 SPs. SSI rates were significantly higher in SPs of INICC compared to CDC/NHSN data: hip prosthesis (3.68% vs 0.67%, relative risk [RR]=5.46, 95% confidence interval [CI]=3.71-8.03, P<.001), knee prosthesis (2.02% vs 0.58%, RR=3.49, 95% CI=1.87-6.49, P<.001), coronary artery bypass (4.16% vs 1.37%, RR=3.03, 95% CI=2.35-3.91, P<.001), peripheral vascular bypass (15.69% vs 2.93%, RR=5.35, 95% CI=2.30-12.48, P<.001), abdominal aortic aneurysm repair (8.51% vs 2.12%, RR=4.02, 95% CI=2.11-7.65, P<.001), spinal fusion (6.47% vs 0.70%, RR=9.27, 95% CI=6.21-13.84, P<.001), laminectomy (2.68% vs 0.72%, RR=3.75, 95% CI=2.36-5.95, P<.001), among others. CONCLUSIONS: Elevated SSI rates in LRCs emphasize the need for effective interventions.

Evaluating the outcome of a bundle with 11 components and the INICC multidimensional approach in decreasing rates of central line-associated bloodstream infections across nine Asian countries.

BACKGROUND: Central line-associated bloodstream infection (CLABSI) rates in intensive care units (ICUs) across Latin America exceed those in high-income countries significantly. METHODS: We implemented the INICC multidimensional approach, incorporating an 11-component bundle, in 122 ICUs spanning nine Asian countries. We computed the CLABSI rate using the CDC/NSHN definition and criteria. The CLABSI rate per 1000 CL-days was calculated at baseline and throughout different phases of the intervention, including the 2nd month, 3rd month, 4-16 month, and 17-29 month periods. A two-sample t-test was employed to compare baseline CLABSI rates with intervention rates. Additionally, we utilized a generalized linear mixed model with a Poisson distribution to analyze the association between exposure and outcome. RESULTS: A total of 124,946 patients were hospitalized over 717,270 patient-days, with 238,595 central line (CL)-days recorded. The rates of CLABSI per 1000 CL-days significantly decreased from 16.64 during the baseline period to 6.51 in the 2nd month (RR = 0.39; 95% CI = 0.36-0.42; p < 0.001), 3.71 in the 3rd month (RR = 0.22; 95% CI = 0.21-0.25; p < 0.001), 2.80 in the 4-16 month (RR = 0.17; 95% CI = 0.15-0.19; p < 0.001), and 2.18 in the 17-29 month (RR = 0.13; 95% CI = 0.11-0.15; p < 0.001) intervals. A multilevel Poisson regression model demonstrated a sustained, continuous, and statistically significant decrease in ratios of incidence rates, reaching 0.35 (p < 0.0001) during the 17-29 month period. Moreover, the all-cause in-ICU mortality rate significantly decreased from 13.23% to 10.96% (p = 0.0001) during the 17-29 month period. CONCLUSIONS: Our intervention led to an 87% reduction in CLABSI rates, with a 29-month follow-up.

Long-Term Effects of a Stepwise, Multimodal, Non-Restrictive Antimicrobial Stewardship Programme for Reducing Broad-Spectrum Antibiotic Use in the ICU.

Information on the long-term effects of non-restrictive antimicrobial stewardship (AMS) strategies is scarce. We assessed the effect of a stepwise, multimodal, non-restrictive AMS programme on broad-spectrum antibiotic use in the intensive care unit (ICU) over an 8-year period. Components of the AMS were progressively implemented. Appropriateness of antibiotic prescribing was also assessed by monthly point-prevalence surveys from 2013 onwards. A Poisson regression model was fitted to evaluate trends in the reduction of antibiotic use and in the appropriateness of their prescription. From 2011 to 2019, a total of 12,466 patients were admitted to the ICU. Antibiotic use fell from 185.4 to 141.9 DDD per 100 PD [absolute difference, -43.5 (23%), 95% CI -100.73 to 13.73; p = 0.13] and broad-spectrum antibiotic fell from 41.2 to 36.5 [absolute difference, -4.7 (11%), 95% CI -19.58 to 10.18; p = 0.5]. Appropriateness of antibiotic prescribing rose by 11% per year [IRR: 0.89, 95% CI 0.80 to 1.00; p = 0.048], while broad-spectrum antibiotic use showed a dual trend, rising by 22% until 2015 and then falling by 10% per year since 2016 [IRR: 0.90, 95% CI 0.81 to 0.99; p = 0.03]. This stepwise, multimodal, non-restrictive AMS achieved a sustained reduction in broad-spectrum antibiotic use in the ICU and significantly improved appropriateness of antibiotic prescribing.

The Impact of Obesity on the Host-Pathogen Interaction with Influenza Viruses - Novel Insights: Narrative Review.

After exposure to a viral pathogen, the host-pathogen interaction is essential to determine whether or not infection will ensue, and what the clinical outline of the infection will be. Recent research has shown that the patient with obesity presents a set of particular pathophysiological changes that lead to higher severity of viral infections, and this is particularly true for infection with influenza viruses. Herein, we describe the main metabolic, endocrine, and immune dysregulations that occur in the presence of obesity and their impact on driving intra-host viral diversity, leading to heightened severity and virulence of influenza. We show that obesity is linked to modified responses of both the innate and adaptive immune systems during viral infections, including influenza. Due to chronic inflammation and metabolic, endocrine, and signaling pathway disruptions, individuals with obesity have a suboptimal immune response. This results in longer illness duration, increased virus shedding, higher risk of hospitalization and complications, and greater mortality rates. Additionally, they may have a blunted response to vaccination and a higher likelihood of genetic mutation selection. Understanding the intricate interplay between obesity and viral pathogenesis is crucial for developing efficacious therapeutic approaches and public health policies, particularly in light of the escalating worldwide incidence of obesity.

Incidence and risk factors for catheter-associated urinary tract infection in 623 intensive care units throughout 37 Asian, African, Eastern European, Latin American, and Middle Eastern nations: A multinational prospective research of INICC.

OBJECTIVE: To identify urinary catheter (UC)-associated urinary tract infection (CAUTI) incidence and risk factors. DESIGN: A prospective cohort study. SETTING: The study was conducted across 623 ICUs of 224 hospitals in 114 cities in 37 African, Asian, Eastern European, Latin American, and Middle Eastern countries. PARTICIPANTS: The study included 169,036 patients, hospitalized for 1,166,593 patient days. METHODS: Data collection took place from January 1, 2014, to February 12, 2022. We identified CAUTI rates per 1,000 UC days and UC device utilization (DU) ratios stratified by country, by ICU type, by facility ownership type, by World Bank country classification by income level, and by UC type. To estimate CAUTI risk factors, we analyzed 11 variables using multiple logistic regression. RESULTS: Participant patients acquired 2,010 CAUTIs. The pooled CAUTI rate was 2.83 per 1,000 UC days. The highest CAUTI rate was associated with the use of suprapubic catheters (3.93 CAUTIs per 1,000 UC days); with patients hospitalized in Eastern Europe (14.03) and in Asia (6.28); with patients hospitalized in trauma (7.97), neurologic (6.28), and neurosurgical ICUs (4.95); with patients hospitalized in lower-middle-income countries (3.05); and with patients in public hospitals (5.89).The following variables were independently associated with CAUTI: Age (adjusted odds ratio [aOR], 1.01; P < .0001), female sex (aOR, 1.39; P < .0001), length of stay (LOS) before CAUTI-acquisition (aOR, 1.05; P < .0001), UC DU ratio (aOR, 1.09; P < .0001), public facilities (aOR, 2.24; P < .0001), and neurologic ICUs (aOR, 11.49; P < .0001). CONCLUSIONS: CAUTI rates are higher in patients with suprapubic catheters, in middle-income countries, in public hospitals, in trauma and neurologic ICUs, and in Eastern European and Asian facilities.Based on findings regarding risk factors for CAUTI, focus on reducing LOS and UC utilization is warranted, as well as implementing evidence-based CAUTI-prevention recommendations.

Assessing the impact of a multidimensional approach and an 8-component bundle in reducing incidences of ventilator-associated pneumonia across 35 countries in Latin America, Asia, the Middle East, and Eastern Europe.

BACKGROUND: Ventilator associated pneumonia (VAP) occurring in the intensive care unit (ICU) are common, costly, and potentially lethal. METHODS: We implemented a multidimensional approach and an 8-component bundle in 374 ICUs across 35 low and middle-income countries (LMICs) from Latin-America, Asia, Eastern-Europe, and the Middle-East, to reduce VAP rates in ICUs. The VAP rate per 1000 mechanical ventilator (MV)-days was measured at baseline and during intervention at the 2nd month, 3rd month, 4-15 month, 16-27 month, and 28-39 month periods. RESULTS: 174,987 patients, during 1,201,592 patient-days, used 463,592 MV-days. VAP per 1000 MV-days rates decreased from 28.46 at baseline to 17.58 at the 2nd month (RR = 0.61; 95% CI = 0.58-0.65; P < 0.001); 13.97 at the 3rd month (RR = 0.49; 95% CI = 0.46-0.52; P < 0.001); 14.44 at the 4-15 month (RR = 0.51; 95% CI = 0.48-0.53; P < 0.001); 11.40 at the 16-27 month (RR = 0.41; 95% CI = 0.38-0.42; P < 0.001), and to 9.68 at the 28-39 month (RR = 0.34; 95% CI = 0.32-0.36; P < 0.001). The multilevel Poisson regression model showed a continuous significant decrease in incidence rate ratios, reaching 0.39 (p < 0.0001) during the 28th to 39th months after implementation of the intervention. CONCLUSIONS: This intervention resulted in a significant VAP rate reduction by 66% that was maintained throughout the 39-month period.

Prospective cohort study of incidence and risk factors for catheter-associated urinary tract infections in 145 intensive care units of 9 Latin American countries: INICC findings.

PURPOSE: Identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in Latin American Countries. METHODS: From 01/01/2014 to 02/10/2022, we conducted a prospective cohort study in 145 ICUs of 67 hospitals in 35 cities in nine Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama, and Peru. To estimate CAUTI incidence, we used the number of UC-days as the denominator, and the number of CAUTIs as numerator. To estimate CAUTI RFs, we analyzed the following 10 variables using multiple logistic regression: gender, age, length of stay (LOS) before CAUTI acquisition, UC-days before CAUTI acquisition, UC-device utilization (DU) ratio, UC-type, hospitalizationtype, ICU type, facility ownership, and time period. RESULTS: 31,631 patients, hospitalized for 214,669 patient-days, acquired 305 CAUTIs. The pooled CAUTI rate per 1000 UC-days was 2.58, for those using suprapubic catheters, it was 2.99, and for those with indwelling catheters, it was 2.21. The following variables were independently associated with CAUTI: age, rising risk 1% yearly (aOR = 1.01; 95% CI 1.01-1.02; p < 0.0001 female gender (aOR = 1.28; 95% CI 1.01-1.61; p = 0.04), LOS before CAUTI acquisition, rising risk 7% daily (aOR = 1.07; 95% CI 1.06-1.08; p < 0.0001, UC/DU ratio (aOR = 1.14; 95% CI 1.08-1.21; p < 0.0001, public facilities (aOR = 2.89; 95% CI 1.75-4.49; p < 0.0001. The periods 2014-2016 and 2017-2019 had significantly higher risks than the period 2020-2022. Suprapubic catheters showed similar risks as indwelling catheters. CONCLUSION: The following CAUTI RFs are unlikely to change: age, gender, hospitalization type, and facility ownership. Based on these findings, it is suggested to focus on reducing LOS, UC/DU ratio, and implementing evidence-based CAUTI prevention recommendations.

Ophthalmological Manifestations in People with HIV from Northeastern Romania.

Background and Objectives: Although ocular disorders can occasionally impact people with HIV over the course of their illness, HIV/AIDS is unmistakably a multisystem disorder. A physician can rule out a wide range of ophthalmic problems with the assistance of an ophthalmologist, from adnexal disorders to posterior segment diseases, including those affecting the optic tract and optic nerve. Materials and Methods: Based on patient medical data from the "St. Parascheva" Clinical Hospital of Infectious Diseases in Iasi, we carried out a retrospective clinical investigation on patients with HIV/AIDS and ophthalmological conditions who were hospitalized in northeastern Romania. We seek to draw attention to the characteristics and ophthalmological comorbidities of HIV/AIDS patients. The studied period was between 1 January 1991 and 31 December 2022. Results: There were a total of 38 recorded cases of ophthalmological manifestations in the HIV-infected patients. The research group's average age was 37.31 years old (standard deviation 9.5693917). Males were primarily impacted, having lower total CD4+ T-lymphocyte levels based on sex and CD4+ T-lymphocyte levels overall. The HIV viral load was 999 268.13 copies/mL on average (standard deviation 1,653,722.9). Of all the patients, we found out that 17 had congenital eye diseases (44.73%) and the others (21, 55.26%) developed ophthalmological diseases. CMV Retinitis was found most frequently, in eight patients (21.05%), followed by Myopia in seven patients (18.42%). Conclusions: The key to the management of HIV-positive patients is a multidisciplinary approach and access to antiretroviral therapy. Anyone who is HIV-positive and experiences ocular symptoms at any time should be directed to seek professional ophthalmologic treatment as soon as feasible. A therapeutic holdup could result in irreversible vision loss. Long-term coordination is required to combat this disease, improving communication between the ophthalmology and infectious disease fields.

Evolution of Plasmodium vivax and resistance patterns for infection based on Duffy genotype and phenotype.

The Duffy protein, a transmembrane molecule, acts as a receptor for various chemokines and facilitates binding between reticulocytes and the Plasmodium Duffy antigen binding protein. Duffy expression is associated with the Duffy chemokine receptor antigen genotype on chromosome 1 and exhibits variation across different geographic regions. Traditionally, the Duffy negative genotype and phenotype have been described to confer a certain level of protection against infection and symptom development. However, recent data suggest a shift in this behavior, with significantly higher prevalence observed in individuals with Duffy negative genotype or phenotype. Given that malaria is an endemic vector-borne disease in regions of Asia, Africa, and Latin America, posing a substantial global burden of disease and prioritizing public and global health, identifying evolutionary changes in infection and resistance patterns holds great importance for the design of strategies and reevaluation of conventional interventions. Hence, the aim of this review was to analyze the evolution of Plasmodium vivax and infection resistance patterns based on Duffy genotype and phenotype. The distribution of genotypes, phenotypes, and polymorphisms of P. vivax ligands and erythrocyte receptors varies geographically, notably resistance patterns of this microorganism in individuals with Duffy negative genotype and phenotype have significantly changed compared to studies conducted 30 years ago. The prevalence of vivax malaria in individuals with a Duffy negative status can reach up to 100%. Consequently, prioritizing research on this topic is essential for public health.

[Characterization of patients with anaphylaxis in a tertiary hospital in Medellin, Colombia (2009-2019)]. / Identificación de pacientes con anafilaxia en una institución de salud de tercer nivel de Medellín, Colombia (2009-2019).

OBJECTIVE: To characterize demographically and clinically the patients with anaphylaxis treated in a third level health institution in Medellin, Colombia. METHODS: A cross-sectional descriptive observational study was carried out, which includedpatients were diagnosed with anaphylaxis between 2009 and 2019. Information was retrieved from medical records through a collection instrument. Subsequently, a descriptive statistical analysis of proportions and measures of central tendency of the variables of interest was performed. RESULTS: A total of 1820 records were reviewed and data from 253 patients were included. Among the reported comorbidities, drug allergy was the most prevalent (28%). The most frequent manifestations of anaphylaxis were cutaneous and respiratory. Most of the cases presented basal tryptase values ≤ 11.4 ng/mL (94.7%). Different etiological agents (food, drugs, insects and latex) were reported, and their frequency varied according to age. Adrenaline, steroids, and antihistamines were the treatments of choice in 39.9, 34.3, and 39.9% of cases, respectively. CONCLUSIONS: The characteristics of anaphylaxis in a medical center in Colombia coincide with those reported in Latin American. The treatment of anaphylaxis is not standardized, which makes it necessary to educate the health personnel and develop national guidelines.

OBJECTIVO: Identificar las características clínicas y demográficas de pacientes con anafilaxia, atendidos en un hospital de tercer nivel de Medellín, Colombia. MÉTODOS: Estudio observacional, descriptivo, de corte transversal, al que se incluyeron pacientes con diagnóstico con anafilaxia entre 2009 y 2019. La información de los pacientes se obtuvo a partir de los expedientes clínicos, mediante un instrumento de recolección. Se realizó un análisis estadístico descriptivo, de proporciones y medidas de tendencia central de las variables de interés. RESULTADOS: Se revisaron 1820 expedientes y se incluyeron los datos de 253 pacientes. Los agentes etiológicos más frecuentes fueron: medicamentos (52.1%), alimentos (34.7%), picadura de insectos (13.8%) y agentes no especificados (17.7%). Las manifestaciones cutáneas y respiratorias fueron las más frecuentes asociadas con anafilaxia. El 94.7% de los casos tuvo concentraciones normales de triptasa. La adrenalina, los corticosteroides y antihistamínicos fueron los fármacos de elección en el 39.9, 34.3 y 39.9% de los casos, respectivamente. CONCLUSIONES: Las características de anafilaxia coinciden con las reportadas en la mayor parte de los estudios en Latinoamérica. Aunque existen guías mundiales de tratamiento de la anafilaxia, no suelen aplicarse de forma uniforme, lo que hace necesario adiestrar al personal de salud y desarrollar guías nacionales al respecto.

Laparoscopic Management of Cholecystoduodenal and Cholecystocolic Fistula: A Clinical Case Report.

Biliary fistula is a rare (less than 8%) cholecystectomy complication, internal fistulae being the most common of them (mainly colonic and duodenal). However, the presence of two fistulas at the same time is extremely rare, with a small number of cases reported in the literature to date. Symptoms tend to be non-specific, leading to a difficult preoperative diagnosis. The standard treatment for bilioenteric fistulas is open cholecystectomy and subsequent closure of the fistula. Nonetheless, modern techniques including laparoscopic and endoscopic approaches have been reported lately for their treatment with favorable results. We present a case of concomitant cholecystoduodenal and cholecystocolic fistula successfully treated with subtotal cholecystectomy and primary closure of the fistulous tracts by laparoscopic approach in a female Hispanic patient.

Voriconazole Pharmacokinetics in Critically Ill Patients and Extracorporeal Membrane Oxygenation Support: A Retrospective Comparative Case-Control Study.

Voriconazole, an antifungal agent, displays high intra- and inter-individual variability. The predictive pharmacokinetic (PK) index requires a minimum plasma concentration (Cmin) in patient serum of between 1-5.5 mg/L. It is common to encounter fungal infections in patients undergoing extracorporeal membrane oxygenation (ECMO) support, and data regarding voriconazole PK changes during ECMO are scarce. Our study compared voriconazole PKs in patients with and without ECMO support in a retrospective cohort of critically-ill patients. Fifteen patients with 26 voriconazole Cmin determinations in the non-ECMO group and nine patients with 27 voriconazole Cmin determinations in the ECMO group were recruited. The ECMO group had lower Cmin (0.38 ± 2.98 vs. 3.62 ± 3.88, p < 0.001) and higher infratherapeutic Cmin values (16 vs. 1, p < 0.001) than the non-ECMO group. Multivariate analysis identified ECMO support (-0.668, CI95 -0.978--0.358) and plasma albumin levels (-0.023, CI95 -0.046--0.001) as risk factors for low Cmin values. When comparing pre- and post-therapeutic drug optimisation samples from the ECMO group, the dose required to achieve therapeutic Cmin was 6.44 mg/kg twice a day. Therapeutic drug optimisation is essential to improve target attainment.

Estimating mortality and disability in Peru before the COVID-19 pandemic: a systematic analysis from the Global Burden of the Disease Study 2019.

Background: Estimating and analyzing trends and patterns of health loss are essential to promote efficient resource allocation and improve Peru's healthcare system performance. Methods: Using estimates from the Global Burden of Disease (GBD), Injuries, and Risk Factors Study (2019), we assessed mortality and disability in Peru from 1990 to 2019. We report demographic and epidemiologic trends in terms of population, life expectancy at birth (LE), mortality, incidence, prevalence, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) caused by the major diseases and risk factors in Peru. Finally, we compared Peru with 16 countries in the Latin American (LA) region. Results: The Peruvian population reached 33.9 million inhabitants (49.9% women) in 2019. From 1990 to 2019, LE at birth increased from 69.2 (95% uncertainty interval 67.8-70.3) to 80.3 (77.2-83.2) years. This increase was driven by the decline in under-5 mortality (-80.7%) and mortality from infectious diseases in older age groups (+60 years old). The number of DALYs in 1990 was 9.2 million (8.5-10.1) and reached 7.5 million (6.1-9.0) in 2019. The proportion of DALYs due to non-communicable diseases (NCDs) increased from 38.2% in 1990 to 67.9% in 2019. The all-ages and age-standardized DALYs rates and YLLs rates decreased, but YLDs rates remained constant. In 2019, the leading causes of DALYs were neonatal disorders, lower respiratory infections (LRIs), ischemic heart disease, road injuries, and low back pain. The leading risk factors associated with DALYs in 2019 were undernutrition, high body mass index, high fasting plasma glucose, and air pollution. Before the COVID-19 pandemic, Peru experienced one of the highest LRIs-DALYs rates in the LA region. Conclusion: In the last three decades, Peru experienced significant improvements in LE and child survival and an increase in the burden of NCDs and associated disability. The Peruvian healthcare system must be redesigned to respond to this epidemiological transition. The new design should aim to reduce premature deaths and maintain healthy longevity, focusing on effective coverage and treatment of NCDs and reducing and managing the related disability.