A Comprehensive Perspective on Intracranial Pressure Monitoring and Individualized Management in Neurocritical Care: Results of a Survey with Global Experts.

BACKGROUND: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. METHODS: We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. RESULTS: From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18-22 mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information. CONCLUSIONS: Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management.

ELISA F29 -A therapeutic efficacy biomarker in Chagas disease: Evaluation in pediatric patients treated with nifurtimox and followed for 4 years post-treatment.

BACKGROUND: Measurement of the success of antitrypanosomal treatment for Chagas disease is difficult, particularly in the chronic phase of the disease, because anti-Trypanosoma cruzi antibodies persist in serum for prolonged periods. We studied the effects of nifurtimox administered by two different treatment regimens on the T. cruzi calcium-binding flagellar protein F29 in children diagnosed with Chagas disease measured using an enzyme-linked immunosorbent assay (ELISA) technique (ELISA F29). METHODS AND PRINCIPAL FINDINGS: In a phase 3, randomized, double-blind, parallel-group, historically controlled study (ClinicalTrials.gov NCT02625974), blood samples obtained from children diagnosed with Chagas disease and treated with nifurtimox for either 60 days or 30 days were analyzed using an ELISA with an F29 recombinant protein as the antigen, as well as conventional serological tests (recombinant ELISA and indirect hemagglutination assay). In an exploratory approach, serological response to nifurtimox treatment was evaluated for 4 years post-treatment. In both treatment groups, the number of patients with negative ELISA F29 values increased over the period of observation. The incidence rate of negative seroconversion using ELISA F29 was 22.94% (95% CI: 19.65%, 26.63%) in the 60-day treatment group and 21.64% (95% CI: 17.21%, 26.86%) in the 30-day treatment group. In the subpopulation of patients who tested seropositive for F29 before nifurtimox treatment, 88 patients (67.7%) in the 60-day regimen and 39 patients (59.1%) in the 30-day regimen were F29 seronegative at 4 years post-treatment. All patients who had a positive ELISA F29 test at baseline and seroconverted to negative measured by conventional serology reached seronegativity in ELISA F29 earlier than in conventional serology. CONCLUSIONS: The results demonstrate a serological response to treatment with nifurtimox measured by the ELISA F29 test in children diagnosed with Chagas disease. The F29-based ELISA can be considered a potential early marker of response to antitrypanosomal therapy for Chagas disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT02625974.

Analysis of the Interactome of the Toxoplasma gondii Tgj1 HSP40 Chaperone.

Toxoplasma gondii is an obligate intracellular apicomplexan that causes toxoplasmosis in humans and animals. Central to its dissemination and pathogenicity is the ability to rapidly divide in the tachyzoite stage and infect any type of nucleated cell. Adaptation to different cell contexts requires high plasticity in which heat shock proteins (Hsps) could play a fundamental role. Tgj1 is a type I Hsp40 of T. gondii, an ortholog of the DNAJA1 group, which is essential during the tachyzoite lytic cycle. Tgj1 consists of a J-domain, ZFD, and DNAJ_C domains with a CRQQ C-terminal motif, which is usually prone to lipidation. Tgj1 presented a mostly cytosolic subcellular localization overlapping partially with endoplasmic reticulum. Protein-protein Interaction (PPI) analysis showed that Tgj1 could be implicated in various biological pathways, mainly translation, protein folding, energy metabolism, membrane transport and protein translocation, invasion/pathogenesis, cell signaling, chromatin and transcription regulation, and cell redox homeostasis among others. The combination of Tgj1 and Hsp90 PPIs retrieved only 70 interactors linked to the Tgj1-Hsp90 axis, suggesting that Tgj1 would present specific functions in addition to those of the Hsp70/Hsp90 cycle, standing out invasion/pathogenesis, cell shape motility, and energy pathway. Within the Hsp70/Hsp90 cycle, translation-associated pathways, cell redox homeostasis, and protein folding were highly enriched in the Tgj1-Hsp90 axis. In conclusion, Tgj1 would interact with a wide range of proteins from different biological pathways, which could suggest a relevant role in them.

Diagnostic Accuracy of Two Molecular Tools for Diagnosis of Congenital Chagas Disease.

BACKGROUND AND OBJECTIVE: The real prevalence of congenital Chagas disease is undefined because of difficulties in the detection of Trypanosoma cruzi by microscopic examination. The aim of this study was to determine the diagnostic accuracy of two molecular diagnostic tools, qPCR and LAMP, in the diagnosis of congenital Chagas disease in a clinical setting. METHODS: To this end, we conducted a prospective cohort study in a tertiary care center, of infants under 9 months of age, born in Buenos Aires to women with Chagas disease. Blood samples were collected for microscopic examination and molecular diagnosis at baseline. If negative, infants were followed up until 9 months of age to determine a final diagnosis by serology. In-house qPCR and LAMP previously validated were challenged as index tests. RESULTS: A total of 154 participants were potentially eligible, 120 of whom were enrolled. Finally, 102 (66.2%) of them fulfilled the follow-up. The diagnosis of congenital Chagas disease was confirmed in 13 infants and excluded in 89. Both the sensitivity and specificity of the qPCR were 100.0% (95% confidence interval 75.3-100.0 and 95% confidence interval 95.9-100.0, respectively), whereas the sensitivity and specificity of LAMP were 69.2% (95% confidence interval 38.6-90.9) and 100% (95% confidence interval 95.9-100.0), respectively. CONCLUSIONS: The qPCR agreed with the current diagnostic algorithm, and was a reliable and sensitive tool to detect congenital Chagas disease earlier, providing an appropriate and timely identification of infected infants requiring treatment. LAMP was able to detect congenital Chagas disease in infected infants by naked-eye visualization in accordance with a microscopic examination. The advantages of molecular diagnostic tools should be taken into account by the health system to improve congenital Chagas disease diagnosis.

Estimation of intracranial pressure by ultrasound of the optic nerve sheath in an animal model of intracranial hypertension.

BACKGROUND: Ultrasound of the optic nerve sheath diameter (ONSD) has been used as a non-invasive and cost-effective bedside alternative to invasive intracranial pressure (ICP) monitoring. However, ONSD time-lapse behavior in intracranial hypertension (ICH) and its relief by means of either saline infusion or surgery are still unknown. The objective of this study was to correlate intracranial pressure (ICP) and ultrasonography of the optic nerve sheath (ONS) in an experimental animal model of ICH and determine the interval needed for ONSD to return to baseline levels. METHODS: An experimental study was conducted on 30 pigs. ONSD was evaluated by ultrasound at different ICPs generated by intracranial balloon inflation, saline infusion, and balloon deflation, and measured using an intraventricular catheter. RESULTS: All variables obtained by ONS ultrasonography such as left, right, and average ONSD (AON) were statistically significant to estimate the ICP value. ONSD changed immediately after balloon inflation and returned to baseline after an average delay of 30 min after balloon deflation (p = 0.016). No statistical significance was observed in the ICP and ONSD values with hypertonic saline infusion. In this swine model, ICP and ONSD showed linear correlation and ICP could be estimated using the formula: -80.5 + 238.2 × AON. CONCLUSION: In the present study, ultrasound to measure ONSD showed a linear correlation with ICP, although a short delay in returning to baseline levels was observed in the case of sudden ICH relief.

SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage.

Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral protein synthesis and its relationship with the protein synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could result in an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis can contribute to understanding how this virus evades the immune response and the etiology of some deleterious collateral effect as a result of the viral replication. In this manner, our finding contributes to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.

Complex regional pain syndrome secondary to sacrococcygeal dislocation following trauma to the lumbosacral region. case report

ABSTRACT Introduction: The complex regional pain syndrome (CRPS) is a rare condition characterized by inflammatory, vasomotor and central nervous system (CNS) involvement. Its clinical presentation can be subacute, acute or chronic, and may have severe effects on the patient's quality of life. Case description: 21-year-old female patient with trauma in the lumbosacral region associated with pain and functional limitation. Diagnostic imaging showed sacrococcygeal dislocation with subsequent inflammatory and acute and chronic autonomic symptoms that were treated medically and surgically. The patient responded to treatment with long-term improvement of the symptoms. Discussion: In this case, CRPS occurred after trauma and caused subacute symptoms that became even more acute until reaching a chronic presentation. Inflammation, vasomotor dysfunction and CNS involvement made this case a multidisciplinary diagnostic and therapeutic challenge. Conclusion: CRPS is a rare disease that is difficult to diagnose. However, diagnosis should be timely in order to initiate personalized treatment, since this disease considerably affects the patient's quality of life.

RESUMEN Introducción. El síndrome doloroso regional complejo (SDRC) es una patología poco frecuente que se caracteriza por causar compromiso a nivel inflamatorio, vasomotor y del sistema nervioso central (SNC). Su presentación clínica puede ser subaguda, aguda o crónica y puede afectar considerablemente la calidad de vida del paciente. Presentación del caso. Paciente femenina de 21 años con trauma en región lumbosacra asociado a dolor y limitación funcional, a quien se le practicaron imágenes diagnosticas que evidenciaron luxofractura sacrococcígea con posterior presencia de síntomas inflamatorios y autonómicos (agudos y crónicos) que se trataron con medicamentos y cirugía. La paciente respondió al tratamiento con mejoría de la sintomatología a largo plazo. Discusión. El SDRC se presentó posterior a un traumatismo y ocasionó sintomatología subaguda que se agudizó hasta llegar a la presentación crónica de la enfermedad. La inflamación, la disfunción vasomotora y el compromiso del SNC hacen de este caso un reto diagnóstico y terapéutico multidisciplinario. Conclusión. El SDRC es una patología poco frecuente y de difícil diagnóstico; sin embrago, es necesario diagnosticarlo de forma oportuna para poder iniciar un tratamiento personalizado, ya que es una enfermedad que compromete considerablemente la calidad de vida del paciente.

Trypanosoma cruzi Virulence Factors for the Diagnosis of Chagas' Disease.

trans-Sialidase and cruzipain are important virulence factors from Trypanosoma cruzi, the etiological agent of Chagas disease, that have highly antigenic domains in their structure and were reported as potential tools for diagnosis of the illness. The aim of the present study is to assess the possibility of using cruzipain and the catalytic domain of trans-sialidase in a Surface Plasmon Resonance-based immunosensor for the diagnosis of chronic Chagas disease. Immunoassays carried out with canine sera verified that cruzipain allows the detection of anti-Trypanosoma cruzi antibodies whereas recombinant trans-sialidase did not yield specific detections, due to the high dilutions of serum used in the immunoassays that hinder the possibility to sense the specific low titer antibodies. The developed cruzipain-based biosensor, whose price per assay is comparable to a commercial enzyme-linked immunosorbent assay (ELISA), was successfully applied for the rapid quantification of specific antibodies against Trypanosoma cruzi in fresh human sera showing an excellent agreement with ELISA.

Drugs, Violence, and Trauma in Mexico and the USA.

The impact of illicit drug markets on the occurrence of violence varies tremendously depending on many factors. Over the last years, Mexico and the USA have increased security border issues that included many aspects of drug-related trade and criminal activities. Mexico experienced only a small reduction in trauma deaths after the enforcement of severe crime reinforcement policies. This strategy in the war on drugs is shifting the drug market to other Central American countries. This phenomenon is called the ballooning effect, whereby the pressure to control illicit drug-related activities in one particular area forces a shift to other more vulnerable areas that leads to an increase in crime and violence. A human rights crisis characterized by suffering, injury, and death related to drug trafficking continues to expand, resulting in the exorbitant loss of lives and cost in productivity across the continent. The current climate of social violence in Central America and the illegal immigration to the USA may be partially related to this phenomenon of drug trafficking, gang violence, and crime. A health care initiative as an alternative to the current war approach may be one of the interventions needed to reduce this crisis.

Perceived versus Observed Patient Safety Measures in a Critical Care Unit from a Teaching Hospital in Southern Colombia.

Introduction. Patient safety is an important topic. The purpose of this study is to evaluate the perceived versus observed patient safety measures (PSM) in critically ill patients in a teaching hospital in Latin America. Materials and Methods. The level of perceived patient safety was evaluated with the patient safety hospital survey. Three months later, a qualitative study was conducted, including video recording of procedures, graded according to adherence to PSM. Levels of adherence were scored during patient mobilization (PM), placement of central catheters (PCC), other invasive procedures (OIP), infection control (IC), and endotracheal intubation (ETI). Results. The perceived adherence of PSM in the prestudy survey was considered fair by 89.1% of the ICU staff. After the survey, 829 ICU procedures were video-recorded. Mean observed adherence for fair patient safety measures was 20.8%. Perceived adherence was higher than the real patient safety protocol measures observed in the videos. Conclusion. Perception of PSM was higher than observed in the management of critically ill patients in a teaching hospital in southern Colombia.

Predictive role of polymerase chain reaction in the early diagnosis of congenital Trypanosoma cruzi infection.

The efficacy of specific chemotherapy in congenital Chagas disease before the first year of life ranges between 90 and 100%. Between this age and 15 years of age, the efficacy decreases to around 60%. Therefore, early infection detection is a priority in vertical transmission. The aim of this work was to assess whether polymerase chain reaction (PCR) plays a predictive role in the diagnosis of congenital Chagas disease as compared to conventional parasitological and serological methods. To this end, we studied a total of 468 children born to Trypanosoma cruzi seroreactive mothers came from Argentina, Bolivia and Paraguay, who lived in the city of Buenos Aires and suburban areas (Argentina), a non-endemic area of this country. These children were assessed by PCR from 2004 to 2009 with the specific primers Tcz1 and Tcz2, and 121 and 122. PCR allowed detecting 49 T. cruzi-positive children. Eight of these 49 children were excluded from the analysis: six because they did not complete follow-up and two because the first control was performed after 12 months of age. Parasitological methods allowed detecting 25 positive children, 7 of whom had been earlier diagnosed by PCR (1.53±2.00 vs. 6.71±1.46 months; p=0.0002). Serological methods allowed detecting 16 positive children, 12 of whom had been earlier diagnosed by PCR (1.46±1.48 vs. 11.77±4.40 months; p<0.0001). None of the children negative by PCR was positive by serological or parasitological methods. This study shows that PCR allows early diagnosis in congenital Chagas disease. At present, an early positive PCR is not indicative for treatment. However, a positive PCR would alert the health system to search only those infected infants diagnosed by early PCR and thus generate greater efficiency in the diagnosis and treatment of congenital T. cruzi infection.

Use of an enzyme-linked immunosorbent assay that utilizes the Tc13Tul antigen of Trypanosoma cruzi to monitor patients after treatment with benznidazole.

Tc13Tul antigen is expressed in the mammalian stages of Trypanosoma cruzi, the etiological agent of Chagas' disease. Here, we designed and validated an enzyme-linked immunosorbent assay using the recombinant Tc13Tul (Tc13Tul-ELISA) and found that it had 82.5% sensitivity and 97.05% of specificity. To evaluate whether the decrease in antibodies against Tc13Tul may be used as an early marker of the effect of chemotherapy with benznidazole, sera from 30 T. cruzi-infected children were evaluated by Tc13Tul-ELISA before and after benznidazole treatment. While in Group A (6 months-4 years old, n = 16) the decrease of more than 30% of Tc13Tul-ELISA values showed a sensitivity similar to that of conventional serology (CS); in Group B, (5-12 years old, n = 14) the decrease of Tc13Tul-ELISA values was a better parameter than negativization of CS to monitor the impact of treatment. Therefore, the dosage of anti-Tc13Tul antibodies may be useful as a methodology complementary to CS to evaluate chagasic patients undergoing chemotherapy with benznidazole.

Protein palmitoylation and pathogenesis in apicomplexan parasites.

Apicomplexan parasites comprise a broad variety of protozoan parasites, including Toxoplasma gondii, Plasmodium, Eimeria, and Cryptosporidium species. Being intracellular parasites, the success in establishing pathogenesis relies in their ability to infect a host-cell and replicate within it. Protein palmitoylation is known to affect many aspects of cell biology. Furthermore, palmitoylation has recently been shown to affect important processes in T. gondii such as replication, invasion, and gliding. Thus, this paper focuses on the importance of protein palmitoylation in the pathogenesis of apicomplexan parasites.

Congenital Trypanosoma cruzi infection. Efficacy of its monitoring in an urban reference health center in a non-endemic area of Argentina.

Congenital transmission (CT) has acquired relevance in Chagas disease (CHD). A cohort of pregnant CHD women (4,355) and their babies were studied in the period 1994-2004. Children were excluded when they had received blood transfusions, or were born or had been in endemic areas; CT rate was 6.1%. Babies were diagnosed between months 1 and 5 in 68.9% of the cases and between months 6 and 12 in 31.1%. In the latter group, parasitemia was detected in 94% and serology in 74.7%. Between months 6 and 9, parasitemia diagnosed 36.2% (P = 0.000) more cases than serology. If serology had been the diagnosis method, those children would have been considered CT free. Taking the overall outcomes, 38.1% of babies were CT free, and 55.8% did not complete the follow-up. Establishing CT as a public health priority and improving first-line health service, congenital CHD coverage could be more efficient in endemic countries.

Early decompressive craniectomy for neurotrauma: an institutional experience.

BACKGROUND: Neurotrauma centers have developed management protocols on the basis of evidence obtained from literature analysis and institutional experience. This article reviews our institutional experience in the management of severe traumatic brain injury (TBI) at Simòn Bolivar Hospital, the district trauma center for Bogotá's north zone. METHODS: This is a case control study comparing a group of patients (n: 16) operated for severe TBI between January 2002 and July 2004 according to an institutional management protocol characterized by an early decompressive craniectomy (DC) approach versus a historical control group (n: 20) managed before the implementation of such protocol. Mortality and Glasgow Outcome Score (GOS) at 6 months were used as the main outcome variables. RESULTS: An early DC protocol implemented within 12 hours from injury in 16 patients with severe isolated TBI and a Marshall score between III or IV was associated with a lesser mortality than the conventional approach with ventriculostomy and Intensive Care Unit (ICU) management alone. The GOS was significantly better in the DC group (p=0.0002) than in the control group. CONCLUSION: The use of an early DC protocol for severe TBI patients (Glasgow Coma Scale <9) had a significantly improved outcome compared with the conventional approach with ventriculostomy and ICU management in Simòn Bolivar Hospital in Bogotá, Colombia.

Chromosomal size conservation through the cell cycle supports karyotype stability in Trypanosoma cruzi.

The Trypanosoma cruzi karyotype shows an extensive chromosomal size polymorphism. Absence of condensed mitotic chromosomes and chromatin fragility are characteristic features of T. cruzi which would allow DNA breaks and chromosomal rearrangements during cell proliferation. We have investigated by pulsed field gel electrophoresis (PFGE) eventual changes in chromosomal size during exponential and stationary phases of T. cruzi epimastigotes in culture, in G0 trypomastigotes and throughout the cell cycle in synchronized epimastigotes. T. cruzi molecular karyotype was stable throughout the cell cycle and during differentiation. Thus, the chromosomal size polymorphism previously reported in T. cruzi contrasts with the stability of the molecular karyotype observed here and suggests that chromosomal rearrangements leading to changes in chromosomal size are scarce events during the clonal propagation of this parasite.