14-day Group Research Articles

Assessing Clinical Outcomes of Vancomycin Treatment in Adult Patients with Vancomycin-Susceptible Enterococcus faecium Bacteremia.

Enterococcal bacteremia is associated with high mortality and long-term hospitalization. Here, we aimed to investigate the clinical outcomes and evaluate the risk factors for mortality in adult patients treated with vancomycin (VCM) for vancomycin-susceptible Enterococcus faecium (E. faecium) bacteremia. This is a retrospective, record-based study. The data were collected from inpatients at a single university hospital between January 2009 and December 2020. The area under the curve (AUC) of VCM was calculated using the Bayesian approach. The primary outcome was a 30-day in-hospital mortality. A univariate analysis showed significant differences in the concomitant use of vasopressors, history of the use of no clinically relevant activity antimicrobial agents against E. faecium, VCM plasma trough concentration, and renal dysfunction during VCM administration between the 30-day in-hospital mortality and survival groups. However, the groups' AUC/minimum inhibitory concentration (MIC) were not significantly different. A multivariate analysis suggested that concomitant vasopressors may be an independent risk factor for 30-day in-hospital mortality (odds ratio, 7.81; 95% confidence interval, 1.16-52.9; p = 0.035). The VCM plasma trough concentrations and the AUC/MIC in the mortality group were higher than those in the surviving group. No association between the AUC/MIC and the treatment effect in E. faecium bacteremia was assumed, because the known, target AUC/MIC were sufficiently achieved in the mortality group. There may be no association between the AUC/MIC and the treatment effect in E. faecium bacteremia. When an immunocompromised host develops E. faecium bacteremia with septic shock, especially when a vasopressor is used in a patient with unstable hemodynamics, it may be difficult to treat it, despite efforts to ensure the appropriate AUC/MIC and therapeutic vancomycin concentration levels.

Change and Regulation of Nutritional Metabolism in Silver Pomfret During Compensatory Growth.

Compensatory growth (CG) in fish is heavily influenced by nutrient metabolism. However, there are limited studies examining how nutrient metabolism is regulated during this process. For silver pomfret, an important commercial marine fish, it's crucial to establish effective starvation and re-feeding strategies to ensure good water quality and fast growth. To identify the complete compensatory growth model of silver pomfret, we conducted an experiment with a control group (normal feeding) and three starvation/re-feeding groups. We observed that the recovery of weight and condition factor in the 14-day starvation and 14-day re-feeding groups was significantly faster than other groups, indicating full compensatory growth. Thus, we selected this group for the next experiment. We performed untargeted metabolomics and transcriptome analysis of muscle tissue on Day 14, 21 and 28 (CG process), and examined the key regulatory genes of nutrient metabolism on Day 0, 7, 14, 21 and 28 (starvation and re-feeding process). Our data revealed that during starvation, silver pomfret first utilized carbohydrates and short-chain lipids, followed by proteins and long-chain lipids. After re-feeding, lipids accumulated first, resulting in rapid growth, followed by the recovery of protein content in muscle. During starvation, the expression of anabolic-related genes such as TER and CALR decreased, and catabolic-related genes such as TSC2 and MLYCD increased, promoting the AMPK pathway. During re-feeding, anabolic-related gene expression increased without AMPK inhibition. Our findings provide insights into the energy utilization strategies of fish and molecular regulation during compensatory growth in fish.

Evaluation of oxidative stress parameters of horses housed with goats in individual boxes

Horses are animals that are affected very quickly by the warnings coming from the environment. In this study, it was aimed to evaluate oxidative stress parameters of horses obtained from saliva analysis related to animal welfare as a result of keeping horses together with goats. While the research was being prepared, three groups were developed based on the time spent sheltering goats and horses. The horses were housed alone in the first and last 15-day groups, and along with the goats in the second 15-day group. In these stages, the levels of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities and ischemia-modified albumin (IMA) level in saliva were examined. Results showed that MDA and IMA levels decreased, but CAT, GPx, and SOD activities increased. It was concluded that goats had a positive effect on horses according to the oxidative stress parameters examined in terms of animal welfare. However, there is still a need for research that will house horses with various animals in acceptable animal welfare circumstances, analyse their stress metrics, and maintain a high level of welfare.

PD-L1 Blockade Improves Survival in Sepsis by Reversing Monocyte Dysfunction and Immune Disorder

Monocyte dysfunction is critical to sepsis-induced immunosuppression. Programmed death ligand-1 (PD-L1) has shown a close relationship with inflammatory disorder among animal models and patients. We aimed to investigate the potential beneficial immunologic mechanisms of anti-PD-L1 on monocyte dysfunction of mice with sepsis. Firstly, we assessed the potential association between PD-L1 expression on monocyte subsets and sepsis severity as well as 28-day mortality. In this study, 52 septic patients, 28 septic shock patients, and 40 healthy controls were enrolled and their peripheral whole blood was examined by flow cytometry. Then, cecal ligation and puncture (CLP) were performed for establishing the mouse sepsis model. Subsequently, effects of anti-PD-L1 antibody on monocyte subset, major histocompatibility complex II (MHC II) expression, cytokine production, and survival were investigated. PD-L1 expression on the classical monocytes (CD14 + + CD16 −) was significantly upregulated among septic shock patients and the 28-day death group than non-septic shock group and 28-day survival group (P < 0.05). Compared to septic mice, anti-PD-L1-treated mice had significantly elevated percentages of major histocompatibility complex (MHC) II on peripheral Ly6chi monocyte at 24 h after CLP. Our results showed that the anti-PD-L1 antibody markedly decreased the level of serum inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 in sepsis mice at 24 h, 48 h, and 72 h, respectively (P < 0.05). The survival rate of CLP mice was significantly improved by anti-PD-L1 antibody treatment. Classical monocytes with high expression of PD-L1 were thought to be connected with sepsis progression. The PD-L1 blockade protects from sepsis, at least partially by inhibiting the reversal of monocyte dysfunction.

Diagnosis of septic shock by serum measurement of human neutrophil lipocalin by a rapid homogeneous assay

BackgroundHuman neutrophil lipocalin (HNL) is a marker of neutrophil activation and has a high efficacy in diagnosing bacterial infections. In this study, we applied the AlphaLISA technique to measure the serum level of HNL, evaluate HNL's efficacy in diagnosing septic shock, and identify any association between HNL level and septic patients' prognosis. MethodsWe collected 146 serum samples from the Fifth Medical Center of Chinese PLA General Hospital. HNL was measured by AlphaLISA and results were compared with commercial ELISA kits. We studied 78 patients admitted to the ICU with sepsis and data on their clinical and physiological characteristics were recorded. Blood levels of HNL, procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), and lactate were measured. A receiver operating characteristic (ROC) curve was used to evaluate the performance of each marker. ResultsThe AlphaLISA assay for serum HNL had a detection range from 1.5 ng/mL to 1000 ng/mL, with a detection limit of 1 ng/mL and a detection time of approximately 25 min. The AlphaLISA assay's results were in high agreement with ELISA results (R2 = 0.9413). HNL levels were analyzed in sepsis patients, and HNL was significantly higher in sepsis patients with shock compared to sepsis patients without shock (median 356.47 ng/mL vs 158.93 ng/mL, P < 0.0001) and in the 28-day non-survivor group compared to the 28-day survivor group (median 331.83 ng/mL vs 175.17 ng/mL, P < 0.0001). ROC curve analysis was performed for the biomarkers. In differentiating the diagnosis of septic shock from sepsis patients, HNL was the most effective marker (AUC = 0.857), followed by PCT (AUC = 0.754) and hs-CRP (AUC = 0.627). In predicting the prognosis of septic patients, lactate had the best effect (AUC = 0.805), followed by HNL (AUC = 0.784), PCT (AUC = 0.721), and hs-CRP (AUC = 0.583). ConclusionsAs an assessment tool, we found that our AlphaLISA had good consistency with an ELISA and had several other advantages, including requiring a shorter processing time and detecting a wider range of serum HNL concentrations. Monitoring serum HNL levels of patients admitted to the ICU might be useful in distinguishing sepsis patients who have septic shock from other sepsis patients, indicating its value in the prediction of sepsis patient prognosis.

Placental insufficiency and heavier placentas in sheep after suppressing CXCL12/CXCR4 signaling during implantation†.

During implantation, trophoblast cell invasion and differentiation is predominantly important to achieving proper placental formation and embryonic development. The chemokine, C-X-C motif chemokine ligand 12 (CXCL12) working through its receptor C-X-C motif chemokine receptor 4 (CXCR4) is implicated in implantation and placentation but precise roles of this axis are unclear. Suppressing CXCL12/CXCR4 signaling at the fetal-maternal interface in sheep reduces trophoblast invasion, disrupts uterine remodeling, and diminishes placental vascularization. We hypothesize these negative impacts during implantation will manifest as compromised fetal and placental growth at midgestation. To test, on day 12 postbreeding, osmotic pumps were surgically installed in 30 ewes and delivered intrauterine CXCR4 inhibitor or saline for 7 or 14days. On day 90, fetal/maternal tissues were collected, measured, weighed, and maternal (caruncle) and fetal (cotyledon) placenta components separated and analyzed. The objectives were to determine if (i) suppressing CXCL12/CXCR4 during implantation results in reduced fetal and placental growth and development and (ii) if varying the amount of time CXCL12/CXCR4 is suppressed impacts fetal/placental development. Fetal weights were similar; however greater placental weight and placentome numbers occurred when CXCL12/CXCR4 was suppressed for 14days. In caruncles, greater abundance of fibroblast growth factor 2, vascular endothelial growth factor A, vascular endothelial growth factor A receptor 1 (FLT-1), and placental growth factor were observed after suppressing CXCL12/CXCR4. Similar results occurred in cotyledons except less vascular endothelial growth factor in 7day group and less fibroblast growth factor in 14day group. Our data underscore the importance of CXCL12/CXCR4 signaling during placentation and provide strong evidence that altering CXCL12-mediated signaling induces enduring placental effects manifesting later in gestation.

Pulsed field ablation for pulmonary vein isolation: Preclinical safety and effectiveness of a novel hexaspline ablation catheter.

Pulsed-field ablation (PFA) has emerged as a nonthermal energy source for cardiac ablation, with potential safety advantages over radiofrequency ablation (RFA) and cryoballoon ablation. To report the preclinical results of a novel hexaspline PFA catheter for pulmonary vein isolation (PVI), and to verify the influence of PFA on esophagus by comparing with RFA. This study included a total of 15 canines for the efficacy and safety study and four swine for the esophageal safety study. The 15 canines were divided into an acute cohort (n = 3), a 30-day follow-up cohort (n = 5) and a 90-day follow-up cohort (n = 7), PVI was performed with the novel hexaspline PFA ablation catheter. In the esophageal safety study, four swine were divided into PFA cohort (n = 2) and RFA cohort (n = 2), esophageal injury swine model was adopted, the esophagus was intubated with an esophageal balloon retractor, under fluoroscopy, the DV8 device was inflated with a mixture of saline and contrast and rotated to displace the esophagus rightward and anteriorly toward the ablation catheter in the inferior vena cava (IVC) and right inferior pulmonary vein (PV). Nine PFA applications were delivered at four locations on IVC and two locations on theright inferior PV in thePFA cohort, six RFA applications were delivered at each location in the RFA group. Histopathological analysis of all PVs, esophagus, IVC, and the adjacent lungs was performed. Acute PV isolation was achieved in all 15 canines (100%), with energy delivery times of less than 3 min/animal. In the 30 and 90 days group, the overall success rates were 88.9% and 88.5% per PVs, respectively. Two right superior pulmonary veins (RSPVs) in the 30-day group, two RSPVs and one left superior PV in the 90-day group with recovered potentials. At follow-up, gross pathological examination revealed the lesions around the PVs were continuous and transmural. Masson's trichrome staining revealed the myocardial cells in the PVs became fibrotic, but small arteries and nervous tissue were preserved. Results of swine esophageal injury model revealed the esophageal luminal surface was smooth and without evidence for esophageal injury in the PFA group, whereas obvious ulceration was detected on the esophagus tunica mucosa in the RFA group. In the chronic canine study, PFA-based PVI were safe and effective with demonstrable sparing of nerves and venous tissue. Compared with RFA, there was also good evidence for safety of PFA, avoiding PV stenosis and esophageal injury. This preclinical study provided the scientific basis for the first-in-human endocardial PFA studies.

A multicenter prospective study of comprehensive metagenomic and transcriptomic signatures for predicting outcomes of patients with severe community-acquired pneumonia

Severe community-acquired pneumonia (SCAP) results in high mortality as well as massive economic burden worldwide, yet limited knowledge of the bio-signatures related to prognosis has hindered the improvement of clinical outcomes. Pathogen, microbes and host are three vital elements in inflammations and infections. This study aims to discover the specific and sensitive biomarkers to predict outcomes of SCAP patients. In this study, we applied a combined metagenomic and transcriptomic screening approach to clinical specimens gathered from 275 SCAP patients of a multicentre, prospective study. We found that 30-day mortality might be independent of pathogen category or microbial diversity, while significant difference in host gene expression pattern presented between 30-day mortality group and the survival group. Twelve outcome-related clinical characteristics were identified in our study. The underlying host response was evaluated and enrichment of genes related to cell activation, immune modulation, inflammatory and metabolism were identified. Notably, omics data, clinical features and parameters were integrated to develop a model with six signatures for predicting 30-day mortality, showing an AUC of 0.953 (95% CI: 0.92-0.98). In summary, our study linked clinical characteristics and underlying multi-omics bio-signatures to the differential outcomes of patients with SCAP. The establishment of a comprehensive predictive model will be helpful for future improvement of treatment strategies and prognosis with SCAP. National Natural Science Foundation of China (No. 82161138018), Shanghai Municipal Key Clinical Specialty (shslczdzk02202), Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100).

Early mortality in German patients with lung cancer: risk factors associated with 30-and 60-day mortality

Despite therapeutic advances, early mortality in lung cancer is still prevalent. In this study, we aimed to assess risk factors for 30- and 60-day mortality in German lung cancer patients. In this retrospective cross-sectional analysis, we used data of lung cancer patients treated at LMU Hospital Munich between 2015 and 2019. We categorized patients into 30-day mortality, 60 day-mortality, and longer survival. We used Student’s t-test and ANOVA to compare means and Chi2-test to compare frequencies. We used logistic regression analysis to identify factors associated with a risk for early mortality. Of the 2454 lung cancer patients, 2.0% (n = 50) died within 30 and 1.7% (n = 41) within 30 to 60 days of diagnosis. Older age and advanced stage at diagnosis were significantly associated with early mortality in the univariate and the multivariate analysis. Patients in the 30-day mortality group significantly more often did not receive tumor-directed therapy. They were also more likely to die in an acute care setting compared to the 60-day mortality group. The group of patients who died unexpectedly (12.0%) was dominantly female, with a high proportion of patients with unintentional weight loss at the time of diagnosis. Our results suggest that in the treatment of patients with lung cancer there is a need for a greater focus on older patients. Moreover, physicians should pay special attention to females with recent weight loss and patients with a comorbidity of diabetes mellitus or renal impairment. Engaging a case manager focused on detecting patients with the above characteristics could help improve overall care.

Predictive Value of Comprehensive Geriatric Assessment Scores for Mortality in Patients With Hip Fracture: A Retrospective Cohort Study.

Objective To assess the predictive value of three scoring systems, namely the American Society of Anesthesiologists (ASA) classification, the Clinical Frailty Scale (CFS), and the Nottingham Hip Fracture Score (NHFS), in predicting mortality among patients with hip fractures. Materials and methods This retrospective cohort study included 628 participants aged 60 years and above who sought treatment at a UK hospital between January 2018 and December 2018. Data on age, gender, mortality, and assessment scores were collected. The area under the curve was calculated for each receiver operator characteristic(ROC). Cross-tabulation was performed to examine the association between various assessment scores and mortality using the chi-square test. Results The mean age was 80.80±11.18 years.Females were 408 (64.97%).Higher CFS (p<0.001) and NHFS (p<0.001) scores were significantly associated with mortality, while the ASA score did not show a significant association (p=0.225). The calculated area under the curve (AUC) values were as follows: 0.71 (95% CI: 0.65 to 0.76) for CFS, 0.46 (95% CI: 0.39 to 0.53) for NHFS, and 0.41 (95% CI: 0.34 to 0.48) for the ASA score. Utilizing a cut-off of ≥6 for CFS, 57 individuals (98.3%) in the 30-day mortality group were correctly identified. Similarly, the ROC analysis determined a ≥5 cut-off for NHFSaccurately predicting 50 patients (86.2%) who deceased within 30 days. Applying an ASA ≥3 cut-off resulted in a predictive mortality rate of 56 (96.6%). The NHFS score demonstrated the highest predictive capability for mortality, with patients scoring ≥5 having a significantly higher risk of mortality compared to those with a score <5. Conclusion This study showed robust correlations between high CFS (≥6) and NHFS(≥5), and mortality within the hip fracture patient cohort.

Medial Forebrain Bundle Axotomy Induced Dopaminergic Neuronal Degeneration is Accompanied with Microglial Activation

Background: We aimed to investigate the role of microglia in the degeneration of dopaminergic neurons by using the medial forebrain bundle (MFB) axotomy model, one of the animal models of Parkinson’s disease. Methods: We performed immunohistochemical staining, immunofluorescence staining, and Western blot assays on rats sacrificed 7, 14, and 28 days after the axotomy of their MFB to study tissue immune responses. Animal sacrifice was performed 30 minutes prior to injection of hydroethidine into the abdominal cavity to investigate the presence of oxidative stress in the brain tissue and the characteristics of cells that produce reactive oxygen species (ROS). Result: Using OX42 and OX6 antibodies, excessive activation of microglia occurred in the surgical site of the substantia nigra on 7 days after the procedure. Activated microglia were still present and clustered even in the 14-day and 28-day groups, although their reactivity had slightly decreased compared to the 7-day group. These cells showed strong immunopositive reactions to ED1, indicating that they were actively engaged in phagocytic activity. Many activated microglia showing positive immunofluorescence staining for OX6 also expressed ethidium fluorescence, indicating that these cells were actively generating and secreting ROS.

Evaluation of a novel polymer coil for endovascular occlusion of intracranial aneurysms in a rabbit model.

The results of the preclinical study of a novel polymer coil in treatment of elastase induced aneurysms will be presented in this paper. We induced 16 aneurysms in 16 New Zealand white rabbits at the origin of the right common carotid artery at the brachiocephalic trunk. Newly developed polymer coils in both groups for six aneurysms each and platinum coils for two aneurysms each were used. Control angiographies followed in both groups immediately after coiling as well as in the first eight animals 30days after intervention (30days group) and in the other eight animals 90days after (90days group). An explanation and histological evaluation of the treated aneurysms followed. The 12 animals in which the aneurysms were treated with polymer coils showed a complete occlusion (grade IV) in only 6 out of 12 aneurysms (50%), an almost complete occlusion (grade III) in 5 out of 12 (42%) and an incomplete occlusion in the treatment of one aneurysm (8%). Histologically, we observed a significantly more pronounced inflammatory response and neoangiogenesis in aneurysms treated with polymer coils only in the 30days group. Most difficulties and concerns with the polymer coils were related to the flexibility and detachment behaviour. Therefore, and due to the technical challenges of delivery, the novel polymer coil cannot be considered an alternative to the current platinum coils.

Ilaprazole-amoxicillin dual therapy at high dose as a first-line treatment for helicobacter pylori infection in Hainan: a single-center, open-label, noninferiority, randomized controlled trial

ObjectivesThis study aimed to evaluate the efficacy, adverse events, patient compliance, and cost of dual therapy with Ilaprazole-amoxicillin (IA) at high dose versus Ilaprazole-amoxicillin-furazolidone-bismuth (IAFB) quadruple therapy for the Helicobacter pylori (H.pylori) infection among Chinese patients.Methods200 patients who had tested positive for H. pylori and undergoing upper gastrointestinal endoscopy after being diagnosed with chronic gastritis participated in this open-label randomized controlled clinical trial. Patients were randomized to Group A and Group B: the 14-day IA dual treatment group (101) and IAFB quadruple treatment group (99). The 13 C urea breath test was conducted to determine whether H. pylori had been eliminated 4–6 weeks after the treatment. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the two treatment groups.ResultsEradication rates in group A were 92.1% and 94.9%, depending on the intention-to-treat (ITT), per-protocol (PP), respectively, which was similar to group B (91.9% and 93.6%). There was no significant difference observed in adverse events between the two groups (P = 0.518). Interestingly, compliance was significantly higher in group A compared to the group B (P = 0.031). In addition, drug costs were significantly lower for group A in comparison to the group B.ConclusionsIA dual therapy was found to be equally effective, safer and less costly than IAFB quadruple therapy. Therefore, these therapies can be potentially considered as first-line regimens for empirical treatment.

A comparative study of visual outcome in patients with optic neuritis treated with five or seven days of intravenous corticosteroid treatment.

Optic neuritis (ON), a major cause of visual impairment in young adults, is generally associated with rapid visual recovery when treated with intravenous methylprednisolone treatment (IVMPT). However, the optimal duration of such treatment is unknown, ranging from three to seven days in clinical practice. We aimed to compare the visual recovery in patients treated with 5-day or 7-day duration IVMPT. We performed a retrospective cohort study of consecutive patients with ON in São Paulo, Brazil, from 2016 to 2021. We compared the proportion of participants with visual impairment in 5-day and 7-day treatment schedules at discharge, at 1 month and between 6 and 12 months after the diagnosis of ON. The findings were adjusted to age, severity of the visual impairment, co-intervention with plasma exchange, time from symptom onset to IVMPT and the etiology of the ON to mitigate indication bias. We included 73 patients with ON treated with 5 or 7-day duration of 1g/d intravenous methylprednisolone therapy. Visual impairment at 6-12 months in the 5-day or the 7-day treatment groups was similar (57% x 59%, p > 0.9, Odds Ratio 1.03 [95% CI 0.59-1.84]). The results were similar after adjusting for prognostic variables and when observed at different time points. Visual recovery is similar in patients treated with 5-day and 7-day duration treatments of 1g/day intravenous methylprednisolone, suggesting a ceiling effect. Limiting the duration of the treatment can reduce hospital stay and costs, without interfering with clinical benefit.

Mangosteen peel extract (mpe) and dfdbbx applied to cavia cobaya tooth extraction sockets for guided bone regeneration

Objectives: The objective of this study was to examine the clinical and microbiological effects of combining mangosteen peel extract (MPE) and demineralized freeze-dried bovine bone xenograft (DFDBBX) on the expression of fibroblast growth factor-2 (FGF-2), the amount of osteoblast, and the amount of osteoclast in the alveolar bone following Cavia cobaya tooth extraction. Tooth extraction followed by alveolar ridge resorption is an unavoidable physiological process. The combination of MPE and DFDBBX is expected to primarily provide osteoconductive properties as well as strengthen the graft in order to stimulate new bone formation. Materials and Methods: Fifty-six Cavia cobaya were divided into two groups for 7-day (group A) and 30-day (group B) examinations, respectively. Each group consisted of twenty-eight animals that received four treatments. In each treatment, seven Cavia cobaya were used. The bottom right incisor was extracted. In groups AI and BI, tooth sockets were filled with 25 grams of polyethylene glycol (PEG). Tooth sockets in groups AII and BII were filled with 0.5 grams of DFDBBX and 24.5 grams of PEG. Tooth sockets in groups AIII and BIII were filled with 0.5 grams of MPE and 24.5 grams of PEG. In groups AIV and BIV, tooth sockets were filled with a mixture of 0.5 grams of DFDBBX, 0.5 grams of MPE, and 24 grams of PEG. Cavia cobaya's mandible was decalcified with ethylene diamine tetraacetic acid (EDTA) at 7 and 30 days. During this time, histopathology (HPA) and immunohistochemistry (IHC) tests were also performed. Statistical analysis: The calculated amounts of osteoblasts, osteoclasts, and FGF-2 expression data were used in the one-way ANOVA test. Results: FGF2 expression and the number of osteoblasts increased significantly after 7-day and 30-day of examination. On the other hand, the number of osteoclasts decreased. Conclusion: The combination of MPE and DFDBBX effectively increases FGF-2 expression and the number of osteoblast cells while decreasing the number of osteoclast cells on the alveolar ridge of Cavia cobaya.

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

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). 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. 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. ClinicalTrials.gov NCT02625974.

Contemporary Patterns of Care in Tetralogy of Fallot: Analysis of The Society of Thoracic Surgeons Data

BackgroundAgainst the background of earlier studies, recent patterns in surgical management of tetralogy of Fallot (TOF) were assessed. MethodsA retrospective review of The Society of Thoracic Surgeons (STS) Congenital Database (2010-2020) was performed on patients aged <18 years with TOF or pulmonary stenosis and primary procedure TOF surgical repair or palliation. Procedural frequencies were examined by epoch. Demographics, clinical variables, and outcomes were compared between the initial palliation and primary repair groups. Among those operated on at 0 to 60 days of age, variation in palliation rates across hospitals was assessed. ResultsThe 12,157 operations included 11,307 repairs (93.0%) and 850 palliations (7.0%); 68.5% of all palliations were modified Blalock-Taussig-Thomas shunts. Of 1105 operations on neonates, 45.4% (502) were palliations. Among neonates, palliations declined from 49.0% (331 of 675) in epoch 1 (2010-2015) to 39.8% (171 of 430) in epoch 2 (2016-2020; P = .0026). Overall, the most prevalent repair technique (5196 of 11,307; 46.0%) was ventriculotomy with transanular patch, which was also used in 520 of 894 (58.2%) of repairs after previous cardiac operations. Patients undergoing initial palliation demonstrated more preoperative STS risk factors (50.1% vs 24.3% respectively; P < .0001) and more major morbidity and mortality than patients undergoing primary repair (21.2% vs 7.46%; P < .0001). In the 0- to 60-day age group, risk factor–adjusted palliation rates across centers varied considerably, with 32 of 99 centers performing significantly more or significantly fewer palliations than predicted on the basis of their case mix. ConclusionsSurgical palliation rates have decreased across all age groups despite increasing prevalence of risk factors. Ventriculotomy with transanular patch remains the most prevalent repair type. The considerable center-level variation in rates of palliation was not completely explained by case mix.

Fertility Augmentation of Non-Descript Delayed Pubertal Cattle Heifers through Mineral Mixture Supplementation and Hormonal Intervention

Normal productive and reproductive behavior in domestic animal is closely associated with interaction between hormonal and nutritional status of the animal system. Twenty-four non-descript delayed pubertal cattle of Rewa district, aged between 3-5 years were used to study the effect of dietary mineral mixture supplementation and double PG protocol on reproductive performance. Cows were randomly allocated into four equal groups (A, B, C &amp; D), comprising three treatment groups (n=6), and control (n=6) group. Control group was fed ration containing same CP and energy level according to the body weight. Group A (n=6) was fed ration containing 0% mineral mixture feeding in total per day. Group B (n=6) was fed ration containing mineral mixture 1 % of ration feeding in total per day diet. Group C (n=6) were subjected for double PG protocol and GnRH. Group D (n=6) was fed ration containing mineral mixture 1 % of ration and double PG protocol and GnRH. Group D has slightly more progesterone levels comparison to group C because of pregnancy in more cows. Plasma progesterone concentration of B, C and D Group, which supplemented with mineral mixture and hormonal protocol were significantly high. At 60-day Group A and C has similar values of progesterone. Group D has low Estrogen values due to more number or non-cyclic cows then other groups. Mineral concentrations were also significantly high in treatment groups comparatively. Pregnancy rate obtained in non-descript delayed pubertal heifers after artificial insemination was recorded as 83.33% in Group D, while it was 100% in all other three groups. Estrus submission rate is 33.33%, 50.00%, 66.66% and 83.33 % in all four groups, respectively. Accordingly reproductive efficiency calculated in experimental groups is 33.33, 50.00, 66.66 and 69.44, respectively. Combination of hormonal protocol with mineral mixture supplementation showed comparatively better result with respect to submission rate and reproductive efficiency.

Serum lactate and the mortality of critically ill patients in the emergency department: A retrospective study.

Serum lactate levels have been widely studied as a prognostic marker in critically ill patients, particularly those in the intensive care unit. However, it remains unknown whether the serum lactate levels affect the mortality rate of critically ill patients admitted to hospital. To investigate this hypothesis, the vital signs and blood gas analysis data of 1,393 critically ill patients who visited the Emergency Department of Affiliated Kunshan Hospital of Jiangsu University (Kunshan, China) between January and December 2021 were collected. Patients were divided into two groups, 30-day survival group and a 30-day death group, and logistic regression analysis was used to investigate the association between vital signs, laboratory results and mortality rates of critically ill patients. A total of 1,393 critically ill patients was enrolled in the present study, with a male-to-female ratio of 1.17:1.00, a mean age of 67.72±19.29 years and a mortality rate of 11.6%. The multivariate logistic regression analysis revealed that increased serum lactate levels were an independent risk factor for mortality rate of critically ill patients [Odds ratio (OR)=1.50, 95% confidence interval (95% CI): 1.40-1.62]. The critical cut-off value for the serum lactate levels was identified as 2.35 mmol/l. In addition, OR values of age, heart rate, systolic blood pressure, transcutaneous oxygen saturation (SpO2) and hemoglobin were 1.02, 1.01, 0.99, 0.96 and 0.99, respectively (95% CI: 1.01-1.04, 1.00-1.02, 0.98-0.99, 0.94-0.98 and 0.98-1.00, respectively). The logistic regression model was found to be of value in terms of identifying the mortality rate of patients and the area under the receiver operating characteristic curve was 0.894 (95% CI: 0.863-0.925; P<0.001). In conclusion, the present study showed that high serum lactate levels in critically ill patients upon admission to hospital are associated with higher 30-day mortality rate.

The complexity of changes in modal choice: A quasi-experimental study

BackgroundChanges in modal choice is argued to be one way to reduce the emission of greenhouse gases. Increasing modal choices in favour of more environmentally friendly travel modes requires a better understanding of how these choices are actually made. The first aim of this study is therefore to examine how modal choice is related to subjective experiences as perceived accessibility, perceived satisfaction, and habit, both before and after an intervention promoting public transport. The second aim is to examine how modal choice is affected by the intervention. Finally, the third aim is to examine how subjective experiences as perceived accessibility, perceived satisfaction, and habit are affected by the intervention. MethodThe design used is a before- and after-study with free public travel passes as the intervention (30- or 14-days free travel pass). Altogether, 52 travelers – distributed on two intervention groups and one control group – participated in the study. The 30-days free travel pass group constitutes 18 participants, the 14-days free travel pass group constitutes 19 participants while the control group constitutes 15 participants. During the before-period the participants were asked to register their modal choice using a digitalized application downloaded on their smart phones (the TravelVu app), to complete a short app-based questionnaire, and a web-based questionnaire. During the after-period, they were once again asked to register their modal choice and to complete a web-based questionnaire. All data collected were analyzed by variance or correlation analyses using the change between before- and after period as the dependent variable. ResultsThe results show that walking was more common than the use of public transport and car, which in turn were more common than the use of bicycle. Perceived accessibility, perceived satisfaction, general health, life quality as well as habit were all rated fairly high. Over time, the use of public transport increased while the use of car decreased overall. With increased use of public transport, the perceived accessibility decreased, but on the other hand, the life quality increased. There was no difference in perceived accessibility, perceived satisfaction, or habit between the three groups, but the participants became overall more satisfied with the standard of their experiences of their everyday travel (cognitive evaluation). At the same time, they became less reflective of their choice of travel mode and less interested in trying out new alternative travel modes during the after- compared to the before period. ConclusionThe intervention did not affect the modal choice or the subjective experiences. Over time, the participants did however increase their use of public transport and their cognitive evaluation of their everyday travel overall, while they decreased their use of car and became less reflective and less interested in trying out new alternative travel modes. These changes might be attributed to their participation in the present study.