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PURPOSE: Toxoplasmosis is caused by the parasite Toxoplasma gondii (T. gondii). In immunocompetent individuals, the infection is often asymptomatic; however, in expectant mothers and those with immune system deficiencies, complications may arise. Consequently, there is a need for new drugs that cause minimal damage to host cells. The purpose of this study was to investigate the in vitro antiparasitic efficacy of quinolone-coumarin hybrids QC1-QC12, derived from quinolone antibacterials and novobiocin, against T. gondii. METHODS: The derivatives were compared with novobiocin and ciprofloxacin during testing, with pyrimethamine used as a positive control. We conducted the MTT assay to examine the anti-toxoplasmic effects of the test compounds and novobiocin. Evaluation included the infection and proliferation indices, as well as the size and number of plaques, based on the viability of both healthy and infected cells. RESULTS: The in vitro assays revealed that QC1, QC3, QC6, and novobiocin, with selectivity indices (SIs) of 7.27, 13.43, and 8.23, respectively, had the least toxic effect on healthy cells and the highest effect on infected cells compared to pyrimethamine (SI = 3.05). Compared to pyrimethamine, QC1, QC3, QC6, and novobiocin Without having a significant effect on cell viability, demonstrated a significant effect on reducing in both infection index and proliferation index, in addition to reducing the quantity and dimensions of plaques ( P < 0.05). CONCLUSION: Based on our results, QC1, QC3, QC6, and novobiocin due to their significant therapeutic effects could be considered as potential new leads in the development of novel anti-Toxoplasma agents.
Subject(s)
Novobiocin , Quinolones , Toxoplasma , Toxoplasma/drug effects , Novobiocin/pharmacology , Animals , Quinolones/pharmacology , Quinolones/chemistry , Fluoroquinolones/pharmacology , Coumarins/pharmacology , Coumarins/chemistry , Antiprotozoal Agents/pharmacology , Humans , Cell Survival/drug effects , Parasitic Sensitivity TestsABSTRACT
INTRODUCTION: Influenza is a common, seasonal infectious disease with broad medical, economic, and social consequences. Real-world evidence on the effect of influenza treatment on household transmission and healthcare resource utilization is limited in outpatient settings in the USA. This study examined the real-world effectiveness of baloxavir vs oseltamivir in reducing influenza household transmission and healthcare resource utilization. METHODS: This prospective electronic survey on patient-reported outcomes was conducted between October 2022 and May 2023 via CVS Pharmacy in the USA. Adult participants (≥ 18 years old) were eligible if they filled a prescription for baloxavir or oseltamivir at a CVS Pharmacy within 2 days of influenza symptom onset. Participant demographics, household transmission, and all-cause healthcare resource utilization were collected. Transmission and utilization outcomes were assessed using χ2 and Fisher exact tests. RESULTS: Of 87,871 unique patients contacted, 1346 (1.5%) consented. Of 374 eligible patients, 286 (90 baloxavir- and 196 oseltamivir-treated patients) completed the survey and were included in the analysis. Mean age of participants was 45.4 years, 65.6% were female, and 86.7% were White. Lower household transmission was observed with baloxavir compared with oseltamivir therapy (17.8% vs 26.5%; relative risk = 0.67; 95% CI 0.41-1.11). Healthcare resource utilization, particularly emergency department visits (0.0% vs 4.6%), was also numerically lower in the baloxavir-treated group; no hospitalizations were reported in either cohort. CONCLUSIONS: The findings from this real-world study suggest that antiviral treatment of influenza with baloxavir may decrease household transmission and reduce healthcare resource utilization compared with oseltamivir.
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BACKGROUND: miniSTONE-2 (NCT03629184) was a global, phase 3, randomized, controlled study that investigated the safety and efficacy of single-dose baloxavir marboxil in otherwise healthy children 1-<12 years of age and showed a positive risk-benefit profile. This post hoc analysis evaluated the safety and efficacy of baloxavir versus oseltamivir in children 5-11 years old with influenza. METHODS: Children received single-dose baloxavir or twice-daily oseltamivir for 5 days. Safety was the primary objective. Efficacy and virological outcomes included time to alleviation of symptoms, duration of fever and time to cessation of viral shedding by titer. Data were summarized descriptively. RESULTS: Ninety-four children 5-11 years old were included (61 baloxavir and 33 oseltamivir). Baseline characteristics were similar between the groups. The incidence of adverse events was balanced and low in both treatment groups, with the most common being vomiting (baloxavir 5% vs. oseltamivir 18%), diarrhea (5% vs. 0%) and otitis media (0% vs. 5%). No serious adverse events or deaths occurred. Median (95% CI) time to alleviation of symptoms with baloxavir was 138.4 hours (116.7-163.4) versus 126.1 hours (95.9-165.7) for oseltamivir; duration of fever was comparable between groups [41.2 hours (23.5-51.4) vs. 51.3 hours (30.7-56.8), respectively]. Median time to cessation of viral shedding was shorter in the baloxavir group versus oseltamivir (1 vs. ≈3 days). CONCLUSIONS: Safety, efficacy and virological results in children 5-11 years were similar to those from the overall study population 1-<12 years of age. Single-dose baloxavir provides an additional treatment option for pediatric patients 5-11 years old with influenza.
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BACKGROUND: The aim of this study was to identify Enterocytozoon bieneusi and Encephalitozoon spp. in fecal samples of HIV + /AIDS and cancer patients undergoing chemotherapy, and comparing the results to healthy individuals in Mazandaran province, north of Iran. METHODS: Stool samples were collected from 50 HIV + /AIDS patients, 50 cancer patients, and 50 healthy samples referred to medical centers in north of Iran. Stool samples were kept in 2.5% potassium dichromate at 4 °C, and stained by modified trichrome for light microscopy examination. The multiplex/nested-PCR targeted the small subunit ribosomal RNA (SSU rRNA) gene. To characterize genotypes, the nested PCR products sequenced by Bioneer Company and was subjected to phylogenetic analyses. RESULTS: Ten of 50 samples (20%) of HIV + /AIDS patients, 5 of 50 samples (10%) of cancer patients, and 1 of healthy individuals (2%) were microscopically positive. From 50 HIV + / AIDS patients, E. bieneusi and Encephalitozoon spp. were detected in 10 (20%) and 6 (12%) cases, respectively. Furthermore, among cancer patients, 7 (14%) and 2 (4%) cases were E. bieneusi and Encephalitozoon spp., respectively. Out of 50 samples of healthy individuals, only 3 (6%) cases of E. bieneusi were observed. The genotypes D and M were detected among positive samples of E. bieneusi. CONCLUSIONS: E. bieneusi and then Encephalitozoon spp. are common intestinal microsporidia in HIV + /AIDS patients and cancer patients undergoing chemotherapy in Mazandaran province. E. bieneusi genotype D seems to be the predominant genotype in Mazandaran province. Due to the considerable prevalence of intestinal microsporidia, physicians are advised to pay more attention to this opportunistic infection in high-risk groups.
Subject(s)
Acquired Immunodeficiency Syndrome , Encephalitozoon , Enterocytozoon , Microsporidia , Microsporidiosis , Neoplasms , Humans , Microsporidiosis/epidemiology , Microsporidiosis/diagnosis , Iran/epidemiology , Phylogeny , Genotype , Enterocytozoon/genetics , Neoplasms/complications , Neoplasms/drug therapy , FecesABSTRACT
BACKGROUND: Current chemical treatments for toxoplasmosis have side effects, researchers are looking for herbal remedies with minimal side effects and the best effectiveness. This study aimed to evaluate the anti-toxoplasmic effects of silver nanoparticles based on Sambucus ebulus (Ag-NPs-S. ebulus) and Feijoa sellowiana (Ag-NPs-F. sellowiana) fruit extracts, in vitro and in vivo. METHODS: Vero cells were treated with different concentrations (0.5, 1, 2, 5, 10, 20, 40 µg/mL) of extracts and pyrimethamine as a positive control. Vero cells were infected with T. gondii and treated with extracts. The infection index and intracellular proliferation of T. gondii were evaluated. The survival rate of infected mice with tachyzoites of T. gondii was examined after intraperitoneal injection of the extracts at a dose of 40 mg/kg/day for 5 days after infection. RESULTS: The Ag-NPs-S. ebulus and Ag-NPs-F. sellowiana, almost similar to pyrimethamine, reduced proliferation index when compared to untreated group. Also, high toxoplasmicidal activity was observed with Ag-NPs-S. ebulus extract. Mice in the treatment groups of Ag-NPs-S. ebulus and pyrimethamine achieved better results in terms of survival than the others. CONCLUSION: The results indicated that Ag-NPs-F. sellowiana and S. ebulus have a significant growth effect on T. gondii in vitro and in vivo. Ag-NPs-S. ebulus extract has a more lethal effect on the parasite than Ag-NPs-F. sellowiana. It is suggested that in future investigate the induction of Toxoplasma-infected cell apoptosis using nanoparticles.
Subject(s)
Feijoa , Metal Nanoparticles , Parasites , Sambucus , Toxoplasma , Chlorocebus aethiops , Animals , Mice , Vero Cells , Silver/pharmacology , Pyrimethamine/pharmacology , Plant Extracts/pharmacologyABSTRACT
Currently, parasitic infections are one of the important health problems in the world, especially in developing countries. This study aims to investigate intestinal parasites with an emphasis on molecular identification through the analysis of mitochondrial COX1 and ITS2 gene sequences of Strongyloides stercoralis (S. stercoralis) and Trichostrongylus spp. in north of Iran. Five hundred forty stool samples were collected from medical diagnostic laboratories affiliated with Mazandaran University of Medical Sciences in Sari city, north of Iran. First, all the samples were examined using direct smear, formalin-ether sedimentation, and trichrome staining technique. Suspected samples of Strongyloides larvae were cultured in agar plate. Then, DNA was extracted from samples containing Trichostrongylus spp. eggs and Strongyloides larvae. To amplify DNA, PCR was performed and the samples with a sharp band in electrophoresis were sequenced by Sanger method. Overall, the prevalence of parasitic infections in the study population was 5.4%. The highest and the lowest level of infection was observed with Trichostrongylus spp. and S. stercoralis at 3% and 0.2%, respectively. No traces of live Strongyloides larvae were seen in the culture medium of the agar plate. The six isolates obtained from the amplification of the ITS2 gene of Trichostrongylus spp. were sequenced, all of which were Trichostrongylus colubriformis. The sequencing results of COX1 gene indicated S. stercoralis. In the present study, the prevalence of intestinal parasitic infections in north of Iran has relatively decreased that its main reason can be due to the coronavirus epidemic and compliance with health principles. However, the prevalence of Trichostrongylus parasite was relatively high that it requires special attention to apply appropriate control and treatment strategies in this field.
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OBJECTIVE: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort. METHODS: Patients with abdominal AGI related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for the definition of AGI. Multivariable regression was performed to identify factors associated with mortality. RESULTS: One hundred and sixty-nine patients with surgically treated abdominal AGI were identified, comprising 43 SC (14 endografts; 53% with a graft enteric fistula [GEF] in total) and 126 RS (26 endografts; 50% with a GEF in total). The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan-Meier estimated five year survival for SC vs. RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan-Meier estimated five year survival for SC patients with a GEF vs. without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC with RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in five year survival comparing SC vs. RS (HR 1.0, 95% CI 0.6 - 1.5). CONCLUSION: In this national AGI cohort, there was no mortality difference comparing SC and RS for AGI when adjusting for comorbidities. Presence of GEF probably negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC treated patients.
Subject(s)
Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Prosthesis-Related Infections , Humans , Blood Vessel Prosthesis/adverse effects , Blood Vessel Prosthesis Implantation/adverse effects , Conservative Treatment/adverse effects , Risk Factors , Retrospective Studies , Endovascular Procedures/adverse effects , Postoperative Complications/etiology , Prosthesis-Related Infections/surgery , Prosthesis-Related Infections/etiology , Treatment Outcome , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/complicationsABSTRACT
In this review, we intend to provide a summary of the activities of researchers in the field of Toxoplasma gondii in Iran, during the past 70 years. Most studies have been limited to epidemiological studies (mostly using ELISA and IFA methods). Designing a standard and reliable method using the specific antigens of this parasite is essential. So far, studies in the field of drug effects have not been able to introduce an effective drug with few side effects. Various types of vaccines have been developed, such as recombinant and DNA vaccines. However, none of them had a good efficacy. The use of multi-epitope vaccines as potential vaccines against toxoplasmosis is recommended. At present, limited studies have been conducted on the patterns of transmission and genetic diversity of isolated isolates in Iran. Future research to determine the genotype of T. gondii could play an important role in the study of population structure, and biological characteristics of this parasite. It is hoped that the results of this study will help control, prevent, and reduce the burden of disease caused by this parasite.
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Toxoplasmosis is a disease with a worldwide prevalence that is caused by Toxoplasma gondii. Pyrimethamine and sulfadiazine are two pharmacological agents commonly used to treat of this infection. However, they are accompanied by some side effects. Therefore, the identifying of new drugs with low toxocytosis seems to be a matter of vital importance. Quinolones are DNA replication inhibitors, exerting inhibitory effects against many pathogens, including bacteria, mycoplasma, and protozoa. Given the importance of quinolones and their efficacy, the present in vitro study was conducted to investigate the antiparasitic activities of new quinolones (NFQ-2, NFQ-5, and NFQ-6) containing nitrofuran moiety against T. gondii. To this end, Vero cells were incubated with various concentrations of new quinolones and pyrimethamine (positive control) to determine their viability. Subsequently, they were infected with T. gondii (RH strain) and then subjected to drug treatment. The obtained IC50 values were 3.60, 4.84, 5.59, 3.44 and 2.75 µg/mL for NFQ-2, NFQ-5, NFQ-6, ciprofloxacin and pyrimethamine, respectively. The CC50 values for the NFQ-2, NFQ-5, and NFQ-6 were 25.20, 29.89, and 28.43 µg/mL, indicating the selectivity indexes more than 5 for these compounds. The anti-Toxoplasma efficiency was determined by evaluating infection index, number and size of plaques, and T. gondii intracellular proliferation. As the results indicated, the administration of new quinolone derivatives resulted in the reduction of intracellular proliferation, infection index, and the number and size of plaques in comparison to uninfected treated cells (P < 0.05). The results were indicative of a considerable synergetic effect when each of the derivatives was used in combination with pyrimethamine, compared to when used alone. Based on our results, the nitrofuran-derived quinolones can be considered as new leads for the design of new anti-Toxoplasma agents.
Subject(s)
Antiprotozoal Agents , Nitrofurans , Quinolones , Toxoplasma , Animals , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Chlorocebus aethiops , Nitrofurans/pharmacology , Pyrimethamine/pharmacology , Pyrimethamine/therapeutic use , Quinolones/pharmacology , Vero CellsABSTRACT
BACKGROUND: Hemodynamic instability due to torso hemorrhage can be managed with the assistance of resuscitative endovascular balloon occlusion of the aorta (REBOA). This is a report of a single-center experience using the ER-REBOA™ catheter for traumatic and non-traumatic cases as an adjunct to hemorrhage control and as part of the EndoVascular resuscitation and Trauma Management (EVTM) concept. The objective of this report is to describe the clinical usage, technical success, results, complications and outcomes of the ER-REBOA™ catheter at Örebro University hospital, a middle-sized university hospital in Europe. METHODS: Data concerning patients receiving the ER-REBOA™ catheter for any type of hemorrhagic shock and hemodynamic instability at Örebro University hospital in Sweden were collected prospectively from October 2015 to May 2020. RESULTS: A total of 24 patients received the ER-REBOA™ catheter (with the intention to use) for traumatic and non-traumatic hemodynamic control; it was used in 22 patients. REBOA was performed or supervised by vascular surgeons using 7-8 Fr sheaths with an anatomic landmark or ultrasound guidance. Systolic blood pressure (SBP) increased significantly from 50 mmHg (0-63) to 95 mmHg (70-121) post REBOA. In this cohort, distal embolization and balloon rupture due to atherosclerosis were reported in one patient and two patients developed renal failure. There were no cases of balloon migration. Overall 30-day survival was 59%, with 45% for trauma patients and 73% for non-traumatic patients. Responders to REBOA had a significantly lower rate of mortality at both 24 h and 30 days. CONCLUSIONS: Our clinical data and experience show that the ER-REBOA™ catheter can be used for control of hemodynamic instability and to significantly increase SBP in both traumatic and non-traumatic cases, with relatively few complications. Responders to REBOA have a significantly lower rate of mortality.
Subject(s)
Balloon Occlusion , Endovascular Procedures , Shock, Hemorrhagic , Aorta , Blood Pressure , Humans , Resuscitation , Shock, Hemorrhagic/therapyABSTRACT
OBJECTIVE: Abdominal aortic graft and endograft infection (AGI) is primarily treated by resection of the infected graft and restoration of distal perfusion through extra-anatomic bypass (EAB) or in situ reconstruction/repair (ISR). The aim of this study was to compare these surgical strategies in a nationwide multicentre retrospective cohort study. METHODS: The Swedish Vascular Registry (Swedvasc) was used to identify surgically treated abdominal AGIs in Sweden between January 1995 and May 2017. The primary aim was to compare short and long term survival, as well as complications for EAB and ISR. RESULTS: Some 126 radically surgically treated AGI patients were identified - 102 graft infections and 24 endograft infections - treated by EAB: 71 and ISR: 55 (23 neo-aorto-iliac systems, NAISs). No differences in early 30 day (EAB 81.7% vs. ISR 76.4%, p = .46), or long term five year survival (48.2% vs. 49.9%, p = .87) were identified. There was no survival difference comparing NAIS to other ISR strategies. The frequency of recurrent graft infection during follow up was similar: EAB 20.3% vs. ISR 17.0% (p = .56). Survival and re-infection rates of the new conduit did not differ between NAIS and other ISR strategies. Age ≥ 75 years (odds ratio [OR] 4.0, confidence interval [CI] 1.1 - 14.8), coronary artery disease (OR 4.2, CI 1.2 - 15.1) and post-operative circulatory complications (OR 5.2, CI 1.2 - 22.5) were associated with early death. Prolonged antimicrobial therapy (> 3 months) was associated with reduced long term mortality (HR 0.3, CI 0.1 - 0.9). CONCLUSION: In this nationwide multicentre study comparing outcomes of radically treated AGI, no differences in survival or re-infection rate could be identified comparing EAB and ISR.
Subject(s)
Aorta, Abdominal/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis/adverse effects , Endovascular Procedures/adverse effects , Prosthesis-Related Infections/surgery , Aged , Aorta, Abdominal/diagnostic imaging , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/mortality , Endovascular Procedures/instrumentation , Endovascular Procedures/mortality , Female , Humans , Male , Middle Aged , Prosthesis-Related Infections/diagnostic imaging , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/mortality , Registries , Reoperation , Retrospective Studies , Risk Assessment , Risk Factors , Sweden , Time Factors , Treatment OutcomeABSTRACT
INTRODUCTION: It is difficult to estimate the ischemic consequences when using partial resuscitative endovascular balloon occlusion of the aorta (REBOA). The aim was to investigate if end-tidal carbon dioxide (ETCO2) is correlated to degree of aortic occlusion, measured as distal aortic blood flow, and distal organ metabolism, estimated as systemic oxygen consumption (VO2), in a porcine model of normovolemia and hemorrhagic shock. MATERIALS AND METHODS: Nine anesthetized pigs (25-32âkg) were subjected to incremental steps of zone 1 aortic occlusion (reducing distal aortic blood flow by 33%, 66%, and 100%) during normovolemia and hemorrhagic grade IV shock. Hemodynamic and respiratory variables, and blood samples, were measured. Systemic VO2 was correlated to ETCO2 and measures of partial occlusion previously described. RESULTS: Aortic occlusion gradually lowered distal blood flow and pressure, whereas ETCO2, VO2 and carbon dioxide production decreased at 66% and 100% aortic occlusion. Aortic blood flow correlated significantly to ETCO2 during both normovolemia and hemorrhage (R = 0.84 and 0.83, respectively) and to femoral mean pressure (Râ=â0.92 and 0.83, respectively). Systemic VO2 correlated strongly to ETCO2 during both normovolemia and hemorrhage (Râ=â0.91 and 0.79, respectively), blood flow of the superior mesenteric artery (Râ=â0.77 and 0.85, respectively) and abdominal aorta (Râ=â0.78 and 0.78, respectively), but less to femoral blood pressure (Râ=â0.71 and 0.54, respectively). CONCLUSION: ETCO2 was correlated to distal aortic blood flow and VO2 during incremental degrees of aortic occlusion thereby potentially reflecting the degree of aortic occlusion and the ischemic consequences of partial REBOA. Further studies of ETCO2, and potential confounders, in partial REBOA are needed before clinical use.
Subject(s)
Aorta/surgery , Balloon Occlusion , Carbon Dioxide/metabolism , Resuscitation , Shock, Hemorrhagic/metabolism , Shock, Hemorrhagic/therapy , Anesthesia , Animals , Disease Models, Animal , Oxygen Consumption , Regional Blood Flow/physiology , Swine , Tidal Volume/physiologyABSTRACT
BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) causes physiological, metabolic, end-organ and inflammatory changes that need to be addressed for better management of severely injured patients. The aim of this study was to investigate occlusion time-dependent metabolic, end-organ and inflammatory effects of total REBOA in Zone I in a normovolemic animal model. METHODS: Twenty-four pigs (25-35 kg) were randomized to total occlusion REBOA in Zone I for either 15, 30, 60 min (REBOA15, REBOA30, and REBOA60, respectively) or to a control group, followed by 3-h reperfusion. Hemodynamic variables, metabolic and inflammatory response, intraperitoneal and intrahepatic microdialysis, and plasma markers of end-organ injuries were measured during intervention and reperfusion. Intestinal histopathology was performed. RESULTS: Mean arterial pressure and cardiac output increased significantly in all REBOA groups during occlusion and blood flow in the superior mesenteric artery and urinary production subsided during intervention. Metabolic acidosis with increased intraperitoneal and intrahepatic concentrations of lactate and glycerol was most pronounced in REBOA30 and REBOA60 during reperfusion and did not normalize at the end of reperfusion in REBOA60. Inflammatory response showed a significant and persistent increase of pro- and anti-inflammatory cytokines during reperfusion in REBOA30 and was most pronounced in REBOA60. Plasma concentrations of liver, kidney, pancreatic and skeletal muscle enzymes were significantly increased at the end of reperfusion in REBOA30 and REBOA60. Significant intestinal mucosal damage was present in REBOA30 and REBOA60. CONCLUSION: Total REBOA caused severe systemic and intra-abdominal metabolic disturbances, organ damage and inflammatory activation already at 30 min of occlusion.
Subject(s)
Aorta/pathology , Balloon Occlusion/methods , Disease Models, Animal , Resuscitation/methods , Animals , Endovascular Procedures/methods , Female , Hemodynamics , Lactic Acid/metabolism , Liver/pathology , Male , Mesenteric Artery, Superior/metabolism , Reperfusion/methods , SwineABSTRACT
EndoVascular and Hybrid Trauma Management (EVTM) has been recently introduced in the treatment of severe pelvic ring injuries. This multimodal method of hemorrhage management counts on several strategies such as the REBOA (resuscitative endovascular balloon occlusion of the aorta). Few data exist on the use of REBOA in patients with a severely injured pelvic ring. The ABO (aortic balloon occlusion) Trauma Registry is designed to capture data for all trauma patients in hemorrhagic shock where management includes REBOA placement. Among all patients included in the ABO registry, 72 patients presented with severe pelvic injuries and were the population under exam. 66.7% were male. Mean and median ISS were respectively 43 and 41 (SD ± 13). Isolated pelvic injuries were observed in 12 patients (16.7%). Blunt trauma occurred in 68 patients (94.4%), penetrating in 2 (2.8%) and combined in 2 (2.8%). Type of injury: fall from height in 15 patients (23.1%), traffic accident in 49 patients (75.4%), and unspecified impact in 1 patient (1.5%). Femoral access was gained pre-hospital in 1 patient, in emergency room in 43, in operating room in 12 and in angio-suite in 16. REBOA was positioned in zone 1 in 59 patients (81,9%), in zone 2 in 1 (1,4%) and in zone 3 in 12 (16,7%). Aortic occlusion was partial/periodical in 35 patients (48,6%) and total occlusion in 37 patients (51,4%). REBOA associated morbidity rate: 11.1%. Overall mortality rate was 54.2% and early mortality rate (≤ 24 h) was 44.4%. In the univariate analysis, factors related to early mortality (≤ 24 h) are lower pH values (p = 0.03), higher base deficit (p = 0.021), longer INR (p = 0.012), minor increase in systolic blood pressure after the REBOA inflation (p = 0.03) and total aortic occlusion (p = 0.008). None of these values resulted significant in the multivariate analysis. In severe hemodynamically unstable pelvic trauma management, REBOA is a viable option when utilized in experienced centers as a bridge to other treatments; its use might be, however, accompanied with severe-to-lethal complications.
Subject(s)
Aorta , Arterial Occlusive Diseases/therapy , Balloon Occlusion/methods , Pelvis/injuries , Registries , Shock, Hemorrhagic/therapy , Adolescent , Adult , Arterial Occlusive Diseases/etiology , Balloon Occlusion/adverse effects , Female , Humans , Hydrogen-Ion Concentration , International Normalized Ratio , Male , Middle Aged , Shock, Hemorrhagic/etiology , Shock, Hemorrhagic/mortality , Systole , Trauma Severity Indices , Young AdultABSTRACT
BACKGROUND: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) may improve Systolic Blood Pressure (SBP) in hypovolemic shock. It has, however, not been studied in patients with impending traumatic cardiac arrest (ITCA). We aimed to study the feasibility and clinical outcome of REBOA in patients with ITCA using data from the ABOTrauma Registry. METHODS: Retrospective and prospective data on the use of REBOA from 16 centers globally were collected. SBP was measured both at pre- and post-REBOA inflation. Data collected included patients' demography, vascular access technique, number of attempts, catheter size, operator, zone and duration of occlusion, and clinical outcome. RESULTS: There were 74 patients in this high-risk patient group. REBOA was performed on all patients. A 7-10Fr catheter was used in 66.7% and 58.5% were placed on the first attempt, 52.1% through blind insertion and 93.2% inflated in Zone I, 64.8% for a period of 30 to 60 min, 82.1% by ER doctors, trauma surgeons, or vascular surgeons. SBP significantly improved to 90 mm Hg following the inflation of REBOA. 36.6% of the patients survived. CONCLUSIONS: Our study has shown that REBOA may be performed in patients with ITCA, SBP can be elevated, and 36.6% of the patients survived if REBOA placement is successful.
Subject(s)
Balloon Occlusion , Shock, Hemorrhagic/therapy , Wounds and Injuries/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Feasibility Studies , Female , Heart Arrest , Humans , Injury Severity Score , Male , Middle Aged , Resuscitation/methods , Retrospective Studies , Young AdultABSTRACT
As current toxoplasmosis chemotherapies have many side effects along with toxicity on patients, we examined the anti-Toxoplasma effect of a biologically important natural antibiotic, kojic acid, in vitro and in vivo. Vero cells were incubated with different concentrations of kojic acid or pyrimethamine (positive control), and the cellular viability was determined. Next, Vero cells were infected with T. gondii (RH strain) and treated with drugs. Then, we calculated the infection index, T. gondii intracellular proliferation and the number and measure of plaque. Moreover, the effect of kojic acid on survival times, serum levels of IFN-γ and TNF-α and histopathological changes in the liver and spleen of Balb/c mice infected with T. gondii were determined. Kojic acid reduced the infection index, intracellular proliferation, the number and measure of plaque in vitro when compared to untreated infected cells. Kojic acid (100â¯mg/kg/day) also showed a better survival rate than infected untreated control mice (Pâ¯<â¯0.05). IFN-γ and TNF-α secretions were significantly increased by kojic acid treatment in comparison to untreated groups (Pâ¯<â¯0.05). In addition, its inhibitory effects on inflammatory alterations, apoptosis, and necrosis have been shown in sections of liver and spleen. We conclude that kojic acid exhibit potent anti-Toxoplasma activity with direct and indirect effects on the parasite, although further studies are needed before consideration of clinical trials.
Subject(s)
Antioxidants/pharmacology , Antiprotozoal Agents/pharmacology , Pyrones/pharmacology , Toxoplasma/drug effects , Toxoplasmosis, Animal/drug therapy , Animals , Antioxidants/therapeutic use , Antiprotozoal Agents/therapeutic use , Apoptosis/drug effects , Cell Survival/drug effects , Chlorocebus aethiops , Female , Interferon-gamma/blood , Liver/parasitology , Liver/pathology , Mice , Mice, Inbred BALB C , Necrosis , Pyrimethamine/pharmacology , Pyrimethamine/therapeutic use , Pyrones/therapeutic use , Spleen/parasitology , Spleen/pathology , Survival Analysis , Toxoplasma/growth & development , Toxoplasma/physiology , Toxoplasmosis, Animal/parasitology , Tumor Necrosis Factor-alpha/blood , Vero CellsABSTRACT
The impact of acute cardiac dysfunction on the gastrointestinal tract was investigated in anesthetized and instrumented pigs by sequential reductions of cardiac output (CO). Using a cardiac tamponade (n = 6) or partial inferior caval vein balloon inflation (n = 6), CO was controllably reduced for 1 h each to 75% (CO75%), 50% (CO50%), and 35% (CO35%) of the baseline value. Cardiac output in controls (n = 6) was not manipulated and maintained. Mean arterial pressure, superior mesenteric arterial blood flow, and intestinal mucosal perfusion started to decrease at CO50% in the intervention groups. The decrease in superior mesenteric arterial blood flow was non-linear and exaggerated at CO35%. Systemic, venous mesenteric, and intraperitoneal lactate concentrations increased in the intervention groups from CO50%. Global and mesenteric oxygen uptake decreased at CO35%. In conclusion, gastrointestinal metabolism became increasingly anaerobic when CO was reduced by 50%. Anaerobic gastrointestinal metabolism in low CO can be detected using intraperitoneal microdialysis.
Subject(s)
Cardiac Output, Low/metabolism , Cardiac Output, Low/physiopathology , Energy Metabolism , Hemodynamics , Mesenteric Artery, Superior/physiopathology , Oxygen Consumption , Splanchnic Circulation , Animals , Arterial Pressure , Biomarkers/blood , Blood Flow Velocity , Disease Models, Animal , Female , Hydrogen-Ion Concentration , Male , Sus scrofaABSTRACT
BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an effective adjunct in exsanguinating torso hemorrhage, but causes ischemic injury to distal organs. The aim was to investigate whether blood pressure targeting by partial REBOA (pREBOA) is possible in porcine severe hemorrhagic shock and to compare pREBOA and total REBOA (tREBOA) regarding hemodynamic, metabolic and inflammatory effects. METHODS: Eighteen anesthetized pigs were exposed to induced controlled hemorrhage to a systolic blood pressure (SBP) of 50 mmHg and randomized into three groups of thoracic REBOA: 30 min of pREBOA (target SBP 80-100 mmHg), tREBOA, and control. They were then resuscitated by autologous transfusion and monitored for 3 h. Hemodynamics, blood gases, mesenteric blood flow, intraperitoneal metabolites, organ damage markers, histopathology from the small bowel, and inflammatory markers were analyzed. RESULTS: Severe hemorrhagic shock was induced in all groups. In pREBOA the targeted blood pressure was reached. The mesenteric blood flow was sustained in pREBOA, while it was completely obstructed in tREBOA. Arterial pH was lower, and lactate and troponin levels were significantly higher in tREBOA than in pREBOA and controls during the reperfusion period. Intraperitoneal metabolites, the cytokine response and histological analyses from the small bowel were most affected in the tREBOA compared to the pREBOA and control groups. CONCLUSION: Partial REBOA allows blood pressure titration while maintaining perfusion to distal organs, and reduces the ischemic burden in a state of severe hemorrhagic shock. Partial REBOA may lower the risks of post-resuscitation metabolic and inflammatory impacts, and organ dysfunction.
Subject(s)
Aorta, Thoracic , Balloon Occlusion , Blood Pressure , Resuscitation , Shock, Hemorrhagic , Animals , Aorta, Thoracic/physiopathology , Balloon Occlusion/methods , Blood Pressure Determination , Disease Models, Animal , Random Allocation , Resuscitation/methods , Shock, Hemorrhagic/physiopathology , Shock, Hemorrhagic/therapy , SwineABSTRACT
BACKGROUND: Toxoplasmosis is a cosmopolitan infection caused by an intracellular obligatory protozoan, Toxoplasma gondii. Infection to this parasite in immunocompetent patients is usually asymptomatic, but today it is believed that the infection can be a risk factor for a variety of diseases, including rheumatoid arthritis (RA). RA is an autoimmune disease and the most common type of inflammatory arthritis that is a major cause of disability. The aim of this systematic review and meta-analysis was to address the association between RA and toxoplasmosis in light of the available research. METHODS: Based on the keywords, a systematic search of eight databases was conducted to retrieve the relevant English-language articles. Then, the studies were screened based on the inclusion and exclusion criteria. The random effect model was used to calculate the odds ratio (OR) using forest plot with 95% confidence interval (CI). RESULTS: Overall, 4168 Individual, extracted from 9 articles were included for systematic review evaluation, with 1369 RA patients (46% positive toxoplasmosis) and 2799 individuals as controls (21% positive toxoplasmosis). Then, eight articles (10 datasets) were used for meta-analysis (1244 rheumatoid arthritis patients and 2799 controls). By random effect model, the combined OR was 3.30 (95% CI: 2.05 to 5.30) with P < 0.0001. CONCLUSION: Although toxoplasmosis could be considered as a potential risk factor for rheumatoid arthritis, more and better quality studies are needed to determine the effect of T. gondii infection on induction or exacerbation of RA. Our study was registered at the International Prospective Register of Systematic Reviews (PROSPERO; code: CRD42017069384).