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BMC Pediatrics Jun 2024Guillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral...
BACKGROUND
Guillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral nerves. Anti-sulfatide antibody-mediated complement is associated with acute sensorimotor peripheral neuropathy in GBS, which is characterized by pain and paresthesias.
CASE PRESENTATION
The child was a 7-year-old girl with headache and abdominal pain, followed by limb numbness and pain. Cranial imaging showed ventricular dilatation, peripheral nerve function conduction examination showed polyradiculopathy, and cerebrospinal fluid tests showed normal cell counts but elevated protein levels, all of which led to the diagnosis of GBS. After treatment with intravenous immunoglobulin (400 mg/kg × 5 days), the symptoms did not improve, and muscle strength progressively worsened, accompanied by paroxysmal complexion flushing, heart rate fluctuation, hyperhidrosis, and a progressive increase in cerebrospinal fluid protein (up to 3780.1 mg/L). On the basis of these findings combined with serum anti-sulfatide IgM positivity, anti-sulfatide antibody-related GBS was considered, and treatment with low-dose prednisolone (1 mg/kg/d) led to symptom improvement.
CONCLUSIONS
Anti-sulfatide antibody-associated GBS is associated with small fiber peripheral neuropathy. The main manifestations are pain, paresthesias and autonomic dysfunction. In addition to the dysfunction of spinal nerve root absorption caused by increased cerebrospinal fluid protein, autonomic dysfunction may be involved in pain. When the therapeutic effect of immunoglobulin is not satisfactory, a low dose and short course of corticosteroids can be considered, and the prognosis is good.
Topics: Humans; Female; Child; Guillain-Barre Syndrome; Abdominal Pain; Headache; Sulfoglycosphingolipids; Autoantibodies; Prednisolone
PubMed: 38926645
DOI: 10.1186/s12887-023-04287-5 -
Scientific Reports Jun 2024Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an effect known as 'FLASH'. This effect has been studied across...
Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an effect known as 'FLASH'. This effect has been studied across several radiation modalities, including photons, protons and clinical energy electrons, however, very little data is available for the effect of FLASH with Very High Energy Electrons (VHEE). pBR322 plasmid DNA was used as a biological model to measure DNA damage in response to Very High Energy Electron (VHEE) irradiation at conventional (0.08 Gy/s), intermediate (96 Gy/s) and ultra-high dose rates (UHDR, (2 × 10 Gy/s) at the CERN Linear Electron Accelerator (CLEAR) user facility. UHDRs were used to determine if the biological FLASH effect could be measured in the plasmid model, within a hydroxyl scavenging environment. Two different concentrations of the hydroxyl radical scavenger Tris were used in the plasmid environment to alter the proportions of indirect damage, and to replicate a cellular scavenging capacity. Indirect damage refers to the interaction of ionising radiation with molecules and species to generate reactive species which can then attack DNA. UHDR irradiated plasmid was shown to have significantly reduced amounts of damage in comparison to conventionally irradiated, where single strand breaks (SSBs) was used as the biological endpoint. This was the case for both hydroxyl scavenging capacities. A reduced electron energy within the VHEE range was also determined to increase the DNA damage to pBR322 plasmid. Results indicate that the pBR322 plasmid model can be successfully used to explore and test the effect of UHDR regimes on DNA damage. This is the first study to report FLASH sparing with VHEE, with induced damage to pBR322 plasmid DNA as the biological endpoint. UHDR irradiated plasmid had reduced amounts of DNA single-strand breaks (SSBs) in comparison with conventional dose rates. The magnitude of the FLASH sparing was a 27% reduction in SSB frequency in a 10 mM Tris environment and a 16% reduction in a 100 mM Tris environment.
Topics: Plasmids; DNA Damage; Electrons; Dose-Response Relationship, Radiation; Humans; Particle Accelerators; DNA Breaks, Single-Stranded
PubMed: 38926450
DOI: 10.1038/s41598-024-65055-8 -
The Journal of Veterinary Medical... Jun 2024Laparoscopic ovariectomy under general anesthesia was planned in a 10-year-old, 146 kg, apparently healthy female African lion (Panthera leo). The lion was immobilized...
Laparoscopic ovariectomy under general anesthesia was planned in a 10-year-old, 146 kg, apparently healthy female African lion (Panthera leo). The lion was immobilized via intramuscular darts containing midazolam (0.033 mg/kg), medetomidine (50 µg/kg) and ketamine (2.5 mg/kg), and intubated using an endotracheal tube (16 mm internal diameter). The anesthesia was maintained using sevoflurane (0.9-2.1% end-tidal concentration), in combination with remifentanil (0.1 µg/kg/min) and ketamine (11 µg/kg/min) at a constant rate infusion (CRI), with Hartmann's solution (5 mL/kg/hr). Surgery was conducted with stable vital signs, but hypotension (mean arterial blood pressure 55 mmHg) developed, requiring dobutamine treatment. The hypotension was effectively controlled by adjusting dobutamine from 5 µg/kg/min to 0.2 to 0.3 µg/kg/min. This case suggests possibilities that dosages in this range can be clinically useful for peri-anesthetic hypotension in lions.
PubMed: 38925983
DOI: 10.1292/jvms.23-0436 -
American Journal of Veterinary Research Jun 2024To collect medication error (ME) data during the perianesthetic period from small animal clinics.
OBJECTIVE
To collect medication error (ME) data during the perianesthetic period from small animal clinics.
SAMPLE
6 small animal general practice veterinary clinics.
METHODS
Small animal general practice veterinary clinics were recruited in this prospective observational study, with staff given a presentation on medical errors and instructed on how to submit medication error reports to an online reporting system. Errors were classified according to type and timing.
RESULTS
A total of 2,728 general anesthesia or sedation procedures were performed, with 49 ME reports submitted. One duplicated report of the same error was excluded, resulting in a ME rate of 1.8%. Most reports (69% [33/48]) were near misses. The remaining 31% were MEs that reached the patient but did not cause harm. Wrong dose errors were the most common type (63% [30/48]), of which 80% (24/30) were calculation errors. Premedication/sedation and maintenance were the most reported stages, at 47% (20/43) and 23% (10/43), respectively. None of the MEs reported resulted in an adverse event, with an approximately 2:1 ratio of near-miss to no-harm MEs. The observed patterns of MEs reported, including type and timing, represent a target for further education.
CLINICAL RELEVANCE
These results quantify the ME rate in general practice veterinary clinics, providing an initial benchmark for MEs during the perianesthetic period.
PubMed: 38925141
DOI: 10.2460/ajvr.24.04.0119 -
Ecotoxicology and Environmental Safety Jun 2024Selenium (Se) pollution is mainly caused by anthropogenic activities, and the resulting biosecurity concerns have garnered significant attention in recent years. Using...
Selenium (Se) pollution is mainly caused by anthropogenic activities, and the resulting biosecurity concerns have garnered significant attention in recent years. Using one-compartmental toxicokinetic (TK) modelling, this study explored the kinetic absorption, sub-tissue distribution, and elimination processes of the main Se species (selenate, Se(VI)) in the cultivated aerobic soil of the earthworm Eisenia fetida. The bio-accessibility of earthworm-derived Se was assessed using an in vitro simulated gastrointestinal digestion test to evaluate its potential trophic risk. The results demonstrated that Se accumulated in the pre-clitellum (PC) and total tissues (TT) of earthworms in a time- and dose-dependent manner. The highest Se levels in the PC, post-clitellum (PoC), and TT were 70.54, 57.93, and 64.26 mg/kg during the uptake phase, respectively. The kinetic Se contents in the earthworms PC and TT were consistent with the TK model but not with PoC. The earthworm TT exhibited a faster uptake (K = 0.83-1.02 mg/kg/day) and elimination rate of Se (K = 0.044-0.049 mg/kg/day), as well as a shorter half-life time (LT = 15.88-14.22 days) than PC at low soil Se levels (≤5 mg/kg). Conversely, the opposite trend was observed with higher Se concentrations (10 and 20 mg/kg). These results are likely attributable to the tissue specificity and concentration of the toxicant. Earthworms PC and TT exhibited a higher kinetic Se accumulation factor (BAF) than steady-state BAF (BAF), with values ranging from 8 to 24 and 3-13, respectively. Furthermore, the bio-accessibility of earthworm-derived Se to poultry ranged from 66.25 % to 84.35 %. As earthworms are at the bottom of the terrestrial food chain, the high bio-accessibility of earthworm-derived Se poses a potential risk to predators. This study offers data support and a theoretical foundation for understanding the biological footprint of soil Se and its toxicological impacts and ecological hazards.
PubMed: 38925033
DOI: 10.1016/j.ecoenv.2024.116643 -
Expert Review of Vaccines 2024The global measles incidence has decreased from 145 to 49 cases per 1 million population from 2000 to 2018, but evaluating the economic benefits of a second...
INTRODUCTION
The global measles incidence has decreased from 145 to 49 cases per 1 million population from 2000 to 2018, but evaluating the economic benefits of a second measles-containing vaccine (MCV2) is crucial. This study reviewed the evidence and quality of economic evaluation studies to guide MCV2 introduction.
METHODS
The systematic review of model-based economic evaluation studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search yielded 2231 articles, with 876 duplicates removed and 1355 articles screened, with nine studies included for final analysis.
RESULTS
Six studies reported a positive benefit-cost ratio with one resulting in net savings of $11.6 billion, and two studies estimated a 2-dose MMR vaccination program would save $119.24 to prevent one measles case, and a second dose could prevent 9,200 cases at 18 months, saving $548.19 per case. The most sensitive variables were the discount rate and vaccination administration cost.
CONCLUSIONS
Two MCV doses or a second opportunity with an additional dose of MCV were highly cost-beneficial and resulted in substantial cost savings compared to a single routine vaccine. But further research using high-quality model-based health economic evaluation studies of MCV2 should be made available to decision-makers.
PROSPERO REGISTRATION
CRD42020200669.
Topics: Humans; Cost-Benefit Analysis; Immunization Programs; Immunization, Secondary; Measles; Measles Vaccine; Measles-Mumps-Rubella Vaccine; Vaccination
PubMed: 38924461
DOI: 10.1080/14760584.2024.2367451 -
Cancer Medicine Jun 2024Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following...
BACKGROUND
Pancreatic cancer (PC) first-line therapy often consists of polychemotherapy regimens, but choosing a second-line therapy after disease progression, especially following first-line FOLFIRINOX, remains a clinical challenge. This study presents results from a large, multicenter, retrospective analysis of Italian patients with metastatic PC (mPC) treated with Nab-paclitaxel/Gemcitabine (AG) as second or later line of treatment. Main objective of the study is to identify prognostic factors that could inform treatment decisions.
METHODS
The study included 160 mPC patients treated with AG in 17 Italian institutions. AG was administered according to labelling dose, until disease progression, unacceptable toxicity or patient refusal. Variations in schedules, dose modifications, supportive measures, and response evaluation were determined by individual clinicians' practice.
RESULTS
AG was well-tolerated and exhibited promising clinical activity. The overall response rate (ORR) and the disease control rate (DCR) were 22.5% and 45.6%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.9 and 6.8 months, respectively. Among the patients who received AG as a second-line therapy (n = 111, 66.9%), median PFS and OS were 4.2 and 7.4 months, respectively. Notably, in the 76 patients (68%) receiving AG after first-line FOLFIRINOX, an ORR of 19.7% and a DCR of 46.0% were observed, resulting in a median PFS of 3.5 and median OS of 5.7 months. The study identified specific clinical or laboratory parameters (LDH, NLR, fasting serum glucose, liver metastases, ECOG PS, and first-line PFS) as independent prognostic factors at multivariate level. These factors were used to create a prognostic nomogram that divided patients into three risk classes, helping to predict second-line OS and PFS.
CONCLUSIONS
This study represents the largest real-world population of mPC patients treated with AG as a second or later line of therapy. It supports the feasibility of this regimen following first-line FOLFIRINOX, particularly in patients with specific clinical and laboratory characteristics who derived prolonged benefit from first-line therapy.
Topics: Humans; Pancreatic Neoplasms; Gemcitabine; Male; Female; Deoxycytidine; Albumins; Paclitaxel; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Aged; Retrospective Studies; Prognosis; Adult; Aged, 80 and over; Treatment Outcome; Italy; Neoplasm Metastasis
PubMed: 38924262
DOI: 10.1002/cam4.7345 -
Epilepsia Open Jun 2024Perampanel belongs to a novel class of antiseizure medications (ASMs). Studies examining the effect of hemodialysis on perampanel serum levels in clinical settings are...
Perampanel belongs to a novel class of antiseizure medications (ASMs). Studies examining the effect of hemodialysis on perampanel serum levels in clinical settings are lacking. We aimed to evaluate the changes in serum perampanel levels during hemodialysis. We studied patients with seizures who received oral perampanel between April 2020 and March 2023 and whose serum concentration of perampanel was measured before and after hemodialysis. We analyzed the serum concentrations of levetiracetam and lacosamide for comparison. Fourteen patients, with a mean age of 76.1 ± 7.88 years, were included. The dose of perampanel was 2.14 ± 1.27 mg. The hemodialysis clearance rate of perampanel, levetiracetam, and lacosamide was 0 ± 13%, 69 ± 11%, and 59.6 ± 8.2%, respectively. The post-dialysis CD ratio decreased significantly with levetiracetam but not with perampanel. Adverse but acceptable effects of perampanel were observed in two patients. The serum concentrations of several ASMs have been shown to be reduced during hemodialysis. Our study revealed that the serum perampanel concentration does not decrease during hemodialysis. Owing to the low rate of adverse effects and the stability of perampanel serum concentration during hemodialysis, perampanel could be a favorable choice as an ASM for patients with seizures undergoing hemodialysis. PLAIN LANGUAGE SUMMARY: Our study looked at how hemodialysis affects the serum levels of perampanel, a new type of medication for seizures. In 14 patients who started treatment between April 2020 and March 2023, perampanel serum levels did not decrease during hemodialysis, unlike other seizure medications. This shows that perampanel can be a good option for patients with seizures who need hemodialysis, with fewer side effects compared to other medications.
PubMed: 38923803
DOI: 10.1002/epi4.12996 -
CPT: Pharmacometrics & Systems... Jun 2024Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained-release (SR) tablets. This study aimed to...
Significant pharmacokinetic (PK) differences exist between different forms of valproic acid (VPA), such as syrup and sustained-release (SR) tablets. This study aimed to develop a population pharmacokinetic (PopPK) model for VPA in children with epilepsy and offer dose adjustment recommendation for switching dosage forms as needed. The study collected 1411 VPA steady-state trough concentrations (C) from 617 children with epilepsy. Using NONMEM software, a PopPK model was developed, employing a stepwise approach to identify possible variables such as demographic information and concomitant medications. The final model underwent internal and external evaluation via graphical and statistical methods. Moreover, Monte Carlo simulations were used to generate a dose tailoring strategy for typical patients weighting 20-50 kg. As a result, the PK characteristics of VPA were described using a one-compartment model with first-order absorption. The absorption rate constant (k) was set at 2.64 and 0.46 h for syrup and SR tablets. Body weight and sex were identified as significant factors affecting VPA's pharmacokinetics. The final PopPK model demonstrated acceptable prediction performance and stability during internal and external evaluation. For children taking syrup, a daily dose of 25 mg/kg resulted in the highest probability of achieving the desired target C, while a dose of 20 mg/kg/day was appropriate for those taking SR tablets. In conclusion, we established a PopPK model for VPA in children with epilepsy to tailor VPA dosage when switching between syrup and SR tablets, aiming to improve plasma VPA concentrations fluctuations.
PubMed: 38923247
DOI: 10.1002/psp4.13191 -
Toxics Jun 2024Chiang Mai province of Thailand is known for having the highest natural background radiation in the country, as well as being recognized as one of the world's most...
Chiang Mai province of Thailand is known for having the highest natural background radiation in the country, as well as being recognized as one of the world's most polluted cities for air quality. This represents the major contributor to the development of lung cancer. This research aims to estimate the comprehensive dose of both internal and external exposure due to natural background radiation and related health perspectives in the highly polluted area of Chiang Mai. The average values of indoor radon and thoron concentrations in 99 houses over 6 months were 40.8 ± 22.6 and 17.8 ± 16.3 Bq/m, respectively. These results exceed the worldwide value for indoor radon and thoron (40 and 10 Bq/m), respectively. During burning season, the average values of indoor radon (56.7 ± 20 Bq/m) and thoron (20.8 ± 20.4 Bq/m) concentrations were higher than the world-wide averages. The radon concentration in drinking water (56 samples) varied from 0.1 to 91.9 Bq/L, with an average value of 9.1 ± 22.8 Bq/L. Most of the drinking water samples (87%) fell below the recommended maximum contamination limit of 11.1 Bq/L. The average values of natural radionuclide (Ra, Th and K) in 48 soil samples were 47 ± 20.9, 77.9 ± 29.7 and 700.1 ± 233 Bq/kg, respectively. All values were higher than the worldwide average of 35, 30 and 400 Bq/kg, respectively. The average value of outdoor absorbed gamma dose rate (98 ± 32.5 nGy/h) exceeded the worldwide average of 59 nGy/h. Meanwhile, the average activity concentrations of Ra, Th and K in 25 plant food samples were 2.7 ± 0.1, 3.2 ± 1.6 and 1000.7 ± 1.9 Bq/kg, respectively. The K concentration was the most predominant in plant foods. The highest concentrations of Ra, Th and K were found in Chinese cabbage, celery and cilantro, respectively. The total annual effective dose for residents in the study area varied from 0.6 to 4.3 mSv, with an average value of 1.4 mSv. This indicates a significant long-term public health hazard due to natural background radiation and suggests a heightened radiation risk for the residents. The excess lifetime cancer risk value (5.4) associated with natural background radiation was found to be higher than the recommended value. Moreover, the number of lung cancer cases per year per million average of 25.2 per million persons per year was in the limit range 170-230 per million people. Overall, our results will be used for future decision making in the prevention of lung cancer risk associated with natural background radiation.
PubMed: 38922108
DOI: 10.3390/toxics12060428