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Acta Bio-medica : Atenei Parmensis Aug 2023Allergen immunotherapy (AIT) is the only treatment which acts on the causes of allergic diseases by modifying their natural history. In the eighties subcutaneous... (Review)
Review
BACKGROUND
Allergen immunotherapy (AIT) is the only treatment which acts on the causes of allergic diseases by modifying their natural history. In the eighties subcutaneous immunotherapy (SCIT) with high biological power allergen extracts caused a number of severe systemic reactions and also fatalities in the UK and the US, resulting in its limitation and in the introduction of other routes of administration. A decisive advance for SCIT safety was understanding that the major cause of mortality was injecting the allergen extract to patients with uncontrolled asthma at the time of injection.
AREAS COVERED
This awareness resulted in a significant decrease in fatalities, but not in their abolition. In 2019, an increase in SCIT-related mortality was observed, suggesting to continue the research for still unidentified factors favoring severe reactions, such as the administration of a wrong extract or of allergen doses higher than listed, unintentional intravenous administration, and missed dose reduction after protracted interruption. Moreover, in the context of the improving of the safety, the role played in tolerance-promoting by adjuvants such as CpG oligodeoxynucleotides has to be taken into account, as well as the potential preventive effect performed by the monoclonal anti-IgE antibody omalizumab against the exacerbation of severe reactions during SCIT.
CONCLUSION
The safety of SCIT is good, but the research to improve it further must continue. In particular, the pathophysiological mechanisms related to AIT for inhalants and for Hymenoptera venom should be studied, based on the evident diversity demonstrated by the complete absence of fatal reactions to Hymenoptera venom immunotherapy from its introduction in comparison with the history of serious and fatal offenses examined in this review.
Topics: Humans; Allergens; Desensitization, Immunologic; Hypersensitivity; Asthma; Injections, Subcutaneous
PubMed: 37539607
DOI: 10.23750/abm.v94i4.14239 -
Saudi Journal of Anaesthesia 2023Elderly patients have a high risk of perioperative morbidity and mortality. Pluri-morbidities, polypharmacy, and functional dependence may have a great impact on... (Review)
Review
Elderly patients have a high risk of perioperative morbidity and mortality. Pluri-morbidities, polypharmacy, and functional dependence may have a great impact on intraoperative management and request specific cautions. In addition to surgical stress, several perioperative noxious stimuli such as fasting, blood loss, postoperative pain, nausea and vomiting, drug adverse reactions, and immobility may trigger a derangement leading to perioperative complications. Older patients have a high risk of major hemodynamic derangement due to aging of the cardiovascular system and associated comorbidities. The hemodynamic monitoring as well as fluid therapy should be the most accurate as possible. Aging is accompanied by decreased renal function, which is related to a reduction in renal blood flow, renal mass, and the number and size of functioning nephrons. Drugs eliminated predominantly by the renal route need dosage adjustments based on residual renal function. Liver mass, hepatic blood flow, and intrinsic metabolic activity are decreased in the elderly, and all drugs metabolized by the liver have a variable half-life, thus requiring dose reduction. Decreased neural plasticity contributes to a high risk for postoperative delirium. Monitoring of anesthesia depth should be mandatory to avoid overdosage of hypnotic drugs. Prevention of postoperative pulmonary complications requires both protective ventilation strategies and adequate recovery of neuromuscular function at the end of surgery. Avoidance of hypothermia cannot be missed. The aim of this review is to describe comprehensive strategies for intraoperative management plans tailored to meet the unique needs of elderly surgical patients, thus improving outcomes in this vulnerable population.
PubMed: 37779561
DOI: 10.4103/sja.sja_579_23 -
The Journal of Infectious Diseases Nov 2023Vesicular stomatitis virus-Ebola virus (VSV-EBOV) vaccine has been successfully used in ring vaccination approaches during EBOV disease outbreaks demonstrating its...
Vesicular stomatitis virus-Ebola virus (VSV-EBOV) vaccine has been successfully used in ring vaccination approaches during EBOV disease outbreaks demonstrating its general benefit in short-term prophylactic vaccination, but actual proof of its benefit in true postexposure prophylaxis (PEP) for humans is missing. Animal studies have indicated PEP efficacy when VSV-EBOV was used within hours of lethal EBOV challenge. Here, we used a lower EBOV challenge dose and a combined intravenous and intramuscular VSV-EBOV administration to improve PEP efficacy in the rhesus macaque model. VSV-EBOV treatment 1 hour after EBOV challenge resulted in delayed disease progression but little benefit in outcome. Thus, we could not confirm previous results indicating questionable benefit of VSV-EBOV for EBOV PEP in a nonhuman primate model.
Topics: Humans; Animals; Ebolavirus; Macaca mulatta; Hemorrhagic Fever, Ebola; Vesiculovirus; Vesicular stomatitis Indiana virus; Ebola Vaccines
PubMed: 37474155
DOI: 10.1093/infdis/jiad280 -
International Journal of Bipolar... Jun 2024Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of... (Review)
Review
BACKGROUND
Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations.
CONTENT
This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections.
CONCLUSIONS
Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.
PubMed: 38914810
DOI: 10.1186/s40345-024-00345-8 -
Scientific Reports Jul 2023Organoids are three-dimensional structures of self-assembled cell aggregates that mimic anatomical features of in vivo organs and can serve as in vitro miniaturized...
Organoids are three-dimensional structures of self-assembled cell aggregates that mimic anatomical features of in vivo organs and can serve as in vitro miniaturized organ models for drug testing. The most efficient way of studying drug toxicity and efficacy requires high-resolution imaging of a large number of organoids acquired in the least amount of time. Currently missing are suitable platforms capable of fast-paced high-content imaging of organoids. To address this knowledge gap, we present the OrganoidChip, a microfluidic imaging platform that incorporates a unique design to immobilize organoids for endpoint, fast imaging. The chip contains six parallel trapping areas, each having a staging and immobilization chamber, that receives organoids transferred from their native culture plates and anchors them, respectively. We first demonstrate that the OrganoidChip can efficiently immobilize intestinal and cardiac organoids without compromising their viability and functionality. Next, we show the capability of our device in assessing the dose-dependent responses of organoids' viability and spontaneous contraction properties to Doxorubicin treatment and obtaining results that are similar to off-chip experiments. Importantly, the chip enables organoid imaging at speeds that are an order of magnitude faster than conventional imaging platforms and prevents the acquisition of blurry images caused by organoid drifting, swimming, and fast stage movements. Taken together, the OrganoidChip is a promising microfluidic platform that can serve as a building block for a multiwell plate format that can provide high-throughput and high-resolution imaging of organoids in the future.
Topics: Hydrogels; Bone Plates; Diagnostic Imaging; Doxorubicin; Organoids
PubMed: 37438409
DOI: 10.1038/s41598-023-38212-8 -
BMC Pregnancy and Childbirth Oct 2023Hypertensive disorders of pregnancy, including preeclampsia, are a leading cause of perinatal morbidity and mortality in the United States, particularly among low-income...
BACKGROUND
Hypertensive disorders of pregnancy, including preeclampsia, are a leading cause of perinatal morbidity and mortality in the United States, particularly among low-income and historically marginalized populations. Evidence suggests low-dose aspirin prophylaxis may help prevent preeclampsia in individuals at increased risk of developing the disease. This study examines associations between preeclampsia risk factors and aspirin prescribing practices among patients receiving prenatal care at a network of federally qualified health centers (FQHC).
METHODS
Researchers conducted retrospective chart reviews (n = 523) of pregnant individuals ages 18-50 who completed two or more prenatal visits at the FQHC between January 1, 2019 and December 31, 2020. Prescription patterns for patients at moderate and high risk for preeclampsia were analyzed using unadjusted and adjusted logistic regression models to identify the patients with the greatest risk of not receiving the recommended prophylactic treatment.
RESULTS
Of 249 total patients considered at risk for preeclampsia, only 39% received an aspirin prescription. 57.89% of patients with any high-risk factor were appropriately prescribed aspirin, but only 27.27% of patients with two or more moderate-risk factors without high-risk factors received a prescription. Clinicians most frequently prescribed aspirin for patients with a history of preeclampsia and history of hypertension. However, aspirin was prescribed a maximum of 78.79% of the time for patients with a prior history of hypertension. Among moderate-risk factors, patients with advanced maternal age, Black race, or nulliparity were significantly more likely in adjusted models to be prescribed aspirin.
CONCLUSIONS
Despite the documented benefits of aspirin prescribing and support from professional societies, there are still many missed opportunities for aspirin prophylaxis to prevent preeclampsia. Future interventions should focus on identifying patients who qualify for aspirin prophylaxis on the basis of having multiple moderate-risk factors without comorbid high-risk factors.
Topics: Female; Humans; Pregnancy; Aspirin; Hypertension; Pre-Eclampsia; Retrospective Studies; Risk Factors; Maternal Mortality; Morbidity
PubMed: 37805449
DOI: 10.1186/s12884-023-06039-w -
Radiation Protection Dosimetry Sep 2023Biomarkers for ionising radiation exposure have great utility in scenarios where there has been a potential exposure and physical dosimetry is missing or in dispute,...
Biomarkers for ionising radiation exposure have great utility in scenarios where there has been a potential exposure and physical dosimetry is missing or in dispute, such as for occupational and accidental exposures. Biomarkers that respond as a function of dose are particularly useful as biodosemeters to determine the dose of radiation to which an individual has been exposed. These dose measurements can also be used in medical scenarios to track doses from medical exposures and even have the potential to identify an individual's response to radiation exposure that could help tailor treatments. The measurement of biomarkers of exposure in medicine and for accidents, where a larger number of samples would be required, is limited by the throughput of analysis (i.e. the number of samples that could be processed and analysed), particularly for microscope-based methods, which tend to be labour-intensive. Rapid analysis in an emergency scenario, such as a large-scale accident, would provide dose estimates to medical practitioners, allowing timely administration of the appropriate medical countermeasures to help mitigate the effects of radiation exposure. In order to improve sample throughput for biomarker analysis, much effort has been devoted to automating the process from sample preparation through automated image analysis. This paper will focus mainly on biological endpoints traditionally analysed by microscopy, specifically dicentric chromosomes, micronuclei and gamma-H2AX. These endpoints provide examples where sample throughput has been improved through automated image acquisition, analysis of images acquired by microscopy, as well as methods that have been developed for analysis using imaging flow cytometry.
Topics: Humans; Flow Cytometry; Health Personnel; Image Processing, Computer-Assisted; Medicine; Microscopy
PubMed: 37721060
DOI: 10.1093/rpd/ncad060 -
Cureus Feb 2024Background Infection in orthopedic surgery is one of the most dreaded complications. It is associated with prolonged morbidity, disability, and increased mortality. One...
Background Infection in orthopedic surgery is one of the most dreaded complications. It is associated with prolonged morbidity, disability, and increased mortality. One of the cornerstones of the prevention of infections is antibiotic prophylaxis. This study assessed the practice of antibiotic prophylaxis in arthroplasty surgeries in our local hospital. Methods One hundred and seventy-one elective joint replacement patients were retrospectively analyzed for documentation of antibiotic plan in postoperative instruction, choice of antibiotic, dose, and dosage. Compliance with the dosage (duration and frequency) of antibiotic prophylaxis was compared among patients who underwent different operations, among patients whose operation notes had antibiotics plans, and among those patients whose operation notes lacked this information. Results Ninety-six females and 75 males with a mean age of 71.4±9.8 years who underwent hip replacement, knee replacement, or shoulder replacement were included in this study. Preoperative and postoperative antibiotics were received by 100% and 94.7% of patients, respectively. In 19.3%, there was no instruction about postoperative antibiotics while 4% missed at least one postoperative dose. The dosage of postoperative prophylactic antibiotics was variable as 26.3% of the patients experienced delayed administration of doses. Not having intravenous access, failure to prescribe antibiotics, and prescribing antibiotics in the "once only" rather than "regular medication" section of the medication chart were the reasons for improper timing of antibiotic doses. Observing surgical safety checklist was effective in ensuring preoperative antibiotic administration, whereas failing to document antibiotic plan in operation note was associated with poor compliance with postoperative dosage. Interprofessional participation is crucial to compliance with antibiotic prophylaxis practice. Conclusion This study identified key areas for improvement in our antibiotics prophylaxis practice. It resulted in implementing strategies to improve staff's awareness about the importance of timely administration of prophylactic antibiotics and proper documentation by all team members.
PubMed: 38481888
DOI: 10.7759/cureus.54075 -
BMC Public Health Aug 2023Increasing body fat or decreasing muscle and bone mass were associated with worse health outcomes in the adult population. The effects of nickel exposure on body...
BACKGROUND
Increasing body fat or decreasing muscle and bone mass were associated with worse health outcomes in the adult population. The effects of nickel exposure on body composition are not known. The aim of the current study was to investigate the relationship between urinary nickel levels and body compositions.
MATERIALS AND METHODS
Two thousand seven hundred sixty-two participants were included in the analysis from the National Health and Nutrition Examination Surveys of 2017-2018 after excluding participants who have missing data on urinary nickel and those with missing all body mass component data. We used weighted generalized linear models to explore the relationship between urinary nickel and body mass components under interpolating missing covariable values. Simultaneously, sensitivity analyses and subgroup analysis were conducted to verify stability of analysis result. Curve fitting and saturation effect analysis were used to explore the possible nonlinear relationship between urine nickel and body compositions.
RESULTS
Among the 2,762 participants, the average urinary nickel level was 1.58 ug/L. The weighted generalized linear models, the sensitivity analyses and subgroup analyses found no significant linear relationship between urinary nickel and body compositions. For body weight, BMI, TLM, ALM, TRF, TOF and BMC, the urine nickel saturation effect values were 0.76, 0.74, 0.5, 0.67, 0.64, 0.48, and 0.45 ug/L, respectively. For each 1 ug/L rise in urinary nickel levels at levels below the turning point, body weight increases (β = 9.06, 95% CI = 2.75, 15.36, p = 0.01), BMI increases (β = 3.20, 95% CI = 1.36, 5.05, p = < 0.001), TLM decreases (β = -47.39, 95% CI = -97.38, 2.59, p = 0.06), ALM decreases (β = -37.25, 95% CI = -63.25, -11.24, p = 0.01), TRF increases (β = 20.68, 95% CI = 1.50, 39.86, p = 0.03), TOF increases (β = 57.92, 95% CI = -0.12, 115.95, p = 0.05), and BMC decreases (β = -6.84, 95% CI = -12.64, -1.04, p = 0.02).
CONCLUSIONS
In summary, our study demonstrated that a dose-response relationship exists between urinary nickel and body compositions, with a low inflection point level of urinary nickel for the saturation effect.
Topics: Adult; United States; Humans; Cross-Sectional Studies; Nickel; Body Composition; Adipose Tissue; Weight Gain
PubMed: 37626316
DOI: 10.1186/s12889-023-16483-0 -
European Journal of Medical Research Nov 2023There have been massive studies to develop an effective vaccine against SARS-CoV-2 which fortunately led to manage the recent pandemic, COVID-19. According to the quite... (Review)
Review
There have been massive studies to develop an effective vaccine against SARS-CoV-2 which fortunately led to manage the recent pandemic, COVID-19. According to the quite rapidly developed vaccines in a fast window time, large investigations to assess the probable vaccine-related adverse events are crucially required. COVID-19 vaccines are available of different platforms and the primary clinical trials results presented acceptable safety profile of the approved vaccines. Nevertheless, the long-term assessment of the adverse events or rare conditions need to be investigated. The present systematic review, aimed at classification of probable vaccine-related unsolicited adverse events in Iranian population through the data collection of the published case report studies.The related published case reports were explored via PubMed, Web of Science and Google scholar according to the available published data up to 14 Dec, 2022 using PRISMA guideline. Out of 437 explored studies, the relevant data were fully investigated which totally led to 40 studies, including 64 case reports with a new onset of a problem post-vaccination. The cases were then classified according to the various items, such as the type of adverse event and COVID-19 vaccines.The reported COVID-19 vaccines in the studied cases included BBIBP-CorV, ChAdOx1-S, Sputnik V and COVAXIN. The results showed that the adverse events presented in 8 different categories, including cutaneous involvements in 43.7% (n = 28), neurologic problems (n = 16), blood/vessel involvement (n = 6), cardiovascular involvement (n = 5), ocular disorders (n = 4), liver disorder/failure (n = 2), graft rejection (n = 2) and one metabolic disorder. Notably, almost 60% of the cases had no comorbidities. Moreover, the obtained data revealed nearly half of the incidences occurred after the first dose of injection and the median duration of improvement after the symptom was 10 days (range: 2-120). In addition, 73% of all the cases were either significantly improved or fully recovered. Liver failure following ChAdOx1-S vaccination was the most serious vaccine adverse event which led to death in two individuals with no related medical history.Although the advantages of COVID-19 vaccination is undoubtedly significant, individuals including with a history of serious disease, comorbidities and immunodeficiency conditions should be vaccinated with the utmost caution. This study provides a comprehensive overview and clinical implications of possible vaccine-related adverse events which should be considered in further vaccination strategies. Nevertheless, there might be a bias regarding potential under-reporting and missing data of the case reports included in the present study. Although the reported data are not proven to be the direct vaccination outcomes and could be a possible immune response over stimulation, the people the population with a medium/high risk should be monitored after getting vaccinated against COVID-19 of any platforms. This could be achieved by a carefull attention to the subjects ' medical history and also through consulting with healthcare providers before vaccination.
Topics: Humans; COVID-19; COVID-19 Vaccines; Iran; SARS-CoV-2; Vaccination; Case Reports as Topic
PubMed: 38008729
DOI: 10.1186/s40001-023-01531-7