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Severe complex neglected infantile Blount disease acute correction by Ilizarov frame: A case report.International Journal of Surgery Case... Jun 2024Blount disease is a disorder causing three proportions of deformity, including varus deformity, procurvatum deformity, and internal tibial rotational deformity. The...
INTRODUCTION
Blount disease is a disorder causing three proportions of deformity, including varus deformity, procurvatum deformity, and internal tibial rotational deformity. The standardized treatment remains controversial despite extensive reviews. The application of Ilizarov external fixators for circumspect corrections is established. The SCARE 2023 criteria have been followed in reporting the case report.
CASE PRESENTATION
We present the case of a nine-year-old girl who's complaining about bowing on both of her knees. From the examination, we found that the metaphyseodiaphyseal angle of both knees was 50 degrees. On the right knee, there is 125 degrees of procurvatum deformity and 115 degrees of deformity on the left knee. After performing deformity correction with the Ilizarov application, there's clinical improvement in the patient.
CLINICAL DISCUSSION
Some experts advise using physeal distraction to manage the deformity in order to achieve correction. The limited popularity of physeal distraction technique may be attributed to the risks of premature closure of the growth plate that we manage to avoid. The Ilizarov frame provides maximum adjustability for aligning all planes, making it suitable for treating severe deformities. Secure fixation, improved patient mobility, being able to assess patient alignment in a functional standing position, and precision.
CONCLUSION
Acute correction and fixation using circular frames as a treatment option for Blount disease show positive outcomes without any significant complications.
PubMed: 38917699
DOI: 10.1016/j.ijscr.2024.109909 -
PLoS Computational Biology Jun 2024Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed...
Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed reduction in recurrent arrhythmias through antiarrhythmic drug therapy, the precise mechanisms underlying their effectiveness in treating ischemic heart disease remain unclear. Moreover, there is a lack of specialized drugs designed explicitly for the treatment of myocardial ischemic arrhythmia. This study employs an electrophysiological simulation approach to investigate the potential antiarrhythmic effects and underlying mechanisms of various pharmacological agents in the context of ischemia and myocardial infarction (MI). Based on physiological experimental data, computational models are developed to simulate the effects of a series of pharmacological agents (amiodarone, telmisartan, E-4031, chromanol 293B, and glibenclamide) on cellular electrophysiology and utilized to further evaluate their antiarrhythmic effectiveness during ischemia. On 2D and 3D tissues with multiple pathological conditions, the simulation results indicate that the antiarrhythmic effect of glibenclamide is primarily attributed to the suppression of efflux of potassium ion to facilitate the restitution of [K+]o, as opposed to recovery of IKATP during myocardial ischemia. This discovery implies that, during acute cardiac ischemia, pro-arrhythmogenic alterations in cardiac tissue's excitability and conduction properties are more significantly influenced by electrophysiological changes in the depolarization rate, as opposed to variations in the action potential duration (APD). These findings offer specific insights into potentially effective targets for investigating ischemic arrhythmias, providing significant guidance for clinical interventions in acute coronary syndrome.
PubMed: 38917196
DOI: 10.1371/journal.pcbi.1012244 -
PloS One 2024Robust testing capacity was necessary for public health agencies to respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus...
Robust testing capacity was necessary for public health agencies to respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 19 (COVID-19) pandemic. As the nation faced the need for robust testing capacity, it became necessary to use all possible resources. In many cases, veterinary diagnostic laboratories rose to meet this demand because these facilities routinely perform high throughput diagnostic testing of large animal populations and are typically familiar with pathogens of high pandemic concern. In this study, we evaluated the impact of veterinary diagnostic laboratories in the United States on SARS-CoV-2 testing. Results of surveys, semi-structured interviews, and analysis of publicly available information showed that veterinary diagnostic laboratories had a substantial impact on human health through population-level testing in the COVID-19 response, supporting timely and informed public health interventions. This success was not without significant hurdles, as many participating veterinary diagnostic laboratories experienced restriction in their response due to difficulties obtaining the Clinical Laboratory Improvement Amendments (CLIA) certification required to conduct human diagnostic testing. Our results point out the importance of reducing hurdles before the next major public health emergency to enhance access to testing resources overall and to ultimately improve population health.
Topics: COVID-19; United States; Humans; Animals; SARS-CoV-2; Laboratories; Public Health; COVID-19 Testing; Pandemics
PubMed: 38917105
DOI: 10.1371/journal.pone.0303019 -
The Journal of Clinical Investigation Jun 2024Leukemia relapse is a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). We tested the potential of targeting TIM-3 for improving...
Leukemia relapse is a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). We tested the potential of targeting TIM-3 for improving graft-versus-leukemia (GVL) effects. We observed differential expression of TIM-3 ligands when hematopoietic stem cells overexpressed certain oncogenic-driver mutations. Anti-TIM-3 Ab-treatment improved survival of mice bearing leukemia with oncogene-induced TIM-3 ligand expression. Conversely, leukemia cells with low ligand expression were anti-TIM-3 treatment-resistant. In vitro, TIM-3 blockade or genetic deletion in CD8+ T cells (Tc) enhanced Tc activation, proliferation and IFN-γ production while enhancing GVL effects, preventing Tc exhaustion and improving Tc cytotoxicity and glycolysis in vivo. Conversely, TIM-3 deletion in myeloid cells did not affect allogeneic Tc proliferation and activation in vitro, suggesting that anti-TIM-3-treatment-mediated GVL effects are Tc-induced. In contrast to anti-PD-1 and anti-CTLA-4-treatment, anti-TIM-3-treatment did not enhance acute graft-versus-host-disease (aGVHD). TIM-3 and its ligands were frequently expressed in acute myeloid leukemia (AML) cells of patients with post-allo-HCT relapse. We deciphered the connection between oncogenic mutations found in AML and TIM-3 ligands expression and identify anti-TIM-3-treatment as a strategy to enhance GVL effects via metabolic and transcriptional Tc-reprogramming, without exacerbation of aGVHD. Our findings support clinical testing of anti-TIM-3 Abs in patients with AML relapse post-allo-HCT.
PubMed: 38916965
DOI: 10.1172/JCI177460 -
Critical Care Explorations Jul 2024While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these... (Observational Study)
Observational Study
OBJECTIVES
While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction.
DESIGN
In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3).
SETTING
Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting.
PATIENTS
Ninety-six adult septic and critically ill nonseptic patients were enrolled.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation.
CONCLUSIONS
Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness.
Topics: Humans; Prospective Studies; Critical Illness; Sepsis; Male; Female; Middle Aged; Multiple Organ Failure; Aged; Organ Dysfunction Scores; Adult; Cytokines; Cohort Studies; Predictive Value of Tests; Lipopolysaccharides
PubMed: 38916619
DOI: 10.1097/CCE.0000000000001106 -
International Journal of... Apr 2024Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease...
BACKGROUND
Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease increases the risk of TB due to diminished glomerular filtration rate, proteinuria, and immunosuppression use. Further, the first-line anti-TB drugs are associated with acute kidney injury (AKI) even in patients with normal kidney functions.
METHODS
We retrospectively identified 10 patients hospitalized with unusual adverse effects of antituberculosis therapy (ATT) from 2013 to 2022.
RESULTS
We found three cases of AKI caused by rifampicin: acute interstitial nephritis, crescentic glomerulonephritis, and heme pigment-induced acute tubular necrosis. We observed rifampicin-induced accelerated hypertension and thrombocytopenia in two patients on maintenance hemodialysis. Isoniazid caused pancreatitis and cerebellitis in two CKD patients, respectively. In a CKD patient, we detected acute gout secondary to pyrazinamide-induced reduced uric acid excretion. We also observed cases of drug rash with eosinophilia and systemic symptoms and hypercalcemia due to immune reconstitution inflammatory syndrome in patients with glomerular disease on ATT. Immediate discontinuation of the offending drug, along with specific and supportive management, led to a recovery in all cases.
CONCLUSION
The adverse effects of ATT may be unusually severe and varied in kidney patients due to decreased renal elimination. Early recognition of these adverse effects and timely discontinuation of the offending drug is essential to limit morbidity and mortality.
Topics: Humans; Antitubercular Agents; Male; Retrospective Studies; Female; Middle Aged; Acute Kidney Injury; Aged; Adult; Renal Insufficiency, Chronic; Rifampin; Isoniazid; Nephritis, Interstitial; Tuberculosis; Pyrazinamide; Glomerulonephritis; Immune Reconstitution Inflammatory Syndrome
PubMed: 38916390
DOI: 10.4103/ijmy.ijmy_33_24 -
Microbiology Spectrum Jun 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus that undergoes rapid mutation. Based on viral whole genome sequencing analysis in Hebei...
UNLABELLED
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus that undergoes rapid mutation. Based on viral whole genome sequencing analysis in Hebei Province, China, we identified several essential single nucleotide variants (SNVs) on primer-probe regions accumulating within some Omicron variants' genomes. In this study, we focused on three SNVs, C28290T, T28297C, and C28311T emerging on 2019-nCoV-N1 (CDC-N1) primer-probe regions, recommended by CDC in 2020, and two SNVs, C26270T, A26275G emerging on E (Charité-E) primer-probe regions recommended by Charité, Germany. Our findings revealed that the presence of one or two SNVs in the primer or probe region affected the sensitivity of reverse transcription-quantitative polymerase chain reaction and droplet digital PCR to varying extents. This discovery underscores the importance of continuously monitoring the whole genome sequences of SARS-CoV-2 variants, especially the primer-probe targeting regions, and correspondingly updating commercial test kits or recommended primer-probe sequence sets.
IMPORTANCE
The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has resulted in a growing number of mutations in its genome, presenting new challenges for the diagnosis of SARS-CoV-2 using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and droplet digital PCR (RT-ddPCR) methods. There is an urgent need to develop refined methods for modifying primers and probes to improve the detection of these emerging variants. In this study, our focus was on the SNVs that have emerged in the CDC-N1 and Charité-E primer-probe regions. Our research has confirmed that the presence of these SNVs in the primer or probe region can significantly affect the results of coronavirus disease 2019 tests. we have developed and validated a modified detection method that can provide higher sensitivity and specificity. This study emphasizes the importance of refining the primer-probe sets to ensure the diagnostic accuracy of RT-qPCR and RT-ddPCR detection.
PubMed: 38916349
DOI: 10.1128/spectrum.04292-23 -
Microbiology Spectrum Jun 2024() is a Gram-negative intracellular pathogen that causes melioidosis in humans, a neglected, underreported, and lethal disease that can reach a fatal outcome in over...
UNLABELLED
() is a Gram-negative intracellular pathogen that causes melioidosis in humans, a neglected, underreported, and lethal disease that can reach a fatal outcome in over 50% of the cases. It can produce both acute and chronic infections, the latter being particularly challenging to eliminate because of the intracellular life cycle of the bacteria and its ability to generate a "persister" dormant state. The molecular mechanism that allows the switch between growing and persister phenotypes is not well understood but it is hypothesized to be due at least in part to the participation of toxin-antitoxin (TA) systems. We have previously studied the link between one of those systems (defined as HigBA) with specific expression patterns associated with levofloxacin antibiotic exposure. Through methods, we predicted the presence of another three pairs of genes encoding for additional putative HigBA systems. Therefore, our main goal was to establish which mechanisms are conserved as well as which pathways are specific among different TA systems from the same family. We hypothesize that the high prevalence, and sometimes even redundancy of these systems in the chromosomes indicates that they can interact with each other and not function as only individual systems, as it was traditionally thought, and might be playing an undefined role in lifecycle. Here, we show that both the toxin and the antitoxin of the different systems contribute to bacterial survival and that toxins from the same family can have a cumulative effect under environmental stressful conditions.
IMPORTANCE
Toxin-antitoxin (TA) systems play a significant role in bacterial persistence, a phenomenon where bacterial cells enter a dormant or slow-growing state to survive adverse conditions such as nutrient deprivation, antibiotic exposure, or host immune responses. By studying TA systems in , we can gain insights into how this pathogen survives and persists in the host environment, contributing to its virulence and ability to cause melioidosis chronic infections.
PubMed: 38916327
DOI: 10.1128/spectrum.00748-24 -
Microbiology Spectrum Jun 2024The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve to give rise to variants of concern that can escape vaccine-induced...
UNLABELLED
The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SARS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy were similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP-vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.
IMPORTANCE
Although existing vaccines have significantly mitigated the impact of the COVID-19 pandemic, none of the vaccines can induce sterilizing immunity. The spike protein is the main component of all approved vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due primarily to its ability to induce neutralizing antibodies. The conformation of the spike protein in the vaccine formulation should be critical for the efficacy of a vaccine. By way of closely resembling the authentic virions, virus-like particles (VLPs) should render the spike protein in its natural conformation. To this end, we utilized the baculovirus vector, BacMam, to express virus-like particles consisting of the spike, membrane, and envelope proteins of SARS-CoV-2. We demonstrated the immunogenicity of our VLP vaccine with neutralizing activity. Our data warrant further evaluation of the virus-like particles as a vaccine candidate in protecting against virus challenges.
PubMed: 38916311
DOI: 10.1128/spectrum.00959-24 -
Medycyna Pracy Jun 2024Cardiovascular diseases (CVDs) are one of the main causes of morbidity and disability worldwide. Due to modern methods of diagnosis and treatment, it is possible to... (Review)
Review
Assessment of qualitative body composition, including phase angle, in the context of primary prevention and secondary prevention of cardiovascular diseases (cardiac rehabilitation).
Cardiovascular diseases (CVDs) are one of the main causes of morbidity and disability worldwide. Due to modern methods of diagnosis and treatment, it is possible to protect patients with acute coronary syndromes from myocardial infarction as well from its early complications. However, the challenge remains to improve the long-term prognosis of CVDs. Analysis of body composition using the bioelectrical impedance (BIA) appears to be a good method for assessing changes in patients' organisms following various cardiac incidents, as well as those participating in rehabilitation programmes. This study aims to provide a complementary analysis of the scientific literature and a critical review of the data from the use of BIA to assess phase angle in people with a history of cardiac diseases. This critical literature review was prepared based on the recommendations. Inclusion criteria included 1) original publications of a research nature, 2) papers indexed in PubMed, Scopus, Embase databases, 3) full-text articles in English, 4) recent papers published between 2013-2023, 5) papers on the use of BIA with phase angle assessment as a prognostic factor in multiple aspects of health and disease, 6) papers showing changes in body composition in the process of cardiac rehabilitation. Based on a review of PubMed, Scopus and Embase databases, 36, 31 and 114 publications were found, respectively, chosen on the basis of precisely selected keywords and included for further full-text analysis. Exploring the role of the BIA holds lots of hope as a non-invasive method that can be used as a predictive marker for changes in the state of health in various fields of medicine. In young, healthy adults, BIA parameters may be important in identifying risk factors for the development of particular diseases, in predicting the rapid development of disease symptoms and in promoting motivation to lifestyle changes. Med Pr Work Health Saf. 2024;75(3).
PubMed: 38916197
DOI: 10.13075/mp.5893.01495