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Nigerian Journal of Clinical Practice Jun 2024Mesenteric panniculitis is rare, usually idiopathic, caused by inflammation of the fatty tissue of the mesentery, especially in the small intestine. The relation between...
Mesenteric panniculitis is rare, usually idiopathic, caused by inflammation of the fatty tissue of the mesentery, especially in the small intestine. The relation between cancer and mesenteric panniculitis is unclear. In some studies, mesenteric pannicullitis precedes cancer diagnosis; on the other hand, some studies suggest no correlations. Immunotherapeutics have a wide range of side effects; virtually, every system and organ in the body can be affected. Herein, we presented a rare case of mesenteric panniculitis in a patient with larnyngeal cancer as a side effect of nivolumab treatment. The patient was presented with nausea and vomiting and diagnosed with intravenous contrast-enhanced computed tomography and fully recovered with corticosteroid treatment. The case report highlights the importance of noticing rarely seen side effects of immunotherapy which can be treated easily with immunosuppressive agents.
Topics: Humans; Panniculitis, Peritoneal; Nivolumab; Male; Antineoplastic Agents, Immunological; Middle Aged; Tomography, X-Ray Computed
PubMed: 38943307
DOI: 10.4103/njcp.njcp_655_23 -
Nigerian Journal of Clinical Practice Jun 2024The burden of perinatal asphyxia remains high in our environment and when asphyxia is severe, vital organs are affected, with resultant multiorgan hypoxic-iscahemic...
BACKGROUND
The burden of perinatal asphyxia remains high in our environment and when asphyxia is severe, vital organs are affected, with resultant multiorgan hypoxic-iscahemic injury to the heart, the brain, adrenals and other organs.
STUDY AIM
To evaluate for myocardial injury in asphyxiated term neonates with hypoxic ischaemic encephalopathy using serum cardiac troponin-I (cTnI).
METHODS
The study was a hospital-based descriptive cross-sectional study involving sixty term asphyxiated neonates and sixty gestational age-and sex-matched controls. The subjects were term neonates with five-minute Apgar score ≤ 6 and HIE while the controls were healthy term neonates with five-minute Apgar score > 6. Five-minute Apgar score was utilized to classify asphyxia into mild, moderate and severe asphyxia. The degree of encephalopathy was determined by modified Sarnat and Sarnat criteria. The serum cTnI was measured in subjects and controls at 12-24 hours of life using Enzyme-linked immunosorbent assay technique. The serum bilirubin levels were also measured in participants to exclude hyperbilirubinemia.
RESULTS
The median serum cTnI levels was significantly higher in the subjects (0.56ng/mL; 0.25-0.94ng/mL) than in the controls (0.50ng/mL; 0.00-0.67ng/mL), respectively; p=0.001. Similarly, the median serum cTnI level in HIE stage II (0.56ng/mL; 0.38-0.72ng/mL) or III (0.56ng/ml; 0.50-0.94ng/mL) was also significantly higher than the median value in HIE stage I (0.38ng/mL;0.25-0.72ng/mL) or in controls (0.50ng/mL; 0.00-0.67ng/mL); p<0.001. There was significant positive correlation between serum cTnI levels and severity of HIE in asphyxiated neonates (rs = 0.505, p < 0.001).
CONCLUSION
serum cTnI levels were elevated in severely asphyxiated neonates with HIE. The concentration of serum cTnI demonstrated significant positive correlation with HIE severity. Hence, the presence of HIE in asphyxiated neonates should prompt an evaluation for myocardial injury using serum cTnI. Any derangement noted should warrant instituting cardiovascular support in order to improve outcome and reduce asphyxia-related mortality.
Topics: Humans; Infant, Newborn; Asphyxia Neonatorum; Troponin I; Female; Nigeria; Male; Cross-Sectional Studies; Case-Control Studies; Hospitals, Teaching; Apgar Score; Biomarkers; Hypoxia-Ischemia, Brain
PubMed: 38943306
DOI: 10.4103/njcp.njcp_169_24 -
Nigerian Journal of Clinical Practice Jun 2024Exercise or exercise capacity is a vital physiological function. It is known that certain cytokines support muscle function during exercise and, as a result, increase...
BACKGROUND
Exercise or exercise capacity is a vital physiological function. It is known that certain cytokines support muscle function during exercise and, as a result, increase exercise capacity.
AIMS
In this study, the effect of metformin administered in combination with exercise on osteocalcin (OCN), insulin, and interleukin-6 (IL-6) levels in rats was investigated.
METHODS
Forty-two male Wistar rats were used in this study. The animals were randomly divided into six groups: control (CONT), only exercise (EXE), metformin_100 mg/kg (Met100), metformin_200 mg/kg (Met200), metformin_100 mg/kg+exercise (Met100+EXE), and metformin_200 mg/kg+exercise (Met200+EXE). A 10-week intervention was conducted, excluding exercise training. During the experiment, the groups receiving metformin application (100 or 200 mg/kg) were administered with metformin. At the end of the study, serum samples were collected from the rats to determine the levels of osteocalcin, insulin, and IL-6 using the enzyme-linked immunosorbent assay method. In addition, glucose levels and body weights were evaluated. GraphPad Prism was used for the analyses.
RESULTS
The OCN and insulin levels of the Met100+EXE and Met200+EXE groups were found to be higher compared to the CONT, Met100, and Met200 groups (P < 0.05). The IL-6 level of the EXE group was determined to be higher than that of the CONT, Met100, and Met200 groups (P < 0.01). It was observed that both exercise and the individual or combined application of metformin resulted in lower blood glucose levels compared to the CONT group. The mean body weight of the EXE group was higher than that of the other groups.
CONCLUSION
The combined application of metformin and exercise has increased osteocalcin and insulin levels compared to metformin application alone.
Topics: Animals; Metformin; Interleukin-6; Osteocalcin; Rats, Wistar; Male; Rats; Physical Conditioning, Animal; Insulin; Hypoglycemic Agents; Blood Glucose; Body Weight
PubMed: 38943302
DOI: 10.4103/njcp.njcp_884_23 -
Nigerian Journal of Clinical Practice Jun 2024Rhinoplasty is a common surgical procedure used in nose esthetics and pathologies. Shaping the nasal bones is a crucial step in achieving successful rhinoplasty surgery....
BACKGROUND
Rhinoplasty is a common surgical procedure used in nose esthetics and pathologies. Shaping the nasal bones is a crucial step in achieving successful rhinoplasty surgery. However, complications such as excessive bleeding, edema, mucosal damage, and periosteal damage may occur during osteotomy for nose shaping.
AIM
To investigate the damage to soft tissue and the effects on oxidative stress and proinflammatory cytokines in the blood caused by osteotomy performed on rabbits, using different osteotomy methods. Methods: Thirty-two albino New Zealand rabbits were divided into four groups. Group A was the sham group (n = 8), Group B the piezoelectric device group (n = 8), Group C the manual saw group (n = 8), and Group D the classical osteotomy group (n = 8). About 3 ml of blood was drawn to compare preoperative and postoperative interleukin-1ß (IL-1ß), thiobarbituric acid-reactive substances (TBARS), tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), interleukin-10 (IL-10), and glutathione (GSH) levels. A 1 mm3 piece of soft tissue from the nasal bone of each animal in the study groups was sent for histopathological examination. The Chi-square test was used to analyze the incidence of postoperative necrosis, inflammation, and edema in the groups.
RESULTS
Histopathologically, edema was significantly higher in Group C and Group D compared to Group B. Inflammation was increased in all groups. The necrosis was significantly higher in Group B compared to Group C and Group D. Except for two parameters, no significant changes were found in the biochemical markers for all groups.
CONCLUSIONS
The piezoelectric device was found to be a better option for reducing edema and inflammation, while manual saws and classical osteotomy may lead to more tissue damage.
Topics: Animals; Oxidative Stress; Rabbits; Osteotomy; Rhinoplasty; Biomarkers; Nitric Oxide; Cytokines; Inflammation; Interleukin-1beta; Tumor Necrosis Factor-alpha; Thiobarbituric Acid Reactive Substances; Glutathione; Edema; Interleukin-10; Piezosurgery; Nose
PubMed: 38943295
DOI: 10.4103/njcp.njcp_686_23 -
Aging Jun 2024Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress...
Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and a dementia onset resembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). Our results show that DS mice show increased liver oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Therefore, DS liver exhibits an altered inflammatory response and mitochondrial fitness as we showed by assaying the expression of HMOX1, CLPP, and the heat shock proteins Hsp90 and Hsp60. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of PPARα, PPARγ, FATP5, and CTP2. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Consistently, histological analysis of DS liver reveals increased fibrosis and steatosis, as showed by Col1a1 increased expression, indicative of potential progression to liver cirrhosis. Therefore, our findings suggest an increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed a light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.
PubMed: 38942607
DOI: 10.18632/aging.205970 -
RMD Open Jun 2024To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and... (Randomized Controlled Trial)
Randomized Controlled Trial
Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study.
OBJECTIVES
To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.
METHODS
In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18.
RESULTS
53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): -1.03 (-1.66 to -0.40) vs -0.58 (-1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement.
CONCLUSIONS
Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA.
TRIAL REGISTRATION NUMBER
NCT04991753.
Topics: Humans; Arthritis, Rheumatoid; Male; Female; Middle Aged; Treatment Outcome; Antirheumatic Agents; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Aged; Adult; Tumor Necrosis Factor-alpha; Double-Blind Method; Patient Reported Outcome Measures; Anti-Citrullinated Protein Antibodies
PubMed: 38942592
DOI: 10.1136/rmdopen-2024-004278 -
RMD Open Jun 2024Discontinuation or continuation of maintenance immunosuppressive therapy (MIST) after a severe lupus nephritis (LN) requires measuring the risk of relapse but reliable... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Discontinuation or continuation of maintenance immunosuppressive therapy (MIST) after a severe lupus nephritis (LN) requires measuring the risk of relapse but reliable clinical and biological markers are lacking. The WIN-IgE study assesses the value of serum anti-dsDNA IgE autoantibodies as a biomarker for the prediction of relapse in severe LN.
METHODS
WIN-IgE is an ancillary study of the WIN-Lupus study (NCT01284725), a prospective controlled clinical trial which evaluated the discontinuation of MIST after 2-3 years in class III or IV±V LN with active lesions. WIN-IgE included all patients with available serum collected at randomisation for continuation or discontinuation of MIST. In these sera, anti-dsDNA antibodies, IgE and IgG, were quantified by ELISA and compared between patients who experienced LN relapse and those who did not during the 24 months of follow-up.
RESULTS
52 patients were included, 25 in the MIST continuation group and 27 in the MIST discontinuation group, 12 experienced a biopsy-proven relapse of LN. Initial anti-dsDNA IgE antibodies levels were higher in patients with subsequent LN relapse. Anti-dsDNA IgG was not associated with relapse. Survival without LN relapse was lower in patients with anti-dsDNA IgE levels above vs below a threshold of 1.9 arbitrary units (p=0.019), particularly in the subgroup of patients randomised to discontinue MIST (p=0.002). In all patients, anti-dsDNA IgE above 1.9 arbitrary units had a positive predictive value of 0.8 for severe LN relapse.
CONCLUSIONS
These results suggest blood anti-dsDNA IgE as a non-invasive predictive marker of LN relapse.
Topics: Humans; Lupus Nephritis; Female; Male; Recurrence; Adult; Biomarkers; Immunoglobulin E; Antibodies, Antinuclear; Middle Aged; Prognosis; Prospective Studies; DNA; Immunosuppressive Agents
PubMed: 38942591
DOI: 10.1136/rmdopen-2024-004255 -
RMD Open Jun 2024The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and...
INTRODUCTION
The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed.
METHODS
Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment.
RESULTS
After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (β coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (β coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis.
CONCLUSION
Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.
Topics: Humans; Male; Female; Atherosclerosis; Middle Aged; Inflammation; Adult; Heart Disease Risk Factors; Sex Factors; Axial Spondyloarthritis; Risk Factors; Biomarkers; Cardiovascular Diseases; C-Reactive Protein
PubMed: 38942590
DOI: 10.1136/rmdopen-2024-004187 -
Korean Journal of Radiology Jul 2024This study systematically reviewed the role of diffusion-weighted imaging (DWI) in the assessment of molecular prognostic biomarkers in breast cancer, focusing on the... (Meta-Analysis)
Meta-Analysis Review
This study systematically reviewed the role of diffusion-weighted imaging (DWI) in the assessment of molecular prognostic biomarkers in breast cancer, focusing on the correlation of apparent diffusion coefficient (ADC) with hormone receptor status and prognostic biomarkers. Our meta-analysis includes data from 52 studies examining ADC values in relation to estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status. The results indicated significant differences in ADC values among different receptor statuses, with ER-positive, PgR-positive, HER2-negative, and Ki-67-positive tumors having lower ADC values compared to their negative counterparts. This study also highlights the potential of advanced DWI techniques such as intravoxel incoherent motion and non-Gaussian DWI to provide additional insights beyond ADC. Despite these promising findings, the high heterogeneity among the studies underscores the need for standardized DWI protocols to improve their clinical utility in breast cancer management.
Topics: Humans; Breast Neoplasms; Diffusion Magnetic Resonance Imaging; Female; Biomarkers, Tumor; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Ki-67 Antigen
PubMed: 38942456
DOI: 10.3348/kjr.2023.1188 -
Journal of Advanced Research Jun 2024The Prime Editing (PE) system is a precise and versatile genome editing tool with great potential in plant breeding and plant synthetic biology. However, low PE...
INTRODUCTION
The Prime Editing (PE) system is a precise and versatile genome editing tool with great potential in plant breeding and plant synthetic biology. However, low PE efficiency severely restricts its application, especially in dicots. PE can introduce small tags to trace target protein or cis-element to regulate gene transcription which is an expertise superior to other gene editing tools. Owing to low efficiency, PE adaption in stably transformed Arabidopsis is lacking.
OBJECTIVES
This study aimed to investigate the issue of low PE efficiency in dicots and develop systematic solutions to improve it. Currently, PE in dicots is undetectable and inconsistent, and this study seeks to address it. Split PE into several parts showed better performance in some target sites in mammal cells. We plan to discover the optimal split PE combination in dicot.
METHODS
We conducted large-scale transformation experiments in dicot model plants Arabidopsis thaliana (At) and Nicotiana benthamiana (Nb) by Agrobacterium-mediated transformation with deep amplicon sequencing (0.2-0.5 million clean total reads).
RESULTS
The editing efficiency decreased upon using a fused reverse transcriptase (RT) or an extended pegRNA separately and further decreased dramatically when these were used together. With the help of the pol II strategy to express PE gRNA (pegRNA), we named the most effective split PE combination as a multi-modular assembled prime editing system (mPE). mPE exhibited improved precise editing efficiency on most gene sites with various editing types, ranging from 1.3-fold to 1288.5-fold and achieved PE on some sites that could not be edited by original PE2. Especially, mPE showed superiority for multi-base insertion with an average improvement of 197.9-fold.
CONCLUSION
The original PE architecture strongly inhibited the cleavage activity of Cas9. Split PE improved PE efficiency extensively and was in favor of introducing small insertions in dicot plants, indicating that different PE variants might have their own expertise.
PubMed: 38942381
DOI: 10.1016/j.jare.2024.06.021