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The Egyptian Heart Journal : (EHJ) :... Jun 2024Cardiovascular diseases are leading causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Cardiac involvement in SLE can often go...
Three-dimensional speckle tracking echocardiography for evaluation of ventricular function in patients with systemic lupus erythematosus: relationship between duration of lupus erythematosus and left ventricular dysfunction by using global longitudinal strain.
BACKGROUND
Cardiovascular diseases are leading causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Cardiac involvement in SLE can often go undetected. Three-dimensional (3D) speckle tracking echocardiography (STE) is a noninvasive imaging technique that can assess the function of the heart's ventricles in an accurate and reproducible way. This makes it an attractive option for detecting early signs of heart disease in SLE patients. By identifying these subclinical cardiac abnormalities, 3D-STE may help reduce the negative impact of cardiovascular diseases in SLE population. Therefore, this study aimed to compare the left ventricular (LV) function between patients with SLE compared to age- and gender-matched controls using two-dimensional (2D) and 3D-STE.
RESULTS
The current study found no significant differences in left ventricle ejection fraction, left ventricle end-diastolic volume, left ventricle end-systolic volume, left ventricle end-diastolic mass, and left ventricle end-systolic mass between the two groups. However, the SLE group exhibited a significantly lower LV global longitudinal strain (GLS) compared to the control group according to all types of echocardiographic assessments, including 3D and 2D long-axis strain, apical 2-chamber, and apical 4-chamber assessments (all P values < 0.05). Furthermore, a good inter-rater reliability and intra-rater reliability were observed regarding the LVGLS measurement with 3D-STE. Additionally, the study identified a significant correlation between LVGLS and SLE duration (r (50) = 0.46, P < 0.001). The use of prednisolone and nephrology disorders was also found to impact LVGLS measurements.
CONCLUSIONS
Despite a normal LVEF in patients with SLE, LVGLS measurements indicated that LV systolic dysfunction was observed more frequently in SLE patients compared to their healthy counterparts. Therefore, advanced 3D-STE techniques may be useful in identifying subtle abnormalities in LV function in SLE patients.
PubMed: 38914877
DOI: 10.1186/s43044-024-00511-4 -
Journal of Indian Association of... 2024Extrahepatic biliary atresia (BA) is seen in infants, with an incidence of 1 in 15,000 live births. The presentation is progressive jaundice, dark-colored urine, and...
BACKGROUND
Extrahepatic biliary atresia (BA) is seen in infants, with an incidence of 1 in 15,000 live births. The presentation is progressive jaundice, dark-colored urine, and clay-colored stools. Kasai portoenterostomy (KPE) is the commonly performed surgical procedure in these patients. Postoperatively, phenobarbitone, ursodeoxycholic acid (UDCA), steroids, and other drugs are given to improve bile drainage and prevent inflammation and fibrosis. However, a definitive protocol regarding the need for different drugs, dosage, and duration varies across individual surgeons and centers. No universally accepted protocol exists for postoperative management after KPE.
AIM
The aim of this study was to know the prevailing postoperative management of BA by subject experts and use the Delphi process to know if the experts want to change their practice based on the results from the survey.
MATERIAL AND METHODS
A questionnaire was made after discussing with two experts in the field of BA. The questionnaire was mailed to 25 subject experts. The first survey data were analyzed and shared with all responders. In the second survey, change in the management based on the results from the first survey was assessed.
RESULTS
The Delphi questionnaire was answered by 17 experts. Postoperatively, prophylactic antibiotics are prescribed for 6-12 weeks by around 40% and >12 weeks by 30% of respondents. Phenobarbitone is prescribed for <3 months by nearly 50%. UDCA is prescribed for <3 months, ≤6 months, and 6 months-1 year by 47.1%, 23.5%, and 23.5% responders, respectively. Nearly 50% prescribe steroids (mostly prednisolone), and among them, two-thirds prescribe it for 6-12 weeks. Approximately 60% give antiviral drugs to children who are cytomegalovirus immunoglobulin M positive. In our survey, 50% of experts perform 5-10 KPE per year, and 25% each perform 10-15 and >15 KPE per year. The second survey noted that a significant percentage of responders want to change their practice according to consensus.
CONCLUSION
From our Delphi survey, an overview of the postoperative management of BA could be made. However, multicentric studies are required for uniform protocol on the postoperative management of BA.
PubMed: 38912031
DOI: 10.4103/jiaps.jiaps_250_23 -
Food Chemistry: X Jun 2024Engineered bacterial magnetic nanoparticles (BMPs) fused with protein A (BMP-PA) can bind antibodies, creating immunomagnetic beads that offer an attractive tool for...
Engineered bacterial magnetic nanoparticles (BMPs) fused with protein A (BMP-PA) can bind antibodies, creating immunomagnetic beads that offer an attractive tool for targets screening. In the study, BMP-PA-IgG was formed by attaching broad-spectrum monoclonal antibodies against glucocorticoids (GCs) to BMP-PA. Immunomagnetic assay was developed for analysis of GCs, using the BMP-PA-IgG and hydrocortisone-horseradish peroxidase. The developed assay exhibited broad specificity for GCs, including hydrocortisone (HCS), betamethasone (BMS), dexamethasone (DMS), prednisolone (PNS), beclomethasone (BCMS), cortisone (CS), 6-α-methylprednisone (6-α-MPNS), and fludrocortisone acetate (HFCS), with half inhibitory concentrations (IC) ranging from 0.88 to 6.57 ng/mL. The proposed assay showed average recoveries of HCS and DMS ranging from 75.6% to 105.2% in chicken and pork samples, which were correlated well with those obtained by LC-MS/MS. This study indicated that the integration of engineered immunomagnetic beads into immunoassay systems offer possibilities for the sensitive and selective detection of GCs.
PubMed: 38911916
DOI: 10.1016/j.fochx.2024.101523 -
Cureus May 2024Background Erythema nodosum leprosum (ENL) is an immune complex-mediated reaction that clinically presents as tender erythematous evanescent nodules, mostly associated...
Background Erythema nodosum leprosum (ENL) is an immune complex-mediated reaction that clinically presents as tender erythematous evanescent nodules, mostly associated with systemic symptoms. Oral prednisolone is the drug of choice, with doses ranging from 0.5 to 1 mg/kg. Some cases may develop new lesions and systemic symptoms despite 1 mg/kg prednisolone, and in ideal practice, physicians escalate the prednisolone dose for immediate arrest of inflammation to prevent complications. However, a high dose of prednisolone has more side effects in the long term and causes more immunosuppression. Methods In cases of ENL, those not responding to a conventional once-daily regimen were given a split dose of oral prednisolone instead of increasing the dose. They were followed up for response, and serum cortisol was measured to see for hypothalamic-pituitary-adrenal (HPA) axis suppression. Results Eight cases of ENL (three nodular, three necrotic, one pustular, and one nodulcerative) had a dramatic response to split-dose therapy without any relapse and HPA axis suppression. Conclusion A split-dosing regimen can be a good treatment option in ENL with better control, less steroid dependency, and a lower relapse rate.
PubMed: 38910715
DOI: 10.7759/cureus.60888 -
International Immunopharmacology Jun 2024Tacrolimus (TAC) has high pharmacokinetic (PK) variability during the early transplantation period. The relationships between whole-blood and intracellular TAC...
Tacrolimus (TAC) has high pharmacokinetic (PK) variability during the early transplantation period. The relationships between whole-blood and intracellular TAC concentrations and clinical outcomes remain controversial. This study identifies the factors affecting the PK variability of TAC and characterizes the relationships between whole-blood and intracellular TAC concentrations. Data regarding whole-blood TAC concentrations of 1,787 samples from 215 renal transplant recipients (<90 days postoperative) across two centers and intracellular TAC concentrations (648 samples) digitized from previous studies were analyzed using nonlinear mixed-effects modeling. The effects of potential covariates were screened, and the distribution of whole-blood to intracellular TAC concentration ratios (R) was estimated. The final model was evaluated using bootstrap, goodness of fit, and prediction-corrected visual predictive checks. The optimal dosing regimens and target ranges for each type of immune cell subsets were determined using Monte Carlo simulations. A two-compartment model adequately described the data, and the estimated mean TAC CL/F was 23.6 L·h (relative standard error: 11.5 %). The hematocrit level, CYP3A5*3 carrier status, co-administration with Wuzhi capsules, and tapering prednisolone dose may contribute to the high variability of TAC PK variability during the early post-transplant period. The estimated R of all TAC concentrations in peripheral blood mononuclear cells (PBMCs) was 4940, and inter-center variability of PBMCs was observed. The simulated TAC target range in PBMCs was 20.2-85.9 pg·million cells. Inter-center variability in intracellular concentrations should be taken into account in further analyses. TAC dosage adjustments can be guided based on PK/PD variability and simulated intracellular concentrations.
PubMed: 38908078
DOI: 10.1016/j.intimp.2024.112535 -
Journal of the American Veterinary... Jun 2024To determine the myelosuppressive effects/hematological toxicities, other general toxicities, and when these occur during vinblastine/prednisolone chemotherapy in dogs...
OBJECTIVE
To determine the myelosuppressive effects/hematological toxicities, other general toxicities, and when these occur during vinblastine/prednisolone chemotherapy in dogs bearing high-grade or metastatic cutaneous/subcutaneous mast cell tumors (MCTs).
METHODS
Medical records were retrospectively reviewed between November 1, 2016, and March 1, 2023. Thirty client-owned dogs with histopathologically confirmed cutaneous high-grade MCTs/metastatic subcutaneous MCTs and that subsequently completed a 12-week vinblastine/prednisolone chemotherapy protocol were included. Hematology was assessed before commencing chemotherapy and before each vinblastine treatment. The effect of each treatment upon hematological values was evaluated. Measured outcomes included the type, frequency, and severity of hematological and other more general toxicities.
RESULTS
24 of 30 dogs experienced at least 1 hematological toxicity, 6 experienced gastrointestinal toxicity, and 4 experienced lethargy. The most common toxicity was anemia (15/30 [50%]), with 93.3% (14/15 dogs) classified as Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events grade I and 6.6% (1/15) classified as grade II. The second most common toxicity was neutropenia (14/30 [46.6%]), with 71.4% (10/14) classified as grade I and 28.6% (4/14) as grade III. The least common hematological toxicity was thrombocytopenia (4/30 [13%]), all grade I. Neutropenia mainly occurred during weeks 2 and 3; however, there was no significant decrease in neutrophil count relative to baseline. Neutrophil count increased and Hct decreased during weeks 6 to 12 of treatment when compared to baseline. No change in platelet count was observed.
CLINICAL RELEVANCE
Vinblastine/prednisolone chemotherapy leads to hematological toxicity; however, this was mostly low-grade and did not require major intervention. Vinblastine/prednisolone chemotherapy is well tolerated in dogs bearing high-grade or metastatic MCTs.
PubMed: 38906172
DOI: 10.2460/javma.24.03.0214 -
Cureus May 2024Congenital chylothorax is the most common form of pleural effusion during the neonatal period; however, no treatment strategy exists. The pathogenesis and etiology of...
Congenital chylothorax is the most common form of pleural effusion during the neonatal period; however, no treatment strategy exists. The pathogenesis and etiology of this disease are not fully understood; hence, several cases are difficult to treat. Some patients with chylothorax may not survive due to severe respiratory distress. Prednisolone (PSL) is sometimes used to treat congenital chylothorax but is rarely used in the early postnatal period. In this report, we describe a neonate with prenatal pleural effusion who was successfully treated with PSL from day one after requiring endotracheal intubation and ventilator management due to a postnatal diagnosis of chylothorax. The patient was extubated at four days of age, weaned from the ventilator at 10 days of age, and discharged home at 40 days of age after a total of 10 days of administration. Although the mechanism of action of PSL in chylothorax is unknown, and because it is a steroid, side effects such as gastrointestinal perforation and susceptibility to infection should be noted. The present case suggests the utility of early PSL administration for the treatment strategy of congenital chylothorax.
PubMed: 38903368
DOI: 10.7759/cureus.60628 -
BMJ Case Reports Jun 2024A man in his 40s with end-stage kidney disease due to IgA nephropathy and receiving peritoneal dialysis presented with a 1-week history of breathlessness, cough and...
A man in his 40s with end-stage kidney disease due to IgA nephropathy and receiving peritoneal dialysis presented with a 1-week history of breathlessness, cough and nosebleeds. CT scan of the chest revealed ground glass changes while blood tests indicated elevated inflammatory markers and a negative vasculitis screen. This included negative ANCA and anti-GBM antibodies. Initial treatment for suspected atypical pneumonia with antibiotics yielded no clinical improvement.Over the course of the admission, his symptoms progressively worsened, leading to oxygen dependency with a FiO2 of 40% and episodes of haemoptysis. Suspicions of pulmonary vasculitis arose due to clinical deterioration, prompting consultation with a tertiary vasculitis centre. It was subsequently concluded that the clinical and radiological findings correlated with ANCA-negative pulmonary vasculitis or a rare case of IgA-associated pulmonary capillaritis. Treatment with methylprednisolone and rituximab led to significant improvement, allowing rapid oxygen withdrawal. The patient was discharged with a tapering prednisolone regimen.
Topics: Humans; Male; Antibodies, Antineutrophil Cytoplasmic; Adult; Rituximab; Vasculitis; Methylprednisolone; Diagnosis, Differential; Tomography, X-Ray Computed; Kidney Failure, Chronic; Lung Diseases; Immunoglobulin A
PubMed: 38901853
DOI: 10.1136/bcr-2023-258766 -
Bilateral Aggressive Mooren Ulcer in the Setting of Bilateral Pterygia and Pregnancy: A Unique Case.Cornea Jun 2024To report an unusual case of bilateral aggressive Mooren ulcer that occurred in the setting of bilateral pterygia and showed a relentless course during pregnancy.
PURPOSE
To report an unusual case of bilateral aggressive Mooren ulcer that occurred in the setting of bilateral pterygia and showed a relentless course during pregnancy.
METHODS
A 39-year-old woman of Black African ethnicity, 36-week pregnant, presented to the eye casualty with bilateral nasal corneal ulcer and associated melt around preexisting pterygia. A detailed workup including microbial evaluation, culture and sensitivity, polymerase chain reaction for herpes simplex virus, varicella zoster virus, and cytomegalovirus, inflammatory blood profile, autoimmune markers, and human leucocyte antigen (HLA) screening was undertaken. Treatment was initiated in a stepwise approach.
RESULTS
Infections and systemic autoimmune and rheumatologic conditions were ruled out. A diagnosis of bilateral Mooren ulcer was made by exclusion. The peripheral blood was positive for HLA DQ2. As the condition seemed refractory to medical management (topical steroids and intravenous pulse methylprednisolone followed by oral prednisolone and topical cyclosporine), urgent bilateral conjunctival resection with multilayered amniotic membrane transplantation was performed to reduce the inflammatory stimulus and keratolysis. Stabilization of the condition warranted the need for systemic immunosuppressive agents. Using a multidisciplinary approach, in liaison with Obstetricians and Rheumatologists, the patient was planned for an earlier elective Cesarean section and commencement of oral mycophenolate mofetil postpartum, which aided in successful control of the disease.
CONCLUSIONS
Mooren ulcer could follow an aggressive course during pregnancy, especially in the setting of preexisting pterygium. The complex hormonal and immunological changes during pregnancy and the delivery of inflammatory mediators directly onto the cornea by pterygium could contribute to the severity. A well-planned, stepwise, and multidisciplinary management is pivotal for the treatment of this condition.
PubMed: 38900823
DOI: 10.1097/ICO.0000000000003591 -
Journal of Virology Jun 2024Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of...
Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of chronic hepatitis E virus (HEV) infection is linked to the type of immunosuppressant used. Animal models are crucial for the study of pathogenesis of chronic hepatitis E. We previously established a stable chronic HEV infection rabbit model using cyclosporine A (CsA), a calcineurin inhibitor (CNI)-based immunosuppressant. However, the immunosuppression strategy and timing may be optimized, and how different types of immunosuppressants affect the establishment of chronic HEV infection in this model is still unknown. Here, we showed that chronic HEV infection can be established in 100% of rabbits when CsA treatment was started at HEV challenge or even 4 weeks after. Tacrolimus or prednisolone treatment alone also contributed to chronic HEV infection, resulting in 100% and 77.8% chronicity rates, respectively, while mycophenolate mofetil (MMF) only led to a 28.6% chronicity rate. Chronic HEV infection was accompanied with a persistent activation of innate immune response evidenced by transcriptome analysis. The suppressed adaptive immune response evidenced by low expression of genes related to cytotoxicity (like and ) and low anti-HEV seroconversion rates may play important roles in causing chronic HEV infection. By analyzing HEV antigen concentrations with different infection outcomes, we also found that HEV antigen levels could indicate chronic HEV infection development. This study optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits and highlighted the potential association between the development of chronic HEV infection and immunosuppressants.IMPORTANCEOrgan transplant recipients are at high risk of chronic hepatitis E and generally receive a CNI-based immunosuppression regimen containing CNI (tacrolimus or CsA), MMF, and/or corticosteroids. Previously, we established stable chronic HEV infection in a rabbit model by using CsA before HEV challenge. In this study, we further optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits. Chronic HEV infection can also be established when CsA treatment was started at the same time or even 4 weeks after HEV challenge, clearly indicating the risk of progression to chronic infection under these circumstances and the necessity of HEV screening for both the recipient and the donor preoperatively. CsA, tacrolimus, or prednisolone instead of MMF significantly contributed to chronic HEV infection. HEV antigen in acute infection phase indicates the development of chronic infection. Our results have important implications for understanding the potential association between chronic HEV infection and immunosuppressants.
PubMed: 38899900
DOI: 10.1128/jvi.00846-24