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Transplantation Direct Jul 2024Mycophenolate dose reduction (MDR) is associated with acute rejection and transplant failure in kidney transplant recipients (KTRs). The optimal dose to prevent...
BACKGROUND
Mycophenolate dose reduction (MDR) is associated with acute rejection and transplant failure in kidney transplant recipients (KTRs). The optimal dose to prevent rejection and reduce complications remains poorly defined in tacrolimus-based regimens.
METHODS
We assessed adult KTRs from 2005 to 2017 initiated on mycophenolate mofetil 2 g/d, tacrolimus, and prednisolone from the Australia and New Zealand Dialysis and Transplant Registry. KTRs with rejection within the first 30 d posttransplant were excluded. The primary outcome was time to first rejection between 30 d and 2 y posttransplant. Mycophenolate dose was modeled as a time-varying covariate using Cox proportional hazards regression. Secondary outcomes included assessment of early MDR to <1.5 g/d within the first 6 mo posttransplant and subsequent patient and death-censored graft survival.
RESULTS
In the primary analysis, 3590 KTRs were included. Compared with mycophenolate dose of ≥2 g/d, both 1.0-<1.5 and <1 g/d were associated with an increased risk of rejection during the 2 y posttransplant (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.29-2.16; < 0.001 and HR 2.06; 95% CI, 1.36-3.13; = 0.001, respectively) but not 1.5-<2 g/d (HR 1.20; 95% CI, 0.94-1.53; = 0.14). Early MDR to <1.5 g/d occurred in 45.3% of KTRs and was an independent risk factor for death-censored graft failure (HR 1.32; 95% CI, 1.05-1.66; = 0.016) but not death (HR 1.18; 95% CI, 0.97-1.44; = 0.10), during a median follow-up of 5.0 (interquartile range, 2.6-8.5) y.
CONCLUSIONS
Early MDR was a risk factor for subsequent rejection and graft failure in KTRs receiving contemporary tacrolimus-based regimens.
PubMed: 38881745
DOI: 10.1097/TXD.0000000000001659 -
The Journal of the Association of... Jun 2024The modified Ponticelli regimen (mPR) is a first-line therapy in patients with idiopathic membranous nephropathy (IMN); however, it has a less favorable safety profile.... (Randomized Controlled Trial)
Randomized Controlled Trial
Mycophenolate Mofetil with Steroid, a Reasonable Alternative to Current First-line Therapy, for Idiopathic Membranous Nephropathy in Resource-constrained Settings: A Randomized, Open-label Study.
BACKGROUND
The modified Ponticelli regimen (mPR) is a first-line therapy in patients with idiopathic membranous nephropathy (IMN); however, it has a less favorable safety profile. Though mycophenolate mofetil (MMF) + steroid (S) is not recommended by Kidney Disease Improving Global Outcomes guidelines, it can be used as an alternative to mPR due to higher tolerability and steroid-sparing effect. Thus, we compared the safety and effectiveness of MMF + S and mPR regimens in patients with IMN.
METHODS
This randomized, open-label study enrolled patients with adult-onset nephrotic syndrome (NS) and biopsy-proven IMN. Forty-two patients were allocated to MMF + S group (MMF 1 gm twice daily + oral prednisolone 0.5 mg/kg/day; = 21) and mPR group [methylprednisolone (1 gm intravenous) for 3 days followed by alternating monthly cycles of oral prednisolone (0.5 mg/kg/day) for the next 27 days and cyclophosphamide (2 mg/kg/day) for 6 months; = 21]. The primary outcome measure was change in urinary protein creatinine ratio (UPCR).
RESULTS
At 6 months, both groups demonstrated a significant increase in serum albumin levels and estimated glomerular filtration rate (eGFR) (both -values <0.0001) as well as a decrease in 24-hour proteinuria (MMF + S group: -value = 0.003, and mPR group: -value <0.0001) and UPCR (both -values <0.0001). However, the groups did not differ in any of these parameters at any of the monthly follow-up visits. Moreover, the groups did not differ significantly in terms of the composite remission rates (61.91% for MMF + S group and 71.43% for mPR group).
CONCLUSION
MMF + S and mPR had comparable tolerability and effectiveness, with MMF-associated advantage of reduced steroid exposure.
Topics: Humans; Glomerulonephritis, Membranous; Mycophenolic Acid; Male; Female; Adult; Immunosuppressive Agents; Drug Therapy, Combination; Prednisolone; Middle Aged; Glucocorticoids; Cyclophosphamide; Methylprednisolone; Treatment Outcome
PubMed: 38881128
DOI: 10.59556/japi.72.0558 -
BMC Geriatrics Jun 2024IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines.
BACKGROUND
IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines.
CASE PRESENTATION
A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz's disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size.
CONCLUSION
Mikulicz's disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.
Topics: Humans; Aged; Female; Mikulicz' Disease; Immunoglobulin G4-Related Disease; Autoimmune Hypophysitis; Immunoglobulin G; Prednisolone; Magnetic Resonance Imaging
PubMed: 38880897
DOI: 10.1186/s12877-024-05142-7 -
Biological & Pharmaceutical Bulletin 2024Secondary lymphedema occurs after cancer surgery involving lymph node dissection owing to the lymphatic system dysfunction. However, the pathophysiology of lymphedema...
Secondary lymphedema occurs after cancer surgery involving lymph node dissection owing to the lymphatic system dysfunction. However, the pathophysiology of lymphedema and the molecular pathways involved remain unknown. This study aimed to develop a rat hindlimb lymphedema model and investigate the mechanisms that drive pathophysiology and the effects of the traditional Japanese medicine goreisan on lymphedema. The rat lymphedema model was induced by combination surgeries of popliteal lymph node dissection, skin cautery incision, and fascial ablation coagulation in the right hindlimb using male Wistar rats. The foot volume was significantly increased, and recovery was delayed by combination surgeries. Dermal thickness and dilated lymphatic vessels of the hindlimb were observed on postoperative day 2. The number of infiltrating leukocytes (CD45 cells), including CD4 T-cells, increased in the lymphedema group compared with that in the sham group. The relative mRNA expression and protein levels of interleukin-6 (IL-6), CC chemokine ligand 2 (CCL2), transforming growth factor β1 (TGF-β1), and Fms-related receptor tyrosine kinase 4 (FLT4) were significantly higher in the lymphedema group than in the sham group. Foot volume was decreased by goreisan, furosemide, and prednisolone treatments. Goreisan diminished the increase in CD4 T-cells, and the same trend was observed for CCL2 and FLT4 expression. In conclusion, the rat hindlimb lymphedema model in this study exhibited increased foot volume, skin-infiltrating cells, and pathological changes accompanied by inflammatory and fibrotic responses, suggesting that the model presented significant clinical features of lymphedema. Goreisan may exert a therapeutic effect on lymphedema by inhibiting CD4 T-cell infiltration.
Topics: Animals; Male; Rats; CD4-Positive T-Lymphocytes; Disease Models, Animal; Hindlimb; Lymphedema; Medicine, East Asian Traditional; Rats, Wistar
PubMed: 38880626
DOI: 10.1248/bpb.b23-00829 -
Colloids and Surfaces. B, Biointerfaces Jun 2024Thin films have been identified as an alternative approach for targeting sensitive site as drug delivery tool. In this work, the preparation of self-rolling thin films...
Thin films have been identified as an alternative approach for targeting sensitive site as drug delivery tool. In this work, the preparation of self-rolling thin films to form tubes for wound healing and easy placement (e.g. in the colon via colonoscopy) have been studied. We explored the use of thin films as a protective dressing combined to local release of an anti-inflammatory in order to improve drug efficacy and limit the side effects of the oral route. Non-cytotoxic poly(ethylene) glycol and poly(lactic acid) photo-crosslinkable star copolymers were used for rapid UV crosslinking of bilayered films loaded with prednisolone. The films, crosslinked under UV lamp without the need of photoinitiator, are optimized and compared in terms of water uptake, swelling ratio, final tube diameter and morphology, anti-inflammatory drug loading and release. Our studies showed the spontaneous rolling of bilayer constructs directly after immersion in water. Tubular geometry allows application of the patch through minimally invasive procedures such as colonoscopy. Moreover, the rolled-up bilayers highlighted efficient release of encapsulated drug following Fickian diffusion mechanism. We also confirmed the anti-inflammatory activity of the released anti-inflammatory drug that inhibits the pro-inflammatory cytokine IL-1β in RAW 264.7 macrophages stimulated by Escherichia coli (E. coli).
PubMed: 38879896
DOI: 10.1016/j.colsurfb.2024.114039 -
Clinical Drug Investigation Jun 2024Evidence on associations between drug-drug interactions (DDIs) and health outcomes in the older community-dwelling population is limited.
BACKGROUND
Evidence on associations between drug-drug interactions (DDIs) and health outcomes in the older community-dwelling population is limited.
OBJECTIVE
We estimate potentially clinically important DDI prevalence and examine the association between DDIs and (1) adverse drug events (ADEs), (2) emergency hospital attendance and (3) health-related quality of life (HRQoL) in an older community-dwelling population in Ireland.
METHODS
This is a prospective cohort study of community-dwelling older adults (N = 904) aged ≥ 70 years from 15 general practices in Ireland recruited in 2010 (wave-1) and followed-up over 2 years (wave-2; 2012-2013), with linked national pharmacy claims data. Individuals dispensed two or more drugs (wave-1: N = 842; wave-2: N = 763) were included. DDI prevalence at baseline, follow-up and 6 months prior to each health outcome was estimated. Multi-level regression was used to model the association between DDI-exposure and health outcomes at follow-up. DDI prevalence, adjusted incidence-rate ratios (aIRR), adjusted odds ratios (aOR), β coefficients and robust standard error (RSE) from multi-level regression analyses, and 95% confidence intervals (CIs) are reported.
RESULTS
At wave-1, n = 196 (23.3% [95% CI 20.5-26.3]), individuals were potentially exposed to ≥ 1 DDI, increasing to n = 345 (45.2% [41.7-48.9]) at wave-2. At 2-year follow-up, the median number of ADEs was 3 (interquartile range [IQR 2-5]); 229 (30.1%) had ≥ 1 emergency hospital attendance, and the mean EQ-5D was 0.74 (± 0.23). Evidence for the association between DDI-exposure and emergency hospital attendance at follow-up was lacking (aOR = 1.38 [0.42-4.53]). DDI-exposure was associated with an increasing number of ADEs (aIRR = 1.26 [1.03-1.55]), and decreasing EQ-5D utility (β = - 0.07, [-0.11 to -0.04], RSE = 0.02). Aspirin-warfarin, clarithromycin-prednisolone, amiodarone-furosemide, clarithromycin-salbutamol, rosuvastatin-warfarin, amiodarone-bisoprolol, and aspirin-nicorandil were common DDIs 6 months preceding these health outcomes.
CONCLUSIONS
We found a two-fold increase in DDI prevalence between wave 1 and 2. DDI exposure was associated with increasing ADEs and declining HRQoL at 2-year follow-up. Common DDIs involved anticoagulants, cardiovascular and antimicrobial drugs, which should be targeted for medicine optimisation.
Topics: Humans; Prospective Studies; Aged; Drug Interactions; Female; Male; Aged, 80 and over; Quality of Life; Drug-Related Side Effects and Adverse Reactions; Independent Living; Ireland; Cohort Studies; Prevalence; Emergency Service, Hospital
PubMed: 38878216
DOI: 10.1007/s40261-024-01369-9 -
Journal of AAPOS : the Official... Jun 2024Hyphema is rarely seen in neonates. Although most cases are secondary to instrument-assisted delivery, neonatal hyphema can occur spontaneously or result from an...
Hyphema is rarely seen in neonates. Although most cases are secondary to instrument-assisted delivery, neonatal hyphema can occur spontaneously or result from an underlying coagulopathy. We report the case of an infant who was born with unilateral hyphema and was subsequently found to have gestational alloimmune liver disease-a condition where maternal antibodies attack the infant's liver, leading to a hypocoagulable state. Our patient was treated with topical prednisolone and cyclopentolate/phenylephrine, with subsequent resolution of the hyphema.
PubMed: 38876158
DOI: 10.1016/j.jaapos.2024.103957 -
Journal of Clinical Neuroscience :... Jun 2024
PubMed: 38875742
DOI: 10.1016/j.jocn.2024.06.008 -
Acute Large Pericardial Effusion With Haemodynamic Compromise Secondary to Undiagnosed Tuberculosis.Cureus May 2024Tuberculous pericardial effusion is uncommon in the developed countries. However, it remains one of the main causes of presentation with a pericardial presentation with...
Tuberculous pericardial effusion is uncommon in the developed countries. However, it remains one of the main causes of presentation with a pericardial presentation with pericardial effusion in the developing world. We present the case of a 24-year-old male patient who presented with a weekly history of diarrhoea, vomiting, shortness of breath and feeling hot. Chest computed tomography revealed a large pericardial effusion with significant haemodynamic compromise. The patient underwent emergency pericardiocentesis, and the pericardial fluid interferon-gamma assay result was positive for tuberculosis. He was unable to tolerate endobronchial biopsy under ultrasound despite heavy sedation and was commenced on anti-tuberculous therapy following a discussion in a multidisciplinary team meeting. He was started on four standard anti-tuberculosis medications, including rifampicin, isoniazid, pyrazinamide, ethambutol and prednisolone. The patient had re-accumulation of pericardial fluid on repeat echocardiography in the first few weeks, which eventually resolved with anti-tuberculous therapy.
PubMed: 38872689
DOI: 10.7759/cureus.60249 -
Clinical Drug Investigation Jun 2024BACKGROUND AND OBJECTIVE: Intravenous immunoglobulin (IVIG) is a prominent therapeutic agent for Kawasaki disease (KD) that significantly reduces the incidence of...
BACKGROUND AND OBJECTIVE: Intravenous immunoglobulin (IVIG) is a prominent therapeutic agent for Kawasaki disease (KD) that significantly reduces the incidence of coronary artery anomalies. Various methodologies, including machine learning, have been employed to develop IVIG non-responder prediction models; however, their validation and reproducibility remain unverified. This study aimed to develop a predictive scoring system for identifying IVIG nonresponders and rigorously test the accuracy and reliability of this system. METHODS: The study included an exposure group of 228 IVIG non-responders and a control group of 997 IVIG responders. Subsequently, a predictive machine learning model was constructed. The Shizuoka score, including variables such as the "initial treatment date" (cutoff: < 4 days), sodium level (cutoff: < 133 mEq/L), total bilirubin level (cutoff: ≥ 0.5 mg/dL), and neutrophil-to-lymphocyte ratio (cutoff: ≥ 2.6), was established. Patients meeting two or more of these criteria were grouped as high-risk IVIG non-responders. Using the Shizuoka score to stratify IVIG responders, propensity score matching was used to analyze 85 patients each for IVIG and IVIG-added prednisolone treatment in the high-risk group. In the IVIG plus prednisolone group, the IVIG non-responder count significantly decreased (p < 0.001), with an odds ratio of 0.192 (95% confidence interval 0.078-0.441). CONCLUSIONS: Intravenous immunoglobulin non-responders were predicted using machine learning models and validated using propensity score matching. The initiation of initial IVIG-added prednisolone treatment in the high-risk group identified by the Shizuoka score, crafted using machine learning models, appears useful for predicting IVIG non-responders.
Topics: Mucocutaneous Lymph Node Syndrome; Humans; Immunoglobulins, Intravenous; Machine Learning; Male; Female; Child, Preschool; Infant; Prednisolone; Child; Retrospective Studies
PubMed: 38869717
DOI: 10.1007/s40261-024-01373-z