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JPGN Reports May 2024Pancreatitis is a condition much more commonly found in adults, but when diagnosed in the pediatric population, is often due to medications, congenital pathology, and...
Pancreatitis is a condition much more commonly found in adults, but when diagnosed in the pediatric population, is often due to medications, congenital pathology, and critical illness. This patient had previously undergone treatment with 6-mercaptopurine and presented with pancreatitis that eventually worsened to a walled-off necrotic collection with paracolic extensions reaching the pelvis. Given clinical worsening with development of shock, procedural options for source control were weighed with gastroenterology, pediatric surgery, and interventional radiology, before pancreatic necrosectomy was determined to be the treatment of choice, given the adjacency of the collection to the stomach. A total of three separate endoscopic pancreatic necrosectomy procedures were performed and the patient s clinical status improved greatly, with vast improvement later seen on outpatient imaging. This successful treatment course argues for the efficacy of pancreatic necrosectomy even in very large walled off collections, and most importantly, lead to a positive outcome in this young patient.
PubMed: 38756110
DOI: 10.1002/jpr3.12052 -
Modern Rheumatology Case Reports May 2024Glucocorticoids (GC) are the standard of care for the induction and maintenance of remission in immunoglobulin G4 (IgG4)-related diseases. However, IgG4-related diseases...
Glucocorticoids (GC) are the standard of care for the induction and maintenance of remission in immunoglobulin G4 (IgG4)-related diseases. However, IgG4-related diseases often relapse with GC dose reduction, not only making GC dose reduction difficult but also necessitating GC dose escalation in many cases. Therefore, other immunosuppressive drugs are required to maintain remission. Here, we report a 39-year-old man with ulcerative colitis and IgG4-related disease who experienced a relapse of both diseases despite treatment with tacrolimus and 6-mercaptopurine. Following the initiation of tofacitinib, a Janus-associated kinase inhibitor, it was possible to reduce the GC dose while maintaining remission of both diseases. This case highlights the potential utility of Janus-associated kinase inhibitors in managing complex cases of IgG4-related disease, especially those with concurrent conditions such as ulcerative colitis.
PubMed: 38748397
DOI: 10.1093/mrcr/rxae025 -
Crohn's & Colitis 360 Apr 2024Since 2009, inflammatory bowel disease (IBD) specialists have utilized "IBD LIVE," a weekly live video conference with a global audience, to discuss the...
BACKGROUND
Since 2009, inflammatory bowel disease (IBD) specialists have utilized "IBD LIVE," a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified "IBD-mimics" with consequent clinical management implications.
METHODS
Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018-February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup.
RESULTS
Confirmed IBD cases made up 82.5% (306/371; 193 Crohn's disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced ( = 8) or vasculitis ( = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies ( = 13, 21%), surgical exploration/pathology ( = 10, 16.5%), biopsies from outside the GI tract ( = 10, 16.5%), genetic/laboratory testing ( = 8, 13%), extensive review of patient history ( = 8, 13%), imaging ( = 5, 8%), balloon enteroscopy ( = 5, 8%), and capsule endoscopy ( = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib.
CONCLUSIONS
The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care.
PubMed: 38720935
DOI: 10.1093/crocol/otae022 -
Advances in Rheumatology (London,... May 2024This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares,...
BACKGROUND
This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data.
METHODS
The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.
RESULTS
Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.
CONCLUSIONS
This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.
Topics: Humans; Lupus Erythematosus, Systemic; Female; Immunosuppressive Agents; Hydroxychloroquine; Male; Glucocorticoids; Adult; Azathioprine; Prednisolone; Standard of Care; Methotrexate; Antimalarials; Cohort Studies; Middle Aged; Mycophenolic Acid; Leflunomide; Calcineurin Inhibitors; Logistic Models; Propensity Score; Severity of Illness Index; Tacrolimus; Symptom Flare Up; Treatment Outcome; Antirheumatic Agents
PubMed: 38720354
DOI: 10.1186/s42358-024-00366-y -
AME Case Reports 2024Lobular capillary hemangioma, also known as pyogenic granuloma (PG), is a relatively common benign rapidly growing friable vascular tumor of the skin and mucus...
BACKGROUND
Lobular capillary hemangioma, also known as pyogenic granuloma (PG), is a relatively common benign rapidly growing friable vascular tumor of the skin and mucus membranes. Although the exact pathogenesis of PG is unknown, many theories discussed the potential of an angiogenic stimulus and an imbalance of inducers and inhibitors triggering the hyperplastic and neovascular response. The most frequently used modality for treatment of PG is surgical treatment. The proposed case represents an unexpected evolution to a possible therapeutic measure.
CASE DESCRIPTION
We represent a case of a 32-year-old male, known to have T-cell acute lymphoblastic leukemia treated successfully with chemotherapy, currently maintained on methotrexate (MTX) 40 mg and 6-mercaptopurine, 100 mg, presented with 1-month history of painful rapidly growing ulcerated nodules on his right-hand palm and middle finger. Both skin lesions developed approximately 3 months following patient initiation of maintenance treatment. Physical examination revealed two crusted nodules. A proximal lesion was observed over the palmar aspect between the second and third fingers, with the other one occurring alongside the distal phalanx of the third finger, measuring 2.5 cm × 1.5 cm, and 2.5 cm × 3.5 cm respectively. Skin biopsy was obtained from both lesions. The results of the histologic examination both revealed inflamed PG. Tissue cultures of both specimens tested positive for growth while no fungal and tuberculosis were cultured. Ciprofloxacin 500 mg twice daily, a 2-week course was started. Both lesions completely resolved at 10-day of antibiotic course with no recurrence.
CONCLUSIONS
This is a case of a patient with lobular capillary hemangioma of the hand treated successfully with no recurrence using an oral antibiotic. The proposed case represents an unexpected evolution to a possible therapeutic measure. The unexpected role of a conservative measure rather than the conventional surgical method in treating vascular tumors has been highlighted. Moreover, the contribution to an excellent cosmetic outcome has also been demonstrated.
PubMed: 38711894
DOI: 10.21037/acr-23-159 -
Cancer Jul 2024Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a-positive/Langerin (CD207)-positive histiocytes and inflammatory... (Review)
Review
Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a-positive/Langerin (CD207)-positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life-threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy. However, fewer than 50% of patients who have disseminated disease are cured with the current standard-of-care vinblastine/prednisone/(mercaptopurine), and treatment failure is associated with long-term morbidity, including the risk of LCH-associated neurodegeneration. Historically, the nature of LCH-whether a reactive condition versus a neoplastic/malignant condition-was uncertain. Over the past 15 years, seminal discoveries have broadly defined LCH pathogenesis; specifically, activating mitogen-activated protein kinase pathway mutations (most frequently, BRAFV600E) in myeloid precursors drive lesion formation. LCH therefore is a clonal neoplastic disorder, although secondary inflammatory features contribute to the disease. These paradigm-changing insights offer a promise of rational cures for patients based on individual mutations, clonal reservoirs, and extent of disease. However, the pace of clinical trial development behind lags the kinetics of translational discovery. In this review, the authors discuss the current understanding of LCH biology, clinical characteristics, therapeutic strategies, and opportunities to improve outcomes for every patient through coordinated agent prioritization and clinical trial efforts.
Topics: Humans; Histiocytosis, Langerhans-Cell
PubMed: 38687639
DOI: 10.1002/cncr.35301 -
Pharmacogenetics and Genomics Jul 2024Acute lymphoblastic leukemia (ALL) is the most frequent pediatric cancer. 6-Mercaptopurine (6-MP) is a key component of ALL treatment. Its use, however, is also...
Acute lymphoblastic leukemia (ALL) is the most frequent pediatric cancer. 6-Mercaptopurine (6-MP) is a key component of ALL treatment. Its use, however, is also associated with adverse drug reactions, particularly myelosuppression. Thiopurine S-methyltransferase (TPMT) and, more recently, Nudix hydrolase 15 (NUDT15) deficiency, due to no-function variants in their respective genes, are well known for their role in the development of this toxicity. Two novel genetic variants, rs12199316 in TPMT and rs73189762 in the NUDT15 gene, were recently identified by targeted sequencing. The latter is particularly interesting because of its potential association with 6-MP intolerance. Here, we assessed the relationship of this variant with the risk of myelosuppression and 6-MP dose intensity in 275 patients treated with Dana Farber Cancer Institute ALL protocols at the Sainte Justine University Health Center. Carriers of the NUDT15 rs73189762 variant allele were at a higher risk of myelosuppression, as shown by absolute phagocyte count reduction during consolidation II and maintenance phases of therapy. Reduction in 6-MP dose intensity was observed in patients with both rs73189762 and known no-function variants in the NUDT15 and TPMT genes. This finding supports the initial observation and suggests that 6-MP dose reduction might be beneficial for individuals with this genotype combination.
Topics: Humans; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrophosphatases; Child; Male; Female; Child, Preschool; Adolescent; Antimetabolites, Antineoplastic; Methyltransferases; Infant; Polymorphism, Single Nucleotide; Nudix Hydrolases
PubMed: 38682355
DOI: 10.1097/FPC.0000000000000533 -
Pharmaceutics Apr 2024Pharmacogenomic knowledge as a biomarker for cancer care has transformed clinical practice, however, as current guidelines are primarily derived from Eurocentric...
BACKGROUND
Pharmacogenomic knowledge as a biomarker for cancer care has transformed clinical practice, however, as current guidelines are primarily derived from Eurocentric populations, this limits their application in Latin America, particularly among Hispanic or Latino groups. Despite advancements, systemic chemotherapy still poses challenges in drug toxicity and suboptimal response. This study explores pharmacogenetic markers related to anticancer drugs in a Chilean cohort, filling a gap in Latin American research. Notably, the influence of native South American Mapuche-Huilliche ancestry.
METHODS
To explore pharmacogenetic markers related to anticancer drugs, we utilized an ethnically Admixed Chilean genome-wide association studies (GWAS) dataset of 1095 unrelated individuals. Pharmacogenomic markers were selected from PharmGKB, totaling 36 level 1 and 2 evidence single nucleotide polymorphisms (SNPs) and 571 level 3 SNPs. Comparative analyses involved assessing SNP frequencies across diverse populations from the 1000 Genomes Project. Haplotypes were estimated, and linkage disequilibrium was examined. Ancestry-based association analyses explored relationships between SNPs and Mapuche-Huilliche and European ancestries. Chi-square distribution with ≤ 0.05 and Bonferroni's multiple adjustment tests determined statistical differences between allele frequencies.
RESULTS
Our study reveals significant disparities in SNP frequency within the Chilean population. Notably, dihydropyrimidine dehydrogenase () variants (rs75017182 and rs67376798), linked to an increased risk of severe fluoropyrimidine toxicity, exhibit an exceptionally low frequency (minor allele frequency (MAF) < 0.005). Nudix hydrolase 15 () rs116855232, associated with hematological mercaptopurine toxicity, is relatively common (MAF = 0.062), and is further linked to Mapuche-Huilliche ancestry. Thiopurine methyltransferase enzyme (TPMT), implicated in severe toxicity to mercaptopurines, SNPs rs1142345 and rs1800460 of gene demonstrate higher MAFs in Admixed Americans and the Chilean population (MAF range 0.031-0.057). Finally, the variant in the UDP-glucuronosyltransferase 1 gene () rs4148323, correlated with irinotecan neutropenia, exhibits the highest MAF in East Asian (MAF = 0.136) and Chilean (MAF = 0.025) populations, distinguishing them from other investigated populations.
CONCLUSIONS
This study provides the first comprehensive pharmacogenetic characterization of cancer therapy-related SNPs and highlights significant disparities in SNP frequencies within the Chilean population. Our findings underscore the necessity for inclusive research and personalized therapeutic strategies to ensure the equitable and effective application of precision medicine across diverse global communities.
PubMed: 38675222
DOI: 10.3390/pharmaceutics16040561 -
Seminars in Arthritis and Rheumatism Jun 2024Immunosuppressive (IS) agents are recommended for the first-line treatment of patients with active Takayasu's arteritis (TAK) together with glucocorticoids (GCs).... (Comparative Study)
Comparative Study
BACKGROUND
Immunosuppressive (IS) agents are recommended for the first-line treatment of patients with active Takayasu's arteritis (TAK) together with glucocorticoids (GCs). However, there is limited data comparing the efficacy and outcomes of different IS agents for this purpose.
OBJECTIVES
In this study, we aimed to compare the outcomes of two most frequently used first-line IS agents, namely methotrexate (MTX) and azathioprine (AZA) in TAK patients.
METHODS
TAK patients who received any IS agent in addition to GCs as the initial therapy were included in this multicentre, retrospective cohort study. Clinical, laboratory and imaging data of the patients were assessed. In addition, a matched analysis (cc match) using variables 'age', 'gender' and 'diffuse aortic involvement' was performed between patients who received MTX or AZA as the first-line IS treatment.
RESULTS
We recruited 301 patients (F/M: 260/41, mean age: 42.2 ± 13.3 years) from 10 tertiary centres. As the first-line IS agent, 204 (67.8 %) patients received MTX, and 77 (25.6 %) received AZA. Less frequently used IS agents included cyclophosphamide in 17 (5.6 %), leflunomide in 2 (0.5 %) and mycophenolate mofetil in one patient. The remission, relapse, radiographic progression and adverse effect rates were similar between patients who received MTX and AZA as the first-line IS agent. Vascular surgery rate was significantly higher in the AZA group (23% vs. 9 %, p = 0.001), whereas the frequency of patients receiving ≤5 mg/day GCs at the end of the follow-up was significantly higher in the MTX group (76% vs 62 %, p = 0.034). Similarly, the rate of vascular surgery was higher in AZA group in matched analysis. Drug survival was similar between MTX and AZA groups (median 48 months, MTX vs AZA: 32% vs 42 %, p = 0.34). IS therapy was discontinued in 18 (12 MTX, 6 AZA) patients during the follow-up period due to remission. Among those patients, two patients had a relapse at 2 and 6 months, while 16 patients were still on remission at the end of a mean 69.4 (±50.9) months of follow-up.
CONCLUSIONS
Remission, relapse, radiographic progression and drug survival rates of AZA and MTX were similar for patients with TAK receiving an IS agent as the first-line f therapy. The rate of vascular surgery was higher and the rate of GC dose reduction was lower with AZA compared to MTX at the end of the follow-up.
Topics: Humans; Takayasu Arteritis; Female; Male; Adult; Azathioprine; Methotrexate; Immunosuppressive Agents; Retrospective Studies; Middle Aged; Treatment Outcome; Glucocorticoids
PubMed: 38669786
DOI: 10.1016/j.semarthrit.2024.152446 -
Value in Health Regional Issues Jul 2024To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system.
OBJECTIVES
To evaluate cost-effective pharmacological treatment in adult kidney transplant recipients from the perspective of the Colombian health system.
METHODS
A decision tree model for the induction phase and a Markov model for the maintenance phase were built. A review of the clinical literature was conducted to extract probabilities, and the life-years were used as the outcome. Costs were calculated using the administrative databases. The evaluating treatment schemes are organized by groups of evidence with direct comparisons.
RESULTS
In the induction phase, anti-thymocyte immunoglobulin+ methylprednisolone is dominant, more effective, and less expensive, compared with basiliximab+methylprednisolone. In the maintenance phase, azathioprine (AZA) is dominant in contrast to mycophenolate mofetil (MFM) both with cyclosporine (CIC)+ corticosteroids (CE); CIC is dominant relative to sirolimus (SIR) and tacrolimus (TAC) (both with MFM+CE or AZA+CE), and TAC is dominant compared with SIR (in addition with MFM+CE or mycophenolate sodium [MFS]+CE); MFM is dominant in relation to MFS and everolimus, and SIR is more effective MFM but it does not exceed the threshold (in sum with TAC+CE); MFS and MFM are dominant relative to everolimus, and SIR is more effective than MFM, but it does not exceed the threshold (in addiction with CIC+CE); MFM is dominant in relation to TAC (in sum with SIR+CE), and CIC+AZA+CE is dominant in relation to TAC+MFM+CE.
CONCLUSIONS
The base-case results for all evidence groups are consistent with the different sensitivity analyses.
Topics: Humans; Kidney Transplantation; Colombia; Cost-Benefit Analysis; Immunosuppressive Agents; Adult; Cyclosporine; Mycophenolic Acid; Tacrolimus; Azathioprine; Markov Chains; Decision Trees; Graft Rejection; Sirolimus; Transplant Recipients; Adrenal Cortex Hormones; Cost-Effectiveness Analysis
PubMed: 38663057
DOI: 10.1016/j.vhri.2024.02.001