Immunosuppressive Drugs Research Articles

The Ameliorative Effect of Betulinic Acid on Oxidative Stress in Mice of Cyclophosphamide-Induced Liver Damage.

As a conventional immunosuppressive drug, cyclophosphamide (CYP) exhibits strong hepatotoxicity in clinical applications. Betulinic acid (BA) is a natural triterpenoid that protects against liver damage. However, the underlying mechanism has not yet been elucidated. The purpose of this study was to evaluate the ameliorative effects of BA on CYP-induced hepatotoxicity and further clarify the underlying mechanism. BA pretreatment mitigated CYP-induced liver oxidative damage by alleviating histopathological lesions, reducing reactive oxygen species (ROS) accumulation, and restoring the mRNA expression of antioxidant enzymes (Cu-Sod, Mn-Sod, Cat, and Gsh-Px). BA treatment also suppressed CYP-induced oxidative stress by activating the NRF2 pathway and inhibiting the MAPK signaling pathway. Moreover, BA attenuated CYP-triggered hepatic apoptosis by suppressing excessive mitochondrial fission, boosting mitochondrial fusion, and ameliorating pro-apoptotic protein expression (CASP9 and the ratio of BCL-2/BAX) by blocking the oxidative stress-activated mitochondrial apoptotic pathway. Furthermore, PD98059 (an inhibitor of ERK) and/or BA abated CYP-provoked hepatotoxicity by inhibiting the ERK-MAPK and mitochondrial apoptotic pathways, implying that deactivation of the ERK-mediated mitochondrial apoptotic pathway contributed to the hepatoprotective efficacy of BA against CYP-induced oxidative stress. Therefore, BA could be used as a complementary medicine in patients undergoing CYP treatment owing to its hepatoprotective effects.

Alternate Sampling Matrices for Therapeutic Drug Monitoring of Immunosuppressants.

Immunosuppressant (IS) therapeutic drug monitoring (TDM) relies on measuring mostly pharmacologically inactive erythrocyte-bound and/or plasma protein-bound drug levels. Variations in hematocrit and plasma protein levels complicate interpretation of blood calcineurin inhibitor (CNI) and inhibitors of themolecular target of rapamycin (mTORi) concentrations. Variable binding of mycophenolic acid (MPA) to albumin similarly complicates its TDM in plasma. A different matrix may improve IS concentration-response relationships and better reflect exposures at sites of action. This review explores the evidence for IS TDM using peripheral blood mononuclear cell (PBMC), graft tissue, and total or unbound plasma concentrations. Tandem mass spectrometry provides the sensitivity for assessing these matrices. But several challenges must be addressed, including minimizing hemolysis during blood collection, preventing IS efflux during PBMC preparation, and determining the need for further purification of the PBMC fraction. Assessing and reducing nonspecific binding during separation of unbound IS are also necessary, especially for lipophilic CNIs/mTORi. Although TDM using PBMC or unbound plasma concentrations may not be feasible due to increased costs, plasma CNI/mTORi levels may be more easily integrated into routine TDM. However, no validated TDM targets currently exist, and published models to adjust blood CNI/mTORi concentrations for hematocrit or to predict PBMC, and total and unbound plasma IS concentrations have yet to be validated in terms of measured concentrations or prediction of clinical outcomes. Even if CNI/mTORi measurements in novel matrices do not become routine, they may help refine pharmacokinetic-pharmacodynamic relationships and improve mathematical models for TDM using whole blood. Notably, there is evidence to support measuring unbound MPA in patients with severe renal dysfunction, hypoalbuminemia, and hyperbilirubinemia, with some proposed TDM targets.

SNMMI PIC case competition finalist: Subcutaneous Panniculitis-Like T-Cell Lymphoma on 18F-FDG PET/CT

Abstract A 9-month-old girl was evaluated for recurrent fevers, rash, and indurated plaques, with laboratories demonstrating hyperferritinemia, hypertriglyceridemia, and pancytopenia, concerning for hemophagocytic lymphohistiocytosis. Biopsy of thigh lesion ultimately demonstrated subcutaneous panniculitis-like T-cell lymphoma. In a rare neoplasm of cytotoxic T-cells, subcutaneous panniculitis-like T-cell lymphoma presents with subcutaneous nodules in all age groups including children. Prognosis is generally good with immunosuppressive drugs being first line of treatment. 18F-FDG PET/CT demonstrates hypermetabolic lesions and is used to determine the extent of disease burden, identify sites of occult disease, and assess response to treatment.

Trial protocol for SiroSkin: a randomised double-blind placebo-controlled trial of topical sirolimus in chemoprevention of facial squamous cell carcinomas in solid organ transplant recipients

BackgroundKeratinocyte carcinomas such as basal cell carcinomas and squamous cell carcinomas are a major burden affecting morbidity and mortality in solid organ transplant recipients (SOTRs). Best treatment includes frequent skin checks for early detection and surgery for high incidence of skin cancers.Sirolimus is an immunosuppressive drug which may reduce the burden of skin cancer but may be poorly tolerated when given orally. Topical sirolimus has been proven effective at reducing the burden of skin cancers in animal models, and its safety has long been established in children with tuberous sclerosis. A recent 12-week phase II trial of topical sirolimus suggested it was safe and effective at reducing the early signs of skin cancer in the absence of major side effects. The aim of the SiroSkin trial is to determine whether topical sirolimus can fill a major gap in current therapies by reducing the onset and number of new skin cancers thus reducing burden of disease and cost-effectiveness.MethodsProtocol for a multi-centred phase III, participant- and clinician assessor-blinded, placebo-controlled randomised trial in SOTRs. A minimum 146 participants randomised 1:1 will be treated with 1% topical sirolimus versus placebo applied to the face on a regular basis for 24 weeks. Participation is 24 months in total—24 weeks of treatment and 18 months of follow-up. Outcomes include the number of keratinocyte carcinomas at 24 weeks of treatment compared to placebo and then at 12 and 24 months after initiation of treatment. Analysis will be as per protocol and intention to treat.DiscussionThe results of this trial will inform management strategies for skin cancers in SOTRs and provide evidence for cost-effectiveness.Trial registrationClinicaltrials.gov NCT05860881. Registered on June 15, 2023, and on anzctr.org.au (registration number NCT05860881).

Exploring the Potential of Stem Cells to Enhance Conventional Cancer Therapies

Abstract. Stem cell-based therapies are emerging as promising adjuncts to conventional cancer treatments, offering innovative strategies to target cancer cells and enhance patient recovery. This paper explores the potential of stem cells, particularly mesenchymal stem cells (MSCs) and human umbilical cord mesenchymal stem cells (HUCMCs), to improve cancer treatment outcomes through their regenerative and differentiation capabilities. MSCs exhibit significant promise due to their ability to inhibit tumor growth, support tissue regeneration, and modulate immune responses. Their unique features, including targeted homing to tumor sites and the secretion of bioactive molecules, present novel approaches to overcoming the limitations of traditional therapies. Despite these advancements, challenges such as immune rejection and tumorigenicity must be addressed. Current strategies to mitigate these issues involve immunosuppressive drugs, genetic engineering, and advanced technologies like CRISPR-Cas9. However, the reviewed studies often involve small sample sizes or remain in the laboratory phase, limiting the generalizability of findings. Future research should focus on larger-scale clinical trials to validate the effectiveness and safety of stem cell therapies, aiming to refine these treatments and integrate them into clinical practice.

A case of superior trunk brachial plexus injury after right mini-thoracotomy mitral valve repair.

We report a case of superior trunk brachial plexus injury following a right mini-thoracotomy mitral valve repair. A 45-year-old woman with systemic lupus erythematosus, who was on steroids and immunosuppressive drugs, underwent mitral valve repair via right mini-thoracotomy. The patient was positioned in the left semisagital position with the right upper arm elevated. Postoperatively, she exhibited focal motor and sensory deficits in the right upper extremity, and a superior trunk brachial plexus injury (BPI) on the right side was diagnosed through brachial plexus MRI and electrophysiological examination. The nerve injury was likely due to excessive left lateral flexion of the head during the procedure. Sensation returned to normal 4 weeks postoperatively, and muscle strength fully recovered 3 months postoperatively. Careful attention to positioning during minimally invasive cardiac surgery is crucial to prevent nerve compression in superficial areas and excessive lateral flexion of the head.

The Research and Application Progress of Heterologous Liver Transplantation

Liver transplantation is an effective treatment for various end-stage liver diseases, and the shortage of donor livers is one of the main obstacles affecting the development of liver transplantation. Xenotransplantation holds promise as a potential solution to the organ shortage. By using gene-editing technology to modify animal genes, their physiological compatibility with humans can be improved. Combining this with new immunosuppressive drugs can reduce the occurrence of rejection, thereby increasing the survival time of the graft. Due to the more complex structure and physiological functions of the liver, inter-species incompatibility is more pronounced in liver xenotransplantation compared to heart or kidney. The molecular mechanisms related to xenograft rejection and coagulation disorders post-operation require further research. This article reviews the latest research progress domestically and internationally, the historical development of liver xenotransplantation, the main current challenges, and clinical applications, aiming to enhance clinicians' understanding of liver xenotransplantation.

Epidemiology and pathogen characteristics of infections following solid organ transplantation.

Solid organ transplantation (SOT) recipients have a heightened risk for infection due to prolonged immunosuppressive drug use following transplant procedures. The occurrence of post-transplant infections is influenced not only by the transplanted organ type but also by varied factors. The kidney is the most common organ in SOT, followed by the liver, heart, and lung. This review aims to provide a comprehensive overview of the current epidemiological characteristics of infections after kidney, liver, heart, and lung transplantation, focusing on bacterial, fungal, and viral infections. The incidence and infection types demonstrated significant variability across different SOTs. Furthermore, this review attempts to elucidate the clinical characteristics of infections across patients following different SOTs and contribute to the development of individualized prevention strategies according to infection incidence, ultimately enhancing the quality of life of transplant recipients.

Therapeutic Drug Monitoring of Immunosuppressive Drugs: A Field Constantly in Motion

Therapeutic Drug Monitoring of Immunosuppressive Drugs: A Field Constantly in Motion

What is proven in the treatment of complement-mediated kidney diseases?

Complement-mediated kidney diseases encompass acomplex group of diseases that are primarily caused by dysregulation of the complement system. The complement system is acrucial component of the innate immune system consisting of soluble and membrane-bound proteins. The complement system is essential for the defence against pathogens and homeostasis but its uncontrolled activation can lead to an exaggerated cellular response to immunogenic, inflammatory and metabolic stimuli. For example, glomerular deposition of immune complexes can activate the complement system and contribute to the progression of kidney diseases. The most well-known complement-mediated kidney diseases are atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy, which falls under the group of membranoproliferative glomerulonephritis (MPGN). Diagnosing these diseases requires detailed investigations with respect to triggering factors, including genetic analyses and the measurement of specific complement factors. New therapeutic approaches with drugs targeting complement system activation are now offering promising treatment options. These medications fundamentally differ from other immunosuppressive drugs and specifically target the pathological processes within the complement system. This article provides an overview of the mechanisms of complement regulation, the pathophysiological foundations of complement-mediated kidney diseases and the latest diagnostic and therapeutic advances. The goal is to provide adeeper understanding of these complex conditions and to emphasize the importance of an interdisciplinary approach in treatment and research.

Immunosuppressive Drugs in Early Limited Cutaneous Systemic Sclerosis May Prevent Global Damage Accrual.

Organ damage in systemic sclerosis (SSc) in individual organs such as the lungs may be prevented by immunosuppressive drugs (IS). A new measure of global organ damage, the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI), has allowed us to investigate whether IS may reduce global organ damage accrual in early SSc. This was a retrospective study of patients with < 2 years disease duration in Canadian and Australian SSc cohorts. Patients with either limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc were observed separately and divided into ever or never exposed to IS groups. The SCTC-DI was the outcome and inverse probability of treatment weighting (IPTW) was used to balance the study groups and to fit a marginal structural generalized estimating equation (GEE) model. In the lcSSc cohort, there were 210 subjects of which 34% were exposed to IS at some time. Exposure to IS was associated with lower damage scores. In the dcSSc cohort, there were 192 subjects of which 76% were exposed to IS at some time. Exposure to IS was not associated with damage scores. In this retrospective observational cohort study, using IPTW to adjust for confounders, we found a protective effect of the use of IS on damage accrual in lcSSc. We were unable to determine such an effect in dcSSc but unknown confounders may have been present and prospective studies of IS in dcSSc should include the SCTC-DI to determine the possible effect of IS on damage accrual.

Protein-losing enteropathy as the first presentation of systemic lupus erythematosus as the first case reported in Palestine, case report with systematic review

Introduction: Systemic lupus erythematosus is a chronic inflammatory disease affecting women, causing gastrointestinal issues like acute pancreatitis, esophagitis, and protein-losing enteropathy. Protein loss is uncommon, but a case study shows protein losing enteropathy as a first sign. Importance: Protein-losing enteropathy (PLE) is a rare gastrointestinal manifestation of SLE, often seen years before diagnosis. Suspecting hypoalbuminemia without protein loss is crucial, but diagnosis is challenging due to imaging and histological findings. Case presentation: A 22-year-old woman with epigastric pain experienced sudden abdominal pain, vomiting, and arthralgia. An abdominal CT scan revealed moderate bilateral hydronephrosis, pelvic free fluid, a kidney stone, and a cyst. Laboratory tests showed normal hemoglobin levels, platelets, white blood cells, C-reactive protein, and ESR. Diagnosis of SLE was confirmed, and pulse steroid therapy and hydroxychloroquine were initiated. Severe ascites required pigtail insertion, and Ceftazidime was added. The patient’s condition improved, and she was discharged with regular follow-ups. Clinical discussion: A 22-year-old female was diagnosed with protein-losing enteropathy, a rare gastrointestinal manifestation of Systemic Lupus erythematosus (SLE). The disease is divided into mesenteric vasculitis, pseudo obstruction, and protein loss enteropathy. The patient also had severe enteritis, abdominal pain, nausea, and diarrhea. The study found that the main complaint was abdominal pain with dysphagia, mainly due to active SLE inflammation. The patient responded well to treatment, with a 62.5% rapid improvement in pulse steroids and a cure for underlying causes through DMARDS or immunosuppressant drugs. Conclusions: The case presents a rare SLE diagnosis with gastrointestinal involvement, pleural effusion, and progressive swelling. Despite correct diagnosis and aggressive treatment, clinical improvement occurred, requiring high clinical suspicion.

Patiromer Does Not Alter Tacrolimus Pharmacokinetics in Kidney Transplant Recipients When Administered Three Hours Post-Tacrolimus.

Hyperkalemia is common in kidney transplant (KTx) recipients. Patiromer, a potassium-binding polymer used to treat acute and chronic hyperkalemia, has the potential to bind charged particles in the gastrointestinal tract and thereby potentially affect the absorption of coadministered drugs. The immunosuppressive drug tacrolimus (Tac) has a narrow therapeutic window, is susceptible to drug-drug interactions (DDIs), and a potential gastrointestinal interaction with patiromer could elevate the risk of allograft rejection. We aimed to investigate the potential DDI between patiromer and Tac pharmacokinetics in KTx with hyperkalemia by sampling capillary blood using volumetric absorptive microsampling (VAMS). Thirteen KTx recipients on Tac twice daily (BID) with plasma potassium levels of >4.6 mmol/L were included. Two 12 h Tac pharmacokinetic investigations were performed with and without 8.4 mg patiromer/d for 1 wk. Oral Tac dose remained unchanged and patiromer was administered 3 h after Tac dose. Tac sampling was self-conducted using VAMS after mastering the technique. Ten patients provided 2 evaluable pharmacokinetic profiles. The Tac area under the curve (AUC)0-12 ratio (AUCTac+patiromer/AUCTac) was 0.99 (90% confidence interval [CI], 0.86-1.14), and the Cmax ratio was 1.01 (90% CI, 0.86-1.19). Tac C0 and C12 fulfilled the bioequivalence criteria with a ratio of 0.98 (90% CI, 0.90-1.07) and 0.93 (90% CI, 0.83-1.04), respectively. When administered 3 h after the Tac morning dose, patiromer has no clinically relevant impact on Tac pharmacokinetics. We demonstrate that VAMS is a well-suited sampling method to simplify the execution of DDI studies.

Abstract 4138738: Clinical Evidence of Immune Response to Transplanted Allogeneic iPS Cell-Derived Cardiomyocytes

Background&amp;Purpose: The clinical application of cell transplantation therapy utilizing induced pluripotent stem cells (iPS cells) for heart failure is progressing, with the primary strategy being the use of pre-prepared allogeneic iPS cells. The immune response to these transplanted cells is crucial and may affect therapeutic efficacy, necessitating the use of immunosuppressive drugs. However, detailed clinical reports on immune responses are sparse. This study aims to analyze the immune response to transplanted cells in clinical iPS cell-derived cardiomyocyte (iPSC-CM) transplants and examine the correlation between immune response and therapeutic efficacy. Methods: In the "Phase 1 multicenter clinical trial of transplantation of iPSC-CMs for ischemic cardiomyopathy" (https://jrct.niph.go.jp/en-latest-detail/jRCT2053190081), conducted as the First-in-Human trial, the immune response to transplanted cells was analyzed in four cases at our hospital. Comprehensive analysis of anti-human leukocyte antigen (HLA) antibodies in serum and single-cell RNA sequencing in peripheral blood mononuclear cells was performed to investigate their relationship with therapeutic effects on cardiac function. Results: Patients received immunosuppressive drugs (tacrolimus, mycophenolate mofetil, and steroids) for 3 months post-transplantation, followed by a 1-year follow-up. In all cases, an increase in transplant cell HLA-specific antibodies was observed after discontinuing immunosuppressive drugs (Figure 1 and 2). Single-cell analysis revealed a decrease in immunocompetent cells in peripheral blood during immunosuppressive therapy. Cardiac function analysis showed improvements in all cases except Case 2 (Figure 3), where pre-existing anti-HLA-DQ antibodies were present before transplantation. Conclusions: No immune response to the transplanted cells was observed during immunosuppressive therapy. In a case with limited therapeutic response, pre-existing antibodies to transplanted cells were detected, potentially impacting the therapeutic outcome.

Pathophysiology of De Novo Food Allergies After Solid Organ Transplant in Pediatric Patients.

De novo food allergy is a common phenomenon among pediatric solid organ recipients (8.5%-57%) when compared with the general population (0.45%-10%). Other associated disorders include non-IgE-mediated immune reactions and clinical predisposition to asthma and alterations in the oral mucosa. Originally, passive mechanisms (passive transfer of IgE and immune cells) were thought to be responsible for acute, transient cases of food allergies with a previous history of sensitization for a specific allergen in the donor. Recently proposed pathophysiological mechanisms to explain de novo allergies include TH2/B-cell imbalance, regulatory T-cell (Treg) disruption, gastrointestinal immaturity, and altered gastrointestinal permeability. Recent studies also suggest that immunosuppressive drugs, especially tacrolimus, promote naïve T-cell differentiation into TH2 cells, IgE-promoting cytokine production, decreased IL-5 and IL-10 levels, increased IgA levels, and Treg disruption. Such immunological interactions, in conjunction with altered intestinal permeability, intestinal immaturity in children, history of viral infection, and a personal history of allergies or eczema, are thought to explain most clinical cases of pediatric de novo food allergy after solid organ transplantation reported in the literature. A better understanding of the immunological mechanisms underpinning organ donors and recipients may unveil some of the caveats concerning therapeutic management and improve the quality of life of affected individuals.

Residual cholesteatoma of the temporal bone in a patient with granulomatosis with polyangiitis

A case of residual temporal bone cholesteatoma in a patient with granulomatosis with polyangiitis (Wegener) (GPA) is presented. At the onset of the disease, the patient developed a symptom complex, which included, along with sinonasal manifestations, left-sided purulent otitis media, refractory to traditional therapy. A separate atticoanthrotomy on the left temporal bone, performed in the active phase, before the diagnosis of vasculitis, did not lead to a clinical improvement in the condition of the middle ear. Despite the subsequent implementation of adequate immunosuppressive therapy and drug remission of GPA, the continuously recurrent course of purulent otitis media of the operated ear contributed to the development of residual cholesteatoma of the temporal bone with the spread of the process to surrounding structures. The presence of cholesteatoma was confirmed by MRI of the temporal bones in the non-EPI DWI mode. During the period of drug remission of GPA, repeated sanitizing surgery was performed on the middle ear with tympanoplasty and obliteration of the parathympanic spaces, which made it possible to achieve remission of purulent otitis media. The development of residual middle ear cholesteatoma in a patient with GPA could be due to the untimely initial diagnosis, the late onset of specific immunotherapy, the rapidly progressive and recurrent nature of the course of the disease, and surgical treatment in the phase of high disease activity. The insufficient volume of primary surgical treatment contributed to the formation of laced cavities and the development of residual cholesteatoma of the temporal bone. The use of MRI in the non-EPI DWI mode for diagnosis made it possible to identify the development of cholesteatoma of the left temporal bone in a patient with GPA and track the results of surgical treatment in the postoperative period. The non-EPI DWI MRI method proved effective both for detecting temporal bone cholesteatoma and tracking changes in the postoperative period of a patient with GPA. Tympanoplasty with surgical obliteration of the parathympanic spaces allowed to stop the inflammation of the middle ear in a patient with a systemic autoimmune disease.

Mesenchymal stem cell application in pulmonary disease treatment with emphasis on their interaction with lung-resident immune cells.

Due to the vital importance of the lungs, lung-related diseases and their control are very important. Severe inflammatory responses mediated by immune cells were among the leading causes of lung tissue pathology and damage during the COVID-19 pandemic. In addition, uncontrolled immune cell responses can lead to lung tissue damage in other infectious and non-infectious diseases. It is essential to control immune responses in a way that leads to homeostasis. Immunosuppressive drugs only suppress inflammatory responses and do not affect the homeostasis of reactions. The therapeutic application of mesenchymal stem cells (MSCs), in addition to restoring immune homeostasis, can promote the regeneration of lung tissue through the production of growth factors and differentiation into lung-related cells. However, the communication between MSCs and immune cells after treatment of pulmonary diseases is essential, and investigating this can help develop a clinical perspective. Different studies in the clinical phase showed that MSCs can reverse fibrosis, increase regeneration, promote airway remodeling, and reduce damage to lung tissue. The proliferation and differentiation potential of MSCs is one of the mechanisms of their therapeutic effects. Furthermore, they can secrete exosomes that affect the function of lung cells and immune cells and change their function. Another important mechanism is that MSCs reduce harmful inflammatory responses through communication with innate and adaptive immune cells, which leads to a shift of the immune system toward regulatory and hemostatic responses.

Case Report and Literature Review of Exophiala dermatitidis Fungal Endocarditis in a Prosthetic Aortic Valve

Abstract Prosthetic valve endocarditis is a rare complication following surgical aortic valve replacement, accounting for a small fraction of all endocarditis cases. This complication is typically caused by bacterial pathogens and carries a high mortality rate. In rare cases, prosthetic valve endocarditis may be attributed to fungal organisms. We present the case of a 47-year-old woman who developed prosthetic valve endocarditis from a fungus known as Exophiala dermatitidis. Prosthetic valve endocarditis caused by this pathogen is extremely rare, with only 3 previously reported cases of prosthetic valve endocarditis attributed to this fungus since 1969. Review of the previous literature revealed an additional 3 cases originating in native aortic valves. These cases tended to occur in relatively young patients and those with risk factors for infective endocarditis such as immunosuppression and intravenous drug use. Septic emboli to various organs, particularly the brain and spleen, appear to be a complication of fungal endocarditis caused by this organism. Management can be difficult due to the lack of guidelines to treat such rare infective complications, but replacement of the infected valve and a prolonged course of antifungal therapy appear to be effective in some cases.

Large inferior vena cava thrombosis in a 25-year-old female patient: A case report.

The incidence of venous thromboembolism is increasing, and it is more common in older than in younger patients. Inferior vena cava (IVC) thrombosis is a rare subtype of deep vein thrombosis, and it is associated with a high incidence of arterial and venous thrombosis in patients with systemic lupus erythematosus (SLE). We present the case of a 25-year-old female patient with a large IVC thrombosis caused by SLE that was intractable to thrombolytic therapy. A 25-year-old previously healthy female patient presented to the emergency department with a 5-day history of fever. Her computed tomography revealed a large thrombus with an approximate length 25 cm extending from the suprarenal IVC to the right common iliac vein and the left external and internal iliac veins. We decided to perform intravenous thrombolysis (alteplase 65 mg) because of the massive thrombus burden followed by an infusion of intravenous heparin. However, the size of the thrombus did not showed reduction 3 days after treatment. For the next step, the catheter-directed thrombolysis (CDT) was performed; however, no changes were observed. She was diagnosed with SLE, and the large IVC thrombus gradually improved after primary treatment for SLE, including immunosuppressive drugs combined with anticoagulant. We found a large IVC thrombus secondary to SLE in a young female patient. In this case, systemic thrombolysis or CDT did not improve the thrombus. The thrombus only improved after immunosuppressive treatment for SLE. Our case highlights the importance of treatment for etiologic disease in an intractable thrombosis developed by provoked cause.

Fraction of Cancer Attributable to Carcinogenic Drugs in Korea from 2015 to 2030.

This study aims to estimate and project the Population Attributable Fraction (PAF) of cancer incidence and death due to carcinogenic drug use in Korea from 2015 to 2030, to estimate the degree of cancer prevention from exposure to carcinogenic drugs in Korea. Selected carcinogenic drugs were immunosuppressive and antineoplastic drugs classified as group I by the International Agency for Research on Cancer (IARC). Systematic review and meta-analyses were conducted to estimate the relative risk (RR) of cancer associated with carcinogenic drug use. Age was standardized using the annual prevalence rate of the National Health Insurance Service sample cohort (NHIS-NSC) from 2002 to 2013 to calculate the standardized prevalence rate of carcinogenic drug use each year. The PAF of specific cancer incidence and death were calculated using Levin's formula and Monte Carlo methods. The prevalence rates were extrapolated to estimate the trend of PAF from 2015 to 2030. In 2015, carcinogenic drugs attributed to 0.003% and 0.002% among the causes of cancer incidence and death in Korea. However, carcinogenic drugs attributed to 1.1% among the causes of both cancer incidence and death in patients with clinical indications of carcinogenic drugs. The PAF in patients with clinical indications of carcinogenic drugs were significantly high and expected to increase rapidly over time. Since these drugs are listed as essential by the World Health Organization (WHO), and may be difficult to replace, a surveillance system on susceptible populations using group I carcinogenic drugs must be discussed and implemented.