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Post-renal transplant malignancies: Opportunities for prevention and early screening.
Turshudzhyan, A
Cancer treatment and research communications. 2021;:100283
Abstract
GOAL OF THE REVIEW While transplant recipients are aware of increased malignancy risk, there is little consensus on the preventative measures. The goal of this review is to bring available preventative measures to light and prompt more research to be done with ultimate goal of developing an individualized prevention plan for each patient based on risk factors and available screening tools. INTRODUCTION Transplant surgery offers patients with end-stage renal disease a longer life expectancy with help of immunosuppressive therapies. Nonetheless, life-long immunosuppression comes at a cost of post-renal transplant malignancies, which have become the leading cause of morbidity in this patient group. DISCUSSION Post-renal transplant cancers can develop through either de novo, by donor-related transmission, or recurrence of recipient's pre-transplant cancer. While immunosuppressive therapy is considered to be the leading cause, weakened immunosurveillance of neoplastic cells and inadequate immune response against oncogenic viruses also plays an important role. The most common cancers seen in renal transplant patients are skin cancers and post-transplant lymphoproliferative disorder (PTLD). Risk factors for skin cancers have are ultraviolet light, human papilloma virus infection, and use of cyclosporin and azathioprine. Numerous viral infections have been associated with transplant-related malignancies post-transplant. CONCLUSION While lowering of immunosuppressive therapy remains the treatment of choice, it may lead to graft failure. Given some of the presented malignancies have modifiable risk factors and options for screening, clinical outcomes can be improved. Limiting skin exposure, dermatologic screening, and prophylactic retinoids can help lower the incidence rate of skin malignancy. Endoscopic screening for renal transplant patients can help identify gastric adenocarcinoma early and improve survival rates. Some of the post-transplant malignancies have been responsive to anti-viral treatment.
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Optimal inflammatory bowel disease management during the global coronavirus disease 2019 pandemic.
El Ouali, S, Rubin, DT, Cohen, BL, Regueiro, MD, Rieder, F
Current opinion in gastroenterology. 2021;(4):313-319
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PURPOSE OF REVIEW This review aims to summarize the current evidence regarding the risks and implications of coronavirus disease 2019 (COVID-19) in patients with inflammatory bowel disease (IBD) and discuss optimal management of IBD during this pandemic. RECENT FINDINGS Patients with IBD are not at increased risk of COVID-19 but several risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection) have been identified, such as active IBD, obesity, and corticosteroid use. COVID-19 outcomes are similar among patients with IBD and the overall population. Although biologics have not been shown to increase the risk of severe COVID-19 complications, several risk factors have been associated with negative COVID-19 outcomes in patients with IBD, including older age, obesity, the presence of comorbidities, active disease, and corticosteroid use. IBD therapy should, therefore, be continued with the aim of attaining or maintaining remission, except for corticosteroids, which should be held or reduced to the minimal effective dose. Although it has been recommended that immunosuppressive therapy be held during a case of COVID-19, the half-lives of these drugs and data on the timing of restarting therapy limit the strength of these recommendations. We recommend COVID-19 vaccination for IBD patients whenever available, as benefits to the individual and to society outweigh the risks. SUMMARY As our understanding of SARS-CoV-2 and COVID-19 continues to evolve, we are learning more about its impact in patients with IBD and how to better manage patients in this setting. Managing IBD during this pandemic has also highlighted the importance of restructuring services in order to adapt to current and potential future outbreaks. The COVID-19 pandemic has transformed IBD care through the expansion of telemedicine and development of novel approaches to remote monitoring.
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IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome.
Trautmann, A, Vivarelli, M, Samuel, S, Gipson, D, Sinha, A, Schaefer, F, Hui, NK, Boyer, O, Saleem, MA, Feltran, L, et al
Pediatric nephrology (Berlin, Germany). 2020;(8):1529-1561
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Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given.
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Targeting immunometabolism as an anti-inflammatory strategy.
Pålsson-McDermott, EM, O'Neill, LAJ
Cell research. 2020;(4):300-314
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The growing field of immunometabolism has taught us how metabolic cellular reactions and processes not only provide a means to generate ATP and biosynthetic precursors, but are also a way of controlling immunity and inflammation. Metabolic reprogramming of immune cells is essential for both inflammatory as well as anti-inflammatory responses. Four anti-inflammatory therapies, DMF, Metformin, Methotrexate and Rapamycin all work by affecting metabolism and/or regulating or mimicking endogenous metabolites with anti-inflammatory effects. Evidence is emerging for the targeting of specific metabolic events as a strategy to limit inflammation in different contexts. Here we discuss these recent developments and speculate on the prospect of targeting immunometabolism in the effort to develop novel anti-inflammatory therapeutics. As accumulating evidence for roles of an intricate and elaborate network of metabolic processes, including lipid, amino acid and nucleotide metabolism provides key focal points for developing new therapies, we here turn our attention to glycolysis and the TCA cycle to provide examples of how metabolic intermediates and enzymes can provide potential novel therapeutic targets.
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Tacrolimus-induced diabetic ketoacidosis with subsequent rapid recovery of endogenous insulin secretion after cessation of tacrolimus: A case report with review of literature.
Maruyama, K, Chujo, D
Medicine. 2019;(36):e16992
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RATIONALE Immunosuppressive agents such as tacrolimus (TAC) and cyclosporin might cause glycemic disorders by suppressing insulin production. However, only a few cases of diabetic ketoacidosis (DKA) with longitudinal evaluation of endogenous insulin secretion related to TAC administration have been reported. PATIENT CONCERNS A 59-year-old Asian woman, who received prednisolone and TAC 4.0 mg for the treatment of anti-aminoacyl-tRNA synthetase antibody-positive interstitial pneumonia, was admitted to our hospital due to impaired consciousness and general malaise. DIAGNOSES She had metabolic acidosis; her plasma glucose, fasting serum C-peptide immunoreactivity (CPR), and urinary CPR levels were 989 mg/dL (54.9 mmol/L), 0.62 ng/mL, and 13.4 μg/d, respectively. No islet-related autoantibodies were detected. Therefore, she was diagnosed with TAC-induced DKA. INTERVENTION Intravenous continuous insulin infusion and rapid saline infusion were administered. TAC was discontinued because of its diabetogenic potential. OUTCOMES Sixteen weeks after cessation of TAC administration, she showed good glycemic control without administration of insulin or any oral hypoglycemic agents; her serum CPR level also improved dramatically. These findings suggested that TAC-induced pancreatic beta cell toxicity is reversible. LESSONS We reported a case of TAC-induced DKA with subsequent recovery of pancreatic beta cell function after cessation of TAC, resulting in good glycemic control. As TAC is widely used, we should pay attention to patients' glucose levels even though the TAC concentrations used are within the target range. Furthermore, dose reduction or cessation of TAC should be considered if hyperglycemia is detected during administration of this agent.
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One year in review 2019: Behçet's syndrome.
Hatemi, G, Seyahi, E, Fresko, I, Talarico, R, Hamuryudan, V
Clinical and experimental rheumatology. 2019;(6):3-17
Abstract
Several epidemiologic studies report on the prevalence of Behçet's syndrome (BS) and demographic and clinical findings in patients from different countries and ethnicities. Although these studies point out geographic differences in disease course, methodologic differences make it difficult to compare the results of these studies. Recent data suggest that neutrophil extracellular trap levels are elevated in patients with BS, and that it may be a potential therapeutic target for the reduction or prevention of BS-associated thrombotic risk. Details on the mode of functioning of ERAP have been delineated and further epigenetic data reported. Wall thickness of lower extremity veins is increased among BS patients without any apparent clinical involvement. Magnetic resonance (MR) venography and Doppler ultrasonography (USG) were comparable in the diagnosis of chronic deep vein thrombosis, while MR venography is more effective in detecting collateral formations. Results were also collected on some dietary and non-dietary factors in triggering oral ulcers, while smoking seems to have a protective role. With regards to the therapy, it has been demonstrated that endovascular interventions carry the risk of inducing pathergy phenomenon. Apremilast has been convincingly shown to be useful for oral ulcers of BS and classical immunosuppressives are effective as first line therapy in more than half of patients with uveitis. While infliximab and adalimumab seem to be equally effective in the treatment of refractory uveitis of BS, the combination of adalimumab and immunosuppressives appears to be superior to immunosuppressives alone for venous thrombosis of the extremities. In addition, tocilizumab might be an alternative to anti-TNF agents for patients with arterial involvement refractory to immunosuppressives. On the other hand, the place of IL-17 inhibition in the treatment of BS still remains questionable.
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TREATMENT STRATEGIES AND OUTCOME OF PARVOVIRUS B19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS: A CASE SERIES AND LITERATURE REVIEW OF 128 PATIENTS.
Rosado-Canto, R, Carrillo-Pérez, DL, Jiménez, JV, Cuellar-Rodríguez, J, Parra-Avila, I, Alberú, J, Morales-Buenrostro, LE
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion. 2019;(4):265-274
Abstract
BACKGROUND There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. OBJECTIVE The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. METHODS We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. RESULTS In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. CONCLUSIONS In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.
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Intravenous Cyclophosphamide for Gastric Antral Vascular Ectasia Associated with Systemic Sclerosis Refractory to Endoscopic Treatment: A Case Report and Review of the Pertinent Literature.
Matsumoto, Y, Hayashi, H, Tahara, K, Yasuda, T, Tsubouchi, S, Yamamoto, Y, Mizuuchi, T, Mori, H, Sawada, T
Internal medicine (Tokyo, Japan). 2019;(1):135-139
Abstract
Gastric antral vascular ectasia (GAVE) is a rare cause of chronic gastric hemorrhaging and iron deficiency anemia and is characterized by a distinctive endoscopic appearance. The main treatment of GAVE is endoscopic; however, medication is necessary in refractory cases. We herein report a 69-year-old woman with systemic sclerosis (SSc) who developed recurrent severe anemia after endoscopic treatment of GAVE that was successfully managed using intravenous cyclophosphamide (IVCY). The recurrence of GAVE after discontinuation of IVCY was successfully managed using a combination of IVCY and endoscopic treatment, without blood transfusion. Long-term IVCY may be indicated for refractory GAVE associated with SSc.
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Cyclosporine A and amlodipine induced gingival overgrowth in a kidney transplant recipient: case presentation with literature review.
Nanda, T, Singh, B, Sharma, P, Arora, KS
BMJ case reports. 2019;(5)
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Drug-induced gingival overgrowth is a condition caused by side effects of treatment with one of three types of drugs: phenytoin (used in epilepsy treatment), cyclosporine A (used in transplantology after allogenic organ transplants) and calcium channel blockers (used in the treatment of hypertension). Gingival overgrowth leads to inflammation within the gums and periodontium and can amplify the existing periodontal disease leading to tooth loss. Patients who have undergone kidney transplant are given immunosuppressants to prevent transplant rejection and mostly it is accompanied with calcium channel blockers to treat hypertension associated with kidney transplant. This article reports a case of recent gingival enlargement associated with cyclosporine A and amlodipine given to a kidney transplant patient from the past 11 years.
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European Crohn's and Colitis Organisation Topical Review on Treatment Withdrawal ['Exit Strategies'] in Inflammatory Bowel Disease.
Doherty, G, Katsanos, KH, Burisch, J, Allez, M, Papamichael, K, Stallmach, A, Mao, R, Berset, IP, Gisbert, JP, Sebastian, S, et al
Journal of Crohn's & colitis. 2018;(1):17-31
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Clinically effective therapies now exist for remission maintenance in both ulcerative colitis [UC] and Crohn's Disease [CD]. For each major class of IBD medications [5-aminosalicyclates, immunomodulators, and biologic agents], used alone or in combination, there is a risk of relapse following reduction or cessation of treatment. A consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the published literature and agreed a series of consensus practice points. The objective of the expert consensus is to provide evidence-based guidance for clinical practice so that physicians can make informed decisions in partnership with their patients. The likelihood of relapse with stopping each class of IBD medication is reviewed. Factors associated with an altered risk of relapse with withdrawal are evaluated, and strategies to monitor and allow early identification of relapse are considered. In general, patients in clinical, biochemical, and endoscopic remission are more likely to remain well when treatments are stopped. Reintroduction of the same treatment is usually, but not always, successful. The decision to stop a treatment needs to be individualized, and shared decision making with the patient should take place.