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1.
Demystifying autoimmune small bowel enteropathy.
Elli, L, Ferretti, F, Vaira, V
Current opinion in gastroenterology. 2019;(3):243-249
Abstract
PURPOSE OF REVIEW We reviewed the current 'state of the art' on autoimmune enteropathy and small-bowel mucosal atrophy, with the aim of supporting clinicians in a frequently challenging diagnosis through different therapeutic options and prognosis. RECENT FINDINGS The diagnosis of small-bowel diseases has radically changed over the last 10 years. The possibility to 'easily' obtain bioptic samples from the jejunum and ileum by means of the enteroscopic techniques (particularly, device-assisted enteroscopy) and the novel cross-sectional imaging studies have opened the window to new insights on intestinal disorders. Consequentially, the detection of small-bowel mucosal atrophy has become a frequent finding in patients undergoing endoscopic investigation and its differential diagnosis can be challenging at times. Among the 'typical' causes of mucosal atrophy, autoimmune enteropathy has become more frequent than previously thought. However, the final diagnosis of autoimmune enteropathy is a 'puzzle' composed by serological, endoscopic, histological and molecular markers, which should be correctly dealt with in order to reach a certain diagnosis. SUMMARY In conclusion, there is an emerging body of literature about autoimmune enteropathy and small-bowel atrophy. The herein presented practical review on autoimmune enteropathy can be of help to clinicians in their daily practice.
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2.
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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Abstract
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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Use of Topical and Systemic Retinoids in Solid Organ Transplant Recipients: Update and Review of the Current Literature.
Herold, M, Good, AJ, Nielson, CB, Longo, MI
Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]. 2019;(12):1442-1449
Abstract
BACKGROUND Solid organ transplant recipients (SOTRs) are at an increased risk of epithelial malignancies, mainly squamous cell carcinoma, and its precursor lesions such as actinic keratoses, warts, and porokeratosis, which may respond to retinoid therapy. OBJECTIVE To review the published evidence on the efficacy and safety of topical and systemic retinoids for the treatment and prophylaxis of malignant and premalignant conditions that mostly afflict SOTRs. MATERIALS AND METHODS Systematic review of the literature to summarize the level of evidence and grade of recommendation for retinoid therapy with emphasis in the SOTR population. RESULTS Acitretin has the highest strength of recommendation (Grade A) for prophylaxis of nonmelanoma skin cancer (NMSC) and treatment and prophylaxis of actinic keratoses in SOTR. In nonimmunosuppressed patients, acitretin and isotretinoin have a Grade B recommendation for treatment of recalcitrant warts. Topical retinoids have not shown efficacy in preventing NMSC in immunocompetent patients. CONCLUSION Retinoids constitute a highly efficacious alternative for the management of the most common conditions that affect SOTRs. Acitretin has the most robust evidence for chemoprophylaxis in SOTRs. Knowledge about the specific indications and expected side effects of topical and systemic retinoids may help optimize their therapeutic potential.
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4.
Exposure to Ultraviolet Radiation in the Modulation of Human Diseases.
Hart, PH, Norval, M, Byrne, SN, Rhodes, LE
Annual review of pathology. 2019;:55-81
Abstract
This review focuses primarily on the beneficial effects for human health of exposure to ultraviolet radiation (UVR). UVR stimulates anti-inflammatory and immunosuppressive pathways in skin that modulate psoriasis, atopic dermatitis, and vitiligo; suppresses cutaneous lesions of graft-versus-host disease; and regulates some infection and vaccination outcomes. While polymorphic light eruption and the cutaneous photosensitivity of systemic lupus erythematosus are triggered by UVR, polymorphic light eruption also frequently benefits from UVR-induced immunomodulation. For systemic diseases such as multiple sclerosis, type 1 diabetes, asthma, schizophrenia, autism, and cardiovascular disease, any positive consequences of UVR exposure are more speculative, but could occur through the actions of UVR-induced regulatory cells and mediators, including 1,25-dihydroxy vitamin D3, interleukin-10, and nitric oxide. Reduced UVR exposure is a risk factor for the development of several inflammatory, allergic, and autoimmune conditions, including diseases initiated in early life. This suggests that UVR-induced molecules can regulate cell maturation in developing organs.
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Facial Transplantation for an Irreparable Central and Lower Face Injury: A Modernized Approach to a Classic Challenge.
Kantar, RS, Ceradini, DJ, Gelb, BE, Levine, JP, Staffenberg, DA, Saadeh, PB, Flores, RL, Sweeney, NG, Bernstein, GL, Rodriguez, ED
Plastic and reconstructive surgery. 2019;(2):264e-283e
Abstract
BACKGROUND Facial transplantation introduced a paradigm shift in the reconstruction of extensive facial defects. Although the feasibility of the procedure is well established, new challenges face the field in its second decade. METHODS The authors' team has successfully treated patients with extensive thermal and ballistic facial injuries with allotransplantation. The authors further validate facial transplantation as a reconstructive solution for irreparable facial injuries. Following informed consent and institutional review board approval, a partial face and double jaw transplantation was performed in a 25-year-old man who sustained ballistic facial trauma. Extensive team preparations, thorough patient evaluation, preoperative diagnostic imaging, three-dimensional printing technology, intraoperative surgical navigation, and the use of dual induction immunosuppression contributed to the success of the procedure. RESULTS The procedure was performed on January 5 and 6, 2018, and lasted nearly 25 hours. The patient underwent hyoid and genioglossus advancement for floor-of-mouth dehiscence, and palate wound dehiscence repair on postoperative day 11. Open reduction and internal fixation of left mandibular nonunion were performed on postoperative day 108. Nearly 1 year postoperatively, the patient demonstrates excellent aesthetic outcomes, intelligible speech, and is tolerating an oral diet. He remains free from acute rejection. CONCLUSIONS The authors validate facial transplantation as the modern answer to the classic reconstructive challenge imposed by extensive facial defects resulting from ballistic injury. Relying on a multidisciplinary collaborative approach, coupled with innovative emerging technologies and immunosuppression protocols, can overcome significant challenges in facial transplantation and reinforce its position as the highest rung on the reconstructive ladder. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, V.
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Anti-TNF combination therapy in inflammatory bowel disease: de novo or selective?
Macaluso, FS, Orlando, A
Minerva gastroenterologica e dietologica. 2019;(4):291-297
Abstract
Anti-TNFs still remain the backbone of advanced therapies in inflammatory bowel diseases, but their efficacy is not universal and tends to diminish over time. As a consequence, there is the need for optimization of these treatments, and the use of combination therapy - i.e. an anti-TNF plus an immunosuppressant - is one of the main strategies. The rationale for this approach lies in the evidence that the immunosuppressant reduces the formation of antibodies directed against the anti-TNF, thus avoiding the reduction or elimination of circulating drug levels, and in the combination of the therapeutic effect of two drugs. Nowadays, two different combination therapies should be distinguished. In the "de novo" combination therapy, the anti-TNF is used in combination with an immunosuppressant from the beginning of the treatment, in order to prevent the formation of anti-drug antibodies. In the "selective" combination therapy, the immunosuppressant is added at a later time in patients who experience a loss of response during anti-TNF monotherapy due to the development of anti-drug antibodies. The purpose of this review is to summarize the available evidence on both de novo and selective combination therapy. In addition, we will express our point of view on the choice between these two different treatment modalities.
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[Immunoglobulin A nephropathy].
Seikrit, C, Rauen, T, Floege, J
Der Internist. 2019;(5):432-439
Abstract
Immunoglobulin A nephropathy (IgAN) is the most prevalent primary form of glomerulopathy in the western world. The pathogenetic relevance of autoimmune mechanisms, genetics and environmental or nutritional factors is not fully established. The majority of IgAN patients present with mild symptoms; however, the exact prognosis of the individual IgAN course is often difficult to predict. In approximately one third of the patients the disease remains on a stable benign course, whereas approximately 30% may develop end-stage renal disease. Risk factors for disease progression are a persistent microhematuria and proteinuria >1 g/day, arterial hypertension and the extent of tubulointerstitial fibrosis at the time of diagnosis. Recent genome-wide association studies (GWAS) identified numerous risk alleles, which can contribute to the pathophysiology of IgAN. The so-called gut-kidney axis as well as the complement system and genes that are linked to mucosal immunity appear to be important for the manifestation of the disease. Intensive supportive care should be initiated as first-line treatment and only rare cases with progressive features require treatment with corticosteroids. Other immunosuppressive treatment strategies have currently no indications for IgAN. Future approaches might be the use of local budesonide or the inhibition of lymphocyte activation.
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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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Diagnosis and treatment of myasthenia gravis.
Mantegazza, R, Cavalcante, P
Current opinion in rheumatology. 2019;(6):623-633
Abstract
PURPOSE OF REVIEW This article provides an update on the most recent advances in diagnostic procedures and therapeutic approaches for myasthenia gravis, spanning from autoantibody and neuroelectrophysiological tests as diagnostic tools, to innovative and promising treatments based on biological drugs. RECENT FINDINGS Novel studies performed by cell-based assays (CBAs) indicate an improvement in the chance of identifying serum autoantibodies in myasthenic patients. Clinical trials on the use of biological drugs were recently concluded, providing important data on safety and efficacy of eculizumab, efgartigimod and amifampridine phosphate: the first, a complement blocker, showed long-term safety and efficacy in acetylcholine receptor (AChR)-positive myasthenic patients with refractory generalized disease; the second, the neonatal Fc receptor blocker, was well tolerated and clinically effective in both AChR-specific and muscle-specific kinase receptor (MuSK)-positive patients; the third, a blocker of presynaptic potassium channels, was found to be well tolerated and effective in MuSK-positive patients. SUMMARY CBAs can lead to a significant reduction of seronegative patients, improving myasthenia gravis diagnostic process. New biological drugs offer innovative approaches to treat myasthenic patients with generalized disease, promising to change the paradigm of treatment and to significantly enhance therapeutic success within a precision medicine framework.
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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.