Steroid Avoidance Research Articles

Immunosuppression in liver transplant oncology: position paper of the Italian Board of Experts in Liver Transplantation (I-BELT).

Liver transplant oncology (TO) represents an area of increasing clinical and scientific interest including a heterogeneous group of clinical-pathological settings. Immunosuppressive management after LT is a key factor relevantly impacting result. However, disease-related guidance is still lacking, and many open questions remain in the field. Based on such a substantial lack of solid evidences, the Italian Board of Experts in Liver Transplantation (I-BELT) (a working group including representatives of all national transplant centers), unprecedently promoted a methodologically sound consensus conference on the topic, based on the GRADE approach. The group final recommendations are herein presented and commented. The 18 PICOs and Statements and their levels of evidence and grades of recommendation are reported and grouped into seven areas: (1) risk stratification by histopathological and bio-molecular parameters and role of mTORi post-LT; (2) steroids and HCC recurrence; (3) management of immunosuppression when HCC recurs after LT; (4) mTORi monotherapy; (5) machine perfusion and HCC recurrence after LT; (6) physiopathology of tumor-infiltrating lymphocytes and immunosuppression, the role of inflammation; (7) immunotherapy in liver transplanted patients. The interest in mammalian targets of rapamycin inhibitors (mTORi), for steroid avoidance and the need for a reduction to CNI exposure emerged from the consensus process. A selected list of unmet needs prompting further investigations have also been developed. The so far heterogeneous and granular approach to immunosuppression in oncologic patients deserves greater efforts for a more standardized therapeutic response to the different clinical scenarios. This consensus process makes a first unprecedented step in this direction, to be developed on a larger scale.

Medium-term Outcomes in Pediatric Heart Transplant Recipients Managed Using a Steroid Avoidance Immune Suppression Protocol.

Short-term outcomes using steroid avoidance immune suppression are encouraging in pediatric heart transplant (HT) recipients at low risk of antibody-mediated rejection. We assessed medium-term outcomes in pediatric HT recipients initiated on a steroid avoidance protocol at our institution using surveillance biopsies. All primary HT recipients during 2006-2020 who did not have a donor-specific antibody were eligible for immune suppression consisting of 5-d Thymoglobulin/steroid induction followed by a tacrolimus-based, steroid-free regimen. We assessed freedom from graft failure (death or retransplant), acute rejection, posttransplant lymphoproliferative disease, and cardiac allograft vasculopathy. Overall, 150 of 181 primary HT recipients were eligible for steroid avoidance regimen. Their median age was 8.7 y, 41% had congenital heart disease, 23% were sensitized, and 35% were on a mechanical support. The median follow-up was 6.1 y. Eleven patients (8%) were on maintenance steroids at discharge and 13% at 1 y. Graft survival was 94% at 1 y and 87% at 5 y. Freedom from rejection was 73% at 1 y and 64% at 5 y. Freedom from posttransplant lymphoproliferative disease was 96% at 1 y and 95% at 5 y. Freedom from moderate cardiac allograft vasculopathy was 94% at 5 y. Eight patients developed diabetes. Estimated glomerular filtration rate was <60 mL/min/1.73 m2 in 5% of the cohort at 5 y. Pediatric HT recipients at low risk of antibody-mediated rejection have excellent medium-term survival and relatively low incidence of posttransplant morbidities when managed using a steroid avoidance immune suppression protocol.

Ayurvedic management of central serous chorioretinopathy: A case report

Abstract: Central Serous Chorioretinopathy (CSCR) is a common cause of the sudden painless onset of diminished distant vision that primarily affects males in their third and fourth decades. Common etiological factors include intake of systemic steroids, hypertension, stress, and type-A personalities as risk factors. The diminished vision may be associated with either metamorphopsia, micropsia, or a relative positive scotoma. Diagnosis is confirmed using ophthalmoscopy, fluorescein angiography, and Optical Coherence Tomography (OCT). Treatment modalities include observation, avoidance of systemic steroids, lifestyle modifications, pan-LASER photocoagulation, and Anti-vascular Endothelial Growth Factor (anti-VEGF) injections. CSCR may be compared with Dhumara (~haziness of vision) in Ayurveda, in which the patient sees objects as though covered by smoke. This condition is curable and hence, treatment modalities may be judiciously expedited. The case of a 33-year-old male who presented with blurring of vision and who was diagnosed as having CSCR by an ophthalmologist is presented in this case report. The patient was managed with Ayurveda interventions including Marsha nasya (~instillation of nasal medication), Takradhara (~therapeutic butter milk-streaming over the body), Talapoticchil (~medicated paste applied overhead), and Anjana (~collyrium). After one month of treatment, improvement in Visual Acuity (VA) from 6/60 in the right eye (OD), 6/6 in the left eye (OS) to 6/6 in the OD, and 6/6 in the OS was observed. OCT scan of both eyes also showed a reduction in the size of the “dome-shaped” elevation and marked absorption of the subretinal fluid. The observations reveal that Ayurvedic management of CSCR is significantly effective in reducing subjective and objective symptoms and improving VA.

Feasibility of steroid-free tacrolimus-basiliximab immunosuppression in pediatric liver transplantation and predictors for steroid requirement.

Avoidance of steroids in pediatric liver transplantation may reduce toxicity and morbidity. The aim of this study was to analyze the feasibility of a steroid-free tacrolimus-basiliximab immunosuppression scheme, the risk factors associated with steroid requirement, and safety parameters. Patients who underwent liver transplantation for biliary atresia between 2011 and 2019 were included and followed for 6 months after transplantation. Immunosuppression consisted of tacrolimus-based treatment with basiliximab induction. Steroid-free survival was estimated, and risk factors for steroid requirement were evaluated using multivariate Cox regression analysis. A total of 76 patients were included, of whom 42 (55.3%) required steroids (>14d) due to biopsy-proven acute rejection (47.6%, n = 20), instability in liver function tests (35.7%, n = 15), tacrolimus-related adverse drug reactions (14.3%, n = 6), or other reasons (bronchospasm episode, n = 1). Steroid-free survival was 45.9% (95% CI, 35.9-58.8). Independent factors associated with steroid requirement included tortuosity in tacrolimus trough levels (≥1.76 vs. <1.76: HR 5.8, 95% CI, 2.6-12.7; p < 0.001) and mean tacrolimus trough levels (≥ 6.4ng/mL vs. < 6.4ng/mL: HR 0.4, 95% CI, 0.2-0.7; p = 0.002). The rate of bacterial and viral infections was comparable between patients with and without steroids, although in the former group, cytomegalovirus infection developed earlier ( p = 0.03). Patients receiving steroids had higher total cholesterol, LDL, and HDL levels ( p < 0.05) during follow-up, but no changes in the height Z-score were observed 1 year after transplantation. Basiliximab induction in combination with tacrolimus-based treatment avoided steroid requirements in 45% of the patients. Tacrolimus variability and trough levels below 6.4ng/mL independently increased the risk of steroid requirement. Further efforts should be focused on personalizing immunosuppressive treatment.

PA08 Do parents and carers of children with eczema understand topical steroid potency? Results of a patient survey

Abstract Dermatologists consider topical corticosteroids (TCS) to be the first-line active treatment for most inflammatory skin disorders, including eczema. Well-known adverse effects can usually be avoided by careful prescribing. However, widespread public antipathy to TCS, sometimes amounting to steroid avoidance and phobia, can impair patient care. This fear is largely independent of steroid potency, even though there can be up to a 100-fold difference between the mildest and the most potent products. National Institute for Health and Care Excellence guidelines refer to the World Health Organization’s four-level grading system (mild, moderate, potent and very potent), but information about potency is never found on TCS packaging and rarely in patient information leaflets (Haider Z, Proctor A, Moss C. Potency of topical steroids should be clearly labelled on all packaging. Br J Dermatol 2023; 188:427–8). We surveyed parents and carers to investigate their knowledge and understanding of steroid potency. A SurveyMonkey® questionnaire was promoted by the National Eczema Society on social media, and by Eczema Outreach Support in a newsletter to supporters in January 2023. Of 984 responses received, 25% were from parents or carers of children with eczema. Of these, 97% knew that TCS could have different strengths (potencies), but 44% did not know how many different grades there were, with only 20% correctly answering four. Despite this, 77% of respondents felt ‘somewhat confident’ or ‘very confident’ that they knew how strong their cream was, but of those who were ‘very confident’, 29% did not know how many potency grades there were. Follow-up questions revealed that of those who had used these specific TCS, 93% knew that hydrocortisone is mild, but only 48% correctly identified Fucidin H as mild. Only 54% correctly identified DermovateTM as very potent. When asked ‘Where would you look to find out how strong your steroid creams and ointments are?’ most (69%) answered ‘on the packaging’. Ninety-seven per cent were in favour of clear potency labelling on all steroid creams and ointments. Sixty-two respondents provided free-text comments that were analysed thematically: 51% expressed confusion about TCS or a need for more information; 18% complained that general practitioners were not sufficiently knowledgeable; 20% voiced concerns about TCS, some vehemently, and most citing ‘topical steroid withdrawal’; 11% were positive about TCS and the information provided, two of whom used the ‘Aron regimen’. Several responses indicated confusion between percentage concentration (stated on the tube) and potency. These findings confirm the clinical impressions that parents of children with eczema have limited understanding of potency and need clearer information on the tube and packaging.

Steroid Sparing Maintenance Immunosuppression in Highly Sensitised Patients Receiving Alemtuzumab Induction.

This analysis reports on the outcomes of two different steroid sparing immunosuppression protocols used in the management of 120 highly sensitised patients (HSPs) with cRF>85% receiving Alemtuzumab induction, 53 maintained on tacrolimus (FK) monotherapy and 67 tacrolimus plus mycophenolate mofetil (FK + MMF). There was no difference in the median cRF or mode of sensitisation between the two groups, although the FK + MMF cohort received more poorly matched grafts. There was no difference in one-year patient or allograft survival, however rejection free survival was inferior with FK monotherapy compared with FK + MMF at 65.4% and 91.4% respectively, p < 0.01. DSA-free survival was comparable. Whilst there was no difference in rates of BK between the cohorts, CMV-free survival was inferior in the FK + MMF group at 86.0% compared with 98.1% in the FK group, p = 0.026. One-year post-transplant diabetes free survival was 89.6% and 100.0% in the FK and FK + MMF group respectively, p = 0.027, the difference attributed to the use of prednisolone to treat rejection in the FK cohort, p = 0.006. We report good outcomes in HSPs utilising a steroid sparing protocol with Alemtuzumab induction and FK + MMF maintenance and provide granular data on immunological and infectious complications to inform steroid avoidance in these patient groups.

Simultaneous Pancreas-kidney Transplantation Candidates With Type 2 Diabetes Mellitus: Elevated C-peptide Levels Warrant Scrutiny, May Portend Worse Outcomes.

Simultaneous Pancreas-kidney Transplantation Candidates With Type 2 Diabetes Mellitus: Elevated C-peptide Levels Warrant Scrutiny, May Portend Worse Outcomes.

Extracorporeal Membrane Oxygenation Support for Interstitial Lung Disease in Idiopathic Inflammatory Myopathies: An ELSO Registry Analysis.

Extracorporeal Membrane Oxygenation Support for Interstitial Lung Disease in Idiopathic Inflammatory Myopathies: An ELSO Registry Analysis.

TOO HOT TO GET DRESSED?

TOO HOT TO GET DRESSED?

S3646 Double Pylorus: A Case of Chronic Peptic Ulcer Disease Leading to Formation of a Gastroduodenal Fistula

Introduction: Double pylorus is a rare condition, either congenital or acquired, that results in a gastroduodenal fistula, forming an additional connection between the antrum of the stomach and the duodenal bulb. Case Description/Methods: A 75-year-old female with past medical history of cervical cancer (in remission), hypertension, tobacco use, chronic constipation, and peptic ulcer disease (PUD) presented to the emergency department (ED) with diffuse abdominal pain and blood in her stool. Patient reported intermittent black stools with occasional rectal bleeding. She was using non-steroidal anti-inflammatory drugs (NSAIDs) for headaches. In the ED, patient was hypertensive to 170/75, but other vital signs were stable. Her labs showed a hemoglobin of 12.6 g/dL (normal 12-16 g/dL) without evidence of coagulopathy. Imaging of the abdomen and pelvis did not show any acute findings. Esophagogastroduodenoscopy (EGD) showed two openings to the duodenal bulb, a functional pylorus inferiorly and an accessory channel superiorly (Figure). The two lumens of the duodenum appeared normal without evidence of acute ulceration. Colonoscopy showed a non-bleeding arteriovenous malformation in the proximal ascending colon and internal hemorrhoids, which were likely the cause of her bleeding. Discussion: Acquired double pylorus (ADP) is usually an incidental finding with a prevalence of approximately 0.001-0.4%, affecting males and females in a 2:1 ratio, respectively. Most cases of ADP are secondary to PUD, often an ulcer in the antrum of the stomach or duodenum penetrating directly into the duodenal bulb. Patients can be asymptomatic with ADP, but some may experience vomiting, epigastric pain, or dyspepsia. Melena may also be present with active ulceration. Initial diagnostic approach to ADP should include EGD, assessing NSAID or corticosteroid use, and H. pylori testing. Treatment involves proton-pump inhibitor administration or other mucosal protective agents, avoidance of NSAIDs and steroids, and eradication of H. pylori. Endoscopic division of the tissue bridge with a sphincterome should be considered if severe symptoms of gastric outlet obstruction persist. In severe cases where perforation, refractory bleeding and/or obstruction occurs, a surgical consultation should be pursued. The accessory pathway will typically remain patent for life, but rarely, the channel will close completely or merge to form a single connection to the duodenal bulb.Figure 1.: Double pylorus on EGD. The accessory channel is observed superiorly, revealing a gastroduodenal fistula.

Recipient and Graft Outcomes in Simultaneous Kidney and Pancreas Transplantation With Steroid Avoidance in the United States.

Steroid avoidance in kidney transplantation has been proven noninferior. Long-term outcome data on steroid avoidance in simultaneous pancreas-kidney (SPK) remains scant. Utilizing the Scientific Registry of Transplant Recipients between 2000 and 2020, we studied all primary crossmatch negative SPK recipients (N = 5683) who received antithymocyte globulin induction and were discharged alive with functioning grafts on tacrolimus and mycophenolate ± steroid maintenance. Recipients were grouped according to steroid use into 2 groups: steroid maintenance (n = 4191) and steroid avoidance (n = 1492). Kaplan-Meier curves censored at 10 y were generated for recipient and allograft survival by steroid maintenance. Predictors for recipient and graft survival were examined using Cox Proportional Hazards. Models were adjusted for age, body mass index, ethnicity, diabetes type, human leukocyte-antigen mismatches, cold ischemia time, transplant era, preemptive transplantation, and pancreas donor risk index with the transplant center included as a random effect. Steroid avoidance gained popularity over time, accounting for over one-fourth of the studied cohort. One-year acute rejection rates by steroid avoidance were comparable for kidney (8.6% versus 9%, P = 0.783); however, the pancreas rejection rate was lower in the steroid avoidance group (7.9% versus 10%; P = 0.035). After adjustment, steroid avoidance did not influence recipient survival (lower level of confidence interval, adjusted hazard ratio, upper level of confidence interval: 0.94, 1.15, 1.39), pancreas (0.75, 0.93, 1.16), or kidney (0.95, 1.18, 1.45) death-censored survival, compared with steroid maintenance. Accounting for the recipient and graft characteristics, steroid avoidance is associated with similar recipient, pancreas, and kidney graft outcomes compared with steroid maintenance in SPK recipients after antithymocyte globulin induction with tacrolimus and mycophenolate maintenance.

214.5: Long-term Outcomes in Primary Simultaneous Kidney and Pancreas Recipients Under Steroid Avoidance in the United States

Background: Steroid avoidance in kidney transplantation has been proven non-inferior. Data on steroid avoidance in simultaneous pancreas-kidney (SPK) is scant. Methods: We utilized the Scientific Registry of Transplant Recipients (SRTR) between 2000 and 2020 we studied all primary crossmatch negative SPK recipients (N=5683) who received anti-thymocyte globulin for induction and were discharged alive on tacrolimus and mycophenolate with or without steroid maintenance. Recipients were grouped according to steroid use into two groups: steroid maintenance n=4191 and steroid avoidance n=1492. Kaplan-Meier curves with generated for Recipient and allografts survival according to steroid maintenance censored at 10 years. Predictors for recipient and grafts survival were examined using Cox proportional Hazards. Models were adjusted for age, BMI, ethnicity, diabetes type, HLA-antigen mismatches, cold ischemia time, transplant era, preemptive transplantation, and PDRI with the transplant center included as a random effect. Results: Steroid avoidance gained popularity over the years, accounting for over one fourth of the studied cohort. One-year acute rejection rates by steroid avoidance were comparable for kidney (8.6 vs. 9%, P= 0.783, however pancreas rejection rate was lower in the steroid avoidance group (7.9 vs. 10%. P=0.035). In the Kaplan-Meier analysis for the pancreas death-censored graft survival (DCGS), steroid avoidance was associated with better pancreas graft survival (log-rank p =0.006). The kidney DCGS did not vary between groups (log-rank p=0.233). In the multivariable models, steroid avoidance did not influence recipient (LLCI, aHR, ULCI) (0.94, 1.15,1.39), death-censored pancreas graft survival (0.75, 0.93, 1.16) or kidney (0.95, 1.18, 1.45) compared to recipients on steroid maintenance. Conclusion: After multivariable adjustment for recipient and grafts characteristics, steroid avoidance is associated with similar patient, pancreas and kidney grafts outcomes when compared with steroid maintenance in SPK recipients following r-ATG induction and tacrolimus plus mycophenolate maintenance. The data reported here have been supplied by the Hennepin Healthcare Research Institute (HHRI) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government.

215.14: Steroid Avoidance and Progression of Interstitial Fibrosis Assessed by Automated Quantification After Kidney Kransplantation: A Multicenter Randomized Non-Inferiority trial (the ASTRONEF Study)

215.14: Steroid Avoidance and Progression of Interstitial Fibrosis Assessed by Automated Quantification After Kidney Kransplantation: A Multicenter Randomized Non-Inferiority trial (the ASTRONEF Study)

Why Does Facial Eczema Differ From Body Eczema?

The pathophysiology of atopic dermatitis (AD) is multifactorial, influenced by genetics, skin barrier dysfunction, and environmental stressors. There is a lack of research comparing the etiologies and pathologic mechanisms accounting for differences in facial vs body eczema. To explore reasons why facial eczema may differ from body eczema. There are key differences in the environments of the face and body that may lead to AD exacerbation. These include differences in the skin microbiome, sebaceous glands concentration, and levels of natural moisturizing factor. The face is exposed to more environmental stress compared with the rest of the body. These stresses include aeroallergens, ultraviolet radiation, and cosmetic products. Management of facial eczema also differs from that of body eczema due to the avoidance of high potency topical steroids on the face. Topical steroids increase microbiome diversity, and lack of topical steroid use on the face can lead to decreased microbiome diversity and increased AD severity. Facial and body eczema differ due to differences seen in anatomical structure and environmental exposures. These differences should be further researched and used in the management of facial vs body eczema and can also be used in the development of new AD treatments. J Drugs Dermatol. 2022;21(10): 1119-1123. doi:10.36849/JDD.6354.

Kidney Transplantation, Immunosuppression and the Risk of Fracture: Clinical and Economic Implications

Rationale & ObjectiveDisorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures.Study DesignRetrospective database study.Setting & ParticipantsKidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims.ExposuresVarious immunosuppression regimens in the first 3 months after kidney transplantation.OutcomesThe development of fractures, as ascertained using diagnostic codes on Medicare billing claims.Analytical ApproachWe used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting.ResultsOverall, fractures were identified in 7.5% of kidney transplant recipients (women, 8.8%; men, 6.7%; age < 55 years, 5.9%; age ≥ 55 years, 9.3%). In time-varying regression, experiencing a fracture was associated with a substantially increased risk of subsequent death within 3 months (adjusted hazard ratio [aHR], 3.06; 95% confidence interval [CI], 2.45-3.81). Fractures were also associated with increased Medicare spending (first year: $5,122; second year: $10,890; third year: $11,083; [P < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women.LimitationsThis was a retrospective study which lacked data on immunosuppression levels.ConclusionsFractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.

Long-Term Outcomes of Kidney Transplant Recipients with Glomerulonephritides by Induction Type and Steroid Avoidance

Kidney transplant programs have different approaches to induction immunosuppression, and conflicting data exist on the role of steroid maintenance in recipients with glomerulonephritis (GN). GN patients are unique because of a higher risk for immune system exhaustion due to prior exposure to immunosuppressants to treat their GN; this raises questions regarding the optimal immunosuppression needed for transplant success and reduction of complications. We sought to assess the effect of induction type and steroid maintenance on the recipient and kidney graft survival in those with IgA nephropathy (IgAN), systemic lupus erythematosus related GN (SLE), small-vessel vasculitis (SVV), and anti-glomerular basement membrane disease (anti-GBM). We analyzed the Scientific Registry of Transplant Recipients (SRTR) database for adult, primary kidney recipients with the above glomerulonephritides through September 2019. Kaplan–Meier curves were generated to examine kidney graft and recipient survival. We used multivariable Cox proportional hazard models to investigate the impact of induction type and steroid maintenance in each group separately. Our study included 9176 IgAN, 5355 SLE, 1189 SVV, and 660 anti-GBM recipients. Neither induction type nor steroid maintenance therapy influenced recipient or death-censored graft survival in this cohort of recipients. Our findings provide an opportunity for recipients with a history of one of the studied glomerulonephritides to receive a more tailored immunosuppression regimen, considering their previous exposure to immunosuppressants.

Rituximab Dosing in Glomerular Diseases: A Scoping Review.

Purpose of Review:Rituximab is increasingly prescribed for glomerular diseases. However, the recently published Kidney Disease Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Glomerular Diseases lacks details on recommended dosing regimens for most individual glomerular diseases. We performed this scoping review summarizing the evidence for rituximab dosing in glomerular disease.Sources of Information:PubMed database.Methods:The PubMed search methodology was developed with a medical librarian and performed by the first, with review by a second, author. Randomized controlled trials (RCTs) and prospective cohort studies (PCSs) examining rituximab efficacy and/or safety in antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), membranous nephropathy (MN), lupus nephritis (LN), or podocytopathies (minimal change disease or focal segmental glomerulosclerosis [FSGS]) were included. Fifty-three studies (14 RCTs and 39 PCSs) were included.Key Findings:We identified 16 different rituximab dosing regimens studied as induction therapy for one or more of the 5 glomerular diseases of interest. The most frequently studied rituximab induction regimens were 1000 mg as 2 doses 2 weeks apart (17 studies, 32%) and 4 doses of 375 mg/m2/week (18 studies, 33.9%). Twenty-six studies (49%) examined rituximab as monotherapy or in conjunction with corticosteroids alone, while the remaining studies examined rituximab as part of combination immunosuppression. Adapting treatment to achieve B-cell depletion, with frequent evaluation of disease-specific biomarkers, might prove the optimal approach to achieving and maintaining remission. Rituximab might also enable steroid minimization or avoidance.Limitations:Restriction of the search to a single database and to studies published in the English language, and with an accompanying abstract, could have led to selection bias. While the search was limited to prospective observational studies and RCTs, no formal assessment of study quality was performed.

A Randomized Controlled Trial on Safety of Steroid Avoidance in Immunologically Low-Risk Kidney Transplant Recipients

IntroductionSteroid-based immunosuppression after transplantation increases the risk of post-transplant diabetes mellitus (PTDM), with adverse effects on patient and graft survival. In the SAILOR study, we investigated the safety and efficacy of complete steroid avoidance in immunologically low-risk kidney recipients without diabetes on the current standard-of-care maintenance regimen with tacrolimus/mycophenolate mofetil (MMF).MethodsIn this 2-year, multicenter, open-label trial, a total of 222 patients were randomized to receive either steroid avoidance protocol (tacrolimus/MMF/antithymocyte globulin [ATG] induction [n = 113]) or steroid maintenance protocol (tacrolimus/MMF/prednisolone/basiliximab-induction [n = 109]).ResultsAt 1 year, no significant differences were found between steroid avoidance and steroid maintenance arms in the incidence of PTDM, the primary end point (12.4% vs. 18.3%, respectively, P = 0.30, CI: 16.3–4.4), or in overall biopsy-proven rejections (15% vs. 13.8%, respectively, P = 0.85). At 2 years, the composite end point of freedom from acute rejection, graft loss, and death (81% vs. 85%, respectively, P = 0.4), kidney function, or adverse events was comparable between the 2 arms. Moreover, 63.9% of the patients in the steroid avoidance arm remained free from steroids at 2 years.ConclusionThe SAILOR study provides further evidence for the feasibility, safety, and efficacy of early steroid-free treatment at 2 years in immunologically low-risk kidney recipients with tacrolimus/MMF maintenance regimen.

Posttransplant Diabetes Mellitus and Immunosuppression Selection in Older and Obese Kidney Recipients

Rationale & ObjectivePosttransplant diabetes mellitus (DM) after kidney transplantation increases morbidity and mortality, particularly in older and obese recipients. We aimed to examine the impact of immunosuppression selection on the risk of posttransplant DM among both older and obese kidney transplant recipients.Study DesignRetrospective database study.Setting & ParticipantsKidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States from US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims.ExposuresVarious immunosuppression regimens in the first 3 months after transplant.OutcomesDevelopment of DM >3 months-to-1 year posttransplant.Analytical ApproachWe used multivariable Cox regression to compare the incidence of posttransplant DM by immunosuppression regimen with the reference regimen of thymoglobulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse propensity weighting.Results12.7% of kidney transplant recipients developed posttransplant DM with higher incidences in older (≥55 years vs <55 years: 16.7% vs 10.1%) and obese (body mass index [BMI] ≥ 30 kg/m2 vs BMI < 30 kg/m2: 17.1% vs 10.9%) patients. The incidence of posttransplant DM was lower with steroid avoidance [TMG/ALEM + no prednisone (8.4%) and IL2rAb + no prednisone (9.7%)] than TMG/ALEM with triple therapy (13.1%). After adjustment for donor and recipient characteristics, TMG/ALEM with steroid avoidance was beneficial for all groups [age < 55 years: adjusted HR (aHR), 0.63 (95% confidence interval [CI], 0.54-0.72); age ≥ 55 years: aHR, 0.69 (95% CI, 0.60-0.79); BMI < 30 kg/m2: aHR, 0.69 (95% CI, 0.60-0.78); BMI ≥ 30 kg/m2: aHR, 0.67 (95% CI, 0.57-0.79)]. However, IL2rAb with steroid avoidance was beneficial only for older patients (aHR, 0.76; 95% CI, 0.58-0.99) and for those with BMI < 30 kg/m2 (aHR, 0.63; 95% CI, 0.46-0.87).LimitationsRetrospective study and lacked data on immunosuppression levels.ConclusionsThe beneficial impact of steroid avoidance using tacrolimus on posttransplant DM appears to differ by patient age and induction regimen.

A real-world study of immune thrombocytopenia management during the COVID-19 pandemic in the UK.

SummaryThe COVID‐19 pandemic has created many challenges in the management of immune thrombocytopenic purpura (ITP). The recommendation for avoidance of steroids by WHO led to the off‐licence use, supported by NHS England, of thrombopoietin mimetics (TPO‐RA) for newly diagnosed or relapsed ITP. This is a real‐world prospective study which investigated the treatment patterns and outcomes in this setting. Twenty‐four hospitals across the UK submitted 343 cases. Corticosteroids remain the mainstay of ITP treatment, but TPO‐RAs were more effective. Incidental COVID‐19 infection was identified in a significant number of patients (9·5%), while 14 cases were thought to be secondary to COVID‐19 vaccination.