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We observed efficacy and safety of ustekinumab in very early-onset inflammatory bowel disease, which has not been previously reported. Clinical remission at 52% was 75%, often persisting beyond 2 years. Further studies including larger numbers of cases are needed to confirm this observation.

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Predicting the therapeutic response to biologics before administration is a key clinical challenge in ulcerative colitis (UC). We previously reported a model for predicting the efficacy of vedolizumab (VDZ) for UC using a machine-learning approach. Ustekinumab (UST) is now available for treating UC, but no model for predicting its efficacy has been developed. When applied to patients with UC treated with UST, our VDZ prediction model showed positive predictive value (PPV) of 56.3% and negative predictive value (NPV) of 62.5%. Given this limited predictive ability, we aimed to develop a UST-specific prediction model with clinical features at baseline including background factors, clinical and endoscopic activity, and blood test results, as we did for the VDZ prediction model. The top 10 features (Alb, monocytes, height, MCV, TP, Lichtiger index, white blood cell count, MCHC, partial Mayo score, and CRP) associated with steroid-free clinical remission at 6 months after starting UST were selected using random forest. The predictive ability of a model using these predictors was evaluated by fivefold cross-validation. Validation of the prediction model with an external cohort showed PPV of 68.8% and NPV of 71.4%. Our study suggested the importance of establishing a drug-specific prediction model.

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OBJECTIVES: Few studies have examined factors affecting steroid-free remission (SFR) in patients with immunoglobulin G4-related disease (IgG4-RD). The aim of this study was to investigate clinical factors affecting SFR in IgG4-RD. METHODS: The medical records of 68 patients who met the 2020 revised comprehensive diagnostic criteria for IgG4-RD were reviewed retrospectively. SFR was defined as remission maintained for at least 6 months without corticosteroids. Cox regression analysis was performed to examine the associations between SFR and various clinical factors. The relapse rate after SFR was examined using the log-rank test. RESULTS: After a median follow-up of 36 months, 30.9% (21/68) of patients with IgG4-RD achieved SFR. Multivariate Cox regression analysis revealed that IgG4-RD diagnosed by complete resection rather than by common diagnostic procedures was the only factor positively associated with SFR (hazard ratio, 7.41; 95% confidence interval, 2.23-24.60; P = .001). Furthermore, relapse after attainment of SFR was significantly less common in the group that underwent complete resection than in the group that did not undergo complete resection (log-rank P = .006). CONCLUSIONS: Patients with IgG4-RD diagnosed by complete resection had a higher likelihood of achieving SFR and a lower rate of relapse after attaining SFR.

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BACKGROUND: This case report highlights a successful steroid-free, low-dose immunosuppressive protocol for renal transplantation in a pediatric patient with Schimke immuno-osseous dysplasia with excellent 7-year patient and graft survival. Schimke immuno-osseous dysplasia is a rare multisystem disorder involving the kidney. Renal transplantation is a therapeutic option, but posttransplant mortality is high due to severe infections and posttransplant lymphoproliferative disease. METHODS: A 10-year-old girl diagnosed with Schimke immuno-osseous dysplasia and end-stage renal disease underwent an AB0-compatible living-related kidney transplantation, with no donor-specific antibodies. Our standard immunosuppression protocol was modified due to the risk of infection. Basiliximab was used as induction therapy, and a reduced dose of mycophenolate mofetil and tacrolimus was initiated following transplantation, maintaining the patient on a low tacrolimus target (3-5 µg/L). Mycophenolate mofetil was discontinued after 8 weeks due to neutropenia and the patient was kept on tacrolimus as monotherapy. Five years posttransplant the patient developed acute onset of neurological symptoms, consisting of ataxia, lack of voluntary coordination, balance, aphasia and dysphagia, and diplopia. She recovered without neurological deficits within 6 weeks. Extensive evaluation revealed no pathology. To avoid a possible a component of tacrolimus-induced cerebral vasoconstriction, the immunosuppressive therapy was changed to everolimus. RESULTS: Seven years posttransplant, the patient has experienced no serious infections, no rejections, and had excellent graft function, and no de novo donor-specific antibodies. CONCLUSIONS: The present results indicate that low-dose immunosuppressive therapy after renal transplantation with low immunological risk should be considered for patients with Schimke immuno-osseous dysplasia.

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Purpose: Atopic and contact dermatitis have been attributed to skin barrier abnormalities, immune system dysfunction and inflammation leading to pruritus. As these factors may involve oxidative stress, emollient devices containing antioxidants furfuryl palmitate and tocopherol may help reduce itching and inflammation. In this study, a post-marketing questionnaire was carried out of 40 users of a novel emollient device containing furfuryl palmitate and tocopherol (Relizema™ cream), who purchased it from a pharmacy or health-care professional to ascertain the emollient device's action on itching, flushing and moisturizing. Patients and Methods: The post-marketing questionnaire, administered by trained pharmacy and health-care staff, collected data on age; diagnosis; number of times per day and for how many days the emollient device was applied; whether the product helped alleviate itching and flushing, and in what time frame if so; and how their skin felt after using the emollient. Results: Most patients had atopic dermatitis (n = 25) or irritant contact dermatitis (n = 10); most were aged ≥19 years (n = 20) or between 3 and 12 years (n = 12). Most used the emollient device twice a day (n = 26) or more (n = 11) with 27 using it for ≤30 days. Patients predominantly reported that the emollient device "significantly improved" itching (n = 34) and flushing (n = 31) with a response being noted within 1 day (n = 17) or 1 week (n = 22). All users felt the product "protected and moisturized" their skin, the product texture was "pleasant" to "excellent" and the "non-fragrance" smell was "acceptable" to "excellent". Conclusion: Use of a novel emollient device containing ingredients aimed at managing atopic or contact dermatitis, including furfuryl palmitate and tocopherol, led to rapid improvements in itching and flushing. The emollient device was acceptable to the users.

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Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Here, we report steroid-free efficacy and safety with tofacitinib among patients with UC who received corticosteroids at baseline of the maintenance study (OCTAVE Sustain). Methods: This analysis included patients with clinical response following OCTAVE Induction 1 and 2 who were re-randomized to receive placebo, or tofacitinib 5 or 10 mg twice daily (b.d.), in OCTAVE Sustain for 52 weeks and were receiving corticosteroids at OCTAVE Sustain baseline. Corticosteroid tapering was mandatory during OCTAVE Sustain. Rates of steroid-free remission, endoscopic improvement, and clinical response were assessed, stratified by baseline characteristics. Adverse events (AEs) were stratified by treatment and steroid-free remission status. Results: Overall, 289/593 patients had corticosteroid use at OCTAVE Sustain baseline. At week 52, steroid-free remission, endoscopic improvement, and clinical response rates were 10.9%, 11.9%, and 17.8% among patients receiving placebo, 27.7%, 29.7%, and 40.6% among patients receiving tofacitinib 5 mg b.d., and 27.6%, 29.9%, and 43.7% among patients receiving tofacitinib 10 mg b.d., respectively (non-responder imputation; all p < 0.05 tofacitinib 5 or 10 mg b.d. versus placebo). Discontinuations due to AEs were lower among patients with steroid-free remission versus without. AEs of special interest were infrequent. Conclusion: For patients with baseline corticosteroid use in OCTAVE Sustain, the odds of achieving steroid-free efficacy endpoints were significantly higher for tofacitinib versus placebo, irrespective of tofacitinib dose. There were no apparent differences in AEs of special interest by steroid-free remission status.ClinicalTrials.gov: NCT01458574.

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BACKGROUND: Mucosal healing (MH) evaluated by endoscopy is a novel target of therapy in UC as it is associated with improved long-term outcomes. It is defined based on the Mayo endoscopic score (MES), but it is still to define whether a value of MES 0 or 1 should be the target. The purpose of this paper is to present the results of a systematic review with meta-analysis which compares long-term outcomes of patients in steroid-free clinical remission with MES 0 with those with MES 1. METHODS: A systematic electronic search of the literature was performed using Medline, Scopus, and CENTRAL through December 2020 (PROSPERO n:CRD42020179333). The studies concerned UC patients, in steroid-free clinical remission, with MES of 0 or 1, and with at least 12-months of follow-up. RESULTS: Out of 4611 citations, 15 eligible studies were identified. Increases in clinical relapse among patients with MES 1 were observed in all the studies included in this review, suggesting that MES of 1 have a higher risk of relapse than a score of 0. MES 0 patients displayed a lower risk of clinical relapse (OR 0.33; 95% CI 0.26-0.43; I2 13%) irrespective of the follow-up time (12-months or longer). On the other hand, no differences were found comparing MES 0 versus MES 1 about the risk of hospitalization or colectomy. CONCLUSIONS: MES 0 is associated with a lower rate of clinical relapse than is MES 1. For this reason, MES 0, rather than MES 0-1, should be considered the therapeutic target for patients with UC.

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BACKGROUND: The elderly inflammatory bowel disease (IBD) population has historically been under-represented in clinical trials, and data on the efficacy of biologic medications in elderly IBD patients are generally lacking. Our study aims to evaluate the efficacy of vedolizumab (VDZ) among elderly IBD patients and compare it with younger IBD patients in a nationwide population-based cohort of IBD patients. METHODS: We conducted a retrospective cohort study of patients within the US national Veterans Affairs Healthcare System (VAHS). Patients were stratified into 2 groups based on age at the time of starting VDZ (60 years of age and older or younger than 60 years of age) with outcomes compared between the 2 groups. The primary outcome was steroid-free remission during the 6- to 12-month period after starting VDZ therapy among those patients who were on steroids when VDZ was started. RESULTS: There were 568 patients treated with VDZ, of whom 56.7% had Crohn's disease and 43.3% had ulcerative colitis. Among them, 316 patients were on steroids when VDZ was started. The percentage of patients who were on VDZ and off steroids during the 6- to 12-month period after VDZ initiation was 46.8% and 40.1% for the younger and elderly groups, respectively (P = 0.2374). Rates of hospitalization for an IBD-related reason within 1 year of VDZ start among the whole cohort were nearly identical in the younger and elderly groups (11.2% vs 11.3%, P = 0.9737). Rates of surgery for an IBD-related reason within 1 year of VDZ start were also similar between the young and elderly (3.9% vs 3.9%, P = 0.9851). CONCLUSIONS: In a nationwide real-world retrospective cohort study of elderly IBD patients, we found that the efficacy of VDZ was similar among younger and older IBD patients and comparable with the published data in clinical trials.

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BACKGROUND: Steroid use in renal transplant is related to multiple adverse effects. Long-term effects of early withdrawal steroids in pediatric renal transplant were assessed. METHODS: Renal transplant children with low immunological risk treated on basiliximab, tacrolimus, and mycophenolate with steroid withdrawal or steroid control were evaluated between 2003 and 2019. Clinical variables, treatment adherence, acute rejection, graft loss, and death were analyzed through hazard ratios, and Kaplan-Meier and multivariate analyses. RESULTS: The study included 152 patients, 71.1% steroid withdrawal, mean follow-up 8.5 years, 64.5% structural abnormalities, and 81.6% deceased donor. At 12 years of transplant, event-free survival analysis for graft loss or death showed no significant difference between steroid withdrawal and control steroid treatment (85.9% vs. 80.4%, p = .36) nor in acute rejection at 10 years (18.5% vs. 20.5%, p = .78) or in donor-specific antibody appearance (19.6% vs. 21.4%, p = .98). Delta height Z-score was increased in the steroid withdrawal group (p < .01). The main predictor of graft loss or death was non-adherence to treatment (p = .001; OR: 17.5 [3.3-90.9]). CONCLUSIONS: Steroid withdrawal therapy was effective and safe for low-risk pediatric renal transplant in long-term evaluation. Non-adherence was the main predictor of graft loss or death.

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Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation. Steroids are key component of induction protocols, maintenance therapy and in the treatment of various forms of rejection. Prolonged steroid use resulted in significant side effects on almost all the body organs owing to the presence of steroid receptors in most of the mammalian cells. Kidney allograft recipients had to accept the short and long term complications of steroids because of lack of effective alternatives. This situation changed with the intro-duction of newer and more effective immune suppression agents with a relatively more acceptable side effect profile. As a result, the clinicians have been contemplating if it is the time to abandon the unquestionable reliance on maintenance steroids in modern transplantation practice. This review aims to evaluate the safety and efficacy of various steroid-minimization approaches (steroid avoidance, early steroid withdrawal, and late steroid withdrawal) in kidney transplant recipients. A meticulous electronic search was conducted through the available data resources like SCOPUS, MEDLINE, and Liverpool University library e-resources. Relevant articles obtained through our search were included. A total number of 90 articles were eligible to be included in this review [34 randomised controlled trials (RCT) and 56 articles of other research modalities]. All articles were evaluating the safety and efficacy of various steroid-free approaches in comparison to maintenance steroids. We will cover only the RCT articles in this review. If used in right clinical context, steroid-free protocols proved to be comparable to steroid-based maintenance therapy. The appropriate approach should be tailored individually according to each recipient immuno-logical challenges and clinical condition.

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BACKGROUND: It is a crucial issue for patients with refractory ulcerative colitis (UC), including steroid-dependent and steroid-refractory patients, to achieve and maintain steroid-free remission. However, clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient. Cytapheresis (CAP) is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects. This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients. AIM: To clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients. METHODS: We retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP. We analyzed the following points: (1) Efficacy of the first course of CAP; (2) Efficacy of the second, third, and fourth courses of CAP in patients who experienced relapses during the observation period; (3) Efficacy of CAP in colonic mucosa; and (4) Long-term efficacy of CAP. Clinical efficacy was evaluated using Lichtiger's clinical activity index or Sutherland index (disease activity index). Mucosal healing was evaluated using Mayo endoscopic subscore. The primary and secondary endpoints were the rate of achievement of steroid-free remission and the rate of sustained steroid-free remission, respectively. Statistical analysis was performed using the paired t-test and chi-squared test. RESULTS: The rates of clinical remission, steroid-free remission, and poor effectiveness after CAP were 69.1%, 45.5%, and 30.9%, respectively. There were no significant differences in rate of steroid-free remission between patients with steroid-dependent and steroid-refractory UC. The mean disease activity index and Lichtiger's clinical activity index scores were significantly decreased after CAP (P < 0.0001). The rates of steroid-free remission after the second, third, and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%, 83.3%, and 60%, respectively. Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP. The rates of sustained steroid-free remission were 68.0%, 60.0%, and 56.0% at 12, 24, and 36 mo after the CAP. Nine patients (36%) had maintained steroid-free remission throughout the observation period. CONCLUSION: Our results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.

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BACKGROUND: De novo malignancy is a worrying complication after kidney transplantation; the type of which may vary due to factors such as the prevalence of viral infection and race. Kaposi sarcoma used to be the most common malignancy among our patients constituting more than one-third of cancers. Nevertheless, we noticed that Kaposi sarcoma has not been observed for a long period. Therefore, we conducted this study to explore such observation. METHODS: Data of all kidney transplant recipients were retrieved and retrospectively analyzed. Their total number was 3126 patients. Their mean age was 28.71 ± 10.97 years and of them, 823 (26.3%) were females. The pattern of Kaposi sarcoma throughout the last decade as well as the preceding three decades was studied. The possible relation between the disappearance of Kaposi sarcoma and three paradigm shifts in our practice, namely the use of mTOR inhibitors, steroid-free regimen and CMV prophylaxis was explored. RESULTS: Since 2010, no new cases of Kaposi sarcoma have been observed. In addition, patients who have been transplanted after 2006 did not develop such malignancy. Patients who received CMV prophylaxis and/or were maintained on mTOR inhibitor or steroid-free regimens have not developed Kaposi sarcoma. Moreover, CMV prophylaxis had a statistically significant difference when compared to a homogenous group without CMV prophylaxis. However, Kaplan-Meier analysis of patients of the three policies and their counterpart groups showed comparable results. CONCLUSION: Kaposi sarcoma, which was previously the most common malignancy, is no longer observed for almost a decade among our kidney transplant recipients. m-TOR inhibitors, steroid-free regimen and CMV prophylaxis policy are possible contributing factors. Nevertheless, only CMV prophylaxis policy had a statistically significant relation to the disappearance of Kaposi sarcoma.

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The American Thoracic Society guidelines recommend long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilation over LAMA or LABA monotherapy as maintenance therapy for patients with chronic obstructive pulmonary disease suffering from dyspnea or exercise intolerance. Previous studies, which included patients receiving background inhaled corticosteroids (ICS), have shown the benefits of dual bronchodilation over monotherapy. This analysis aimed to confirm the benefits of LAMA/LABA over LAMA alone, without any confounding effects from ICS use. This pooled post hoc analysis compared the efficacy of tiotropium/olodaterol with tiotropium alone in patients from the TONADO® and OTEMTO® clinical trials who were not receiving ICS at study entry or during the studies. We analyzed change from baseline in trough forced expiratory volume in 1 s (FEV1), St. George's Respiratory Questionnaire (SGRQ) score and Transition Dyspnea Index (TDI) score in all patients, by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, baseline SGRQ score, and Baseline Dyspnea Index score. In this analysis of 1596 patients, tiotropium/olodaterol improved trough FEV1, SGRQ and TDI compared with tiotropium alone. The observed mean differences were: trough FEV1, 0.054 L (95% confidence interval [CI] 0.036, 0.073; p < 0.001); SGRQ, -1.918 (95% CI -2.994, -0.843; p < 0.001); and TDI, 0.575 (95% CI 0.301, 0.848; p < 0.001). Similar improvements were seen in each of the subgroup analyses. Tiotropium/olodaterol therapy significantly improved lung function, symptoms and health status compared with tiotropium alone. In a population free from ICS treatment, these data confirm the benefits of dual bronchodilation versus monotherapy.

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RATIONALE & OBJECTIVES: Posttransplantation membranous nephropathy (MN) represents a rare complication of kidney transplantation that can be classified as recurrent or de novo. The clinical, pathologic, and immunogenetic characteristics of posttransplantation MN and the differences between de novo and recurrent MN are not well understood. STUDY DESIGN: Multicenter case series. SETTING & PARTICIPANTS: We included 77 patients from 5 North American and European medical centers with post-kidney transplantation MN (27 de novo and 50 recurrent). Patients with MN in the native kidney who received kidney allografts but did not develop recurrent MN were used as nonrecurrent controls (n = 43). To improve understanding of posttransplantation MN, we compared de novo MN with recurrent MN and then contrasted recurrent MN with nonrecurrent controls. FINDINGS: Compared with recurrent MN, de novo MN was less likely to be classified as primary MN (OR, 0.04; P < 0.001) and had more concurrent antibody-mediated rejection (OR, 12.0; P < 0.001) and inferior allograft survival (HR for allograft failure, 3.2; P = 0.007). HLA-DQ2 and HLA-DR17 antigens were more common in recipients with recurrent MN compared with those with de novo MN; however, the frequency of these recipient antigens in recurrent MN was similar to that in nonrecurrent MN controls. Among the 93 kidney transplant recipients with native kidney failure attributed to MN, older recipient age (HR per each year older, 1.03; P = 0.02), recipient HLA-A3 antigen (HR, 2.5; P = 0.003), steroid-free immunosuppressive regimens (HR, 2.84; P < 0.001), and living related allograft (HR, 1.94; P = 0.03) were predictors of MN recurrence. LIMITATIONS: Retrospective case series, limited sample size due to rarity of the disease, nonstandardized nature of data collection and biopsies. CONCLUSIONS: De novo and recurrent MN likely represent separate diseases. De novo MN is associated with humoral alloimmunity and guarded outcome. Potential predisposing factors for recurrent MN include recipients who are older, recipient HLA-A3 antigen, steroid-free immunosuppressive regimen, and living related donor kidney.

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BACKGROUND: The number of ulcerative colitis (UC) patients is increasing in Japan and other countries. Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn (JIMRO, Takasaki, Japan) was introduced as a nonpharmacologic treatment strategy in UC patients in 2000. GMA has been reported to be effective in clinical trials; however, the effect of concomitant prednisolone (PSL) on GMA needs to be clarified. METHODS: Thirty-nine patients with active UC were treated with GMA at our institute between June 2009 and September 2018. All patients received GMA therapy once or twice a week with the Adacolumn. Conventional medication was to be continued during the whole GMA treatment course. The clinical response was retrospectively evaluated. RESULTS: According to the partial Mayo score, remission was 33.3%, significant efficacy 25.6%, effective 25.6%, and no response 15.4%. The average partial Mayo score was 6.2 ± 1.4 at entry and significantly declined to 1.8 ± 1.8 after GMA sessions (p < 0.0001). The average number of bowel movements was 9.5 ± 5.6 at entry and significantly declined to 3.0 ± 2.8 after GMA sessions (p < 0.0001). In a comparison between the group treated with concomitant PSL and the group without PSL, the change in partial Mayo score or the number of bowel movements from entry to after GMA sessions was not significantly different. Among 24 patients treated by GMA with concomitant PSL, 75% (18/24) became steroid free. CONCLUSIONS: The effect of GMA with concomitant PSL and that of GMA without PSL were not different, and GMA was effective irrespective of PSL administration. The present study showed that GMA had efficacy and led many UC patients treated by PSL to be steroid free with no safety concern in the real world, although there is the possibility of recruitment bias due to the retrospective nature of the study.

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BACKGROUND: Vedolizumab (VDZ) is a humanized monoclonal IgG1 antibody which inhibits leukocyte vascular adhesion and migration into the gastrointestinal tract through α4ß7 integrin blockade. AIMS: We retrospectively assessed the 12-month, real-world efficacy and safety of VDZ as induction and maintenance therapy in adult patients with ulcerative colitis (UC). METHODS: The rates of clinical remission (CR, partial Mayo score < 2), steroid-free clinical remission (SFCR), and mucosal healing were assessed with nonresponder imputation analysis. Baseline independent predictors of clinical remission were investigated, and adverse events were recorded. RESULTS: We analyzed outcomes in 74 patients; 32% were anti-TNF naïve, 68% had pancolitis, and 46% were on systemic steroids at baseline. At week six, week 14, six months and one year, the CR rates were 26%, 34%, 39% and 39% respectively, and the SFCR rates were 24%, 31%, 38% and 39%, respectively. Among patients not in CR after induction, the probability of remission at six months was 20%. Sustained SFCR between weeks 14 and 52 and between weeks 22 and 52 was found in 69% and 86% of the patients, respectively. Steroid-free clinical remission at 12 months was significantly associated with remission after the induction phase (OR = 30.4; 95% CI, 6 to 150; P < 0.001). Mucosal healing rate at one year was 39%. The most common side effect was headache (7%). CONCLUSIONS: Increasing remission rates were observed over the first six months of VDZ treatment. One-fifth of patients not in remission post-induction achieved remission by six months of continued therapy. Mucosal healing was associated with higher rates of one-year steroid-free remission and VDZ treatment continuation.

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OBJECTIVE: To evaluate the efficacy of treatments based on GnRH, GnRH-PGF2α, and/or intense exposure to novel rams to induce fertile estrus without the use of steroid hormones in seasonally anestrous Suffolk ewes. METHODS: In the first experiment, ewes were treated with one injection of GnRH, two injections of GnRH administered 7 days apart, or a sequence of GnRH-PGF2α-GnRH. In the second experiment anestrous ewes were exposed, for 36 days starting on the day of weaning, to groups of four rams of three different breeds that were alternated every day. Besides exposure to the males, the ewes were injected with saline solution (ME group, n=20), with GnRH (ME-GnRH group, n=20) or with a sequence of GnRH-PGF2α-GnRH (ME-GPG group, n=20). The rams used for male-effect were fitted with aprons to prevent mating, and ewes detected in estrus were bred to selected fertile rams. Ovarian activity was monitored by progesterone determinations in both experiments. RESULTS: In the first experiment sustained induction of ovarian activity was not achieved and no ewe was detected in estrus. In the second experiment induction of sustained ovarian activity was achieved in all groups. Most of the ewes were detected in estrus, 76.7 % of the ewes were mated during a 36-d breeding period and 71.7 % of all the ewes became pregnant during that period. No significant differences between groups were found for any of these variables. However, estrus detection efficiency was higher in the ME-GnRH group than in the ME group (p&lt;0.05). CONCLUSION: An intense male-effect, that included the continuous presence and frequent alternation of several rams of different breeds, was sufficient to induce ovarian activity and fertile estrus in Suffolk ewes during the period of deep anestrus without the use of hormones, although addition of GnRH improved the efficiency of estrus detection.

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Danon disease (DD) is an X-linked dominant disorder caused by a mutation in the lysosomal-associated membrane protein-2 (LAMP-2) gene coding for the LAMP-2 protein. We report two cases of successful heart transplantation (HT) in adolescent brothers with DD, including one who was bridged to HT for 34 days with a HeartWare left ventricular assist device. In both patients, the post-transplant course was complicated by profound skeletal muscle weakness that resolved with corticosteroid withdrawal. These cases highlight that both HT and ventricular assist device support are feasible in patients with DD. Corticosteroid use may exacerbate skeletal myopathy, and therefore, steroid minimization may be warranted whenever possible.

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OBJECTIVE: Whether maintaining steroid-free remission is feasible in Indian patients with systemic lupus erythematosus (SLE). METHODS: In 148 patients with SLE including 78 lupus nephritis (LN) previously put into remission, steroid therapy was gradually tapered off. RESULTS: Patients received glucocorticoids for median 1855 days (interquartile range (IQR) 901-2834) before discontinuing. Median duration of follow-up was 539 days (IQR 266.25-840.75). Flare occurred in 31 patients (20.9%; 95% confidence interval (CI) 15.17-28.19, renal flare in 12.16% (18/148, 95% CI 7.83-18.41)). Most of the flares occurred in the first year of follow-up (41.9%, 13/31). Overall 93.5% (29/31) of flares occurred in those who received ≤ 8 years of glucocorticoids, compared to 6.5% (2/31) of flares in others (p = 0.009). Median flare-free survival was 611 days (95% CI 518-704). Multivariate Cox regression identified the following predictors of flare-free survival: duration of disease (hazard ratio (HR) 0.89, 95% CI 0.84-0.94, p < 0.001), duration of glucocorticoid before discontinuing (HR 1.000086, 95% CI 1.000047-1.00012, p < 0.001) and second immunosuppressive (HR 1.89, 95% CI 1.251-2.87, p = 0.003). Additional risk factors of a renal flare-free survival among patients with LN were initial dose of glucocorticoids (HR 0.97, 95% CI 0.94-0.99, p = 0.005) and presence of haemolytic anaemia (HR 2.43, 95% CI 1.067-5.54, p = 0.035). CONCLUSIONS: About 20% patients undergo exacerbation of disease activity after glucocorticoid withdrawal. Treatment for ≥ 8 years before discontinuing and an additional immunosuppressive agent improve the chance of flare-free survival.

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Lupus nephritis (LN) occurs in up to 60% of systemic lupus erythematosus patients. Combination therapy involving a corticosteroid and cyclophosphamide or mycophenolate mofetil (MMF) has been a standard therapy for LN. However, clinicians generally prefer to minimize steroid use in LN treatment. We herein report the case of a Japanese man with LN whose severe chronic heart failure prevented us from using steroid therapy. Instead, his LN was successfully treated with MMF monotherapy. Based on our experience with this case, we suggest that MMF monotherapy may represent a feasible LN treatment option in patients who cannot tolerate steroid therapy.

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