Conventional Steroid Research Articles

Allergic bronchopulmonary aspergillosis in resistant asthmatics

Background: Allergic bronchopulmonary aspergillosis (ABPA) is an immune mediated lung disease caused due to hypersensitivity reaction of antigen Aspergillus fumigates. ABPA is more prevalent in patients with asthma and cystic fibrosis. Thus, the current investigation was done to estimate the prevalence and association of ABPA with resistant asthma, to identify the clinical and laboratory pointers of ABPA and to identify the effect of ABPA and its treatment on the course of resistant asthma.Methods: Current investigation was a prospective and non-blinded study conducted on patients of Rajiv Gandhi government general hospital, Chennai with bronchial asthma, having frequent exacerbation related problems. Demographic, clinical (hematological) and radiological investigations were performed for staging and treatment of all the enrolled patients. Follow up of patients was done periodically to investigate re-admission of respiratory events or other illnesses. All the collected data was statistically analyzed.Results: Prevalence of ABPA in treatment resistant bronchial asthma patients was 19%. Positive family history, history of atopy and recurrent exacerbations were identified as significant risk factors among ABPA patients. Whereas duration and severity of asthma had no significant association with ABPA patients, bronchiectasis and parenchymal damage were significantly observed in patients of ABPA. Skin prick test serum eosinophils and IgE antibody levels were observed as good screening test parameters to identify ABPA. Prednisolone and itraconazole are considered as highly reliable and effective treatment strategies in ABPA.Conclusions: Current investigation revealed that ABPA must be considered as a possible prevailing disease in treatment refractory cases of asthma on conventional steroids.

Improved Treatment Effect of Triamcinolone Acetonide Extended-Release in Patients with Concordant Baseline Pain Scores on the Average Daily Pain and Western Ontario and McMaster Universities Osteoarthritis Index Pain Scales.

IntroductionA phase 3 randomized controlled study comparing triamcinolone acetonide extended-release (TA-ER) to conventional TA crystalline suspension (TAcs) reported variable efficacy results. Enrollment criteria may have contributed to this discrepancy, as moderate-to-severe average daily pain (ADP) was required at baseline, whereas no limitations were placed on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A) pain severity. We conducted a post hoc sensitivity analysis to compare treatment effects in patients reporting moderate-to-severe osteoarthritis (OA) pain on both scales.MethodsParticipants > 40 years old with symptomatic knee OA were randomly assigned to a single intra-articular injection of TA-ER 32 mg, TAcs 40 mg, or saline-placebo and followed for 24 weeks. Patient-reported ADP, WOMAC-A, rescue medication usage, and adverse events (AEs) were assessed. Participants who reported moderate-to-severe OA pain at baseline using both instruments (ADP ≥ 5 to ≤ 9, maximum 10 and WOMAC-A ≥ 2, maximum 4) were categorized as “concordant” pain reporters; patients with baseline moderate-to-severe OA on ADP only were termed “discordant” pain reporters.ResultsTwo-hundred-ninety-two concordant pain reporters of 484 total subjects received TA-ER 32 mg (n = 95), TAcs 40 mg (n = 100), or saline-placebo (n = 97). Baseline characteristics and AE profiles of the concordant and discordant pain responders were consistent with the full analysis population. Among concordant pain reporters, TA-ER significantly (p < 0.05) improved ADP scores vs. TAcs (weeks 5–19; area-under-the-effect [AUE]weeks1–12; AUEweeks1–24) and saline-placebo (weeks 1–20; AUEweeks1–12; AUEweeks1–24). At week 12, a higher proportion reported no knee pain (ADP = 0) with TA-ER (~ 28%) vs. TAcs (~ 8%). TA-ER significantly improved WOMAC-A vs. TAcs at weeks 4, 8, and 12, with significant reduction in rescue medication usage observed with TA-ER from weeks 2 to 20 vs. TAcs.ConclusionsIn patients reporting moderate-to-severe knee OA pain at baseline based on concordant ADP and WOMAC-A scores, TA-ER provided statistically significant pain relief for ≥ 12 weeks compared with conventional TAcs.Trial RegistrationClinicalTrials.gov Identifier: NCT02357459.

A Phase 1/2 Study of a Novel Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT103A) in Patients with Relapsed and/or Refractory Multiple Myeloma

Background： CT103A, a fully human BCMA-specific chimeric antigen receptor (CAR) T-cell therapy product showed excellent safety and promising efficacy in heavily pretreated relapsed and refractory multiple myeloma (RRMM) patients in our previous report [Blood. 2021; 137 (21): 2890-2901]. The unique CAR structure containing fully human single-chain variable fragments (scFvs) may bypass the potential host anti-CAR immunogenicity and retain antitumor activity. Here we reported the safety and efficacy results of 71 patients in 1.0×10 6 CAR+ T cells/kg cohort from the ongoing phase1/2 study (ChiCTR1800018137/ ChiCTR2000033946). Notably, it was the first time that prior BCMA CAR-T exposed patients were eligible to participate in an anti-BCMA CAR-T cell trial.Methods： This phase 1/2 study of CT103A is single-arm designed and is conducted in 13 centers in China. The study enrolled RRMM patients who had received ≥ 3 lines of prior therapies containing at least a proteasome inhibitor and an immunomodulatory agent and were refractory to their last line of treatment. 1.0 × 10 6 CAR+ T cells/Kg was previously identified as recommended phase 2 dose (RP2D). Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days. After 1-day rest, patients received CT103A. The primary objectives of this study were to assess the safety and efficacy of CT103A at RP2D. The cellular pharmacokinetic profile of CT103A in peripheral blood was investigated by measuring CAR transgene levels using droplet digital polymerase chain reaction (ddPCR) and CAR-T cells by flow cytometry. Minimal residual disease (MRD) negativity was evaluated in bone marrow aspirate by standardized Euroflow 8-color flow cytometry with a minimum sensitivity of 10 -5 nucleated cells. Immunogenicity was assessed by MSD-based antidrug antibody (ADA) assay.Results: As of the July 15, 2021, 71 patients [59.2% male; median age 58.0 years (range 41-71)] with RRMM received CT103A (9 in phase 1a; 17 in phase 1b; 45 in phase 2). The median follow-up time was 147 days (range 31 to 1029). The treated patients had received a median of 4 (range 3-13) lines of prior therapy. 28.2% and 18.3% were previously treated with auto-HSCT and anti-CD38 antibody respectively. Notably, 18.3% had previously received CAR-T therapy. What's more, 7% of the patients had the extramedullary disease at baseline, and 76.1% had high-risk cytogenetics.The most common ≥ grade 3 treatment-related AEs were hematological toxicities. 93.0% of the patients experienced CRS, among which only 2.8% were grade 3. All CRS cases were rapidly relieved after conventional CRS intervention, including tocilizumab and steroids. The median time to CRS onset was 6 days (range 1-12) with a median duration of 4 days (range 1-27). Only one (1.4%) patient experienced grade 2 ICANS which manifested as a transiently decreased level of consciousness and soon recovered without intervention.All 71 patients were evaluable for at least one month of efficacy assessment. The median time to first response was 15 days (range 11-124). A 94.4% ORR was observed, with 50.7% ≥ CR, 26.8% VGPR, and 16.9% PR. Among them, 50 patients who have completed follow-up of 3 months achieved 96.0% ORR, with 54.0% ≥ CR, 28% VGPR, and 14% PR. For 13 patients who have previously been treated with CAR-T therapy, ORR was 76.9%, with ≥ CR rate of 38.5%，VGPR of 15.4%, and PR of 23.1%. Of the 69 patients with evaluable bone marrow aspirate, 92.8% achieved MRD-negativity with a median time to MRD-negative of 17 days (range 13-180), and among them, 75.0% (95%CI 53.1-87.6%) achieved sustained MRD negativity over six months.The expansion of CT103A reached the peak at a median of 12 days (range 5 to 29). CT103A was still detectable in 88.5% (23/26) patients at 6 months and 87.5% (14/16) patients at 12 months after infusion. The first enrolled patient remains in sCR for 34 months with significant persistence of CT103A transgene. In addition, only 2 of 71 patients were detected positive for anti-drug antibody, which was reported to be a high-risk factor for disease relapse/progression after CAR-T therapy.Conclusion: The impressive efficacy of CT103A, including time to response, overall response rate, and durability, was corroborated by robust expansion and prolonged persistence of CT103A. The expansion and clinical benefits of CT103A did not seem to be influenced by prior murine BCMA CAR-T. DisclosuresNo relevant conflicts of interest to declare.

Comparison of a Platelet-Rich Plasma Injection and a Conventional Steroid Injection for Pain Relief and Functional Improvement of Partial Supraspinatus Tears.

Background:Partial supraspinatus tendon tears have frequently been treated using a subacromial corticosteroid injection or surgery. The clinical use of a platelet-rich plasma (PRP) injection is an alternative treatment method for the condition, despite the paucity of evidence of its efficacy.Purpose:To compare pain relief, functional improvement, and complications after an intratendinous PRP injection versus a subacromial corticosteroid injection for partial supraspinatus tears.Study Design:Randomized controlled trial; Level of evidence, 1.Methods:A total of 32 patients with partial supraspinatus tears were randomly assigned to receive a leukocyte-poor PRP (LP-PRP) injection or a corticosteroid injection. One patient withdrew from the PRP group, leaving 15 patients in the PRP group and 16 patients in the corticosteroid group. The ultrasound-guided procedures were performed by a single experienced pain physician. Pain relief and functional improvement were evaluated using the visual analog scale (VAS) and the Oxford Shoulder Score (OSS), respectively. Treatment efficacy and complications were documented, and the 2 groups were compared at 1- and 6-month follow-up.Results:There were no differences in VAS and OSS scores between the PRP and corticosteroid groups at 1-month follow-up. However, the PRP group had better scores than the corticosteroid group had on both the VAS and OSS at 6-month follow-up (VAS: 14.5 ± 15.4 vs 37.5 ± 24.9, respectively; OSS: 16.2 ± 3.9 vs 25.0 ± 10.2, respectively; P < .01 for both). Both groups showed significant improvement in VAS and OSS scores from before treatment to 1-month follow-up (mean difference, 35.67 and 11.47 points, respectively, for the PRP group; mean difference, 29.69 and 11.13 points, respectively, for the corticosteroid group; P < .01 for all). The VAS and OSS scores did not change significantly at 6-month follow-up in the corticosteroid group; however, the PRP group showed continued improvement in both VAS and OSS scores between 1- and 6-month follow-up (mean difference, 15.87 and 7.40 points, respectively; P < .01 for both). There were no complications in either group.Conclusion:An injection using either a corticosteroid or LP-PRP resulted in a similar reduction in pain and improvement in function at 1 month in patients with a partial supraspinatus tear. However, PRP showed superior benefits over the corticosteroid at 6-month follow-up.

Therapeutic approach with squaric acid dibutylester for steroid resistant-alopecia areata incognita: A pilot study of a single center.

Topical immunotherapy is widely used in the treatment of alopecia areata (AA). Alopecia areata incognita (AAI) is a relatively common disorder, predominantly affecting females, characterized by widespread hair thinning in the absence of typical alopecic patches. AAI can have a chronic relapsing course and in some cases can be resistant to current standard treatments. Topical immunotherapy has been used in the management of AA with encouraging results, but to date there are no literature studies reporting the efficacy of topical immunotherapy with squaric acid dibutylester (SADBE) in AAI. The aim of our study is to evaluate the efficacy and tolerance of topical immunotherapy with SADBE in AAI not responding to conventional steroid therapy. A total of 12 patients were enrolled in our Hair Disease Outpatient Service, with a proved histological diagnosis of AAI, and resistant to classical steroid therapy. Each patient underwent global photography, pull test, and trichoscopy at beginning and during the follow-ups. The efficacy of topical immunotherapy with SADBE was assessed by evaluating the changes of clinical and trichoscopic signs. Complete regrowth was achieved in 66.7% of cases (8/12), three patients remained unchanged on clinical evaluation but showed subclinical improvement on trichoscopy, whereas one patient progressed and worsened both on clinical and trichoscopic examination. All patients reported scalp diffuse mild erythema and itching the day after the application of SADBE, which were well tolerated. Three patients developed reactive cervical lymphoadenomegaly. No other side effects were observed. Topical immunotherapy with SADBE is widely used in the management of patchy AA and can be considered an effective alternative in resistant AAI, providing visible clinical and trichoscopic improvement in the majority of cases. Further studies are warranted to confirm and validate our findings.

Yasser's COVID-19 Discrepancy Phenomenon; A Novel Phenomenon And Effective Regimen; Retrospective-Observational Study

Aim of the study: Clarification for the time of the clinical improvement after management COVID-19 pneumonia versus normal gradation of common workup is the target for the current study. Background: COVID-19 pneumonia is a current serious international pandemic infection. Generally, in medical diseases, the clinical response is commonly parallel to laboratory and radiological improvement. This rule may be different in COVID-19 pneumonia. Method of study and patients: The author reported retrospective-observational 47-case report series. The study was conducted in a physician outpatient clinic thorough nearly 12-months, starting from Jun 9, 2020, and, ended on May 8, 2021. All included cases were COVID-19 pneumonia and treated with conventional antibiotics, anticoagulants, and steroids. Results: The mean ±SD age was: 50.08 (14.9) years, with male sex predominance (55.32%). The mean days of clinical versus leukocytosis, neutrophilia, and lymphopenia improvement (0.84 ±0.49, 13.05 ±6.44, 13.05 ±7.01, 13.05 ±7.01).The mean ±SD days of clinical versus CRP, D-dimer, s. ferritin, and LDH improvement (0.84 ±0.49, 12.2 ±3.25, 12.2 ±6.21, 12.3 ±5.46, 20.92± 9.48). The mean days of clinical versus radiological and electrocardiographic improvement (0.84 ±0.49, 15.74 ±5.25, 11.45 ±5.45). The test was statistically significant in all the above tests (p-value is &lt; .00001) Conclusions: Yasser’s COVID-19 Discrepancy phenomenon is a novel descriptive phenomenon that is always seen in all COVID-19 pneumonia. Initial dramatic improvement of the clinical status of COVID-19 pneumonic patient, not a simultaneously after the management, not a coincide with laboratory, radiological, and electrocardiographic workup. Further larger studies for the study medical regimen with considering of “Yasser’s COVID-19 Discrepancy phenomenon” is recommended.

Comparison of Oral Prednisolone, Budesonide and Probiotics in the Treatment of Canine Inflammatory Bowel Disease

Background: Inflammatory bowel disease (IBD) is the common cause of chronic gastrointestinal signs in dogs. The treatment possesses numerous difficulties due to the idiopathic nature of the disease. Conventional steroid therapy usually produces side effects on long term usage. Thus, there is a need for alternative therapies. When compared to human medicine, there is no published data on the use of budesonide and probiotic in the treatment of canine IBD in India. The present study was proposed to compare oral prednisolone, budesonide and probiotics in the management of canine inflammatory bowel disease. Methods: Thirty dogs with idiopathic IBD were selected and randomly grouped. They were subjected to therapy involving prednisolone, budesonide or probiotics. Clinical assessment was performed by calculation of the post treatment Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) score, faecal score and endoscopy. Biochemical analysis of alkaline phosphatase and alanine transaminase were done to record side effects of steroid administration. Result: It was observed from the present study that both prednisolone and budesonide are equally effective in the management of IBD in dogs. Probiotics were found to be less effective when compared to prednisolone and budesonide in the treatment of IBD.

Effects of Allogeneic Mesenchymal Stem Cell Transplantation in Dogs with Inflammatory Bowel Disease Treated with and without Corticosteroids.

Simple SummaryThe conventional treatment of canine inflammatory bowel disease (IBD) includes corticosteroids, but they cannot contain the disease effectively in a percentage of patients. Still, their suppression can lead to a worsening. Moreover, the application of mesenchymal stem cells (MSCs) as an alternative has yielded promising results. However, they have been always infused after a washout period of any other immunosuppressants. Therefore, the feasibility and effects of the combination of stem cells and prednisone in IBD-dogs will be evaluated for the first time in this study. A single infusion of MSCs were administered to a group of IBD-dogs without any treatment and to another having prednisone treatment with poor response. The changes in two clinical indices, albumin and cobalamin concentration were assessed after one, three, six and 12 months. In both groups, an alleviation of the disease severity and an increase in albumin and cobalamin concentrations were observed at each visit. In parallel, the steroid dosage was gradually reduced until it was suppressed in all patients a year after the stem cell infusion. Therefore, the benefits of stem cell transplantation in dogs with inflammatory bowel disease receiving or not prednisone are significant and lasting.Mesenchymal stem cells have proven to be a promising alternative to conventional steroids to treat canine inflammatory bowel disease (IBD). However, their administration requires a washout period of immunosuppressive drugs that can lead to an exacerbation of the symptoms. Therefore, the feasibility and effects of the combined application of stem cells and prednisone in IBD-dogs without adequate response to corticosteroids was evaluated for the first time in this study over a long- term follow up. Two groups of dogs with IBD, one without treatment and another with prednisone treatment, received a single infusion of stem cells. The clinical indices, albumin and cobalamin were determined prior to the infusion and after one, three, six and 12 months. In both groups, all parameters significantly improved at each time point. In parallel, the steroid dosage was gradually reduced until it was suppressed in all patients a year after the cell therapy. Therefore, cell therapy can significantly and safely improve the disease condition in dogs with IBD receiving or not receiving prednisone. Furthermore, the steroid dosage can be significantly reduced or cancelled after the stem cell infusion. Their beneficial effects are stable over time and are long lasting.

Chimeric Anti CD-20 Monoclonal Antibody-Rituximab in Refractory Childhood Idiopathic Thrombocytopenic Purpura: An Indian Experience.

The treatment of chronic idiopathic thrombocytopenic purpura (ITP) continues to be a challange. A significant proportion of patients continue to be symptomatic despite all available means of therapy. Recently Rituximab, a chimeric anti CD-20 monoclonal antibody has been shown to be an effective mode of therapy in such patients with an overall response rate of appx 50 %.We studied the efficacy and side effects of this therapeutic modality in 10 children (6 girls) with chronic ITP. The patients belonged to pediatric age group (median age: 9 years, range 4–18 years) with 4 children less than 10 years of age. All the patients were screened for systemic illnesses and different secondary causes leading to thrombocytopenia. They all had been treated with standard therapies using conventional and high dose steroids, ciclosporin cyclophosphamide, vincristine, periodic use of high dose IVIG and splenectomy in 6 patients, but had continued to be symptomatic with recurrent mucocutaneous bleeds and markedly low platelet counts (< 20x 109/L). All patients received intravenous Rituximab at a dose of 375 mg/M2 as weekly dose for 4 consecutive weeks. The infusion related side effects were a few (n= 3) and minor. They included urticarial rash (1) and fever(2) that responded to antipyretics. None of these were severe enough to interrupt the treatment. A complete response was defined as a platelet count > 100 x 109/L, partial response (PR) as count > 50x109/L and a minor response as a count < 50x109/L but without the need of continued treatment. Patients showing no significant rise in platelet count were marked as showing no response. Of the 10 evaluable children, 9 (90%) showed overall response; 4 (40%) showed complete response and 4 (40 %) showed partial response. Two (20%) patients showed minor responses. Patients have been under follow up for last 3 years. The patients with CR and PR have been in remission for longer periods (as much as 150 weeks ).The side effects due to the therapy have been few and very mild. Besides infusional reactions in 3 patients (Transient fever in 2 and mild rash in 1) there were no significant toxicities. No correlation could be found between clinical/laboratory parameters with the responsiveness or the duration of response except that patients showing a higher degree of response continued to be in remission for a longer period as compared to the ones with lesser degree of response. The high percentage of response in our patients as compared to the ones in other studies could be due to the fact that our patients belonged to a younger age group. Probably children show a better response.In conclusion, Rituximab offers a safe and convenient modality of treatment in symptomatic children with refractory ITP. Its use is certainly cost effective even in a developing country in view of the good degree of a sustained response in these refractory patients wherein all modalities of treatment have failed.

Combined Acupuncture-Hyperbaric Oxygen-Steroids Therapy for Idiopathic Sudden Sensorineural Hearing Loss: A Retrospective Observational Study.

Objectives: Acupuncture, widely used in Chinese society, has been studied as an adjunct treatment of idiopathic sudden sensorineural hearing loss (ISSNHL). The purpose of this study is to investigate the effectiveness of combined acupuncture and hyperbaric oxygen therapy (HBOT) with conventional steroid therapy for ISSNHL. Methods: This retrospective chart review enrolled 154 patients who met the ISSNHL criteria and were categorized into three groups according to the different treatment regimens. Among these patients, 43 underwent steroid therapy only (S) group, 74 received steroid and HBOT (S-H) group, and the remaining 37 were treated with combined acupuncture-HBOT in addition to steroid therapy (S-H-A) group. The outcome was determined by comparing the differences in pure-tone thresholds and absolute hearing gains after treatment calculated at each audiometric octave frequency or grouped frequencies of audiograms. Hearing recoveries classified into three grades: complete, partial, and poor were also analyzed and compared among different treatment groups. Results: All subjects presented with initial severe hearing loss with averaged hearing thresholds >70 dB. The S-H-A group exhibited good hearing improvement outcomes at each audiometric octave frequency and grouped frequencies of audiograms, with greater hearing gain and had more favorable outcomes in hearing recovery grades compared with the S group and the S-H group. Conclusions: The results obtained in this study revealed a preliminary finding of ISSNHL patients benefiting from combined acupuncture, HBOT, and conventional steroid therapy. Acupuncture is a safe and nonpharmacologic treatment option and can be considered as an initial treatment strategy in such a clinical scenario.

Development of a Novel Tetracycline-Inducible Kiss1-Cre Mouse Line for Temporally Controlled Gene Deletion in Kisspeptin Neurons

The tetracycline (Tet)-controlled inducible system is the most widely used reversible system for transgenic expression in mice. Previously, we generated a GnRH-CreTeR mouse model, using a first-generation Tet-inducible system to temporally induce expression of Cre recombinase in GnRH neurons. Recently, the Tet-inducible system has undergone several modifications to significantly reduce previous limitations that include leaky background expression and lower sensitivity to tetracycline induction. Therefore, we have developed a novel mouse model bearing a Tet-inducible kisspeptin-Cre allele (iKiss-Cre mouse) that will enable temporal control over the selective deletion of genes from Kiss1 neurons. This temporally controlled gene deletion will eliminate a longstanding technical limitation of conventional steroid receptor knockout models in which steroid regulation of the axis is confounded by steroid developmental and organizational effects in the reproductive axis. Two mouse lines were generated. The first line targets kisspeptin neurons with a third generation Tet-inducible reverse tetracycline transactivator (rtTA, Tet-On 3G) expressed under the control of the Kiss1 allele. Using CRISPR-Cas9 technology, we inserted a cassette containing an internal ribosome entry site (IRES) sequence followed by the rtTA downstream of the Kiss1 coding region as was previously done using Cre recombinase. Transcription of the recombinant Kiss1 allele yields a bicistronic messenger RNA, from which both kisspeptin and rtTA are independently translated. The second mouse line, TRE-Cre mice, was constructed to express Cre recombinase under control of the PTRE3G promoter. The PTRE3G promoter is bidirectional to allow simultaneous monitoring of Cre expression and a second florescent protein reporter (ZsGreen1). The Kiss1-rtTA only binds to and activates the PTRE3G promoter in the presence of doxycycline (an analog of tetracycline). Offspring from breeding of these mouse lines, iKiss-Cre, result in a system capable of generating Tet-induced expression of Cre recombinase in kisspeptin neurons. In order to document specificity and sensitivity of this system, we performed immunofluorescent staining and observed colocalization of kisspeptin with Cre recombinase in brain sections of iKiss-Cre mice only after doxycycline treatment. We will use this model to investigate negative feedback actions of E2 on the adultpulse generator after E2 exerts its organizational actions on maturing kisspeptin neurons. We expect that this mouse model will become a major tool used by the neuroendocrine community and serve as proof of principle for development of similar inducible knockout models employing the current generation of inducible methodologies.

Long-term prospective assessment of subconjunctival triamcinolone acetonide in addition to topical therapy in the management of chronic superficial keratitis

Chronic superficial keratitis (CSK) is a progressive inflammatory disease in adult dogs, associated with corneal vascular proliferation, edema and melanic pigment deposition. In the absence of a curative therapy, the current approach for the management of CSK aims to control disease progression and eventually decrease the severity of corneal lesions. Subconjunctival injections of corticosteroids may be effective in severe cases, where topical therapy alone is inadequate. The aim of this study was to comprehensively evaluate the effectiveness of subconjunctival triamcinolone acetonide (TA) injection in addition to topical steroid treatment for the long-term management of CSK, in dogs unresponsive to conventional topical steroids. Treatment efficacy was assessed in 11 dogs with bilateral CSK by periodic evaluation of the cornea in terms of vascularization, edema and pigmentation for up to 120 weeks. Clinically significant reductions in corneal pigmentation (P&amp;lt;0.0001), vascularization (P&amp;lt;0.0001) and edema scores (P&amp;lt;0.0001) were achieved during therapy. The greatest reduction was exhibited by corneal edema, closely followed by vascularization. Corneal pigmentation was less responsive and complete regression has not been achieved in any of the dogs. Severely affected corneas exhibited greater improvements in terms of pigmentation, whereas moderately affected corneas showed a slight decrease. Corneal edema and vascularization were adequately controlled, whereas corneal pigmentation exhibited a lower decrease in severity and was more difficult to manage on a long-term basis. This study suggests that subconjunctival injection of TA in addition to topical steroids could represent an effective option for long-term management of CSK in dogs unresponsive to topical steroids alone

Therapeutic efficacy of super-high-dose steroid therapy in patients with profound sudden sensorineural hearing loss: a comparison with conventional steroid therapy

Background In patients with sudden sensorineural hearing loss (SSNHL), steroid therapy is an optional treatment method, but there is controversy about its dose. Objective We aimed to compare the efficacy of super-high-dose steroid therapy with that of conventional steroid therapy in patients with profound SSNHL (pSSNHL). Material and methods Fifty-two patients diagnosed with pSSNHL between March 2010 and May 2017 were divided into the following groups based on their steroid regimen: a conventional steroid regimen (prednisolone at 1.0 mg/kg/day for 10 days) was applied in Group 1, and a super-high-dose steroid regimen (prednisolone at 1.5 mg/kg/day for 14 days) was applied in Group 2. The treatment outcomes were compared between the groups at 2 and 4 weeks after the initial treatment by use of Siegel’s criteria. Results Of the 52 patients, 31 were classified into Group 1 and 21 into Group 2. When comparing the proportion of patients in complete or partial recovery by Siegel’s criteria, the recovery rate was significantly higher in Group 2 than in Group 1 (19% vs 0%, p = .022 at 2 weeks; 35.7% vs 7.4%, p = 0.035 at 4 weeks). Conclusions and significance Patients with pSSNHL treated using the super-high-dose steroid regimen demonstrated better recovery rates to serviceable hearing than did those treated using the conventional steroid regimen without significant complications.

Efficacy of the exhalation delivery system with fluticasone in patients who remain symptomatic on standard nasal steroid sprays.

Standard nasal steroid sprays are often first-line treatment for chronic rhinosinusitis (CRS), but many patients remain symptomatic despite their use. The exhalation delivery system with fluticasone (EDS-FLU) has been shown to be efficacious in mixed populations of symptomatic patients, but the question remains whether benefits would be similar in those already on traditional steroid sprays. The goal of this study was to compare EDS-FLU treatment outcomes in patients who have previously failed nasal steroids. Using pooled data from the NAVIGATE I and II trials, EDS-FLU efficacy was compared in the subgroup treated with a conventional nasal steroid at trial entry (mean duration, ≈3 years) to efficacy in the overall study population. Sensitivity analyses were performed for more restrictive definitions of the subgroup changing from prior standard nasal steroids. Of482 total subjects, 218 (45.2%) reported using standard nasal steroid sprays at entry (mean duration, 1051 days). Across multiple outcome measures, improvements for "switchers" receiving EDS-FLU (least squares mean change from baseline vs EDS plus placebo) were comparable with improvements in the overall population. For EDS-FLU 372 μg, comparable improvements were observed in congestion (-0.73 vs -0.62), rhinorrhea (-0.71 vs -0.57), facial pain/pressure (-0.48 vs -0.41), and sense of smell (-0.35 vs -0.30) at week 4 and 22-item Sino-Nasal Outcome Test (-21.01 vs -20.52), Patient Global Impression of Change, and other outcomes at week 16. Results for EDS-FLU 186 μg were similar. EDS-FLU comparably improves symptoms, irrespective of whether patients are symptomatic while using conventional nasal steroids before treatment.

Corticosteroids in Inflammatory Bowel Disease Patients: A Practical Guide for Physicians.

Inflammatory Bowel Diseases (IBDs) are chronic conditions characterized by unknown etiology and pathogenesis with deregulation of mucosal immunity. Among possible treatments, corticosteroids, already available from the '50s, are still the mainstay of treatment for moderate to severe disease. Nonetheless, the use of steroids is still largely empirical and solid evidence about therapeutic schemes are lacking. Moreover, due to the important side-effects and for the unsatisfactory impact on the long-term natural history of the disease, the steroid-sparing has become an important therapeutic goal in IBD management. Besides conventional steroids, the so-called "low bioavailability" steroids, which are steroids with high affinity for peripheral receptors and elevated hepatic first-pass metabolism, have demonstrated efficacy and a more favorable safety profile. In the present review of the literature evidence of efficacy and safety of conventional and low bioavailability steroids in IBD patients are evaluated, and practical suggestions for a correct use in clinical practice are presented according to the current clinical guidelines.

Bilateral Pulmonary Embolism in a 12-Year-Old Girl with Steroid-Resistant Nephrotic Syndrome

Nephrotic syndrome is the most common glomerular disease among children. Although most cases respond to steroid therapy, approximately 10–20% of patients exhibit resistance to conventional steroid therapy and are labeled as steroid-resistant. Such patients are at risk of complications, including infection, thrombosis, and chronic kidney disease. Nephrotic syndrome is considered a thrombogenic condition. Pulmonary embolism is associated with high mortality, and early treatment is essential for the survival of patients. Here, we report the case of a 12-year-old girl with late steroid resistance who developed bilateral pulmonary embolism.

Anti-fertility properties of Cissus rotundifolia (Forssk.) Vahl. Extract using female Wistar rats

A third of the worldwide disease burden among women in their reproductive age ( 15-45 years) is associated with sexual and reproductive complications. The developing world experiences an unmet contraceptive demand that affects nearly 200 million women. The high rates of unintended pregnancies in sub-Saharan Africa increase the prevalence of unsafe abortions in nations. The use of conventional steroids and non-steroid based contraceptives though effective is also linked to increasing side effects. The roots decoction of Cissus rotundifolia is used by women in Tana River County, Kenya as a fertility regulator. The study evaluated the phytochemical compounds present in the Cissus rotundifolia aqueous extract. It also evaluated the effect of the plant extract on oestrus cycle and other selected female reproductive parameters; mating success, fertility index, gestation length, and litter size using female Wistar rats. The phytochemical screening established the presence of alkaloids, tannins, saponins, phenols, and glycosides in the root aqueous extract of Cissus rotundifolia. The plant extract caused a dose-dependent significance increase in proestrus and metestrus phases and a significant reduction in estrus and diestrus phases (P&lt;0.05). There was no significant difference in mating success. It caused a dose-dependent reduction in fertility index compared to the control. Gestation length was significantly increased and litter size significantly reduced (P&lt;0.05).This probably is the reason for the traditional use of the plant as a fertility regulator. However, further work on reversibility, reproductive hormonal profile and ovarian histomorphology should be undertaken to improve the novel contraceptive pool.Â

Effect of intracameral phenylephrine 1.0%-ketorolac 0.3% on postoperative cystoid macular edema, iritis, pain, and photophobia after cataract surgery.

To assess the effectiveness of intracameral phenylephrine-ketorolac during cataract surgery compared with postoperative topical steroids in reducing the incidence of postoperative clinical cystoid macular edema (CME) confirmed via optical coherence tomography (OCT), breakthrough iritis, pain, and photophobia. Ambulatory surgical center/clinical practice. Retrospective 2-cohort study. This study of cataract surgery patients compared the incidence of postoperative CME, breakthrough iritis, pain, and photophobia between patients receiving either intracameral phenylephrine 1.0%-ketorolac 0.3% during surgery or topical loteprednol 0.5% 2 days preoperatively, tapered postoperatively. Patients with prior CME or at high risk for postoperative CME, combined cataract/glaucoma surgery, and medication protocols different from those studied here were excluded. All eyes received bromfenac 2 days preoperatively and 10 weeks postoperatively. The study enrolled 2218 eyes (n = 1402). The phenylephrine/ketorolac treatment group included 1334 eyes (n = 830) and the topical loteprednol control group included 884 eyes (n = 572). The groups were comparable in age, race, gender, and perioperative characteristics. Clinical CME incidence was significantly lower in the phenylephrine-ketorolac group (0.52% vs 1.47%, P = .021). The phenylephrine-ketorolac group also had significantly lower breakthrough iritis (1.72% vs 4.86%, P < .001) and pain (1.27% vs 4.19%, P < .001) than the topical loteprednol group. The incidence of photophobia trended lower for the phenylephrine/ketorolac group relative to the topical loteprednol group (0.90% vs 1.13%, respectively, P = .590) but was not statistically significant. Intracameral phenylephrine/ketorolac and topical nonsteroidal antiinflammatory drugs (NSAIDs) without postoperative topical steroids significantly reduced postoperative clinical CME, breakthrough iritis, and pain after cataract surgery when compared with conventional perioperative topical steroids and NSAIDs.

The clinical, laboratory, and radiologic improvement due to siltuximab treatment in idiopathic multicentric Castleman's disease.

Background/AimsIdiopathic multicentric Castleman disease (iMCD) comprises approximately 30% of all cases of Castleman disease. It is characterized by constitutional symptoms, enlarged lymph nodes at multiple anatomical sites, and laboratory test abnormalities, which are primarily related to the overproduction of interleukin 6 (IL-6). Siltuximab is a human-mouse chimeric immunoglobulin G1κ monoclonal antibody against human IL-6. In view of the limited treatment options for iMCD, this study aimed to evaluate the efficacy and safety of siltuximab in the management of this condition.MethodsIn this real-world retrospective study, we administered siltuximab to 15 patients with iMCD who previously received conventional chemotherapy and/or steroid pulse therapy. The median time to a durable symptomatic response was 22 days (range, 17 to 56). The serum hemoglobin and albumin levels and erythrocyte sedimentation rates significantly normalized after the first 3 months of siltuximab treatment. Lymph node involution, assessed using imaging, was relatively gradual, demonstrating a complete or partial response at 6 months.ResultsOn an average, the improvements in clinical, laboratory, and radiologic parameters of iMCD in responders were observed after one, three, and eight cycles of siltuximab treatment, respectively. Siltuximab demonstrated a favorable safety profile, and prolonged treatment was well-tolerated.ConclusionsDespite the small sample size of the present study, the results are encouraging and demonstrate the potential of siltuximab as the first-line treatment of iMCD. Further large multicenter studies are needed to evaluate the clinical outcomes and adverse events associated with siltuximab.

Favorable Outcome with Durable Chimerism after Allogeneic Hematopoietic Cell Transplantation Using Busulfan and Fludarabine-Based Reduced-Intensity Conditioning for Children with Hemophagocytic Lymphohistiocytosis

Purpose Hematopoietic Stem Cell Transplantation (HSCT) is the only curative treatment for patients with familial, relapsing, or persistent hemophagocytic lymphohistiocytosis (HLH). Here, we present a single center experience of using busulfan (Bu) and fludarabine (Flu) based reduced intensity conditioning regimen (RIC) for treatment of HLH. Methods Medical records of pediatric patients with HLH, who received HSCT using Bu/Flu based RIC regimen.from January 2008 to December 2017, were reviewed retrospectively. HSCT outcomes including engraftment, survival, and GVHD were analyzed. Results Nine patients were received HSCT using Bu/Flu based RIC regimen. Three patients received HSCT after diagnosis of familial HLH and the other 6 received after reactivation. All 3 patients with familial HLH had UNC13D mutations. Median 8.35 × 106 /kg (range, 2.84-10.05 × 106) CD34 positive cells were infused. All patients achieved WBC and PLT engraftment at median 11 days (range, 10-21) and 19 days (range, 13-32) from HSCT with full donor chimerism which sustained until last visit. Cyclosporine and mycophenolate mofetil were applied as GVHD prophylaxis except one patient who received HSCT from syngeneic sibling. Three patients (33%) experienced acute graft-versus-host disease (GVHD) of grade 2 which was well controlled after conventional steroid treatment. Two patients (22%) underwent chronic GVHD, and one of them died. One patient (11%) had reactivation 4 months after HSCT from syngeneic sibling donor, and died. The 5-year overall survival was 78%. Two patients died; one died of disease and the other died of treatment related mortality (TRM). No TRM other than chronic GVHD was existed. Conclusion Our experience suggests that Bu/Flu based RIC regimen can be effective option for pediatric patients with HLH who need HSCT showing durable chimerism and long-term survival with decreased toxicity.