Addition Of Steroids Research Articles

DOP03 The use and efficacy of biological therapies 2010–2020 for Inflammatory Bowel Disease in a Danish tertiary centre

Abstract Background Direct health care costs have shifted towards drug-related expenditures in patients with inflammatory bowel disease (IBD). Frequently, patients will have to switch to a second- or third-line biological therapy due to no response or loss of response. The aim of this study was to describe the use and efficacy of biological therapy in a tertiary centre during a 10-year period and investigate the need for surgery. Methods The study population consisted of all bio-naïve IBD patients who initiated biological therapy between January 1, 2010 and February 19, 2020 at the Gastro unit, Hvidovre Hospital, Denmark. The electronic medical records were reviewed, and data were systematically registered. Failure of the biological therapy as no response and loss of response was defined by the need for surgery, steroid or shift in biological therapy. Results The study population consisted of 291 (46.9%) patients with ulcerative colitis (UC), 327 (52.7%) with Crohn’s disease (CD) and 3 with (0.5%) IBD Unclassified (IBDU), who initiated biological therapy with a median follow-up of 3 (IQR=2–5) years from initiation of therapy. The annual number of patients who initiated biological therapy was increasing throughout the study period. Most patients (457, 73.6%) received one biological drug, 126 (20.3%) received two, and 38 (6.1%) received three or more different types of biological drugs during the study period. Systemic steroid was required in 99 patients (15.9%) and the 5-year surgery-free survival was 76.5% (120 patients with surgery). 302 patients (54.3%) had effect of the first biological therapy at one year follow-up. In multivariate Cox-regression analyses, concurrent treatment with thiopurines decreased the risk of failure of the first biological therapy in UC patients (hazard ratio (HR) 0.745, 95% CI: 0.559–0.992) but not in CD patients (HR 0.969, 95% CI: 0.722–1.300). Male gender decreased the risk of failure (HR: 0.677, 95% CI: 0.505–0.908) while higher age at initiation of biological therapy increased the risk (HR: 1.0152, 95% CI: 1.004–1.027) in CD patients. These factors had no impact in UC patients. Prior surgery, disease duration and location were not associated with increased risk of failure of first biological therapy. Conclusion In conclusion, an increasing number of IBD patients received biological therapy during the 10-year period at our tertiary centre. A considerable part of IBD patients in biological therapy will require surgery, additional steroids, or second line biological therapy. Our findings suggest a beneficial role of thiopurine in combination with biological therapy. Improved identification of patients not responding to first line biological therapy is of great importance.

Parallel targeted and non-targeted quantitative analysis of steroids in human serum and peritoneal fluid by liquid chromatography high-resolution mass spectrometry

We developed and validated a liquid chromatography high-resolution mass spectrometry method for the absolute quantification of 51 steroids for clinical analysis of human serum and, for the first time, peritoneal fluid. Data acquisition was performed in both targeted and untargeted mode simultaneously, thus allowing the accurate and precise quantification of the main components of the classical steroid pathways (17 steroids) as well as the analysis of 34 additional non-classical steroids. For targeted analysis, validation was performed according to FDA guidelines, resulting, among other parameters, in accuracy < 13% RSD and precision < 10% relative error, for both inter- and intra-day validation runs. By establishing steroid-specific response factors, the calibration curves of the targeted analytes can be extended to untargeted analytes. This approach opens novel possibilities for the post hoc analysis of clinical samples as the data can be examined for virtually any steroid even after data acquisition, enabling facile absolute quantification once a standard becomes available. We demonstrate the applicability of the approach to evaluate the differences in steroid content between peripheral serum and peritoneal fluid across the menstrual cycle phases, as well as the effect of the synthetic gestagen dienogest on the steroid metabolome.Graphical abstract

Living with severe asthma as a teenager

Living with severe asthma as a teenager

Myasthenia Gravis: Novel Findings and Perspectives on Traditional to Regenerative Therapeutic Interventions.

The prevalence of myasthenia gravis (MG), an autoimmune disorder, is increasing among all subsets of the population leading to an elevated economic and social burden. The pathogenesis of MG is characterized by the synthesis of autoantibodies against the acetylcholine receptor (AChR), low-density lipoprotein receptor-related protein 4 (LRP4), or muscle-specific kinase at the neuromuscular junction, thereby leading to muscular weakness and fatigue. Based on clinical and laboratory examinations, the research is focused on distinguishing MG from other autoimmune, genetic diseases of neuromuscular transmission. Technological advancements in machine learning, a subset of artificial intelligence (AI) have been assistive in accurate diagnosis and management. Besides, addressing the clinical needs of MG patients is critical to improving quality of life (QoL) and satisfaction. Lifestyle changes including physical exercise and traditional Chinese medicine/herbs have also been shown to exert an ameliorative impact on MG progression. To achieve enhanced therapeutic efficacy, cholinesterase inhibitors, immunosuppressive drugs, and steroids in addition to plasma exchange therapy are widely recommended. Under surgical intervention, thymectomy is the only feasible alternative to removing thymoma to overcome thymoma-associated MG. Although these conventional and current therapeutic approaches are effective, the associated adverse events and surgical complexity limit their wide application. Moreover, Restivo et al. also, to increase survival and QoL, further recent developments revealed that antibody, gene, and regenerative therapies (such as stem cells and exosomes) are currently being investigated as a safer and more efficacious alternative. Considering these above-mentioned points, we have comprehensively reviewed the recent advances in pathological etiologies of MG including COVID-19, and its therapeutic management.

Variation in Pharmacologic Management of Patients with Kawasaki Disease with Coronary Artery Aneurysms

To evaluate practice variation in pharmacologic management in the International Kawasaki Disease Registry (IKDR). Practice variation in intravenous immunoglobulin (IVIG) therapy, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy, and anticoagulation was described. We included 1627 patients from 30 IKDR centers with maximum coronary artery aneurysm (CAA) z scores 2.5-4.99 in 848, 5.0-9.99 in 349, and ≥10.0 (large/giant) in 430 patients. All centers reported IVIG and acetylsalicylic acid (ASA) as primary therapy and use of additional IVIG or steroids as needed. In 23 out of 30 centers, (77%) infliximab was also used; 11 of these 23 centers reported using it in <10% of their patients, and 3 centers used it in >20% of patients. Nonsteroidal anti-inflammatory agents were used in >10% of patients in only nine centers. Beta-blocker (8.8%, all patients) and abciximab (3.6%, all patients) were mainly prescribed in patients with large/giant CAAs. Statins (2.7%, all patients) were mostly used in one center and only in patients with large/giant CAAs. ASA was the primary antiplatelet modality for 99% of patients, used in all centers. Clopidogrel (18%, all patients) was used in 24 centers, 11 of which used it in >50% of their patients with large/giant CAAs. In the IKDR, IVIG and ASA therapy as primary therapy is universal with common use of a second dose of IVIG for persistent fever. There is practice variation among centers for adjunctive therapies and anticoagulation strategies, likely reflecting ongoing knowledge gaps. Randomized controlled trials nested in a high-quality collaborative registry may be an efficient strategy to reduce practice variation.

Delayed skin reaction after mRNA-1273 vaccine against SARS-CoV-2: a rare clinical reaction

BackgroundThe coronavirus disease 2019 (COVID‐19) is associated with a wide clinical spectrum of skin manifestations, including urticarial, vesicular, vasculitic and chilblain‐like lesions. Recently, delayed skin reactions have been reported in 1% individuals following mRNA vaccination against SARS-CoV-2. The exact pathophysiology and the risk factors still remain unclear.Patients and methods6821 employees and patients were vaccinated at our institutions between February and June 2021. Every patient received two doses of the mRNA-1273 vaccine in our hospitals, and reported back in case of any side effects which were collected in our hospital managed database.ResultsEleven of 6821 vaccinated patients (0.16%) developed delayed skin reactions after either the first or second dose of the mRNA-1273 vaccine against SARS-CoV-2. Eight of 11 patients (73%) developed a rash after the first dose, while in 3/11 (27%), the rash occurred after the second dose. More females (9/11) were affected. Four of 11 patients required antihistamines, with two needing additional topical steroids. All the cutaneous manifestations resolved within 14 days. None of the skin reactions after the first dose of the vaccine prevented the administration of the second dose. There were no long-term cutaneous sequelae in any of the affected individuals.ConclusionOur data suggests that skin reactions after the use of mRNA-1273 vaccine against SARS-CoV-2 are possible, but rare. Further studies need to be done to understand the pathophysiology of these lesions.

A case of rheumatoid meningoencephalitis induced by pembrolizumab

AbstractImmune checkpoint inhibitors occasionally cause various side effects, but the occurrence of a severe immune‐related adverse event (irAE) is rare in neurology. We report on a 56‐year‐old woman who suffered from rheumatoid arthritis and recurrent uterine cancer. After treatment with pembrolizumab, she showed visual disturbance followed by acute fever and consciousness disturbance with high‐intensity lesions around the midbrain aqueduct and bilateral caudate heads on FLAIR images of a brain MRI. Her symptoms improved after steroid therapy. However, symptoms relapsed leading to an elevation of the anti‐CCP antibody index. Pembrolizumab‐induced rheumatoid meningoencephalitis was suspected, so additional steroid therapy was provided. This improved her symptoms, turning the anti‐CCP antibody index negative. The present case is the first case of rheumatoid meningoencephalitis induced by pembrolizumab. The combination of MRI findings and elevated anti‐CCP index seems useful for diagnosing rheumatoid meningoencephalitis.

Comparison of the Effect of Steroids on the Treatment of Phimosis according to the Steroid Potencies.

This study aimed to evaluate the outcomes of topical steroid therapy according to potency as the first-line treatment for boys with symptomatic phimosis. From April 2017 to March 2019, we retrospectively reviewed 45 boys with severe phimosis (Kikiros retractability grade 4 or 5) who presented with phimosis-related complications. During the first year of the study period, methylprednisolone aceponate (MPA, Advantan®, potent topical steroid) was administered in 24 boys. Hydrocortisone butyrate (HCB, Bandel®, moderately potent topical steroid) was administered in 21 boys in the subsequent period. Topical steroids were administered for 4-8 weeks in all patients. Success of the therapy was determined by two conditions at 3 months after therapy: achieving Kikiros grade 3 and less with disappearance of symptoms. Of 45 boys, 35 (77.8%) achieved success of the therapy. Mean age was 46.64±22.42 months. Recurrence of phimosis with clinical complications was confirmed in three of 35 patients with initial success (8.6%) during the follow-up period. All boys with recurrence showed remission after additional topical steroid therapy. Success rate of the MPA group was higher than that of the HCB group (91.7% and 61.9% respectively, P = .029). Side effects associated with the topical steroid application were not observed in all children. Topical steroid application is an effective and safe procedure as first-line treatment in symptomatic boys with severe phimosis. Moreover, the potency of topical steroids for the treatment of phimosis is considered a factor affecting the success rate.

Pharmacological prevention of delayed hypersensitivity reactions caused by iodinated contrast media

BackgroundDelayed hypersensitivity reactions (DHRs) to radiocontrast media (RCM) occur in approximately 0.5–23.0% of patients and are thought to be caused by T cell-mediated mechanisms. However, an optimal pharmacological preventive strategy is not yet established in patients with histories of delayed reactions to RCM. ObjectiveWe aimed to evaluate the efficacy of pharmacological prevention in patients with histories of delayed reactions to non-ionic low-osmolar RCM when re-exposed to RCM. MethodsA retrospective review of electronic medical records of 117 patients with previous histories of DHRs to RCM who visited an allergy clinic for the prevention of reactions after the re-exposure to RCM was conducted. The effects of pharmacological prevention were compared according to the symptom scores of previous reactions based on their intensities and durations with electronic medical records (EMRs). ResultsOf the 117 patients who experienced DHRs after RCM injection, we confirmed the outcomes of RCM re-exposure in 101 patients. For pharmacological prevention, 92 patients (91.1%) received steroids before RCM injection and among them, 50 patients (49.5%) received additional steroids after RCM injection. With this pharmacological prevention, patients of symptoms improved or no recurrence, recurrence of similar previous symptoms, and recurrence of worse symptoms were 98 (97.0%), 2 (2.0%), and 1 (1.0%), respectively. The proportions of no recurrence after pharmacological prevention were lower in patients with severe reactions and higher symptom scores. ConclusionPharmacological prevention showed a beneficial effect in most patients with delayed hypersensitivity to RCM. Further investigations are needed to establish an effective protocol for the prevention of delayed reactions to RCM.

Measuring steroids from dried blood spots using tandem mass spectrometry to diagnose congenital adrenal hyperplasia

BackgroundCongenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders that occur due to defects in the steroidogenesis pathway. Approximately 90% of CAH cases can be diagnosed by the measurement of serum 17-hydroxyprogesterone alone. However, the quantification of six additional steroids could significantly improve CAH laboratory diagnosis. Using dried blood spot (DBS) as specimen of choice can further improve patient care due to the small sample volume required for CAH diagnosis in neonates. MethodsAn optimized DBS sample preparation method was employed for steroids quantification without the need of derivatization. A LC-MS/MS assay was developed and optimized using a reverse phase-ultra high-pressure liquid chromatography (RP-UHPLC) system combined with triple quadrupole mass spectrometry using positive electrospray ionization mode. ResultsThe assay was validated according to CLSI analytical guidelines, including lower limit of quantification (LLOQ), linearity, precision, accuracy, carryover, and method comparison. The analytical measuring range of the method for all steroids was 2.5, 5, or 10 ng/ml to 250 ng/ml in DBS, r2 ≥ 0.995. The LLOQ, intra-day and inter-day precision were 0.11–1.8 ng/ml, 1.2–6.4 ng/ml, 1.8–11.5%, and 5.3–13.8%, respectively. ConclusionsOur LC-MS/MS assay simultaneously detects 7 steroids for the diagnosis of CAH and can be readily implemented in clinical laboratories to provide superior analytical performance over traditional immunoassays.

Birth Weight- or Gestational Age-adjusted Second-tier LCMSMS Cutoffs Improve Newborn Screening for CAH in New Zealand.

The positive predictive value of newborn screening for congenital adrenal hyperplasia (CAH) in New Zealand is approximately 10%. The use of a second tier liquid chromatography-tandem mass spectrometry bloodspot steroid profile test with birth weight- or gestational age-adjusted screening cutoffs may result in further screening improvements. Three years of newborn screening data with additional second-tier steroid metabolites was evaluated (n = 167 672 births). Data from babies with a negative screening test and confirmed CAH cases were compared. First- and second-tier steroid measurements were correlated with both birth weight and gestational age. Analysis of variance was used to determine birth weight and gestational age groups. Screening cutoffs were determined and applied retrospectively to model screening performance. First-tier immunoassay data correlated better with gestational age than with birth weight, but there was no difference with second-tier steroid measurements. Four distinct birth weight and gestational age groups were established for 17-hydroxyprogesterone and a steroid ratio measurement. Application of 97.5th percentile second-tier birth weight- or gestational age-adjusted cutoffs would result in 10 positive tests over the period of the study with 8 true-positive screens and 2 false-positive tests. The positive predictive value of screening would be increased from 10.8% to 80%. The use of either birth weight- or gestational age-adjusted cutoffs for second-tier screening tests can significantly reduce the false positive rate of newborn screening for CAH in New Zealand without loss in screening sensitivity.

MO168MANAGEMENT OF ANTICOAGULANT RELATED NEPHROPATHY: SLOVENIAN CASE SERIES AND REVIEW OF CURRENT KNOWLEDGE

Abstract Background and Aims Anticoagulant-related nephropathy is a recently recognized form of acute kidney injury associated with previously underdiagnosed kidney damage in addition to (usually) excessive anticoagulation. It occurs in patients receiving warfarin as well as those receiving direct oral anticoagulants. Method We collected and analyzed cases of Slovenian patients with pathohistologically documented anticoagulant-related nephropathy associated with all types of anticoagulant treatment from the first case in 2014 to 2020. We also performed an analysis of previously documented cases of anticoagulant-related nephropathy in the global literature (PubMed) in the period from their first mention until recently. Results In Slovenia, 13 patients with anticoagulant-related nephropathy have been histologically verified so far. All patients were diagnosed with concomitant underlying renal disease, and 80% had IgA nephropathy, which was disproportionately mild according to the degree of renal function impairment. After supportive measures and reversal of excessive anticoagulation, 8 of 13 patients were further treated with corticosteroids, resulting in significant improvement in renal function. During the follow-up period, a total of one steroid-treated patient died due to infectious complications and one patient progressed to end-stage renal failure. In the worldwide literature, we found 46 case reports or case series of patients with anticoagulant-related nephropathy. Failure of restitution of renal function with the need for maintenance dialysis was reported much more frequently compared to the results of our cohort (up to 67% vs. 8.3%) Conclusion To our knowledge, the Slovenian cohort of patients with histologically established anticoagulant-related nephropathy is the largest reported series to date that received corticosteroid therapy in addition to conservative measures. Our results indicate that steroids have a beneficial effect, likely exerted via suppression of hemoglobin-associated oxidative stress and inflammation. However, considering the polimorbidity of these patients, the benefit of additional steroid therapy must be weighed against the potential risks of side effects, especially life-threatening infections.

Feasibility and preliminary effect of anabolic steroids in addition to strength training and nutritional supplement in rehabilitation of patients with hip fracture: a randomized controlled pilot trial (HIP-SAP1 trial)

BackgroundAnabolic steroid has been suggested as a supplement during hip fracture rehabilitation and a Cochrane Review recommended further trials. The aim was to determine feasibility and preliminary effect of a 12-week intervention consisting of anabolic steroid in addition to physiotherapy and nutritional supplement on knee-extension strength and function after hip fracture surgery.MethodsPatients were randomized (1:1) during acute care to: 1. Anabolic steroid (Nandrolone Decanoate) or 2. Placebo (Saline). Both groups received identical physiotherapy (with strength training) and a nutritional supplement. Primary outcome was change in maximal isometric knee-extension strength from the week after surgery to 14 weeks. Secondary outcomes were physical performance, patient reported outcomes and body composition.ResultsSeven hundred seventeen patients were screened, and 23 randomised (mean age 73.4 years, 78% women). Target sample size was 48. Main limitations for inclusion were “not home-dwelling” (18%) and “cognitive dysfunction” (16%). Among eligible patients, the main reason for declining participation was “Overwhelmed and stressed by situation” (37%). Adherence to interventions was: Anabolic steroid 87%, exercise 91% and nutrition 61%. Addition of anabolic steroid showed a non-significant between-group difference in knee-extension strength in the fractured leg of 0.11 (95%CI -0.25;0.48) Nm/kg in favor of the anabolic group. Correspondingly, a non-significant between-group difference of 0.16 (95%CI -0.05;0.36) Nm/Kg was seen for the non-fractured leg. No significant between-group differences were identified for the secondary outcomes. Eighteen adverse reactions were identified (anabolic = 10, control = 8).ConclusionsEarly inclusion after hip fracture surgery to this trial seemed non-feasible, primarily due to slow recruitment. Although inconclusive, positive tendencies were seen for the addition of anabolic steroid.Trial registrationClinicaltrials.gov NCT03545347.

Conservative Management of Thyroid Eye Disease.

The aim of the study was to determine the result of conservative management of Graves ophthalmopathy in a multi-disciplinary setting by a team of ophthalmologists and endocrinologists. Twenty-seven patients of thyroid eye disease were included in the study who underwent complete ocular examination and complete thyroid biochemical profile. Each patient was advised lubrication with artificial tears, cool compresses, sleeping with elevated head at bed, taping of the eyelids while sleeping and avoidance of smoking. Follow-ups were done at one and six months. EUGOGO classification was used to classify severity of the disease in mild, moderate, severe, and very severe; whereas, clinical activity score (CAS) was implied to categorise the disease activity. Mild to moderate Graves ophthalmopathy responded very well to conservative management. Moderate cases required additional steroids. Whereas, severe and very severe cases require additional surgical intervention. Key Words: Graves ophthalmology, Conservative management, Lubrication, Multidisciplinary approach.

Heart Transplantation Single Center Experience of 63 Heart Transplantation Procedures Performed during the COVID 19 Pandemic

PurposeThe COVID19 (C19) pandemic has resulted in a significant reduction in cardiac surgical procedures worldwide and in particular heart (OHT) transplantations. This was primarly due to increased risk of C19 infection and severity in immunocompromised patients (pts). Donor aviability decreased steeply, as intensive care units are struggling with C19 patients. Yet, number of patients requiring OHT increased rapidly, comprising of individuals with dreadful complications of untreated acute coronary syndromes.MethodsBetween March and October 2020 63 pts underwent OHT. The age range was 21-65 yrs and a median of 52 yr. All patients were evaluated by a multidisciplinary heart failure team (MDT), and placed on the HT waiting list once eligible. Once a donor has been identified, clinical history and examination obtained, a chest CT was taken and real time RTPCR test is ordered. Every recipient was subject to clinical screening, chest XRay, real RTPCR (24 hrs within HT)upon admission. All pts were looked after by experienced staff who tested negative for SARS-CoV-2, wearing PPE, working in isolation, single room care and visitors were not admitted.ResultsNo recipient or donor tested positive for SARS-CoV-2 at any stage in their care. 5 (8%) pts died, >30 days after the procedure, of multiorgan failure; all 5 pts were in INTERMACS II at the time of OHT. All patients were managed with our standard immunosuppression therapy consisting of mycofenolante mofetil and steroids in addition to calcineurin inhibitor (tacrolimus). According to recent results 25 patients (40%) had allograft rejection of ISHLT grade 3a detected by routine endomyocardial biopsies within first 3 months. The highdose steroids therapy was involved and positive response (ISHLT grade 0) was observed. 56 pts had a hospital stay of 30 d or less, 7 pts more than 30 d. Follow up visits were conducted using telemedicine unless it was absolutely necessary to see the pt in hospital. Also, we raised the threshold for endomyocardial biopsies by relying on clinical judgement and stable allograft function.ConclusionBy creating a robust system of care based on team work, early testing and retesting of patients and staff for SARSCoV2, the use of proper PPE's, adequate isolation and subsequent minimization of contact with pts, we were able to demonstrate that HT in the era of COVID19 pandemic can be performed safely.

Carfilzomib-Induced Pneumotoxicity in a Lung Transplant Recipient

Introduction Development of de novo donor-specific antibodies (DSA) in lung transplant (LTx) recipients is a risk factor for antibody-mediated rejection (AMR). There is no consensus on treatment protocols for patients who develop de novo DSA, but strategies include plasmapheresis (PLEX), intravenous immunoglobulin (IVIG), and carfilzomib (CFZ), a second-generation proteasome inhibitor. Dyspnea is common in patients with multiple myeloma treated with CFZ; however, lung injury in LTx recipients has not been reported. We report a case of CFZ-related pneumotoxicity in a bilateral LTx recipient undergoing treatment for possible AMR. Case Report A 71-year-old bilateral LTx recipient (October 2011) with moderate mitral regurgitation was diagnosed with probable AMR in June 2018, characterized by de novo DSA (DQ7, MFI 20,634) and FEV1 decline, but no radiographic changes or capillaritis. He was treated with PLEX, IVIG, and rituximab and had monthly PLEX/IVIG until January 2020. He tolerated the treatment well and his FEV1 stabilized. After a 5-month moratorium of PLEX/IVIG, the patient's MFI increased from 4,337 in November 2019 to 15,444 in June 2020; however, FEV1 remained stable. PLEX was resumed and CFZ was administered in August 2020, which led to a hypertensive emergency, hypoxemic respiratory failure requiring mechanical ventilation, renal failure requiring continuous renal replacement therapy, and corticosteroid therapy for persistent hypoxemia and radiographic infiltrates despite a negative fluid balance. He was extubated, his renal function recovered, and he was discharged home on supplemental oxygen and a corticosteroid taper. On outpatient follow-up, he had a 600-ml drop in FEV1, complained of severe dyspnea on exertion with hypoxemia, appeared euvolemic on physical exam, and was readmitted with evidence of ongoing lung injury. Radiographic infiltrates and hypoxemia improved with additional steroid therapy. Summary A bilateral LTx recipient presented with hypoxemic respiratory failure immediately after a 5-day course of PLEX and an infusion of CFZ. Although volume overload was a factor, persistent lung injury despite aggressive diuresis and blood pressure control suggests CFZ pneumotoxicity. Although the mechanism of CFZ lung injury is not understood, it appears to be steroid responsive, both in our patient and in other cases of proteasome inhibitor-induced pneumotoxicity.

Implementing steroid profiling by liquid chromatography-tandem mass spectrometry improves newborn screening for congenital adrenal hyperplasia in New Zealand.

To evaluate the impact of a liquid chromatography-tandem mass spectrometry (LCMSMS) second-tier test on newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) in New Zealand. In a prospective study, a LCMSMS method to measure 17-hydroxyprogesterone (17OHP) was adapted to measure four additional steroids. Steroid concentrations were collected on all second-tier CAH screening tests while protocols remained unchanged. Steroid ratio parameters with recommended or published screening cuts-offs were evaluated for their impact on newborn screening performance. Precision, accuracy, linearity and recovery of the second-tier LCMSMS method were evaluated. Second-tier specimens were divided in 3 groups; newborn screening bloodspots from neonates with confirmed CAH (n=7) and 2 groups specimens from neonates with a birthweight (BW) ≤1500g (n=795) and with a BW>1500g (n=806) with a negative newborn screening test. Six protocols using four steroid ratio parameters were evaluated. The sensitivity, specificity, false positive rate and positive predictive value of screening was calculated for each protocol. The LCMSMS method was sufficiently accurate and precise to be used as a second-tier test for CAH. Screening sensitivity remained at 100% for each protocol apart from (17OHP+androstenedione)/cortisol when the highest cut-off of 3.75 was applied. The false positive rate was significantly improved when (17OHP+androstenedione)/cortisol and (17OHP+21-deoxycortisol)/cortisol were evaluated with cut-offs of 2.5 and 1.5 respectively (P<.01) and both with a positive predictive value of 64%. A second-tier LCMSMS newborn screening test for CAH offers significant improvements to screening specificity without any other changes to screening protocols.

Triple treatment in ear keloids: Comparison of post-excisional intralesional steroid and platelet-rich plasma treatment

PurposeEar keloids lead to psychological problems in the patient by causing complaints, such as itching and swelling. It is highly resistant to treatment, and recurrences are frequent. In the present study, the purpose was to investigate the treatment success of the intralesional steroid and PRP combination in addition to surgical excision in ear keloids. The 5-year recurrence rates and adverse effects of both treatments were also compared in this respect. Materials and methodsIn this study, 60 patients between the ages of 16 and 65 who were followed up between 2015 and 2020 due to ear keloids were evaluated retrospectively. Patients were divided into 3 different groups (n = 20) as (A-B-C). There were patients who had only intralesional steroid injections due to ear keloids in Group A, patients who had intraoperative/postoperative steroid injections combined with surgical excision were in Group B, and patients who had intraoperative/postoperative steroid+intraoperative Platelet-Rich Plasma (PRP) injections combined with surgical excision were in Group C. ResultsIt was found that the 5-year recurrence rate was the lowest in Group C (Surgical Excision+PRP + TAC). The 5-year recurrence rate of Group C was significantly lower when compared with other groups (p < 0.05). When the 5-year recurrence rate of Group A (TAC) and B (Surgical Excision+TAC) was compared, the recurrence rate of Group B was significantly lower (p < 0.05). When the adverse effects were compared, no significant differences were detected between two Groups (A-B) in terms of Skin Atrophy and Telangiectasia. Significant differences were detected between patients in Group C and other groups (p < 0.05). No significant differences were detected between Group B and C (p = 0.832). ConclusionThe combination of surgical excision with Intralesional TAC and PRP treatment in patients with ear keloids should be considered as a highly successful multimodal treatment in terms of low recurrence and adverse effects.

Evaluating tertiary adrenal insufficiency in rheumatology patients on long-term systemic glucocorticoid treatment.

Patients with rheumatic diseases are often treated with prolonged, high-dose systemic glucocorticoids which can cause hypothalamic-pituitary-adrenal (HPA) axis suppression and development of tertiary adrenal insufficiency. Adrenal insufficiency carries the risk of serious, potentially life-threatening adrenal crisis. Our study evaluated the prevalence, characteristics and recovery of patients with underlying rheumatology conditions who had received prolonged glucocorticoid treatment. Retrospective, cross-sectional study. We evaluated 238 patients seen in outpatient rheumatology clinic, managed in accordance with current nationally and internationally accepted clinical guidelines. Data collected included patient demographics, historical steroid data, 09.00h cortisol/short synacthen test (SST) results and follow-up data on those with repeat assessments. Overall, 65% of our cohort had a 09.00h cortisol <350nmol/L. On SST, 43% of patients demonstrated evidence of possible tertiary adrenal insufficiency. Prednisolone equivalent dose at time of SST was significantly higher in the group who failed SST vs. those who passed; mean of 5.57mg vs. 3.59mg (p=.005). 09.00h cortisol result correlated with 30-min cortisol on SST (R2 =.20, p=.002). 0-min cortisol on SST correlated more strongly with 30-min cortisol than 09.00h cortisol (R2 =.59, p-value<.001). Patients with 0-min cortisol >350nmol/L, all passed their SST. Patients who remained on prednisolone were more likely to recover (71%) vs. those switched to hydrocortisone (27%), P=.02. Peak steroid dose was predictive of recovery; significantly lower in those who recovered (mean of 22.3mg vs. 33.8mg, P=.03). Steroid duration was not found to be a predictor of recovery [recovery (64.2months) vs. non-recovery (55.6months), P=.58]. There was no correlation found to outcome on SST with age, sex, peak steroid dose, steroid duration, underlying rheumatological condition, additional exogenous steroid use or serum sodium. Forty three percent of our patients demonstrated sub-optimal adrenal function on SST. Steroid dose at the time of SST was the only significant predictive risk factor for tertiary adrenal insufficiency. 09.00h cortisol demonstrated good correlation with outcome on SST and could represent a valid screening test to reduce need for SST if 09.00h >350nmol/L. Further prospective data are required to further characterize risk factors, predictive features of recovery and establish optimal management strategy of steroids (prednisolone vs hydrocortisone) to encourage adrenal recovery.

Influence of Saw palmetto and Pygeum africana extracts on the urinary concentrations of endogenous anabolic steroids: Relevance to doping analysis

BackgroundOver the counter preparations containing Saw palmetto and Pygeum africana extracts are commonly used in the treatment of benign prostatic hyperplasia with lower urinary tract symptoms. Their effects are likely due to their anti-androgenic activity, involving the interaction with type 1 and type 2 isoenzymes of the 5α-reductase family. Hypothesis/purposeFor effects similar to the above, the inhibitors of 5α-reductase (e.g., finasteride) are classified as confounding factors in the evaluation of the urinary steroid profile in sport doping. We aimed to verify whether the oral intake of products containing Saw palmetto and Pygeum africana could affect the urinary concentration of a series of steroids, not limited to those included in the “steroidal module” of the Athlete Biological Passport (ABP). Study designWe have followed the effects of a five-day administration of Saw palmetto (320 mg) and Pygeum africana (100 mg) to three non-smokers male subjects on the urinary parameters constituting the “steroidal module” of the ABP, and on the concentration of additional steroid markers. In parallel, we have also measured the urinary concentration of β-sitosterol, which is the active component of Saw palmetto and Pygeum Africana. MethodsSample collection was performed five days before starting the controlled administration study to obtain the baseline urinary steroid pattern for each subject. After this period, the three volunteers took a dose of Saw palmetto (320 mg) and Pygeum africana (100 mg) formulation orally, once a day, for five consecutive days. Urine samples were collected at different times of the day and stored at −20 °C until analysis. Samples were analyzed by a previously developed and validated method based on gas chromatography coupled to tandem mass spectrometry (GC–MS/MS). ResultsOur results show that the intake of a single oral dose of Saw palmetto and Pygeum africana for five consecutive days leads to a broader data dispersion of the target steroids' concentration levels, and, consequently, to a variation of the corresponding individual normality ranges. ConclusionThe intake of dietary supplements containing Saw palmetto and Pygeum africana could be a source of interference in the correct longitudinal evaluation of the individual steroid profile, as described in the framework of ABP. We believe their urinary levels should be monitored as it is presently done for other confounding factors of the steroidal module of the ABP.