Prolonged Steroid Treatment Research Articles

#1153 Short course of steroids as a treatment for immune checkpoint inhibitors-associated acute kidney injury

Abstract Background and Aims Immune checkpoint inhibitors (ICPi) have been a revolution in oncology. Due to their mechanism of action they can produce inflammatory adverse events, called “immune related adverse events” (IrAEs). Immune-mediated renal toxicity appears to be infrequent (2.2-5%), with acute tubulointerstitial nephritis being the most common form, clinically manifested as acute kidney injury (AKI). Corticosteroids are a highly effective treatment. However, the most suitable regimen has not been established. Method Retrospective multicenter study to evaluate the efficacy and safety of a short course of steroids (Group A) versus a long course (Group B) in patients with a clinical or histologic diagnosis of ICPi-associated acute kidney injury (ICPi-AKI). Short-duration regimen was considered to be that with a duration ≤3 months. Renal response was assessed 3 months after initiation of steroid therapy. Partial and complete renal response rates were compared in both groups, as well as relapses of ICPi-AKI with the lowering or suspension of steroid treatment. The development of adverse effects attributable to corticosteroids and the evolution of the oncologic disease were also evaluated. Results Sixty-three patients were included, 30 (48%) of whom received a short course of corticosteroids. Type of malignancy and oncologic treatment were similar in both groups. Baseline serum creatinine (1.1 mg/dL Group A and 0.9 mg/dL Group B; p = 0.53) and at ICPi-AKI diagnosis (3.0 mg/dL in Group A and 2.8 mg/dL in Group B; p = 0.43) were comparable. As shown in the table below, cumulative prednisone dose was lower in Group A than in Group B (1654 mg vs 4030 mg; p = 0.001). The overall renal response was 92% (87% Group A and 97% Group B; p = 0.2). There were no differences in complete response (40% Group A and 40% Group B; p = 1) or partial response (47% Group A and 57% Group B; p = 0.4). There were no recurrences of AKI after rechallenge of ICPi treatment. Adverse events related to corticosteroids were similar. There was a trend towards greater progression of oncologic disease in group B (64% versus 40%; p = 0.08). Conclusion A short course of steroids (< 3 months) is equally effective as a treatment for ICPi-AKI as longer courses, both in terms of renal response and relapse rate of ICPi-AKI. Adverse events related to steroid treatment were comparable in both groups. There appeared to be greater oncologic progression in the prolonged steroid treatment group.

Steroid Use in the NICU: Treatment and Tapering

The adrenal gland cortex produces life-sustaining steroid hormones that are critical for the development and survival of the fetus and neonate. Antenatal and postnatal administration of steroids has critical therapeutic effects in preterm infants. However, prolonged postnatal steroid therapy for more than 1 to 2 weeks is associated with iatrogenic adrenal insufficiency and should prompt consideration of a steroid taper and stress dose precautions. In this review, we will describe fetal adrenal development and steroidogenesis, the effect of antenatal exogenous steroids, the therapeutic role of postnatal steroids, evaluation and treatment of adrenal insufficiency, and the role of steroid tapers after prolonged steroid treatment.

LABORATORY INVESTIGATIONS FOR FUNGAL INFECTION OF ORAL CAVITY : AN EAGLE EYE VEIW

The incidence of invasive infections caused by fungi has been increasing for the last few decades. This is primarily due to the significant increases in the populations of at-risk patients; this includes those receiving immunosuppressive chemotherapy for various malignancies, solid organ transplant recipients and those receiving prolonged steroid treatment. New diagnostic approaches have been developed based on non-culture-based methods, which may allow early diagnosis and treatment of fungal infections. Laboratory procedures in diagnostic mycology are directed mainly toward the direct demonstration of the pathogenic fungi in clinical specimens by microscopy along with successful isolation of pathogenic fungi by using various culture techniques. They also help in the prediction of possible therapeutic outcome by determining antifungal susceptibility and can also be used in epidemiological studies by tracing the source of infection. The purpose of our review is to provide the reader with comprehensive and up-to-date information on diagnostic methods.

Predictors of complete 24-month remission and flare in patients with polymyalgia rheumatica.

To date, few papers investigated the predictive factors of sustained 24-month remission and of flare in patients with polymyalgia rheumatica (PMR). We retrospectively evaluated clinical charts from PMR patients. Patients were evaluated at baseline, at 1month, 3months and subsequently at 6, 12 and 24months. We analyzed the differences between patients who achieved remission within 6months of diagnosis, those who achieved remission at 24months, and patients who did not. Among 137 patients, 57 (41.6%) achieved remission at 6months and complete remission at 24months was achieved by 104 patients (75.9%). The erythrocyte sedimentation rate at baseline was higher in patients who did not achieve remission than in patients who achieved it (p = 0.012). Female patients were less likely to achieve complete remission (45/68, 66.2% vs. 59/69, 85.5%, p = 0.01) compared to males. Fifty-four patients (39.4%) experienced at least one flare. Patients who did not achieve sustained complete remission suffered a flare more often (22/39 vs. 32/98, p = 0.01) and earlier than patients who did (10.33 ± 7.89months vs. 13.64 ± 6.97months, p = 0.011). Multivariate analysis confirmed that female sex (RR = 3.2, 95% CI 1.3-7.9) and higher baseline prednisone dosage (RR = 1.1, 95% CI 1.007-1.109) were negative independent predictors of complete remission at 24months. A significant percentage of patients with PMR requires prolonged steroid treatment and may experience flares at 24months of follow-up. Female sex and higher baseline prednisone dosage are negative independent predictors of complete remission at 24months.

Steroid treatment suppresses the CD4+ T-cell response to the third dose of mRNA COVID-19 vaccine in systemic autoimmune rheumatic disease patients

Prolonged steroid treatment has a suppressive effect on the immune system, however, its effect on the cellular response to mRNA vaccine is unknown. Here we assessed the impact of prolonged steroid treatment on the T-cell and humoral response to the SARS-CoV-2 spike (S) peptide following the third dose of the BNT162b2 vaccine in systemic autoimmune rheumatic disease patients. We found that CD4 T-cell response to the S peptide in patients on high-dose long-term steroid treatment showed significantly less S-peptide specific response, compare to low-dose or untreated patients. Remarkably, these results were not reflected in their humoral response, since almost all patients in the cohort had sufficient antibody levels. Moreover, S-peptide activation failed to induce significant mRNA levels of IFNγ and TNFα in patients receiving high-dose steroids. RNA-sequencing datasets analysis implies that steroid treatments' inhibitory effect of nuclear factor kappa-B signaling may interfere with the activation of S-specific CD4 T-cells. This reveals that high-dose steroid treatment inhibits T-cell response to the mRNA vaccine, despite having sufficient antibody levels. Since T-cell immunity is a crucial factor in the immune response to viruses, our findings highlight the need for enhancing the efficiency of vaccines in immune-suppressive patients, by modulation of the T-cell response.

PATH-43. HISTOLOGY OF RADIATION-INDUCED PSEUDOPROGRESSION WITH MULTIPLE FOCI IN TREATED GLIOBLASTOMA

Abstract Radiation induced pseudoprogression (PsP) of brain tumors is defined radiologically as new or enlarging areas of non-tumor magnetic resonance imaging (MRI) contrast enhancement developing within the initial 3-6 months after completing radiation. Distinguishing PsP from genuine tumor progression is of the utmost importance in deciding the clinical course of a patient. Although it is typically diagnosed radiologically, obtaining tissue histopathology can clarify diagnostic uncertainty. However, there is no consensus on defining PsP pathologically. We present the case of a 38-year-old man with a glioblastoma, IDH-wild type, CNS WHO Grade 4 (MGMT promoter methylated) with steroid-refractory PsP, and correlate both radiologic and pathologic features. After initial treatment with a gross total resection and radiation with concurrent temozolomide, he developed a new contrast-enhancing, mass-neutral enhancing lesion consistent with PsP, which did not resolve despite 4 cycles of temozolomide and prolonged steroid treatment. The enhancing lesion was resected, and the pathological examination demonstrated areas of non-pseudopallisading necrosis, numerous macrophages, astrocytosis, hyalinization of blood vessels, and low mitotic activity in the brain parenchyma with residual infiltrative glioma. These features were consistent with radiation-treatment effect and supported a diagnosis of PsP. Over time, varying definitions for PsP include a percentage threshold of treatment effect or necrosis per sample. However, the authors recognize potential sampling bias. Therefore, we recommend including treatment-related effects coupled with the absence of tumor proliferation in the results. These features include fibrinoid necrosis, hyalinization of blood vessels, and eosinophilic coagulation necrosis. From a therapeutic standpoint, it is important to comment on the presence or absence of residual glioma cell proliferation. This case highlights a unique paring of focal histopathology with correlative sections on MRI for pseudoprogression which has not been previously presented.

Treatment of severe Kaposiform lymphangiomatosis positive for NRAS mutation by MEK inhibition.

Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly involving most commonly the mediastinum, lung, skin and bones with few effective treatments. In recent years, RAS-MAPK pathway mutations were shown to underlie the pathogenesis of several complex lymphatic anomalies. Specifically, an activating NRAS mutation (p.Q61R) was found in the majority of KLA patients. Recent reports demonstrated promising results of treatment with the MEK inhibitor, Trametinib, in patients with complex lymphatic anomalies harboring gain of function mutations in ARAF and SOS1, as well as loss of function mutation in the CBL gene, a negative regulator of the RAS-MAPK pathway. We present a 9-year-old child with a severe case of KLA harboring the typical NRAS (p.Q61R) mutation detected by plasma-derived cell free DNA, responsive to trametinib therapy. The NRAS somatic mutation was detected from plasma cfDNA using droplet digital PCR. Concurrent in-vitro studies of trametinib activity on mutant NRAS affected lymphatic endothelial cells were performed using a three-dimensional spheroid sprouting assay. Trametinib treatment lead to resolution of lifelong thrombocytopenia, improvement of pulmonary function tests and wellbeing, as well as weaning from prolonged systemic steroid treatment. Concurrent studies of mutant NRAS-expressing cells showed enhanced lymphangiogenic capacity along with over activation of the RAS-MAPK and PI3K-AKT-mTOR pathways, both reversed by trametinib. Trametinib treatment can substantially change the prognosis of patients with RAS pathway associated lymphatic anomalies. This is the first description of successful trametinib treatment of a patient with KLA harboring the most characteristic NRAS p.Q61R mutation. Treatment can significantly change the prognosis of patients with RAS pathway-associated lymphatic anomalies. We devised an in vitro model of KLA enabling a reproducible method for the continued study of disease pathogenesis. Mutated NRAS p.Q61R cells demonstrated increased lymphangiogenic capacity.

POS0019 PREDICTORS OF SUSTAINED 6 MONTHS REMISSION AND FLARE IN PATIENTS WITH POLYMYALGIA RHEUMATICA

Background:Polymyalgia rheumatica (PMR) is a typical inflammatory disease of the elderly. The mainstay of treatment is usage of oral glucocorticoids (GC) usually leading to a dramatic response. However, long-term treatment is often required. In some instances, remission cannot be achieved and disease flares can occur. To date, few papers investigated the predictive factors of response to GC therapy suggesting a role for weight, elevated plasma viscosity and C-reactive protein (CRP). Moreover, there are no data on predictor factors of disease flares after 6 months of sustained remission.Objectives:To evaluate the factors predictive of sustained 6 months remission and of flare in patients with PMR.Methods:We evaluated clinical data from 137 PMR patients treated with GC for more than 6 months between September 2002 and June 2020. Patients were evaluated at baseline, re-evaluated at 1 month and after 3 months and then at least every 3 months. We analyzed the differences between patients who achieved remission within 6 months of diagnosis, who maintained it for at least 6 months, and patients who did not. Remission was defined as 1) the absence of clinical symptoms, 2) <7.5 mg / day of prednisone equivalents and 3) negativity of ESR and CRP. Patients treated with methylprednisolone were excluded from the analysis.Results:Among the 137 patients (baseline F68: M69, mean age ± SD 74.5±6.6 years, mean ESR ± SD 49.9±27.7 mm/h, mean CRP ± SD 6.1±11.4 mg/dl), 57 achieved remission at 6 months (41.6%), and after this period, another 47 went into remission for a total of 104 patients (75.9%). The months required to achieve remission averaged 6.4 ± 3. No differences were observed between patients who achieved remission and patients who did not regarding age, sex, CRP, starting dose of GC, anti-CCP and rheumatoid factor. The ESR at baseline was higher in patients who did not achieve remission (58.1±33.4 mm/h) than in patients who achieved it (46±24.8 mm/h, p=0.06). ESR at baseline correlated with the time needed to reach normalization of both ESR and CRP (p=0.01, Figure 1). Thirty-six of 104 patients (34.6%) had a disease flare after a mean of 6.1±2.7 months of remission. The mean GC intake at flare was 2.8±3 mg/day. Only 15/36 (41.6%) patients were able to withhold GCs after flare, compared with 48/68 (70.5%) patients who achieved remission and did not experience flare. There were no significant differences in any analyzed parameters between patients who experienced flares and those who did not, including ESR and CRP values at baseline (50.3±26.7 mm/h and 6.8±12.1 mg/dl, respectively). A higher percentage of patients who did not achieve remission experienced flare than patients who went into remission (p=0.009).Conclusion:Achieving complete remission at 6 months occurs in a consistent percentage of patients with PMR. Despite this, a significant percentage of patients may need prolonged steroid treatment and may experience flare, even after 12 months of follow-up. Remission at 6 months is likely to be a good predictor of remission at 12 months, as already reported in recent studies (1, 2). Elevated ESR at diagnosis appears to be a negative predictor for remission at 6 months. Patients who achieve complete remission are less likely to develop flare. True remission should coincide with the discontinuation of steroid treatment; in fact, the maintenance of steroid therapy, even at low doses, is predictive of the development of flare.

Pulmonary Aspergillosis: An Evolving Challenge for Diagnosis and Treatment.

Aspergillus is a mold that may lead to different clinical pictures, from allergic to invasive disease, depending on the patient’s immune status and structural lung diseases. Chronic pulmonary aspergillosis is an infection with a locally invasive presentation, reported especially in patients with chronic pulmonary disease, while aspergilloma is typically found in patients with previously formed cavities in the lungs. Allergic bronchopulmonary aspergillosis is due to a hypersensitivity reaction to Aspergillus antigens and is more frequently described in patients with moderate-severe asthma or cystic fibrosis. Invasive pulmonary aspergillosis mainly occurs in patients with neutropenia or immunodeficiency, but has increasingly been recognized as an emerging disease of non-neutropenic patients. The significance of this infection has dramatically increased in recent years, considering the high number of patients with an impaired immune state associated with the management and treatment of neoplasm, solid or hematological transplantation, autoimmune diseases, and inflammatory conditions. Moreover, prolonged steroid treatment is recognized as an important risk factor, especially for invasive disease. In this setting, critically ill patients admitted to intensive care units and/or with chronic obstructive pulmonary disease could be at higher risk for invasive infection. This review provides an update on the clinical features and risk factors of pulmonary aspergillosis. Current approaches for the diagnosis, management, and treatment of these different forms of pulmonary aspergillosis are discussed.

P0238LONG-TERM OUTCOME OF CHILDHOOD IDIOPATHIC NEPHROTIC SYNDROME

Abstract Background and Aims Little is known about the long-term outcome of childhood idiopathic nephrotic syndrome (INS), in particular long-term complications, rate of relapses, frequency of prolonged steroid (S) and immunosuppressive treatment (IS). The choice of immunosuppressive drug remains discussed. Our aim was to study the long-term outcome in adulthood of patients with INS diagnosed during childhood. Method In this monocentric retrospective study, we included all adult patients (>18 years) admitted in our nephrology department between 2013 and 2019 with INS diagnosed during childhood. Patients who reached ESRD during childhood were excluded. Data regarding the outcome in adulthood were obtained through clinical database and medical charts. Results Eighty-two patients (M/F = 2/1) were included. Sixty-height patients had steroid-sensitive nephrotic syndrome (SSNS), including 52 with steroid-dependant nephrotic syndrome (SDNS). The other 14 patients had steroid-resistant nephrotic syndrome (SRNS). The median age at diagnosis was 3.9 years (1.2-16.5). The median number of relapses during childhood was 12 (0-52), 0.9/patient/year. 89% of patients received IS therapy in addition to S during childhood: median number of successive therapeutic lines was 3 (0-10) per child. Median follow-up during adulthood was 4.6 (0.1-25) years. 67% of patients experienced at least one relapse during adulthood, with a median number of relapses of 0.53 (0-3.7)/patient/year. Risk of relapse during adulthood was significantly associated with the total number of relapses during childhood (p=0.015) and with the number of relapses per year during childhood (p=0.007). 45% of patients received IS in addition to S during adulthood, mainly mycophenolate mofetil (23/82), calcineurin inhibitors (21/82) and rituximab (12/82). High blood pressure was observed in 22% of patients. At last follow-up, median eGFR was 90 (64-117) mL/min/1.73m in SSNS patients, 86 (57-126) mL/min/1.73m in SDNS patients and 70 (23-113) mL/min/1.73m in SRNS patients. Only 4/82 patients presented with eGFR lower than 60 mL/min/1.73m. Among them, 3 had SRNS. Only 1 thrombo-embolic event and 3 severe infections were reported. Bone densitometry was performed in 26 adult patients and osteopenia was found in 19 of them (73%). Conclusion The incidence of relapses in adulthood was relatively high in our study. However bias related to inclusion criteria could play a role. Whereas renal function remained normal in most patients, high blood pressure and osteopenia were frequent but major complications were rarely reported.

Adrenal Insufficiency in Children With Nephrotic Syndrome on Corticosteroid Treatment

Background: Adrenal insufficiency can result from impaired functions at all levels of hypothalamic-pituitary-adrenal (HPA) axis. We here studied risk factors associated with adrenal insufficiency in children receiving prolonged exogenous steroid treatment for nephrotic syndrome.Method:We performed low-dose Synacthen tests (LDSTs, 0.5 μg/m2) in children with steroid-sensitive nephrotic syndrome 4–6 weeks after discontinuation of the corticosteroid therapy. We measured early morning serum cortisol levels at baseline and at intervals of 10, 20, 30, and 60 min following the stimulation test. We defined normal HPA axis stimulation responses as those with peak cortisol cut-off values >550 nmol/L.Result:We enrolled 37 children for this study research. All children enrolled had normal early morning cortisol levels. However, 13 (35.1%) demonstrated HPA axis suppression (by LDST) 4–+6 weeks after discontinuation of oral prednisolone. Nephrotic syndrome diagnosed before 5 years of age (OR, 0.75; 95% CI, 0.57–0.99; p = 0.043), and steroid-dependence [OR, 5.58; 95% confidence interval (CI), 1.06–29.34; p = 0.042] were associated with increased risk of developing adrenal suppression after steroid discontinuation.Conclusion:HPA axis suppression, may go unnoticed without proper screening. A normal early morning cortisol level (275–555 nmol/L) does not exclude adrenal insufficiency in children with steroid-sensitive nephrotic syndrome. Further screening with LDSTs, particularly in children younger than 5 years at diagnosis, may be warranted.

A young man with convulsive laughter.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) can manifest with a wide range of neurological and psychiatric symptoms. A previously healthy man in his late twenties was admitted several times over the course of half a year. He had acute episodes of reduced consciousness, involuntary movements and psychotic symptoms (e.g. hallucinations and delusions). Initial examinations were normal except for a positive urine drug screen (tetrahydrocannabinol), and the patient was diagnosed with cannabinoid intoxication. During the next admission cerebrospinal fluid analysis showed mild pleocytosis. Screening for anti-neuronal antibodies was negative, but anti-thyroid peroxidase antibodies were detected in serum and cerebrospinal fluid. He was successfully given steroid treatment on a tentative diagnosis of SREAT, but relapsed when the steroids were discontinued. After receiving a prolonged steroid treatment with gradual dose reduction over a year, he remains symptom-free 18months after treatment discontinuation. The diagnostic delay might have been mitigated with an earlier inclusion of neuroimmunological disorders in the differential diagnosis. Unexplained pleocytosis in the cerebrospinal fluid in the presence of paroxysmal neuropsychiatric symptoms should trigger an investigation that includes autoimmune encephalopathies.

Basic neuroendocrine events before puberty in cattle, sheep and pigs

Neuroendocrine events before puberty are compared in male and female cattle, sheep and pigs. The patterns of secretion of gonadotrophin, the age-related LH responses to castration or LH-RH administration and the effects of prolonged steroid treatment give information about the maturity of the hypothalamic-pituitary axis. It appears that in all three species the mechanisms involved in the expression of puberty are progressive rather than abrupt events. Some original contributions reported here, such as age-related changes in plasma levels and pulses of LH in the gilt, and the variations in pituitary cytosol receptors to 5 alpha-dihydrotestosterone and oestradiol-17 beta in the male lamb support this contention. Finally, this brief review of the neuroendocrine events known to occur before puberty in three domestic mammals underlines numerous missing links in our understanding of the prepubertal processes.

Incidence of Prolonged Systemic Steroid Treatment after Surgery for Acoustic Neuroma and Its Implications.

Objectives To determine the incidence of prolonged postoperative systemic corticosteroid therapy after surgery for acoustic neuroma as well as the indications and associated risk factors that could lead to prolonged steroid administration, and the incidence of steroid-related adverse effects. Study Designs Retrospective chart review. Methods Retrospective chart review of patients undergoing resection of acoustic neuroma between 2010 and 2017 at two tertiary care medical centers. Patient and tumor characteristics, operative approach, hospital length of stay, initial postoperative taper length, number of discrete postoperative steroid courses, and postoperative complications were analyzed. Results There were 220 patients (99 male, 121 female) with an average age of 49.4 (range 16-78). There were 124 left-sided tumors and 96 right-sided tumors. Within the group, 191 tumors were operated through a retrosigmoid approach, 25 tumors through a translabyrinthine approach, and 4 tumors with a combined retrosigmoid-translabyrinthine approach under the same anesthetic. In total, 35 (15.9%) patients received an extended initial course of postoperative systemic steroids, defined as a taper longer than 18 days. Twenty six (11.8%) patients received additional courses of systemic steroids after the initial postoperative taper. There were 5 (2.3%) patients who required an extended initial taper as well as additional courses of steroids. Aseptic meningitis, often manifested as headache, was the most common indication for additional steroids (14 cases of prolonged taper and 17 cases of additional courses). None of the patient or tumor factors including age, gender, side, size, and approach were statistically significantly associated with either a prolonged initial steroid taper or additional courses of steroids. An extended hospital length of stay was associated with a prolonged initial steroid taper ( p = 0.03), though the initial taper length was not predictive of additional courses of steroids. The cumulative number of days on steroids was associated with need for additional procedures ( p < 0.01) as well as steroid-related side effects ( p = 0.05). The administration of steroids was not found to significantly improve outcomes in postoperative facial paresis. Steroid-related complications were uncommon, seen in 9.26% of patients receiving steroids, with the most common being psychiatric side effects such as agitation, anxiety, and mood lability. Conclusions Systemic corticosteroids are routinely administered postoperatively for patients undergoing craniotomy for the resection of acoustic neuromas. In a review of 220 patients operated by a single neurotologist, no patient or tumor factors were predictive of requiring prolonged initial steroid taper or additional courses of steroids. The cumulative number of days on systemic steroids was associated with undergoing additional procedures and steroid-related side effects. The most common indications for prolonged or additional steroids were aseptic meningitis, cerebrospinal fluid leak, and facial paresis. Additional steroids for postoperative facial paresis did not significantly improve outcomes. Patient-reported steroid-related complications were infrequent and were most commonly psychiatric including agitation, anxiety, and mood lability.

Contralateral adrenal width predicts the duration of prolonged post-surgical steroid replacement for subclinical Cushing syndrome.

To identify pre-treatment factors affecting the duration of post-surgical steroid replacement in patients undergoing adrenalectomy for subclinical Cushing syndrome. The present retrospective analysis included 64 patients who underwent unilateral laparoscopic adrenalectomy for subclinical Cushing syndrome. Adrenal tumor and contralateral adrenal sizes together with various clinical factors were studied in association with the duration of post-surgical steroid replacement. Adrenal tumor and contralateral adrenal size were measured at the level of the maximum transverse plane of the adrenal glands using computed tomography scan or magnetic resonance imaging. Cox's proportional hazards model was used for the statistical analysis. All 64 patients were treated with post-surgical steroid replacement after adrenalectomy. The median duration of the steroid treatment was 6 months. When assessing the duration of post-surgical steroid replacement, contralateral adrenal volume <0.745 cm3 , contralateral adrenal width <6.15 mm and serum cortisol after a 1-mg dexamethasone suppression test >2.65 μg/dL were significant predictors of prolonged post-surgical steroid treatment on univariate analysis. On multivariate analysis, contralateral adrenal width <6.15 mm was the only independent predictive factor for the prolonged post-surgical steroid replacement. Contralateral adrenal width seems to represent a significant predictive factor for the duration of post-surgical steroid replacement in subclinical Cushing syndrome patients. Pre-surgical assessment of image findings might help clinicians determine the total duration of steroid therapy after adrenalectomy.

Chronic rhinosinusitis with nasal polyps in the elderly: Assessing current evidence.

The recently reported prevalence of chronic rhinosinusitis (CRS) among people >60 years old was 4.7%, with CRS emerging as the sixth most common chronic condition in the elderly. There is still a dearth of studies that focused on older patients, however, regarding the characteristics of CRS with nasal polyps (CRSwNP). The emerging role of CRSwNP endotyping to enable a tailored medical approach (for elderly patients also) was investigated. The present review of data reported predominantly in the past 5 years aimed to critically discuss the pathophysiologic, clinical, and prognostic features of CRSwNP in elderly patients. Although the existing data were not final, they supported the notion that geriatric patients can be managed safely by adopting the same surgical algorithm as for younger adults, including endoscopic sinus surgery (ESS). As for medical therapies, prolonged systemic steroid treatment for CRSwNP should be given with caution to elderly patients because they risk significant adverse effects. There is increasing evidence of a lower CRSwNP recurrence rate after ESS in the elderly than in young adult patients. Contrary to findings in younger patients, recently, analysis of preliminary data showed that histologically eosinophilic CRSwNP or high blood eosinophil counts were not significantly associated with a higher recurrence rate in elderly patients. A great challenge in the field of geriatric CRSwNP is to investigate the different endotypes in large series (also by means of biomarker assay in blood and polyp tissue) to identify rational and tailored diagnostic, therapeutic (medical and/or surgical), and follow-up modalities.

Longitudinal in vivo tracking of adverse effects following topical steroid treatment.

Topical steroids are known for their anti-inflammatory properties and are commonly prescribed to treat many adverse skin conditions such as eczema and psoriasis. While these treatments are known to be effective, adverse effects including skin atrophy are common. In this study, the progression of these effects is investigated in an in vivo mouse model using multimodal optical microscopy. Utilizing a system capable of performing two-photon excitation fluorescence microscopy (TPEF) of reduced nicotinamide adenine dinucleotide (NADH) to visualize the epidermal cell layers and second harmonic generation (SHG) microscopy to identify collagen in the dermis, these processes can be studied at the cellular level. Fluorescence lifetime imaging microscopy (FLIM) is also utilized to image intracellular NADH levels to obtain molecular information regarding metabolic activity following steroid treatment. In this study, fluticasone propionate (FP)-treated, mometasone furoate (MF)-treated and untreated animals were imaged longitudinally using a custom-built multimodal optical microscope. Prolonged steroid treatment over the course of 21 days is shown to result in a significant increase in mean fluorescence lifetime of NADH, suggesting a faster rate of maturation of epidermal keratinocytes. Alterations to collagen organization and the structural microenvironment are also observed. These results give insight into the structural and biochemical processes of skin atrophy associated with prolonged steroid treatment.

Mutational analysis of podocyte genes in children with sporadic steroid-resistant nephrotic syndrome.

Recent studies have demonstrated that mutations in 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1, are associated with the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). Systematic investigation of all 4 genes for sporadic SRNS in China has not been performed. We examined 10 Chinese children with sporadic SRNS who showed no response to immunosuppressive agents and 20 SRNS controls who exhibited a response to prolonged steroid or immunosuppressive treatment and achieved complete remission. We analyzed mutations in the 4 podocyte genes, NPHS1, NPHS2, CD2AP, and WT1. Mutational analysis was performed using polymerase chain reaction and direct sequencing. Of the 10 SRNS children who showed no response to immunosuppressive agents, the compound heterozygous NPHS1 mutations 2677A>G (T893A) and *142T>C were identified in 1 patient, while a heterozygous mutation in WT1, 1180C>T (R394W), was found in another patient. Of the 20 SRNS children showing complete remission who responded to prolonged steroid therapy or immunosuppressive agents, 4 heterozygous NPHS1 mutations, 928G>A, IVS8+30C>T, IVS21+14G>A, and IVS25-23C>T, were identified in 4 patients and a heterozygous CD2AP mutation, IVS7-135G>A, was identified in 1 patient. Our results indicate the necessity of genetic examination for mutations in podocyte genes in Chinese SRNS children who show no response to immunosuppressive agents.

Endocrinopathies after allogeneic and autologous transplantation of hematopoietic stem cells.

Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.

Recurrent Inflammatory Chondritis Following Ear Piercings

Auricular chondritis is an uncommon complication of ear trauma, including ear piercing, that carries a risk of permanent deformity. Auricular chondritis in young adults is typically infectious and without recurrence. Other rare cases of chondritis, which are more common in older adults, are inflammatory and occur as part of an autoimmune disorder called relapsing polychondritis (RP). We present a case of an 18 year old girl with two separate episodes of auricular chondritis in each ear following cartilage piercing that responded to prolonged steroid treatment.