Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Standard of Care in Latin America for Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Propensity Score Matching Analysis.

INTRODUCTION: The phase 3 ALCYONE study demonstrated significantly longer progression-free and overall survival (PFS/OS) and higher overall response rates (ORR) with daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) versus VMP alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). In Latin America, bortezomib- or thalidomide-based regimens remain standard of care (SoC) for this population. No head-to-head trials have compared D-VMP with SoC regimens used in Latin America. METHODS: Propensity score matching (PSM) was used to control for baseline differences between patient populations and compare outcomes for D-VMP versus SoC regimens used in Latin America. Data for the D-VMP cohort were from the D-VMP arm of the ALCYONE trial (n = 350). Data for the SoC cohort were from the retrospective, observational Hemato-Oncology Latin America (HOLA) study, which included patients with NDMM who did not receive a transplant (n = 729). Propensity scores were estimated using logistic regression. Exact, optimal, and nearest-neighbor PSM were applied to pick the best-performing method. Doubly robust estimation was the base case, since some baseline imbalances persisted. RESULTS: All 350 patients from the D-VMP arm of ALCYONE were included in OS/PFS analyses and 338 in ORR analysis; 478 and 324 patients, respectively, from HOLA were included in these analyses. Naïve comparison revealed important differences in baseline characteristics (age, chronic kidney disease, hypercalcemia, and International Staging System [ISS] stage). After nearest-neighbor matching, baseline characteristics, except ISS stage, were well balanced; comparisons favored D-VMP over SoC for OS (hazard ratio = 0.41; 95% confidence interval [CI] 0.25-0.66; P = 0.002) and PFS (hazard ratio = 0.48; 95% CI 0.35-0.67; P < 0.001). After exact matching, imbalances remained in age and ISS stage; comparisons favored D-VMP over SoC for ORR (odds ratio = 5.44; 95% CI 2.65-11.82; P < 0.001). CONCLUSION: In transplant-ineligible patients with NDMM, D-VMP showed superior effectiveness versus bortezomib- and thalidomide-based regimens, supporting adoption of daratumumab-containing regimens in Latin America.

[Fournier gangrene in a child with steroid-resistant nephrotic syndrome. Report of one case]. / Gangrena de Fournier en un niño con síndrome nefrótico corticorresistente. A propósito de un caso.

Fournier gangrene is a necrotizing fasciitis that affects the genital, perineal and perianal regions, of sudden onset and rapidly progressive dissemination. Its diagnosis requires an urgent and interdisciplinary intervention. The association with nephrologic diseases is rare. We present a case of Fournier gangrene in a child with steroidresistant nephrotic syndrome and anasarca with severe scrotal edema. He received a broad-spectrum antibiotic scheme and extensive an immediate surgical debridement of the necrotic lesion was carried out. Subsequently, it was repaired by Plastic Surgery. He presented a favourable clinical response.

La gangrena de Fournier es una fascitis necrotizante que afecta las regiones genital, perineal y perianal, de inicio súbito y diseminación rápidamente progresiva. Su diagnóstico obliga a una urgente intervención interdisciplinaria. La asociación con enfermedades nefrológicas es rara. Se presenta un caso de gangrena de Fournier en un niño con síndrome nefrótico corticorresistente y anasarca con edema escrotal grave. Recibió un esquema antibiótico de amplio espectro y se realizó un desbridamiento quirúrgico extenso e inmediato de la lesión necrótica. Posteriormente, requirió reparación por parte de Cirugía Plástica. Presentó una respuesta clínica favorable a la terapéutica instaurada.

Is 9ß-dehydrohalogenation of betamethasone and dexamethasone hindering the detection of banned co-eluting meprednisone? A reverse-phase chiral liquid chromatography high-resolution mass spectrometry approach.

Mass spectral analysis of dexamethasone and betamethasone reveal intense signals at m/z 373.19994 (using a Thermo Q Exactive high-resolution mass spectrometer coupled with Dionex UltiMate 3000 UHPLC + operated in the positive ion mode), matching the signal of meprednisone, the 11-oxo version of methylprednisolone, along with its parent signal; possibly due to dehydrohalogenation of these drugs at MS. The parent mass of meprednisone is exactly same as that of dehydrohalogenated mass of dexamethasone and betamethasone; and are co-eluting, displaying same mass spectra. Specifically when they are administered together, identifying meprednisone (a drug for which there is zero tolerance in some regions of the world), is a great challenge with currently available techniques because it could be easily mistaken for dexamethasone or betamethasone, drugs allowed at certain threshold limits for therapeutic considerations. False negative results could be obtained in conventional reverse-phase chromatography and are liable to be abused; hence, establishing "zero tolerance" limits for these compounds often proves ineffective. In this paper, present an effective and reliable analytical method for simultaneously separating and identifying dexamethasone, betamethasone and meprednisone in equine urine and plasma using chiral liquid chromatography-electrospray ionization-mass spectrometry. From the various columns screened, the Lux i-Cellulose-5 chiral column produced high-quality results with extremely good separation. During this study, it is quite evident that dehydrohalogenation occurs only in the mass ionization source; the compounds are very stable in-vivo/in-vitro and do not break down either on-column or during sample preparation.

Penfigoide gestacional y erupción ampollar en el recién nacido / Bullous pemphygoid and blisters in the newborn

El penfigoide gestacional es una dermatosis rara, que se presenta durante el embarazo. Se caracteriza por una respuesta autoinmune contra las proteínas de los hemidesmosomas, que genera un clivaje entre la epidermis y la dermis tanto de la piel como de las mucosas. Clínicamente, presenta prurito intenso, placas y pápulas eritematosas, que evolucionan a apollas con distribución en el abdomen y los miembros. Como complicaciones, en el feto puede generar parto prematuro y bajo peso para la edad gestacional, con alto riesgo de mortalidad. (AU)

Gestational pemphygoid is a rare, autoimmune dermatosis that occurs during pregnancy. It is characterized by an autoimmune response against hemidesmosome proteins, generating a cleavage between the epidermis and the dermis in the skin and mucous membranes. Clinically it presents with intense pruritus, plaques and erythematous papules that evolve to blisters that are distributed mainly in the abdomen and limbs. The complications are preterm birth and low weight for gestational age, with high risk of mortality. (AU)

Miositis como forma de presentación de panarteritis nodosa / Myositis as the initial presentation of panarteritis nodosa

Varón de 47 años que consulta por pérdida de peso, dolor con tumefacción en pantorrillas, fiebre, hipertensión arterial, orquitis y oligoartritis. Laboratorio: anemia y aumento de enzimas musculares. Resonancia magnética: hiperintensidad en gemelos (miositis). Histología de músculo: infiltrado inflamatorio con atrofia y regeneración perifascicular. Tratamiento: pulsos de metilprednisolona y ciclofosfamida. Mialgias, tumefacción muscular y deambulación dificultosa son hallazgos comunes en poliarteritis nodosa (PAN), no así la miositis demostrada histológicamente y más infrecuente aún como forma de inicio de esta vasculitis

A 47-year-old man presented with weight loss, bilateral calf pain, fever, hypertension, orchitis and oligoarthritis. Lab tests: anemia and elevated muscle enzymes. Resonance magnetic imaging: hyperintensity in gastrocnemius muscles (myositis). Histologic exam of the muscles: inflammatory infiltrate with atrophy and perifascicular regeneration. Treatment: methylprednisone (bolus) and cyclophosphamide. Muscle pain and swelling and difficulty in walking are common in panarteritis nodosa (PAN), whereas histologically demonstrated myositis is not. Even more rare is myositis as the initial presentation of this vasculitis

Myositis as the initial presentation of panarteritis nodosa. / Miositis como forma de presentación de panarteritis nodosa.

A 47-year-old man presented with weight loss, bilateral calf pain, fever, hypertension, orchitis and oligoarthritis. Lab tests: anemia and elevated muscle enzymes. Resonance magnetic imaging: hyperintensity in gastrocnemius muscles (myositis). Histologic exam of the muscles: inflammatory infiltrate with atrophy and perifascicular regeneration. Treatment: methylprednisone (bolus) and cyclophosphamide. Muscle pain and swelling and difficulty in walking are common in panarteritis nodosa (PAN), whereas histologically demonstrated myositis is not. Even more rare is myositis as the initial presentation of this vasculitis.

Effect of Time of Administration of Teriparatide on Bone Mineral Density in Glucocorticoid-Induced Osteoporosis.

Teriparatide (TPTD) (recombinant DNA origin human parathormone [1-34]) is approved for the treatment of glucocorticoid-induced osteoporosis (GIO). There are reports of factors that affect the response to TPTD in GIO treatment. This work describes the case of a 71-yr-old woman diagnosed with lupus nephropathy treated with 40 mg/d of meprednisone, and who suffered multiple vertebral fractures. Despite treatment with a single 5 mg dose of zoledronic acid, the patient continued to have vertebral fractures. Treatment with 20 µg/d of subcutaneous TPTD (PTH1-34, Forteo; Eli Lilly Co., Indianapolis, IN) was initiated. Nine months after the onset of treatment, bone mineral density (BMD) assessment showed a 5% decrease in lumbar spine BMD. Factors potentially affecting the results were analyzed. The patient reported injecting TPTD at night and was instructed to inject TPTD in the morning before breakfast. After changing the time of TPTD administration and 22 mo after initiating treatment, BMD assessment was repeated and showed an 18% increase at the lumbar spine and no new vertebral fractures. The time of TPTD administration might affect the response to TPTD in GIO treatment.

Comparative analysis the binding affinity of mycophenolic sodium and meprednisone with human serum albumin: Insight by NMR relaxation data and docking simulation.

Mycophenolic sodium is an immunosuppressive agent that is always combined administration with corticosteroid in clinical practice. Considering the distribution and side-effect of the drug may change when co-administrated drug exist, this paper comparatively analyzed the binding ability of mycophenolic sodium and meprednisone toward human serum albumin by nuclear magnetic resonance relaxation data and docking simulation. The nuclear magnetic resonance approach was based on the analysis of proton selective and non-selective relaxation rate enhancement of the ligand in the absence and presence of macromolecules. The contribution of the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index. This approach allowed the comparison of the binding affinity of mycophenolic sodium and meprednisone. Molecular modeling was operated to simulate the binding model of ligand and albumin through Autodock 4.2.5. Competitive binding of mycophenolic sodium and meprednisone was further conducted through fluorescence spectroscopy.

Glucocorticosteroids do not impact directly growth rate and biomass of Rhizopus arrhizus (syn. R. oryzae) in vitro.

Glucocorticoid (GC) use is a common risk factor for invasive fungal infections. This is attributed to the complex dysregulation of immunity caused by GCs. However, studies have demonstrated increased growth with GC exposure for some molds, such as Aspergillus fumigatus and Exserohilum rostratum. No such data exist for Mucorales. Therefore, we investigated the influence of GC exposure on the growth of Rhizopus arrhizus (syn. R. oryzae) in different culture media and in different atmospheres. We measured continuous spore growth using spectrophotometry and biomass variations using XTT assay. We did not observe enhanced growth or biomass variation with any of the GCs regardless of the medium or conditions. These results support the existence of fungus-specific differences in the effect of GCs on fungal biology.

Fulminant presentation of autoimmune hepatitis: clinical features and early predictors of corticosteroid treatment failure.

BACKGROUND AND AIMS: Classical features of autoimmune hepatitis (AIH) may be altered during the abrupt onset of the disease. Corticosteroid therapy can be life-saving, but its use in the fulminant presentation of AIH (F-AIH) remains controversial. We aimed to assess the clinical features of patients with F-AIH and to describe the role of corticosteroids in this population. PATIENTS AND METHODS: We retrospectively analyzed 154 adult patients with fulminant hepatic failure who were admitted to six liver transplantation (LT) programs. The AIH simplified criteria were used to identify patients with F-AIH. RESULTS: We identified 40 (26%) patients with F-AIH. Compared with other etiologies, patients with F-AIH presented a longer interval from jaundice to encephalopathy (26 vs. 16 days, P=0.02) and a lower Model for End-Stage Liver Disease (MELD) score on admission (29 vs. 33, P=0.002). Overall, 25 (62%) patients with F-AIH underwent LT, eight (20%) patients survived, and seven (18%) died without LT. Seventeen patients received corticosteroids therapy, of whom seven (41%) survived without LT. Among the treated patients, higher MELD score and encephalopathy grade of 3 or more were associated significantly with corticosteroid failure. CONCLUSION: Patients with F-AIH have a more indolent presentation compared with the non-F-AIH population. Altogether, only eight (20%) patients presenting with F-AIH survived without LT. A subset of patients with F-AIH and an initial MELD score less than 27 and low-grade hepatic encephalopathy might benefit from administration of corticosteroids.

Antifouling steroids from the South China Sea gorgonian coral Subergorgia suberosa.

Two new unusual cholestane derivatives, pentacyclic steroid 16,22-epoxy-20ß,23S-dihydroxycholest-1-ene-3-one (1) and 20ß,23S-dihydroxycholest-1-ene-3,22-dione (2), along with two new pregnane derivatives, 15ß,17α-dihydroxypregna-4,6-diene-3,20-dione (3) and 11α-hydroxypregna-4-ene-3,6,20-trione (4), were isolated from the South China Sea gorgonian coral Subergorgia suberosa. Their structures were established based on the extensive analyses of 2D NMR, IR, and HRMS. Antifouling tests against Balanus amphitrite larvae settlement indicated that 1 and 2 exhibited inhibitory effect with EC50 values of 5.3, and 14.5 µg/mL, respectively.

Effect of premedication with systemic steroids on surgical field bleeding and visibility during nasosinusal endoscopic surgery.

INTRODUCTION: Chronic rhinosinusitis (CRS) is the inflammation of the nasal and paranasal sinus mucosa persisting for at least 12 weeks. The success of endoscopic sinus surgery (ESS) depends on minimising oedema and intraoperative bleeding. For this purpose, some surgeons advocate the use of preoperative systemic steroids (SS). Our aim was to assess if the administration of preoperative SS in patients with CRS with or without nasal polyps (NP) facilitates the surgical procedure. METHODS: Non-randomized clinical trial in CRS patients with or without NP. Patients in the ESS group received oral meprednisone preoperatively, whereas the control group did not. The visibility of the surgical field, intraoperative bleeding and surgery duration were recorded. RESULTS: Each group (SS group and control group) included 27 patients. The administration of SS reduced the values of all the parameters in patients without NP, with no significant differences. In patients with NP, only operative bleeding was reduced significantly. CONCLUSIONS: Even though all the parameters decreased with the preoperative administration of SS, only operative bleeding was significantly reduced in patients with CRS with NP.

Interstitial cystitis: a rare manifestation of primary Sjögren's syndrome, successfully treated with low dose cyclosporine.

Chronic interstitial cystitis (IC), mostly affecting middle-aged women, is a very rare manifestation of primary Sjögren's syndrome (pSS). Hereby, we report a 42-year-old woman with pSS, presenting with dysuria, urinary frequency, and suprapubic pain. She was diagnosed to have chronic IC, based upon the cystoscopic biopsy finding of chronic inflammation in the bladder wall. Systemic corticosteroid and azathioprine treatments together with local intravesical therapies were not effective. Therefore, cyclosporine (CSA) therapy was initiated. Initial low dose of CSA (1.5 mg/kg/d) improved the symptoms of the patient, with no requirement for dose increment. After 4 months of therapy, control cystoscopic biopsy showed that bladder inflammation regressed and IC improved. This case suggests that even low doses of CSA may be beneficial for treating chronic IC associated with pSS syndrome.

Corticosteroid administration for patients with coronary artery aneurysms after Kawasaki disease may be associated with impaired regression.

INTRODUCTION: Corticosteroid administration in Kawasaki disease (KD) is controversial but accepted as treatment for patients who do not respond to initial treatment. The impact of corticosteroids on evolving coronary artery aneurysms (CAA) and future vascular remodelling is unknown. METHODS AND RESULTS: The clinical history of 80 patients (73% male; median age at diagnosis 2.2 years) seen from 1990 to 2008 with CAAs after KD were reviewed, 19 (24%) of whom received systemic corticosteroids in the acute phase (14 for ≤ 3 days, 5 for 4+ days). CAA z-scores were assessed at baseline, 2-3 months, and 1 year after the acute phase. Linear regression models adjusted for repeated measures were used to determine the association between change in CAA z-score over time and corticosteroid use, adjusting for patient age at diagnosis, gender, intravenous immunoglobulin use, total days of fever, albumin level, hemoglobin level and platelet count. RESULTS: The corticosteroid treated group had longer duration of fever in the acute phase (median 17 vs. 11 days, p=0.04). Adjusted CAA z-scores at diagnosis, 2-3 months and 1 year follow-up for CAA in the left anterior descending decreased (from +5.5 to +3.5 to +1.9) in those not treated with corticosteroids, but progressed for those treated with corticosteroids (from +7.4 to +17.5 to +15.8), regardless of duration of corticosteroid treatment. Similar results were noted for CAA of the right coronary artery and the left main coronary artery. CONCLUSIONS: The use of corticosteroids in the acute phase of KD for patients with evolving CAAs may be associated with worsening involvement and impaired vascular remodelling and warrants further study.

Frosted branch angiitis, neuroretinitis as initial ocular manifestation in Behçet disease.

Behçet disease is an idiopathic, multisystem disorder characterized by recurrent episodes of orogenital ulceration and vasculitis of the veins and arteries of all calibers. Ocular involvement may affect the conjunctiva, sclera, uveal tract, vitreous, blood vessels, and retina. Many theories have pointed toward an autoimmune response behind its pathogenesis, which may be triggered by exposure to an infectious agent. Frosted branch angiitis is characterized by vascular inflammation, sheathing, retinal edema, and retinal hemorrhages. The disease may be idiopathic in a majority of the cases or may be associated with ocular and systemic pathology. Association between Behηet disease, Frosted branch angiitis, and neuroretinitis is not reported in literature. This uncommon combination reflects the varied systemic and ocular manifestations in Behçet disease, especially in patients who are not diagnosed and treated in time. We hereby report a case of bilateral frosted branch angiitis and neuroretinitis in a young male from Middle-east, suffering from Behçet disease.