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.

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)

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.

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.

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.

17alpha,21-Dihydroxy-16beta-methylpregna-1,4-diene-3,11,20-trione (meprednisone).

The title compound, C(22)H(28)O(5), is a commercial therapeutic agent of the steroid class. Both independent molecules in the asymmetric unit have six-membered A rings that are planar, while the B and C rings adopt normal chair conformations. The five-membered D ring is in a 13beta,14alpha-half-chair conformation, and the B/C and C/D ring junctions are in trans positions. Cohesion in the crystal is provided by O-H.O hydrogen bonds, which generate chains of molecules that are organized in a plane that lies along the crystallographic b axis.

Effect of deflazacort versus methylprednisone on growth, body composition, lipid profile, and bone mass after renal transplantation. The Deflazacort Study Group.

Kidney function, growth velocity, weight/height ratio, body composition, lipid profile, and bone mass were studied in a randomized, multicenter trial of deflazacort versus methylprednisone in 27 prepubertal patients with kidney transplantation. Methylprednisone (0.20+/-0.03) was replaced by deflazacort (13 patients, 0.30+/-0.03 mg/kg per day). After 12 months, creatinine clearance decreased significantly only during methylprednisone therapy. Growth velocity increased only in patients treated with deflazacort from 3.3+/-0.6 to 5.6+/-0.5 cm/year. Serum levels of several components of the insulin-like growth factor axis did not change. Weight/height ratio was increased in methylprednisone-treated patients (P<0.05) and decreased in deflazacort-treated patients (P<0.005). Lean body mass increased in both groups (P<0.005). Fat body mass and serum leptin increased only in methylprednisone-treated patients (P<0.025). Total cholesterol and low-density lipoprotein-cholesterol increased in methylprednisone-treated patients by 9.9% (P<0.05) and 12.5% (P<0.025). High-density lipoprotein-cholesterol increased by 21% (P<0.005) and apolipoprotein B decreased by 11% (P<0.005) in deflazacort-treated patients. Total skeleton and lumbar spine bone mineral density decreased in both groups, but at 1 year methylprednisone-treated patients had lost 50% more bone. Bone mineral content decreased only in methylprednisone-treated patients (P<0.01). Our data suggest that substituting deflazacort for maintenance methylprednisone might prevent height loss, excessive bone loss, and fat accumulation; and leads to an improvement in the lipoproteins of these children.

Binding of the anti-inflammatory steroid deflazacort to glucocorticoid receptors in brain and peripheral tissues. In vivo and in vitro studies.

Deflazacort (DFC) is a heterocyclic glucocorticoid with anti-inflammatory activity but with decreased side effects. In this study, we have evaluated the capacity of DFC and other glucocorticoids to reach the central nervous system (CNS) in vivo by measuring changes of [3H]dexamethasone (DEX) binding to glucocorticoid receptors (GR) in vitro. GR occupation was effected by DEX in the cerebral cortex, hippocampus, pituitary, liver and thymus, with DFC showing a similar profile except for the cerebral cortex. In contrast, corticosterone weakly occupied GR in the thymus, pituitary and hippocampus and methyl-prednisolone was active only in peripheral tissues. Furthermore, IC50 for DEX in vitro amounted to 15-17 nM in the hippocampus and liver, whereas IC50 for the active metabolite 21-deacetyl-DFC (21-OH-DFC) was 4 times higher. 21-OH-DFC bound to type II and was absent from type I GR. When tested in equipotent doses based on IC50 analysis, DFC and DEX similarly induced in vivo ornithine decarboxylase activity in hippocampus and liver, although body weight loss after chronic treatment was significantly less for DFC. The results show that DFC distributes on the CNS similarly to DEX, induces ornithine decarboxylase activity but presents less intensive catabolic effects, making it suitable for use as an anti-inflammatory steroid during chronic therapeutic regimes.

Uso de los glucocorticoides en el tratamiento de la neuritis óptica / Use of glucocorticoids in optic neuritis treatment

Se presenta una síntesis del estudio multicéntrico de tratamiento de la neuritis óptica efectuado en varios centros de los Estados Unidos de Norteamérica. Se presentan las características clínicas de la neuritis óptica de este grupo de pacientes. Además se informa de los hallazgos neurológicos en el examen inicial, la incidencia de esclerosis múltiple, los hallazgos de la resonancia magnética cerebral y finalmente el valor terapéutico de los corticoides

Therapy with a new glucocorticoid: effect of deflazacort on linear growth and growth hormone secretion in renal transplantation.

In children who have undergone successful renal transplantation, the failure of linear growth, a cushingoid appearance and obesity decrease self-esteem and hamper rehabilitation. Changes in kidney function, growth velocity, weight to height ratio and growth hormone (GH) secretion were studied before, and 2 years after, replacement of methylprednisone (6 +/- 0.3 mg/day; mean +/- SEM) by deflazacort (9.6 +/- 0.5 mg/day) 4 years after renal transplantation in 10 patients aged 9-16 years with stable renal function. Serum creatinine and creatinine clearance did not change significantly during deflazacort treatment. In 8 patients at Tanner stage I, growth velocity increased significantly during the 1st and 2nd year of deflazacort therapy (p < 0.01 and p < 0.005, respectively). Weight to height ratio decreased significantly during the 1st and 2nd year of deflazacort treatment (p < 0.005, p < 0.02, respectively) though in 3 patients, this returned to base levels after 2 years of deflazacort therapy. The mean spontaneous GH secretion increased significantly (p < 0.05). There was a correlation between growth velocity and spontaneous GH secretion during deflazacort therapy. The cushingoid appearance decreased in the majority of patients. Renal function remained stable.

Long-term low-dose glucocorticoid therapy in hyperandrogenized women: utility and effects on bone mineral content and hypothalamic-pituitary-adrenocortical function.

The effect of chronic low-dose glucocorticoid administration on bone mineral content and corticotrope reserve was investigated in 12 hyperandrogenized women treated with 1-6 mg oral evening doses of 16 beta-methylprednisone for 12-58 months. The hypothalamic-pituitary-adrenal axis was evaluated in 9 patients by a standard metyrapone test after 45-75 days off steroid therapy. All the patients had a normal rise in serum 11-deoxycortisol after metyrapone. Bone densitometry was assessed at the end of therapy using dual photon absorptiometry. No significant differences between patients and age-matched hyperandrogenic controls were found either in spine (1.048 +/- 0.096 vs. 1.023 +/- 0.175 g/cm2) or femoral neck (0.863 +/- 0.115 vs. 0.899 +/- 0.216 g/cm2), respectively. In conclusion, absence of quantitative bone mass reduction and normal corticotrope reserve were observed even after 58 months of daily steroid administration.

[POEMS syndrome: report of a case and review of the literature]. / Síndrome de POEMS: presentación de un caso y revisión de la literatura.

A case of POEMS Syndrome of six years of evolution is reported. This syndrome is characterized by Raynaud phenomenon, polyneuropathy, edema, anasarca, papilledema, osteosclerosis and lymphadenopathy with the histopathology of Castleman's disease, hypothyroidism, hypogonadism, cutaneous sclerosis, hyperpigmentation, axillary alopecia and the presence of urinary lambda light chains. A bone marrow biopsy did not show plasmocytic infiltration and there was no evidence of extramedullary plasmocytoma. Methylprednisone was given at the dose of 1 mg/kg/day and subjective and objective improvement was observed. The edema and anasarca disappeared as well as the lymphadenopathies; muscle strength improved and the patient was able to walk without aid. Papilledema persisted. The pathogenesis of this syndrome remains unknown; some of the symptoms have been attributed to paraprotein deposits in peripheral nerves, high capillary permeability due to vascular alterations, accelerated conversion of androgen to estrogen, or to the production by plasma cells of a toxic substance. Mortality is related to complications of the polyneuropathy. Some patients in whom POEMS syndrome was associated, or not, with myeloma were treated with chemotherapy and/or radiotherapy with different responses; in others, corticosteroids were of short lived benefit. Our patients remains well after 42 months treatment with 20 mg methylprednisone every other day.

Mass spectrometric identification and confirmation of 16-methylprednisone acetate in Mexican pills.

The identification and confirmation of an unusual corticosteroid, 16-methylprednisone acetate, in Mexican pills is described. Identification is based on molecular structure illucidation from the electron impact fragmentation pattern. Characteristic m/e peaks at 121 (base peak), 241, 256 and 414 (molecular ion) are observed. Fragmentation pathways leading to these ions are presented. Confirmatory studies, employing NMR are also presented.