Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound.
OBJECTIVE: To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks.
METHODS: A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain).
METHODS: Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines.
METHODS: Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis.
RESULTS: Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol (n = 68), glucocorticoids (n = 112), both (n = 510), or neither (n = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) (p < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both (p = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol (p < 0.001). This difference was not found for corticosteroids.
CONCLUSIONS: The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation.

OBJECTIVE: There is growing evidence supporting the role of inflammatory mechanisms in complex regional pain syndrome (CRPS). Corticoids, as most effective anti-inflammatory drugs, are widely used in treating inflammation. The aim of this study was to retrospectively assess the efficacy of oral corticoid treatment in CRPS patients.
METHODS: Patients treated at the center of pain medicine in the Erasmus University Medical Centre between January 2015 and January 2020 were approached to partake in this study. Medical records were screened for age, gender, medical history, duration of CRPS, and CRPS severity score. Also, treatment effect, dose and duration, pain scores (NRS), and side effects were extracted from medical records. In addition, global perceived effect was completed in patients treated with corticoids.
RESULTS: Between January 2015 and January 2020, twenty-nine CRPS patients received corticoids and met the inclusion criteria. One extreme outlier was excluded and treatment effect was unknown for one patient. Average daily dose was 28.9 mg (range 10-30 mg) and the mean treatment duration was 10.5 days (7-21 days). Fourteen patients (51.9%) responded positively to treatment and thirteen (48.1%) did not respond. Side effects were reported in five patients (17.9%).
CONCLUSIONS: Corticoid treatment was effective in more than half of the patients. With only mild side effects reported the treatment also appears to be relatively safe. Further research is needed to investigate the efficacy of corticoids in treating (early) CRPS, preferably in an intervention study.

OBJECTIVE: To assess the effectiveness and safety of the intravitreal fluocinolone-acetonide implant (FAc-i) in patients with chronic diabetic macular edema who did not sufficiently respond to other available therapies.
METHODS: This was a multicenter, prospective, non-randomized, and phase-IV observational study conducted on patients with recurrent-DME who were insufficient responders to currently available therapies (REACT-Study). The primary end-point was the mean change in best-corrected-visual-acuity from baseline to month-24 values.
RESULTS: Thirty-one eyes from 31 patients were included in the study. Mean age was 68.0 ± 7.7 years, and 10 (32.3%) were women. Study patients had received 5.3 ± 7.3 previous DME treatments before starting the study. In the overall study sample, BCVA improved from 56.1 ± 12.3 letters at baseline to 62.4 ± 17.0 letters at month-24 (p = 0.0510). The eyes with a baseline BCVA < 70 ETDRS letters had a significant improvement in BCVA from 53.2 ± 10.2 letters at baseline to 61.5 ± 17.9 letters at month-24 (p = 0.0165). In the overall study population, central-subfoveal-thickness (CST) was significantly reduced from 474.0 ± 135.1 µm at baseline to 333.4 ± 135.6 at month-24 (p < 0.0001). Similarly, macular-volume (MV) was significantly reduced from 10.7 ± 2.7 mm3 at baseline to 9.6 ± 2.9 mm3 (p = 0.0027) at month-24. Among the 31 study eyes, 19 (61.3%) required an additional treatment for DME. Throughout the study, 9 (29.0%) eyes required ocular hypotensive medication for controlling their intraocular-pressure and 5 (16.1%) eyes underwent cataract surgery.
CONCLUSIONS: In DME eyes who did not sufficiently respond to previous therapies, the FAc-i was associated with an improvement in visual and anatomic outcomes. There were no unexpected adverse-events.
BACKGROUND: EudraCT identifier: 2016-001680-37.

BACKGROUND: Dexamethasone-cyclophosphamide pulse (DCP) and dexamethasone pulse (DP) have been successfully used to treat pemphigus, but DCP/DP outcomes comparing pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are scarce.
OBJECTIVE: To compare DCP/DP outcomes in a Brazilian cohort of PV and PF patients according to demographic and clinical data.
METHODS: Retrospective analytical cohort study, reviewing medical charts of PV and PF patients (for DCP/DP Phases I‒IV consult Pasricha et al.16‒18).
RESULTS: 37 PV and 41 PF patients non responsive to usual treatments were included similarly for DCP or DP therapy. Disease duration was longer among PF before DCP/DP prescription (p < 0.001); PF required a higher number of monthly pulses to acquire remission in Phase I (median 10 and 6 pulses, respectively; p = 0.005). DCP/DP outcomes were similar in both groups: remission in 37.8% of PV and 34.1% of PF after completed DCP/DP cycles following a median of 13 months (1-56 months follow-up); failure occurred in 13.5% of PV and 14.6% of PF in Phase I; relapse in 13.5% of PV and 12.2% of PF, and dropout in 27% of PV and 24.4% of PF in Phases II to IV. Mild side effects were documented.
CONCLUSIONS: The severity of PV and PF disease was not assessed by score indexes.
CONCLUSIONS: PV and PF patients presented similar DCP/DP outcomes. DCP/DP should be initiated earlier in PF patients due to the longer duration of their disease in order to decrease the number of pulses and the duration of Phase I to acquire remission.

BACKGROUND: Whether they are injected peri- or intraocularly, corticosteroids are still essential tools in the therapeutic arsenal for treating inflammatory macular oedema. A few years ago, however, only triamcinolone acetonide was available to ophthalmologists. While this compound was initially developed for rheumatological or dermatological use, it has been increasingly deployed in ophthalmology, despite still being off-label. In 2011, the system for delivery of dexamethasone from a biodegradable, injectable implant into the vitreous cavity obtained approval for use in inflammatory macular oedema. While the efficacy and safety of triamcinolone in macular oedema, including inflammatory oedema, have already been studied, there are currently no publications on subconjunctival triamcinolone injections, which are simple, effective and well tolerated. To date, the dexamethasone 700 μg implant has been authorized for the treatment of noninfectious intermediate and posterior uveitis, but there have been no studies to evaluate the efficacy and safety of the different peri- and intraocular strategies, including the treatment of inflammatory macular oedema.
METHODS: This protocol is therefore designed to compare the efficacy and safety of peri- and intraocular corticosteroid injections in the treatment of inflammatory macular oedema. In this ongoing study, 142 patients will be included, and the oedematous eye will be randomised to treatment with either subconjunctival triamcinolone injection or an intravitreal implant containing 700 μg dexamethasone. Follow-up is planned for 6 months with monthly visits. Each visit will include visual acuity measurement, a slit lamp examination, fundoscopy, intraocular pressure measurement, laser flare measurement (if available) and spectral domain optical coherence tomography.
CONCLUSIONS: The results of this trial will have a real impact on public health if it is shown that a Kenacort retard® (i.e. triamcinolone) injection costing just €2.84 and performed in the physician\'s office (with no additional overhead costs) is at least as effective as the dexamethasone 700 μg implant (Ozurdex®; costing approximately €960 with the injection performed in a dedicated room), with no increased side effects.
BACKGROUND: ClinicalTrials.gov, NCT02556424. Registered on 22 September 2015.

To assess whether dexamethasone (DXM) decreases the time to recovery in patients with parapneumonic pleural effusion.
This was a multicenter, randomized, double blind, parallel-group, placebo-controlled clinical trial of 60 children, ranging in age from 1 month to 14 years, with community-acquired pneumonia (CAP) and pleural effusion. Patients received either intravenous DXM (0.25?mg/kg/dose) or placebo every 6 hours over a period of 48 hours, along with antibiotics. The primary endpoint was the time to recovery in hours, defined objectively. We also evaluated complications and adverse events.
Among the 60 randomized patients (mean age, 4.7 years; 58% female), 57 (95%) completed the study. Compared with placebo recipients, the patients receiving DXM had a shorter time to recovery, after adjustment by severity group and stratification by center (hazard ratio, 1.95; 95% CI, 1.10-3.45; P?=?.021). The median time to recovery for patients receiving DXM was 68 hours (2.8 days) shorter than patients receiving placebo (109 hours vs 177 hours; P?=?.037). In exploratory subgroup analysis, the median time to recovery for patients with simple effusion receiving DXM was 76 hours (3.1 days) shorter than for patients with simple effusion receiving placebo (P?=?.017). The median time to recovery for patients with complicated effusion receiving DXM was 14 hours (0.5 days) shorter than for patients with complicated effusion receiving placebo (P?=?.66). The difference in the effect of DXM in the 2 severity groups was not statistically significant (P?=?.138 for interaction). There were no significant differences in complications or adverse events attributable to the study drugs, except for hyperglycemia.
In this trial, DXM seemed to be a safe and effective adjunctive therapy for parapneumonic pleural effusion.
ClinicalTrials.gov: NCT01261546.

Although much has evolved in our understanding of the pathogenesis and factors affecting outcome of patients with acute respiratory distress syndrome (ARDS), still there is no specific pharmacologic treatment for ARDS. Several clinical trials have evaluated the utility of corticoids but none of them has demonstrated a definitive benefit due to small sample sizes, selection bias, patient heterogeneity, and time of initiation of treatment or duration of therapy. We postulated that adjunctive treatment of persistent ARDS with intravenous dexamethasone might change the pulmonary and systemic inflammatory response and thereby reduce morbidity, leading to a decrease in duration of mechanical ventilation and a decrease in mortality.
This is a prospective, multicenter, randomized, controlled trial in 314 patients with persistent moderate/severe ARDS. Persistent ARDS is defined as maintaining a PaO2/FiO2 ≤ 200 mmHg on PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 after 24 hours of routine intensive care. Eligible patients will be randomly allocated to two arms: (i) conventional treatment without dexamethasone, (ii) conventional treatment plus dexamethasone. Patients in the dexamethasone group will be treated with a daily dose of 20 mg iv from day 1 to day 5, and 10 mg iv from day 6 to day 10. Primary outcome is the number of ventilator-free days, defined as days alive and free from mechanical ventilation at day 28 after intubation. Secondary outcome is all-cause mortality at day 60 after enrollment.
This study will be the largest randomized controlled clinical trial to assess the role of dexamethasone in patients with persistent ARDS.
Registered on 21 November 2012 as DEXA-ARDS at ClinicalTrials.gov website ( NCT01731795 ).

OBJECTIVE: To evaluate the influence of treatment with different doses of methylprednisolone on the mechanical resistance and possible histological alterations of the rotator cuff tendon in rats.
METHODS: Male Wistar rats were divided randomly into four treatment groups: sham, vehicle or 0.6 mg/kg or 6.0 mg/kg of methylprednisolone. Changes to mechanical resistance (in N) and histological parameters (fibrillar appearance, presence of collagen, edema and vascular proliferation) of the rotator cuff tendon were evaluated. The analyses were conducted after administration of one treatment (24 h afterwards), two treatments (7 days afterward) or three treatments (14 days afterwards), into the subacromial space.
RESULTS: Seven and fourteen days after the treatments were started, it was found that in a dose-dependent manner, methylprednisolone reduced the mechanical resistance of the rotator cuff tendon (p < 0.05 in relation to the vehicle group). Modifications to the histological parameters were observed on the 7th and 14th days after the first infiltration, especially regarding the presence of collagen and vascular proliferation, for the dose of 0.6 mg/kg of methylprednisolone, and also regarding the presence of collagen, edema and vascular proliferation for the dose of 6.0 mg/kg of corticoid.
CONCLUSIONS: The results obtained demonstrated a relationship between methylprednisolone use through infiltration into the subacromial space and reduction of the mechanical resistance of and histological modifications to the rotator cuff tendon in rats.
Avaliar a influência do tratamento com diferentes doses de metilprednisolona sobre a resistência mecânica, bem como possíveis alterações histológicas do tendão do manguito rotador (MR) em ratos.
Ratos Wistar machos foram divididos aleatoriamente em quatro grupos de tratamento como sham, veículo, 0,6 mg/kg ou 6 mg/kg de metilprednisolona. Alterações na resistência mecânica (em N) e em parâmetros histológicos (aparência fibrilar, presença de colágeno, edema e proliferação vascular) do tendão do manguito rotador (MR) foram avaliadas. As análises foram feitas após o tratamento com uma (24 horas após), duas (sete dias após) ou três (14 dias após) administrações no espaço subacromial.
Após sete e 14 dias do início do tratamento a metilprednisolona reduziu, de maneira dependente de dose, a resistência mecânica do tendão do MR (p < 0,05 em relação ao grupo veículo). Também foram observadas modificação em parâmetros histológicos nos dias sete e 14 após a primeira infiltração, principalmente quanto à presença de colágeno e proliferação vascular para a dose de 0,6 MG/kg de metilprednisolona e presença de colágeno, edema e proliferação vascular para a dose de 6 mg/kg do corticoide.
Os resultados obtidos demonstram uma relação entre o uso de metilprednisolona por infiltração no espaço subacromial e a redução da resistência mecânica e modificações histológicas no tendão do MR de ratos.

OBJECTIVE: to compare healing strength of the infraspinatus tendon of rats with corticoid inoculation, regarding maximum tension, maximum force and rupture force, after injury and experimental repair.
METHODS: a total of 60 Wistar rats were subjected to tenotomy of the infraspinatus tendon, which was then sutured. Before the surgery, they were divided into a control group (C) inoculated with serum and a study group (S) inoculated with corticoids over the tendon. After repair, the rats were sacrificed in groups of 10 individuals in the control group and 10 in the study group at the times of one week (C1 and S1), three weeks (C3 and S3) and five weeks (C5 and S5). The rats were dissected, separating out the infraspinatus tendon with the humerus. The study specimens were subjected to a traction test, with evaluation of the maximum tension (kgf/cm(2)), maximum force (kgf) and rupture force (kgf), comparing the study group with the respective control groups.
RESULTS: among the rats sacrificed one week after the procedure, we observed greater maximum tension in group C1 than in group S1. The variables of maximum force (kgf) and rupture force did not differ statistically between the groups investigated. In the same way, among the rats sacrificed three weeks after the procedure, group C3 only showed greater maximum tension than group S3 (p = 0.007), and the other variables did not present differences. Among the rats sacrificed five weeks after the procedure (C5 and S5), none of the parameters studied presented statistical differences.
CONCLUSIONS: we concluded that corticoid diminished the resistance to maximum tension in the groups sacrificed one and three weeks after the procedure, in comparison with the respective control groups. The other parameters did not show differences between the study and control groups.
comparar a resistência da cicatrização, com relação a tensão máxima, força máxima e força de ruptura, do tendão infraespinhal de ratos submetidos a inoculação de corticoides após a lesão e a reparos experimentais.
foram submetidos 60 ratos Wistar a tenotomia do tendão infraespinhal e suturados. Previamente à cirurgia foram divididos em grupo controle (C), inoculados com soro, e grupo de estudo (E), inoculados com corticoides sobre o tendão. Após o reparo os ratos foram sacrificados em grupos de 10 indivíduos do grupo controle e 10 do grupo de estudo em intervalos de uma semana (C1 e E1), três semanas (C3 e E3) e cinco semanas (C5 e E5). Os ratos foram dissecados com a separação do tendão infraespinhal do úmero. As peças de estudo foram submetidas a teste de tração e avaliadas – tensão máxima (kgf/cm2), força máxima (kgf) e força de ruptura (kgf) – e comparando os grupos de estudo com os grupos controle.
dentre os ratos sacrificados com uma semana observamos maior tensão máxima do grupo C1 em comparação com o grupo E1. As variáveis força máxima (kgf) e força de ruptura (kgf) não diferiram estatisticamente entre os grupos pesquisados. Da mesma forma, nos ratos sacrificados com três semanas o grupo C3 mostrou apenas resistência maior na tensão máxima em comparação com o grupo E3 (p = 0.007). As demais variáveis não apresentaram diferenças. Nos ratos sacrificados com cinco semanas (C5 e E5), nenhum dos parâmetros estudados apresentou diferenças estatísticas.
a inoculação com corticoide sobre o manguito rotador levou a diminuição da resistência a tensão máxima da cicatriz pós reparo cirúrgico experimental em uma e três semanas em comparação com os respectivos grupos controle. Os demais parâmetros não tiveram diferença entre os grupos de estudo e os grupos controle.