Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial.

Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients. Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization. Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39-1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360-842] vs. 870 mg [IQR 364-1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00-17.5] vs. 18.5 days [3.00-53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05-2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC. Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19. Clinical Trial Registration: Identifier [NCT04341038/EudraCT: 2020-001445-39].

Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness.

OBJECTIVES: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). METHODS: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. RESULTS: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. CONCLUSIONS: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.

The value of repeat biopsy in lupus nephritis flares.

Whether a repeat renal biopsy is helpful during lupus nephritis (LN) flares remains debatable. In order to analyze the clinical utility of repeat renal biopsy in this complex situation, we retrospectively reviewed our series of 54 LN patients who had one or more repeat biopsies performed only on clinical indications. Additionally, we reviewed 686 well-documented similar cases previously reported (PubMed 1990-2015).The analysis of all patients reviewed showed that histological transformations are common during a LN flare, ranging from 40% to 76% of cases. However, the prevalence of transformations and the clinical value of repeat biopsy vary when they are analyzed according to proliferative or nonproliferative lesions.The great majority of patients with class II (78% in our series and 77.5% in the literature review) progressed to a higher grade of nephritis (classes III, IV, or V), resulting in worse renal prognosis. The frequency of pathological conversion in class V is lower (33% and 43%, respectively) but equally clinically relevant, since almost all cases switched to a proliferative class. Therefore, repeat biopsy is highly advisable in patients with nonproliferative LN at baseline biopsy, because these patients have a reasonable likelihood of switch to a proliferative LN that may require more aggressive immunosuppression.In contrast, the majority of patients (82% and 73%) with proliferative classes in the reference biopsy (III, IV or mixed III/IV + V), remained into proliferative classes on repeat biopsy. Although rebiopsy in this group does not seem as necessary, it is still advisable since it will allow us to identify the 18% to 20% of patients that switch to a nonproliferative class. In addition, consistent with the reported clinical experience, repeat biopsy might also be helpful to identify selected cases with clear progression of proliferative lesions despite the initial treatment, for whom it is advisable to intensify inmunosuppression. Thus, our experience and the literature data support that repeat biopsy also brings more advantges than threats in this group.The results of the repeat biopsy led to a change in the immunosuppresive treatment in more than half of the patients on average, intensifying it in the majority of the cases, but also reducing it in 5% to 30%.

Nefritis lúpica mesangial proliferativa: descripción de una cohorte de 27 pacientes / Proliferative mesangial lupus nephritis: description of a cohort of 27 patients

Fundamento y objetivo: Describir nuestra cohorte de pacientes con nefritis lúpica mesangial proliferativa y su seguimiento a largo plazo, con especial atención a los factores de mal pronóstico.Pacientes y método: Se evaluaron 27 pacientes de forma retrospectiva y controlados en el Servicio de Medicina Interna del Hospital Universitario de Bellvitge entre 1974 y 2010. Se realizó un control al año, a los 3 y a los 5 años de la biopsia. Resultados: Había 22 mujeres (81,5%), con una edad media (DE) en el momento del diagnóstico de la nefritis de 34,83 (13,45) años. Al año de la biopsia 21 pacientes habían alcanzado la remisión parcial o completa (80,77%) y a los 5 años de control 21 pacientes (77,77%) estaban en remisión. Cuatro pacientes sufrieron transformación a otra clase histológica. Recidivaron 7 pacientes (29,63%). En estos 36 años de seguimiento fallecieron 7 pacientes, 3 de ellos por causas relacionadas con el lupus eritematoso sistémico. Conclusiones: El factor pronóstico más claramente relacionado con una mala respuesta es el inicio de la nefritis por encima de los 45 años, por lo que se debería valorar el uso de inmunodepresores de entrada asociados a glucocorticoides en estos pacientes (AU)

Background and objective: To describe our cohort of 27 biopsy-proven patients and their long-term follow-up, with special attention to prognostic factors. Patients and methods: Twenty seven patients were retrospectively collected. They were controlled in the Internal Medicine Department of the Bellvitge's Hospital (Spain) between 1974 and 2010. Evaluation was performed at one, 3 and 5 year follow-up. Results: There were 22 women (81.5%). Mean age at onset of nephritis was 34.83 years (SD 13.45). Partial or complete remission was achieved by 21 patients (80.77%) in the one-year follow-up, 22 patients (84.61%) in the third-year follow-up and 21 patients (77.77%) in the fifth-year follow-up. A change in the histology class was diagnosed in 4 patients. Seven patients suffered flares of nephritis. Seven patients died in the long term follow-up, 3 out of this 7 died because of systemic erythematosus lupus. Conclusion: Nephritis onset beyond 45 years old is the factor mostly related with a poor prognosis. That is the reason why we recommend co-therapy with immunosuppressors from the beginning in such patients (AU)

Nefritis lúpica mesangial proliferativa: descripción de una cohorte de 27 pacientes / Proliferative mesangial lupus nephritis: description of a cohort of 27 patients

Fundamento y objetivo: Describir nuestra cohorte de pacientes con nefritis lúpica mesangial proliferativa y su seguimiento a largo plazo, con especial atención a los factores de mal pronóstico.Pacientes y método: Se evaluaron 27 pacientes de forma retrospectiva y controlados en el Servicio de Medicina Interna del Hospital Universitario de Bellvitge entre 1974 y 2010. Se realizó un control al año, a los 3 y a los 5 años de la biopsia. Resultados: Había 22 mujeres (81,5%), con una edad media (DE) en el momento del diagnóstico de la nefritis de 34,83 (13,45) años. Al año de la biopsia 21 pacientes habían alcanzado la remisión parcial o completa (80,77%) y a los 5 años de control 21 pacientes (77,77%) estaban en remisión. Cuatro pacientes sufrieron transformación a otra clase histológica. Recidivaron 7 pacientes (29,63%). En estos 36 años de seguimiento fallecieron 7 pacientes, 3 de ellos por causas relacionadas con el lupus eritematoso sistémico. Conclusiones:El factor pronóstico más claramente relacionado con una mala respuesta es el inicio de la nefritis por encima de los 45 años, por lo que se debería valorar el uso de inmunodepresores de entrada asociados a glucocorticoides en estos paciente (AU)

Background and objective: To describe our cohort of 27 biopsy-proven patients and their long-term follow-up, with special attention to prognostic factors. Patients and methods: Twenty seven patients were retrospectively collected. They were controlled in the Internal Medicine Department of the Bellvitge's Hospital (Spain) between 1974 and 2010. Evaluation was performed at one, 3 and 5 year follow-up. Results: There were 22 women (81.5%). Mean age at onset of nephritis was 34.83 years (SD 13.45). Partial or complete remission was achieved by 21 patients (80.77%) in the one-year follow-up, 22 patients (84.61%) in the third-year follow-up and 21 patients (77.77%) in the fifth-year follow-up. A change in the histology class was diagnosed in 4 patients. Seven patients suffered flares of nephritis. Seven patients died in the long term follow-up, 3 out of this 7 died because of systemic erythematosus lupus. Conclusion: Nephritis onset beyond 45 years old is the factor mostly related with a poor prognosis. That is the reason why we recommend co-therapy with immunosuppressors from the beginning in such patients (AU)

[Proliferative mesangial lupus nephritis: description of a cohort of 27 patients]. / Nefritis lúpica mesangial proliferativa: descripción de una cohorte de 27 pacientes.

BACKGROUND AND OBJECTIVE: To describe our cohort of 27 biopsy-proven patients and their long-term follow-up, with special attention to prognostic factors. PATIENTS AND METHODS: Twenty seven patients were retrospectively collected. They were controlled in the Internal Medicine Department of the Bellvitge's Hospital (Spain) between 1974 and 2010. Evaluation was performed at one, 3 and 5 year follow-up. RESULTS: There were 22 women (81.5%). Mean age at onset of nephritis was 34.83 years (SD 13.45). Partial or complete remission was achieved by 21 patients (80.77%) in the one-year follow-up, 22 patients (84.61%) in the third-year follow-up and 21 patients (77.77%) in the fifth-year follow-up. A change in the histology class was diagnosed in 4 patients. Seven patients suffered flares of nephritis. Seven patients died in the long term follow-up, 3 out of this 7 died because of systemic erythematosus lupus. CONCLUSION: Nephritis onset beyond 45 years old is the factor mostly related with a poor prognosis. That is the reason why we recommend co-therapy with immunosuppressors from the beginning in such patients.

Sarcoidosis and autoimmune thyroid disease. A case series of ten patients.

BACKGROUND: Sarcoidosis coexisting with autoimmune disorders, especially with autoimmune thyroid disease (ATD), has been previously described and a common immunopathogenesis has been proposed. We report a series of ten new cases of this association from a large series of patients with sarcoidosis. METHODS: The clinical records of patients diagnosed with sarcoidosis between 1984 and 2006 in the Bellvitge University Hospital were reviewed, and those who were also diagnosed as having ATD were selected. A review of the literature was performed as well. RESULTS: Ten out of 348 (2.9%) patients with sarcoidosis were identified as having ATD. Sarcoidosis presented as Löfgren's syndrome in 8 patients. Three patients developed Graves' disease, 6 Hashimoto's thyroiditis with hypothyroidism and one had postpartum thyroiditis. In one case, ATD had developed 15 years before sarcoidosis. In the remaining nine cases, sarcoidosis preceded between 4 months to 17 years the development of ATD. In 3 of these cases, sarcoidosis was active when ATD was diagnosed. In one patient, Graves' disease developed immediately after the administration of potassium iodide to treat erythema nodosum. CONCLUSIONS: Sarcoidosis may be associated with ATD at some time of its evolution, either as hyperthyroidism or hypothyroidism. Usually, ATD does not develop during the period of activity of sarcoidosis. We suggest considering personal and family past history of thyroid disease before administering potassium iodide for erythema nodosum in patients with sarcoidosis, as it could trigger hyperthyroidism, especially in patients with iodine deficiency.

The effect of cephalosporin resistance on mortality in adult patients with nonmeningeal systemic pneumococcal infections.

PURPOSE: To evaluate the clinical relevance of cephalosporin (ceftriaxone/cefotaxime) resistance among patients with nonmeningeal systemic pneumococcal infection. SUBJECTS AND METHODS: From January 1994 to October 2000, we prospectively studied 522 episodes of nonmeningeal systemic pneumococcal infections (448 pneumonias) in 499 adults who were treated according to hospital guidelines. In vitro antibiotic susceptibility, as the minimum inhibitory concentration (MIC), was determined by microdilution method. The MIC methods and breakpoints (cutoffs) were established by the National Committee for Clinical Laboratory Standards. RESULTS: Of the 522 pneumococcal strains, 413 strains (79%) were susceptible to ceftriaxone/cefotaxime, MIC < or =0.5 microg/mL; 79 (15%) were intermediate, MIC = 1 microg/mL; and 30 (6%) were resistant, MIC = 2 microg/mL. After adjusting for several variables, including pneumococcal serogroups/serotypes, infections due to nonsusceptible (intermediate and resistant) pneumococcal strains were independently associated with prior antibiotic therapy, with an odds ratio of 5.9 (95% confidence interval: 2.6 to 13.6). Thirty-day mortality among the 185 patients who were treated with ceftriaxone (1 g/d) or cefotaxime (1.5 g every 8 hours) did not differ by cephalosporin susceptibility: 18% (26/148) among those with susceptible organisms, 13% (3/24) with intermediate organisms, and 15% (2/13) in resistant cases (P = 0.81). CONCLUSION: Ceftriaxone or cefotaxime were effective in treating patients with nonmeningeal systemic pneumococcal infections caused by strains with MIC < or =2 microg/mL. These results support the newly established ceftriaxone/cefotaxime MIC breakpoints (cutoffs) for nonmeningeal pneumococcal infections.