Early Corticosteroid Research Articles

Long-term seizure outcomes in patients with anti-Leucine-rich glioma-inactivated 1 encephalitis

BackgroundThis study aimed to investigate the semiology of seizure disorders, including electroencephalographic characteristics, and seizure outcomes in participants with anti-leucine-rich glioma-inactivated 1 (LGI-1) encephalitis. MethodsSeventy participants who presented with seizures during the acute phase of anti-LGI-1 encephalitis at Peking Union Medical College Hospital from May 2013 to July 2020 were reviewed. All participants underwent follow-up for longer than 2 years. ResultsAt the time of presentation, 48 (68.6%) participants had generalized seizures and 57 (81.4%) had focal seizures. The most common focal motor seizures were faciobrachial dystonic seizures (FDS). The main manifestations of focal nonmotor seizures were dyscognitive features, goosebumps, and disorders of sensation. All participants received immunomodulatory therapy. Thirty-five (50%) participants were seizure free after 1 year of follow-up, and 48 (68.6%) participants were seizure free over a follow-up of 2 years. Participants with seizures continued longer than 1 year were older than participants whose seizure duration was shorter than 1 year (P = 0.021). However, after an extended follow-up period, the difference between the incidences of seizures based on age was not significant. The frequency of focal motor seizures was higher in participants who became seizure free within 1 year, compared to participants who had seizures for longer than 1 year (75% vs 54.3%, respectively; P = 0.015). Participants with seizures continued over 2 years tended to have focal nonmotor seizures, and tended to show an elevated incidence of abnormal EEG results. Participants receiving early corticosteroid and longer duration immunosuppressant treatments, tended to have a lower risk of persistent seizures and better seizure outcomes, with no statistical significance. ConclusionsMost participants obtained remission from seizures after immunomodulatory therapy. The seizure manifestation of anti-LGI1 encephalitis is diverse and variable. The type of focal seizures may affect the outcome of participants with seizures. Older age could lead to longer duration of the seizure disorder, but did not affect the rate of seizures over the long term. Early and prolonged administration of immunomodulatory therapy may be useful for shortening the time to becoming seizure free.

Predictors of mortality for hospitalized young adults aged less than 60 years old with severe COVID-19: a retrospective study.

BackgroundTo analyze the clinical characteristics and predictors for mortality of adult younger than 60 years old with severe coronavirus disease 2019 (COVID-19).MethodsWe retrospectively retrieved data for 152 severe inpatients with COVID-19 including 60 young patients in the Eastern Campus of Wuhan University affiliated Renmin Hospital in Wuhan, China, from January 31, 2020 to February 20, 2020. We recorded and analyzed patients’ demographic, clinical, laboratory, and chest CT findings, treatment and outcomes data.ResultsOf those 60 severe young patients, 15 (25%) were died. Male was more predominant in deceased young patients (12, 80%) than that in recovered young patients (22, 49%). Hypertension was more common among deceased young patients (8, 53%) than that in recovered young patients (7, 16%). Compared with the recovered young patients, more deceased young patients presented with sputum (11, 73%), dyspnea (12, 80%) and fatigue (13, 87%). Only sputum, PSI and neutrophil counts were remained as independent predictors of death in a multivariate logistic regression model. Among ARDS patients, the recovered were administrated with corticosteroid earlier and anticoagulation. The addition of neutrophil counts >6.3×109/L to the SMART-COP score resulted in improved area under the curves.ConclusionsSevere acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection in young deceased patients appears to cause exuberant inflammatory responses, leading to compromised oxygen exchange, coagulation and multi-organ dysfunction. In addition, young patients with ARDS could benefit from adjuvant early corticosteroid and anticoagulation therapy. The expanded SMART-COP could predict the fatal outcomes with optimal efficiency.

Effects of early corticosteroid use in patients with severe coronavirus disease 2019

BackgroundCoronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome, and corticosteroids have been considered as possible therapeutic agents for this disease. However, there is limited literature on the appropriate timing of corticosteroid administration to obtain the best possible patient outcomes.MethodsThis was a retrospective cohort study including patients with severe COVID-19 who received corticosteroid treatment from March 2 to June 30, 2020 in seven tertiary hospitals in South Korea. We analyzed the patient demographics, characteristics, and clinical outcomes according to the timing of steroid use. Twenty-two patients with severe COVID-19 were enrolled, and they were all treated with corticosteroids.ResultsOf the 22 patients who received corticosteroids, 12 patients (55%) were treated within 10 days from diagnosis. There was no significant difference in the baseline characteristics. The initial PaO2/FiO2 ratio was 168.75. The overall case fatality rate was 25%. The mean time from diagnosis to steroid use was 4.08 days and the treatment duration was 14 days in the early use group, while those in the late use group were 12.80 days and 18.50 days, respectively. The PaO2/FiO2 ratio, C-reactive protein level, and cycle threshold value improved over time in both groups. In the early use group, the time from onset of symptoms to discharge (32.4 days vs. 60.0 days, P = 0.030), time from diagnosis to discharge (27.8 days vs. 57.4 days, P = 0.024), and hospital stay (26.0 days vs. 53.9 days, P = 0.033) were shortened.ConclusionsAmong patients with severe COVID-19, early use of corticosteroids showed favorable clinical outcomes which were related to a reduction in the length of hospital stay.

Clinical Implications of Tacrolimus Time in Therapeutic Range and Intrapatient Variability in Urban Renal Transplant Recipients Undergoing Early Corticosteroid Withdrawal.

Background.Tacrolimus demonstrates wide intrapatient and interpatient variability requiring therapeutic drug monitoring. The utility of tacrolimus time in therapeutic range (TTR) after renal transplantation (RT) under an early corticosteroid withdrawal (ECSWD) protocol is unknown. The purpose of this study is to assess the impact of tacrolimus TTR in an ECSWD RT population.Materials.A retrospective analysis of adult RT recipients maintained on tacrolimus was conducted. Patients were excluded if they were on nonstandard protocol immunosuppression agents <12 months post-RT. Tacrolimus TTR was calculated using the Rosendaal method. Patients were divided into high (TTR-H) and low (TTR-L) TTR groups based on cohort median. The primary outcome was to compare the incidence of acute rejection 12 months post-RT. Secondary outcomes included comparing rejection subtypes, incidence of donor-specific antibody (DSA) and de novo DSA (dnDSA), risk factors for acute rejection and dnDSA development, and allograft function (serum creatinine and estimated glomerular filtration rate).Results.A total of 193 patients were analyzed (TTR-H = 98 and TTR-L = 95). There was no difference in the incidence of acute rejection (TTR-H 20.4% versus TTR-L 20.0%; P = 0.944). Positive DSA posttransplant (odds ratio [OR], 3.62; 95% confidence interval [CI], 1.41-9.26; P = 0.007) was associated with a higher acute rejection at 12 months posttransplant. Mycophenolate dose reduction (OR, 2.82; 95% CI, 1.13-6.97; P = 0.025) and acute rejection (OR, 2.99; 95% CI, 1.09-8.18; P = 0.032) were associated with dnDSA formation. No difference in serum creatinine or estimated glomerular filtration rate was observed (P > 0.05).Conclusions.Tacrolimus TTR was not significantly different with regards to acute rejection in an ECSWD population. Future studies are still needed to determine tacrolimus TTR thresholds post-RT and identify populations that may benefit from this intrapatient variability monitoring parameter.

Role of the early short-course corticosteroids treatment in ARDS caused by COVID-19: A single-center, retrospective analysis

PurposeSevere coronavirus disease 2019 (COVID-19) is strongly related to interstitial pneumonia with frequent development of acute respiratory distress syndrome (ARDS). The role of corticosteroids (CS) treatment in these patients is still controversial. Some studies evidenced a possible role of an early short-term course of CS treatment in the treatment of severe pneumonia. Patients and methodsThis is a single-center, retrospective study considering the patients with confirmed COVID-19 pneumonia admitted to our hospital between 9th March and 15th June 2020. Two groups were considered: early high-dose of methyl-prednisolone (eHDM; n ​= ​31) and the control group (n ​= ​52). Patients in the eHDM group received the dose of 5-8 ​mg/kg/day of methyl-prednisolone for 2 consecutive days. Primary outcome was the mortality evaluation; secondary outcomes were clinical improvement, side-effects and laboratory/radiographic changes. ResultsSignificant differences between the two groups were: length of hospitalization (21.5 vs 28.4 days, p ​= ​0.026), length of non-invasive ventilation (NIV) or mechanical ventilation (11.5 vs 14.5 days, p ​= ​0.031), death (5 vs 12, p ​= ​0.006) and clinical improvement (16 vs 11, p=0.018). The following factors were related to in-hospital mortality in the multivariate analysis: comorbidities (OR ​= ​2.919; 95%CI ​= ​1.515-16.705; p<0.001), days from the onset of symptoms and the hospital admission (OR ​= ​1.404; 95%CI ​= ​1.069-12.492; p ​= ​0.011), PaO2/FiO2 (P/F) ratio (OR ​= ​3.111; 95%CI ​= ​2.334-16.991; p ​= ​0.009) and eHDM treatment (OR ​= ​0.741; 95%CI ​= ​0.129-0.917; p ​= ​0.007). ConclusionThe eHDM is an interesting and promising approach in the ARDS related to COVID-19 pneumonia, which reduces mortality, length of hospitalization and the need for mechanical ventilation.

Prognostic impact of early adjunctive corticosteroid therapy in non-HIV oncology or haematology patients with Pneumocystis jirovecii pneumonia: A propensity score analysis.

PurposeWhile early adjunctive corticosteroid therapy (EACST) has been proven effective in HIV patients with Pneumocystis Jirovecii Pneumonia (PJP), data remains controversial concerning non-HIV oncology or haematology patients.MethodsThis retrospective study included cancer patients without HIV and with diagnosis of PJP admitted in a cancer referral centre, from January-1-2010 to March-31-2017. We compared 30-day and 1-year mortality rate, change in the respiratory item of the Sequential Organ Failure Assessment score(SOFA-resp worsening), use of tracheal intubation between day-1 and day-5 of anti-pneumocystis therapy and occurrence of coinfections between patients with EACST and those with no or late corticosteroid therapy, using an inverse probability weighting propensity score-based (IPW) analysis.Results133 non-HIV oncology or haematology PJP patients were included (EACST n = 58, others n = 75). The main underlying conditions were haematological malignancies (n = 107, 80,5%), solid tumour (n = 27, 20,3%) and allogeneic stem cell transplantation (n = 17, 12,8%). Overall 30-day and 1-year mortality rate was 24,1% and 56,4%, respectively. IPW analysis found no difference on 30-day (HR = 1.45, 95% CI [0.7–3.04], p = 0.321) and 1-year (HR = 1.25, CI 95% [0.75–2.09], p = 0.39) mortality rate between groups.ConclusionNo difference in SOFA-resp worsening, tracheal intubation and coinfections was found between groups. Combination of EACST with anti-pneumocystis therapy in non-HIV onco-haematology PJP-patients was not associated with clinical improvement.

Management of Unsatisfactory Postoperative Double Eyelid With Intralesional Corticosteroid Injection.

Purpose: The present study was designed to observe the curative effect of early intralesional corticosteroid injection to treat unsatisfactory double eyelid.Methods: This retrospective, observational study included 30 female patients (age 22–35 years) receiving intralesional corticosteroid injection after complaining about the unsatisfactory double eyelid post-transcutaneous upper eyelid blepharoplasty. The postoperative double eyelid anomalies included multiple folds, sunken eyelids, and severe postoperative eyelid edema. The evaluation of the clinical effect was based on the bilateral symmetry of the eyelid, the placement of the lid fold, the radian of the double eyelid, and the extent of the swelling and depression.Results: Multiple folds were observed in 11 (36.67%) patients, sunken eyelids in 9 (30.00%) patients, and severe postoperative eyelid edema in 10 (33.33%) patients. Among them, 17 (56.67%) patients received one intralesional injection and experienced significant improvement in the eyelid, while 8 (26.67%) accepted another injection at 1 month after the first injection and achieved marked improvement. The remaining 5 (16.67%) patients were dissatisfied with the results and might need further repair surgery: 2 patients had multiple folds, 2 showed postoperative edema, and 1 presented sunken eyelids. None of the patients reported any adverse reactions.Conclusion: Intralesional corticosteroid injection for the correction of the postoperative unsatisfactory double eyelid is safe and convenient, and provides a novel method for early intervention.

Macrolide-Resistant and Macrolide-Sensitive Mycoplasma pneumoniae Pneumonia in Children Treated Using Early Corticosteroids.

We have found that early corticosteroid therapy was effective for reducing morbidity during five Korea-wide epidemics. We evaluated the clinical and laboratory parameters of 56 children who received early corticosteroid treatment for pneumonia that was caused by macrolide-resistant Mycoplasma pneumoniae (M. pneumoniae) or macrolide-sensitive M. pneumoniae between July 2019 and February 2020. All subjects had dual positive results from a PCR assay and serological test, and received corticosteroids within 24–36 h after admission. Point mutation of residues 2063, 2064, and 2067 was identified in domain V of 23S rRNA. The mean age was 6.8 years and the male:female ratio was 1.2:1 (31:25 patients). Most of the subjects had macrolide-resistant M. pneumoniae (73%), and all mutated strains had the A2063G transition. No significant differences in clinical and laboratory parameters were observed between macrolide-resistant and macrolide-sensitive M. pneumoniae groups that were treated with early dose-adjusted corticosteroids. Higher-dose steroid treatment may be needed for patients who have fever that persists for >48 h or increased biomarkers such as lactate dehydrogenase concentration at follow-up despite a usual dose of steroid therapy.

Bacterial Meningitis in Children: Neurological Complications, Associated Risk Factors, and Prevention.

Bacterial meningitis is a devastating infection, with a case fatality rate of up to 30% and 50% of survivors developing neurological complications. These include short-term complications such as focal neurological deficit and subdural effusion, and long-term complications such as hearing loss, seizures, cognitive impairment and hydrocephalus. Complications develop due to bacterial toxin release and the host immune response, which lead to neuronal damage. Factors associated with increased risk of developing neurological complications include young age, delayed presentation and Streptococcus pneumoniae as an etiologic agent. Vaccination is the primary method of preventing bacterial meningitis and therefore its complications. There are three vaccine preventable causes: Haemophilus influenzae type b (Hib), S. pneumoniae, and Neisseria meningitidis. Starting antibiotics without delay is also critical to reduce the risk of neurological complications. Additionally, early adjuvant corticosteroid use in Hib meningitis reduces the risk of hearing loss and severe neurological complications.

Early Corticosteroid Cessation vs Long-term Corticosteroid Therapy in Kidney Transplant Recipients

The complications of corticosteroids make the inclusion of these drugs in immunosuppressive protocols for kidney transplant patients undesirable. However, cessation of corticosteroids is associated with a higher risk of short-term rejection, and the long-term outcomes of patients withdrawn from corticosteroids remain uncertain. To compare long-term kidney transplant outcomes of patients randomized to continue or withdraw corticosteroids. This prospective multicenter randomized double-blind placebo-controlled trial was conducted between November 1999 and December 2002 with linkage to a mandatory national registry with validated outcome ascertainment until June 8, 2018. The study included 28 kidney transplant centers in the United States, including 386 low- to moderate-immune risk adult recipients of a living or deceased donor kidney transplant without delayed graft function or short-term rejection in the first week after transplant. Analyses were intention to treat. Analysis began September 2018 and ended June 2019. Patients were randomized to receive tacrolimus and mycophenolate mofetil with or without corticosteroids 7 days after transplant. Kidney allograft failure from any cause including death and allograft failure censored for patient death defined by the requirement for long-term dialysis or repeat transplant. Of 385 patients, 191 were assigned to withdraw from corticosteroids (mean [SD] age, 46.5 [12.1] years), and 194 patients were assigned to continued corticosteroids (mean [SD] age, 46.3 [12.6] years). The median (interquartile range) follow-up time was 15.8 (12.0-16.3) years after transplant. The adjusted hazard ratios of allograft failure from any cause including death was 0.83 (95% CI, 0.62-1.10; P = .19) and for allograft failure censored for patient death was 0.78 (95% CI, 0.52-1.19; P = .25) and did not differ between the patients assigned to withdraw from corticosteroids vs assigned to continued corticosteroids. Results were consistent in a per-protocol analysis among 223 patients who continued the trial-assigned treatment of corticosteroid withdrawal (n = 114) or corticosteroids (n = 109) through at least 5 years after transplant. The outcomes of trial participants in either treatment group did not differ from similarly treated contemporary registry patients who met trial eligibility criteria and were treated with the same immunosuppressive drugs. Long-term corticosteroids may not be necessary as part of a calcineurin-based multiple drug immunosuppressive regimen in low- to moderate-immune risk kidney transplant recipients.

Immunotherapy in Autoantibody-Associated Psychiatric Syndromes in Adults.

Background: Autoantibody-associated psychiatric syndromes are often distinct from, but might also be part of autoimmune encephalitis. Our article focuses on potential immunotherapy in these patients with a probable autoimmune origin of their psychiatric syndrome.Methods: We searched through PubMed for appropriate articles on immunotherapy in autoantibody-associated psychiatric syndromes between 2010 and 2020 for this narrative review.Results: In line with prior recommendations for autoimmune encephalitis and autoimmune psychosis, we suggest that in patients with a probable autoimmune-based psychiatric syndrome should be given early corticosteroids, intravenous immunoglobulins, or plasmapheresis as first line immunotherapy. If these therapeutic options fail, second-line immunotherapy should be applied within 1 month consisting of rituximab or cyclophosphamide. Maintenance therapy is best for those patients responding to steroids including mycofenolate mofetil or azathioprine. So far, there is evidence from a few retrospective cohort studies supporting the usage of first- and second-line, and maintenance immunotherapies for autoantibody-associated psychiatric syndromes. Some immunological agents are discussed that might exert an effect in autoimmune-based psychiatric syndromes, but the latest evidence is low and derived from case reports or series with autoimmune encephalitis patients.Conclusions: Taken together, the immunotherapeutic landscape for patients with autoantibody-associated psychiatric syndromes is delineated. Our suggestions rely on observational studies in autoantibody-associated psychiatric syndromes and a few placebo-controlled, randomized trials for patients with autoimmune encephalitis and psychosis. Thus, adequate powered, prospective as well as placebo-controlled clinical trials in patients with autoantibody-associated psychiatric syndromes are warranted in order to enlighten efficacy and safety aspects of current and novel therapy strategies.

Early corticosteroids are associated with lower mortality in critically ill patients with COVID-19: a cohort study

BackgroundCritically ill patients with coronavirus disease 19 (COVID-19) have a high fatality rate likely due to a dysregulated immune response. Corticosteroids could attenuate this inappropriate response, although there are still some concerns regarding its use, timing, and dose.MethodsThis is a nationwide, prospective, multicenter, observational, cohort study in critically ill adult patients with COVID-19 admitted into Intensive Care Units (ICU) in Spain from 12th March to 29th June 2020. Using a multivariable Cox model with inverse probability weighting, we compared relevant outcomes between patients treated with early corticosteroids (before or within the first 48 h of ICU admission) with those who did not receive early corticosteroids (delayed group) or any corticosteroids at all (never group). Primary endpoint was ICU mortality. Secondary endpoints included 7-day mortality, ventilator-free days, and complications.ResultsA total of 691 patients out of 882 (78.3%) received corticosteroid during their hospital stay. Patients treated with early-corticosteroids (n = 485) had lower ICU mortality (30.3% vs. never 36.6% and delayed 44.2%) and lower 7-day mortality (7.2% vs. never 15.2%) compared to non-early treated patients. They also had higher number of ventilator-free days, less length of ICU stay, and less secondary infections than delayed treated patients. There were no differences in medical complications between groups. Of note, early use of moderate-to-high doses was associated with better outcomes than low dose regimens.ConclusionEarly use of corticosteroids in critically ill patients with COVID-19 is associated with lower mortality than no or delayed use, and fewer complications than delayed use.

Time-course analysis reveals that corticosteroids resuscitate diminished CD8+ T cells in COVID-19: a retrospective cohort study

Objective To illustrate the effect of corticosteroids and heparin, respectively, on coronavirus disease 2019 (COVID-19) patients’ CD8+ T cells and D-dimer. Methods In this retrospective cohort study involving 866 participants diagnosed with COVID-19, patients were grouped by severity. Generalized additive models were established to explore the time-course association of representative parameters of coagulation, inflammation and immunity. Segmented regression was performed to examine the influence of corticosteroids and heparin upon CD8+ T cell and D-dimer, respectively. Results There were 541 moderate, 169 severe and 156 critically ill patients involved in the study. Synchronous changes of levels of NLR, D-dimer and CD8+ T cell in critically ill patients were observed. Administration of methylprednisolone before 14 DFS compared with those after 14 DFS (β = 0.154%, 95% CI=(0, 0.302), p=.048) or a dose lower than 40 mg per day compared with those equals to 40 mg per day (β = 0.163%, 95% CI=(0.027, 0.295), p=.020) significantly increased the rising rate of CD8+ T cell in 14–56 DFS. Conclusions The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.

Rabbit Antithymocyte Globulin Induction in Heart Transplant Recipients at High Risk for Rejection.

Background: Induction with lymphocyte-depleting antibodies may improve allograft outcomes in heart transplant recipients who are at high immunologic risk for rejection.Methods: We conducted a single-center retrospective cohort study that compared outcomes between adult patients receiving rabbit antithymocyte globulin (rATG) induction vs no induction from 2011 through 2017. Key exclusion criteria were patients who did not receive tacrolimus and mycophenolate and patients who did not meet high immunologic risk criteria.Results: A total of 50 patients were included in the analysis. At 1 year, the composite primary outcome of ≥2R rejection as defined by the International Society for Heart and Lung Transplantation, any treated rejection, development of cardiac allograft vasculopathy, or graft loss was not different between groups (P=0.474). Serious infections were also similar between groups (P=0.963). In accordance with institutional guidelines, prednisone exposure was decreased in the rATG induction group at 1 month (24.04 mg ± 13.74 vs 35.18 mg ± 16.95; P=0.014).Conclusion: These results suggest that while rATG induction does not improve heart allograft outcomes, it may enable reducing early corticosteroid exposure in patients at high immunologic risk.

Immunotherapy in advanced Non-Small Cell Lung Cancer patients with poor performance status: The role of clinical-pathological variables and inflammatory biomarkers

BackgroundThe introduction of immunotherapy has improved the prognosis of patients with Non-Small Cell Lung Cancer (NSCLC). However, data in poor ECOG Performance Status (PS) patients remain scant due to their exclusion from randomized trials. Material and methodsWe analyzed data of patients with advanced NSCLC treated with immunotherapy in two Italian Centers, to evaluate the impact of PS (0-1 vs 2) on disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Chi-square test was used to compare clinical-pathological variables, their impact on survival was evaluated through Cox proportional hazard models. ResultsAmong 404 patients included, PS was 0 in 137 (33.9 %), 1 in 208 (51.5 %) and 2 in 59 (14.6 %) patients; 143 were female and 90 had squamous NSCLC. Clinical-pathological variables were uniformly distributed except for higher prevalence of liver metastases in patients with poor PS. We found that PS2 patients showed worse outcomes in terms of DCR (21.8 % vs 50.3 %, p = 0.001), PFS [2.0 (95 % CI 1.6–3.0) vs 3.0 (95 % CI 2.7–4.0) months, p < 0.0001] and OS [4.0 (95 % CI 2.8–5.7) vs 13.2 (95 % CI 11.0−15.8) months, p < 0.0001]. PS2 status, negative PDL1 expression and early corticosteroids exposure as well as higher Neutrophil to Lymphocyte Ratio and LDH at baseline were associated with worse outcomes at univariate and multivariable analysis. Subgroup analysis confirmed poor outcomes in PS2 patients with high LDH and concomitant corticosteroid therapies. The incidence of Grade 3/4 adverse events was 11.3 % in PS 0−1 and 10.2 % in PS 2 patients (p = 0.81). ConclusionOur data confirm reduced efficacy of immunotherapy in patients with poor PS even though a good safety. Despite PS remains the most powerful independent prognostic factor for NSCLC, LDH levels and steroids exposure could support the decision making in PS2 patients.

What are the effects of moderately early (7 to 14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants?

What are the effects of moderately early (7 to 14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants?

34: The Effect of Early Corticosteroid Therapy on Outcomes in Children With Septic Shock

Kamps, Nicole1; Banks, Russell2; Reeder, Ron3; Cengiz, Pelin4; Zimmerman, Jerry5 Author Information

Viral clearance after early corticosteroid treatment in patients with moderate or severe covid-19

The aim of this study was to evaluate the impact of early treatment with corticosteroids on SARS-CoV-2 clearance in hospitalized COVID-19 patients. Retrospective analysis on patients admitted to the San Raffaele Hospital (Milan, Italy) with moderate/severe COVID-19 and availability of at least two nasopharyngeal swabs. The primary outcome was the time to nasopharyngeal swab negativization. A multivariable Cox model was fitted to determine factors associated with nasopharyngeal swab negativization. Of 280 patients included, 59 (21.1%) patients were treated with steroids. Differences observed between steroid users and non-users included the proportion of patients with a baseline PaO2/FiO2 ≤ 200 mmHg (45.8% vs 34.4% in steroids and non-steroids users, respectively; p = 0.023) or ≤ 100 mmHg (16.9% vs 12.7%; p = 0.027), and length of hospitalization (20 vs 14 days; p < 0.001). Time to negativization of nasopharyngeal swabs was similar in steroid and non-steroid users (p = 0.985). According to multivariate analysis, SARS-CoV-2 clearance was associated with age ≤ 70 years, a shorter duration of symptoms at admission, a baseline PaO2/FiO2 > 200 mmHg, and a lymphocyte count at admission > 1.0 × 109/L. SARS-CoV-2 clearance was not associated with corticosteroid use. Our study shows that delayed SARS-CoV-2 clearance in moderate/severe COVID-19 is associated with older age and a more severe disease, but not with an early use of corticosteroids.

LOW DOSE (4.5 MG/KG) OF THYMOGLOBULIN IS EFFECTIVE TO CONTROL T CELLS BUT NOT B CELLS AND CD56DIMCD57+, CD56DIMNKG2A+ NATURAL KILLER CELLS RESULTING IN DE NOVO DONOR-SPECIFIC ANTIBODY FORMATION AND ACUTE REJECTION IN NON-SENSITIZED LIVING DONOR KIDNEY RECIPIENTS WITH EARLY STEROID WITHDRAWAL

The optimal dose of Thymoglobulin as an induction regimen in Asian living donor kidney recipients has been rarely reported. Patients were randomly assigned to receive either 4.5 mg/kg (ATG4.5 group, n=19) or 6.0 mg/kg (ATG6.0 group, n=17) Thymoglobulin. All patients had corticosteroid withdrawal within 7 days. The primary end point was a composite of biopsy-proven acute rejection, de novo donor specific antibody, or graft failure. Until 49 months post-transplant, the rate of the composite end point was 47.4% in the ATG4.5 group whereas 17.6% in the ATG6.0 group. There was one case of death-censored graft failure in the ATG4.5 group whereas there was no mortality during the follow-up period (22 to 49 months). This study was ceased earlier than expected because we concerned about the more increasing risk of the composite end point in the ATG4.5 group. Compared to pre-transplantation, T (CD3+CD56-) cells, NK (CD3-CD56+) cells, and NKT (CD3+CD56+) cells were significantly decreased whereas B (CD19+) cells were not significantly affected by Thymoglobulin in the first week. Although T and NKT cells had recovered to the pre-transplant value in both groups, NK cells in the ATG6.0 were kept suppressed while NK cells in the ATG4.5 group had recovered to the pre-transplant value. Interestingly, CD56dimCD57+ cells were significantly increased whereas CD56dimNKG2A+ cells was significantly decreased in the ATG4.5 group compared with the ATG6.0 group until six months post-transplant. ATG 4.5 mg/kg induction and early corticosteroid withdrawal tended to increase the rate of de novo donor-specific antibody and biopsy-proven acute rejection. (ClinicalTrials.gov: NCT02447822)

Infarctus cérébral et tuberculose : rapport d'un cas et analyse de la littérature

IntroductionAlthough tuberculous meningitis is an uncommon presentation of tuberculosis, it still remains one of the deadliest forms of this disease. In this context, the occurrence of a cerebral infarct is an aggravating factor. ObservationA 48-year-old Asian man presented himself in the emergency room for dysarthria and dysphagia of progressive onset. Cerebral CT showed a recent ischemic defect of the right internal capsule. Lumbar puncture showed meningitis with low sugar levels. Pulmonary micronodules on the thoracic CT suggested tuberculosis, which was confirmed by a broncho-alveolar lavage. Anti-tuberculosis treatment and early corticosteroid resulted in an improvement of the patient's state. ConclusionCerebral infarctions in patients with tuberculous meningitis are events that cannot be underestimated in terms of frequency or severity. Their poor prognosis is partly the result of insufficiently defined management, which combines anti-tuberculosis treatment and early corticosteroid therapy.